@article {pmid36977893,
year = {2023},
author = {Zvolensky, MJ and Shepherd, JM and Clausen, BK and Garey, L and Redmond, BY and Santiago-Torres, M and Bricker, JB},
title = {Role of perceived discrimination and anxiety sensitivity in cigarette smoking among english-speaking latinx adults living in the United States.},
journal = {Journal of behavioral medicine},
volume = {},
number = {},
pages = {},
pmid = {36977893},
issn = {1573-3521},
support = {U54MD015946/MD/NIMHD NIH HHS/United States ; },
abstract = {OBJECTIVE: The Latinx/Hispanic (hereafter, Latinx) population in the United States (US) experiences significant tobacco-related health disparities. Extant work suggests social determinants of health (SDoH) such as perceived discrimination is an individual differences factor for cigarette smoking behavior among Latinx individuals who smoke cigarettes. Other research has suggested sensitivity to internal cues, referred to as anxiety sensitivity, is related to smoking among Latinx adults, but this work has not explored whether anxiety sensitivity may moderate the association between perceived discrimination and smoking behavior.<br><br>METHOD: Therefore, the present investigation sought to explore the main and interactive association of perceived discrimination and anxiety sensitivity in relation to cigarettes smoked per day, severity of problems experienced when quitting, and perceived barriers for smoking cessation among 338 English-speaking Latinx individuals living in the US (Mage = 35.5 years; SD&#x2009;=&#x2009;8.65; age range 18-61; 37.3% female) who smoke cigarettes.<br><br>RESULTS: Results supported statistically significant main effects for perceived discrimination and anxiety sensitivity in relation to increased severity of problems experienced when quitting and perceived barriers for smoking cessation. These associations were evident after adjusting for a sociodemographic covariates.<br><br>CONCLUSION: Overall, the present investigation suggests that both perceived discrimination and anxiety sensitivity are important constructs relevant to understanding smoking processes among Latinx adults who smoke cigarettes and should be integrated in theoretical models of smoking among this population.},
}
@article {pmid36977698,
year = {2023},
author = {Carrico, C and Cruz, A and Walter, M and Meyer, J and Wehrfritz, C and Shah, S and Wei, L and Schilling, B and Verdin, E},
title = {Coenzyme A binding sites induce proximal acylation across protein families.},
journal = {Scientific reports},
volume = {13},
number = {1},
pages = {5029},
pmid = {36977698},
issn = {2045-2322},
support = {1S10 OD016281/RR/NCRR NIH HHS/United States ; DK085610/DK/NIDDK NIH HHS/United States ; },
mesh = {*Lysine/metabolism ; Acylation ; Acetylation ; *Acyl Coenzyme A/metabolism ; Protein Processing, Post-Translational ; Binding Sites ; },
abstract = {Lysine Nɛ-acylations, such as acetylation or succinylation, are post-translational modifications that regulate protein function. In mitochondria, lysine acylation is predominantly non-enzymatic, and only a specific subset of the proteome is acylated. Coenzyme A (CoA) can act as an acyl group carrier via a thioester bond, but what controls the acylation of mitochondrial lysines remains poorly understood. Using published datasets, here we found that proteins with a CoA-binding site are more likely to be acetylated, succinylated, and glutarylated. Using computational modeling, we show that lysine residues near the CoA-binding pocket are highly acylated compared to those farther away. We hypothesized that acyl-CoA binding enhances acylation of nearby lysine residues. To test this hypothesis, we co-incubated enoyl-CoA hydratase short chain 1 (ECHS1), a CoA-binding mitochondrial protein, with succinyl-CoA and CoA. Using mass spectrometry, we found that succinyl-CoA induced widespread lysine succinylation and that CoA competitively inhibited ECHS1 succinylation. CoA-induced inhibition at a particular lysine site correlated inversely with the distance between that lysine and the CoA-binding pocket. Our study indicated that CoA acts as a competitive inhibitor of ECHS1 succinylation by binding to the CoA-binding pocket. Together, this suggests that proximal acylation at CoA-binding sites is a primary mechanism for lysine acylation in the mitochondria.},
}
@article {pmid36975801,
year = {2023},
author = {Carter, KA and Fodor, AA and Balkus, JE and Zhang, A and Serrano, MG and Buck, GA and Engel, SM and Wu, MC and Sun, S},
title = {Vaginal Microbiome Metagenome Inference Accuracy: Differential Measurement Error according to Community Composition.},
journal = {mSystems},
volume = {},
number = {},
pages = {e0100322},
doi = {10.1128/msystems.01003-22},
pmid = {36975801},
issn = {2379-5077},
abstract = {Several studies have compared metagenome inference performance in different human body sites; however, none specifically reported on the vaginal microbiome. Findings from other body sites cannot easily be generalized to the vaginal microbiome due to unique features of vaginal microbial ecology, and investigators seeking to use metagenome inference in vaginal microbiome research are "flying blind" with respect to potential bias these methods may introduce into analyses. We compared the performance of PICRUSt2 and Tax4Fun2 using paired 16S rRNA gene amplicon sequencing and whole-metagenome sequencing data from vaginal samples from 72 pregnant individuals enrolled in the Pregnancy, Infection, and Nutrition (PIN) cohort. Participants were selected from those with known birth outcomes and adequate 16S rRNA gene amplicon sequencing data in a case-control design. Cases experienced early preterm birth (<32 weeks of gestation), and controls experienced term birth (37 to 41 weeks of gestation). PICRUSt2 and Tax4Fun2 performed modestly overall (median Spearman correlation coefficients between observed and predicted KEGG ortholog [KO] relative abundances of 0.20 and 0.22, respectively). Both methods performed best among Lactobacillus crispatus-dominated vaginal microbiotas (median Spearman correlation coefficients of 0.24 and 0.25, respectively) and worst among Lactobacillus iners-dominated microbiotas (median Spearman correlation coefficients of 0.06 and 0.11, respectively). The same pattern was observed when evaluating correlations between univariable hypothesis test P values generated with observed and predicted metagenome data. Differential metagenome inference performance across vaginal microbiota community types can be considered differential measurement error, which often causes differential misclassification. As such, metagenome inference will introduce hard-to-predict bias (toward or away from the null) in vaginal microbiome research. IMPORTANCE Compared to taxonomic composition, the functional potential within a bacterial community is more relevant to establishing mechanistic understandings and causal relationships between the microbiome and health outcomes. Metagenome inference attempts to bridge the gap between 16S rRNA gene amplicon sequencing and whole-metagenome sequencing by predicting a microbiome's gene content based on its taxonomic composition and annotated genome sequences of its members. Metagenome inference methods have been evaluated primarily among gut samples, where they appear to perform fairly well. Here, we show that metagenome inference performance is markedly worse for the vaginal microbiome and that performance varies across common vaginal microbiome community types. Because these community types are associated with sexual and reproductive outcomes, differential metagenome inference performance will bias vaginal microbiome studies, obscuring relationships of interest. Results from such studies should be interpreted with substantial caution and the understanding that they may over- or underestimate associations with metagenome content.},
}
@article {pmid36973965,
year = {2023},
author = {Li, CI and Weiss, NS and Madeleine, MM and Mueller, BA and Malone, KE},
title = {In Memoriam: Janet R. Daling, 1934-2022.},
journal = {American journal of epidemiology},
volume = {},
number = {},
pages = {},
doi = {10.1093/aje/kwad066},
pmid = {36973965},
issn = {1476-6256},
}
@article {pmid36973557,
year = {2023},
author = {Persad, S and Choo, ZN and Dien, C and Sohail, N and Masilionis, I and Chaligné, R and Nawy, T and Brown, CC and Sharma, R and Pe'er, I and Setty, M and Pe'er, D},
title = {SEACells infers transcriptional and epigenomic cellular states from single-cell genomics data.},
journal = {Nature biotechnology},
volume = {},
number = {},
pages = {},
pmid = {36973557},
issn = {1546-1696},
support = {R35 GM147125/GM/NIGMS NIH HHS/United States ; U54 CA209975/CA/NCI NIH HHS/United States ; U2C CA233284/CA/NCI NIH HHS/United States ; },
abstract = {Metacells are cell groupings derived from single-cell sequencing data that represent highly granular, distinct cell states. Here we present single-cell aggregation of cell states (SEACells), an algorithm for identifying metacells that overcome the sparsity of single-cell data while retaining heterogeneity obscured by traditional cell clustering. SEACells outperforms existing algorithms in identifying comprehensive, compact and well-separated metacells in both RNA and assay for transposase-accessible chromatin (ATAC) modalities across datasets with discrete cell types and continuous trajectories. We demonstrate the use of SEACells to improve gene-peak associations, compute ATAC gene scores and infer the activities of critical regulators during differentiation. Metacell-level analysis scales to large datasets and is particularly well suited for patient cohorts, where per-patient aggregation provides more robust units for data integration. We use our metacells to reveal expression dynamics and gradual reconfiguration of the chromatin landscape during hematopoietic differentiation and to uniquely identify CD4 T cell differentiation and activation states associated with disease onset and severity in a Coronavirus Disease 2019 (COVID-19) patient cohort.},
}
@article {pmid36973349,
year = {2023},
author = {Siebert, R and Schuh, A and Ott, G and Cree, IA and Du, MQ and Ferry, J and Hochhaus, A and Naresh, KN and Solary, E and Khoury, JD},
title = {Response to the Comments from the Groupe Francophone de Cytogénétique Hématologique (GFCH) on the 5th edition of the World Health Organization classification of haematolymphoid tumors.},
journal = {Leukemia},
volume = {},
number = {},
pages = {},
pmid = {36973349},
issn = {1476-5551},
}
@article {pmid36973099,
year = {2023},
author = {Ehler, ED and Turcotte, LM and Skamene, S and Baker, KS and Das, SK and Constine, LS and Yuan, J and Dusenbery, KE},
title = {Idiopathic Pneumonitis Syndrome After Total Body Irradiation in Pediatric Patients Undergoing Myeloablative Hematopoietic Stem Cell Transplantation: A PENTEC Comprehensive Review.},
journal = {International journal of radiation oncology, biology, physics},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.ijrobp.2023.02.037},
pmid = {36973099},
issn = {1879-355X},
abstract = {PURPOSE: Pulmonary complications, especially idiopathic pneumonitis syndrome (IPS), are potentially life altering or fatal sequelae of hematopoietic cell transplantation (HCT). Total body irradiation (TBI) as part of the conditioning regimen has been implicated in IPS. A comprehensive PENTEC (Pediatric Normal Tissues in the Clinic) review was performed to increase our understanding of the role of TBI in the development of acute, noninfectious IPS.<br><br>METHODS AND MATERIALS: A systematic literature search was conducted using the MEDLINE, PubMed, and Cochrane library databases for articles describing pulmonary toxicity in children treated with HCT. Data pertaining to TBI and pulmonary endpoints were extracted. Risk of IPS was analyzed in relation to patient age, TBI dose, fractionation, dose rate, lung shielding, timing, and type of transplant, with the goal to better understand factors associated with this complication in children undergoing HCT. A logistic regression model was developed using a subset of studies with comparable transplant regimens and sufficient TBI data.<br><br>RESULTS: Six studies met criteria for modeling of the correlation of TBI parameters with IPS; all consisted of pediatric patients undergoing allogeneic HCT with a cyclophosphamide-based chemotherapy regimen. IPS was variably defined, but all studies that reported IPS were included in this analysis. The mean incidence of post-HCT IPS was 16% (range, 4%-41%). Mortality from IPS, when it occurred, was high (median, 50%; range, 45%-100%). Fractionated TBI prescription doses encompassed a narrow range of 9 to 14 Gy. Many differing TBI methods were reported, and there was an absence of 3-dimensional dose analysis of lung blocking techniques. Thus, a univariate correlation between IPS and total TBI dose, dose fractionation, dose rate, or TBI technique could not be made. However, a model, built from these studies based on prescribed dose using a normalized dose parameter of equivalent dose in 2-Gy fractions (EQD2), adjusted for dose rate, suggested correlation with the development of IPS (P&#xa0;=&#xa0;.0004). The model-predicted odds ratio for IPS was 24.3 Gy[-1] (95% confidence interval, 7.0-84.3). Use of TBI lung dose metrics (eg, midlung point dose) could not be successfully modeled, potentially because of dosimetric uncertainties in the actual delivered volumetric lung dose and imperfections in our modeling process.<br><br>CONCLUSIONS: This PENTEC report is a comprehensive review of IPS in pediatric patients receiving fractionated TBI regimens for allogenic HCT. IPS was not clearly associated with 1 single TBI factor. Modeling using dose-rate adjusted EQD2 showed a response with IPS for allogeneic HCT using a cyclophosphamide-based chemotherapy regimen. Therefore, this model suggests IPS mitigation strategies can focus on not just the dose and dose per fraction but also the dose rate used in TBI. More data are needed to confirm this model and to determine the influence of chemotherapy regimens and contribution from graft-versus-host disease. The presence of confounding variables (eg, systemic chemotherapies) that affect risk, the narrow range of fractionated TBI doses found in the literature, and limitations of other reported data (eg, lung point dose) may have prevented a more straightforward link between IPS and total dose from being observed.},
}
@article {pmid36973008,
year = {2023},
author = {Ahmed, A and Hippe, DS and Snidarich, M and Crothers, K and Triplette, M},
title = {Delays in Recommended Follow-up after Positive Findings in Lung Cancer Screening .},
journal = {Annals of the American Thoracic Society},
volume = {},
number = {},
pages = {},
doi = {10.1513/AnnalsATS.202210-891OC},
pmid = {36973008},
issn = {2325-6621},
abstract = {RATIONALE: Lung cancer screening (LCS) is an effective tool to reduce mortality; However, barriers along the LCS care continuum including delay in follow-up care may reduce effectiveness. Objectives: The primary goals of this study were to evaluate delays in follow-up in patients with positive findings on LCS, and examine the impact of delay on lung cancer staging. Methods: This was a retrospective cohort study of patients enrolled in a multisite LCS program with positive LCS findings, defined as Lung-RADS 3, 4A, 4B or 4X. Time-to-first-follow-up was evaluated with delay considered >30 days beyond standardized Lung-RADS recommendation. Multivariable Cox models were used to evaluate the likelihood of delay by Lung-RADS category. Participants with resultant non-small cell lung cancer (NSCLC) were evaluated to determine if delay in follow-up was associated with clinical upstaging.<br><br>RESULTS: Three-hundred sixty-nine patients with 434 exams had positive findings; 16% of findings were ultimately diagnosed as lung cancer. In 47% of positive exams, there was a delay in follow-up (median delay: 104 days); 59% (210 days) of Lung-RADS 3 exams, 35% (64 days) of Lung-RADS 4A exams, and 40% (34 days) of Lung-RADS 4B/4X exams (p<0.001). In the 54 patients diagnosed with NSCLC through LCS, delay was associated with increased likelihood of clinical upstaging (p<0.001).<br><br>CONCLUSION: In this study of delay in follow-up after positive LCS findings, we found that nearly half of patients had delays in follow-up and that delay was associated with clinical upstaging in patients whose positive findings represent lung cancer. Further targeted interventions to ensure timely follow-up after positive LCS exam are critical.},
}
@article {pmid36971848,
year = {2023},
author = {Bhimani, J and O'Connell, K and Kuk, D and Du, M and Navarro, SL and Kantor, ED},
title = {Glucosamine and Chondroitin Use and Mortality Among Adults in the United States from 1999 to 2014.},
journal = {Journal of integrative and complementary medicine},
volume = {},
number = {},
pages = {},
doi = {10.1089/jicm.2022.0783},
pmid = {36971848},
issn = {2768-3613},
abstract = {Introduction: Glucosamine and chondroitin are supplements that are often, but not always, used in combination for arthritis and joint pain. Multiple studies have suggested that glucosamine and chondroitin may be associated with reduced risk of several diseases, as well as all-cause, cancer- and respiratory disease-specific mortality. Methods: Nationally representative data from the National Health and Nutrition Examination Survey (NHANES) were used to further evaluate the association between glucosamine and chondroitin with mortality. Participants include 38,021 adults, ages 20+ years and older, who completed the detailed NHANES between 1999 and 2014. Participants were followed for death through linkage with the National Death Index through the end of 2015, over which time 4905 deaths occurred. Adjusted hazard ratios (HRs) for overall and cause-specific mortality were estimated using Cox regression models. Results: Despite glucosamine and chondroitin use appearing to be inversely associated with mortality in the minimally adjusted models, no association was observed in multivariable models (glucosamine: HR = 1.02; 95% confidence interval [CI]: 0.86-1.21, chondroitin: HR = 1.04, 95% CI: 0.87-1.25). No association with cancer mortality or other mortality rate was observed after multivariable adjustment. There was a suggestive, nonsignificant inverse association for cardiovascular-specific mortality (glucosamine HR = 0.72; 95% CI: 0.46-1.15, chondroitin: HR = 0.76; 95% CI: 0.47-1.21). Conclusion: The lack of significant relationship between glucosamine and chondroitin use and all-cause or cause-specific mortality after adjusting extensively for multiple covariates in this nationally representative adult population was in contrast to prior literature. Given the limited power to explore the cause-specific mortality, future well-powered studies will be needed to better understand the potential association with cardiovascular-specific mortality.},
}
@article {pmid36971561,
year = {2023},
author = {Kher, G and Sabin, C and Lun, JH and Devant, JM and Ruoff, K and Koromyslova, AD and von Itzstein, M and Pancera, M and Hansman, GS},
title = {Direct Blockade of the Norovirus Histo-Blood Group Antigen Binding Pocket by Nanobodies.},
journal = {Journal of virology},
volume = {},
number = {},
pages = {e0183322},
doi = {10.1128/jvi.01833-22},
pmid = {36971561},
issn = {1098-5514},
abstract = {Noroviruses are the leading cause of outbreaks of acute gastroenteritis. These viruses usually interact with histo-blood group antigens (HBGAs), which are considered essential cofactors for norovirus infection. This study structurally characterizes nanobodies developed against the clinically important GII.4 and GII.17 noroviruses with a focus on the identification of novel nanobodies that efficiently block the HBGA binding site. Using X-ray crystallography, we have characterized nine different nanobodies that bound to the top, side, or bottom of the P domain. The eight nanobodies that bound to the top or side of the P domain were mainly genotype specific, while one nanobody that bound to the bottom cross-reacted against several genotypes and showed HBGA blocking potential. The four nanobodies that bound to the top of the P domain also inhibited HBGA binding, and structural analysis revealed that these nanobodies interacted with several GII.4 and GII.17 P domain residues that commonly engaged HBGAs. Moreover, these nanobody complementarity-determining regions (CDRs) extended completely into the cofactor pockets and would likely impede HBGA engagement. The atomic level information for these nanobodies and their corresponding binding sites provide a valuable template for the discovery of additional "designer" nanobodies. These next-generation nanobodies would be designed to target other important genotypes and variants, while maintaining cofactor interference. Finally, our results clearly demonstrate for the first time that nanobodies directly targeting the HBGA binding site can function as potent norovirus inhibitors. IMPORTANCE Human noroviruses are highly contagious and a major problem in closed institutions, such as schools, hospitals, and cruise ships. Reducing norovirus infections is challenging on multiple levels and includes the frequent emergence of antigenic variants, which complicates designing effective, broadly reactive capsid therapeutics. We successfully developed and characterized four norovirus nanobodies that bound at the HBGA pockets. Compared with previously developed norovirus nanobodies that inhibited HBGA through disrupted particle stability, these four novel nanobodies directly inhibited HBGA engagement and interacted with HBGA binding residues. Importantly, these new nanobodies specifically target two genotypes that have caused the majority of outbreaks worldwide and consequently would have an enormous benefit if they could be further developed as norovirus therapeutics. To date, we have structurally characterized 16 different GII nanobody complexes, a number of which block HBGA binding. These structural data could be used to design multivalent nanobody constructs with improved inhibition properties.},
}
@article {pmid36969261,
year = {2023},
author = {Martinez-Sanz, P and Laurent, ARG and Slot, E and Hoogenboezem, M and Bąbała, N and van Bruggen, R and Rongvaux, A and Flavell, RA and Tytgat, GAM and Franke, K and Matlung, HL and Kuijpers, TW and Amsen, D and Karrich, JJ},
title = {Humanized MISTRG as a preclinical in vivo model to study human neutrophil-mediated immune processes.},
journal = {Frontiers in immunology},
volume = {14},
number = {},
pages = {1105103},
pmid = {36969261},
issn = {1664-3224},
mesh = {Humans ; Mice ; Animals ; *Neutrophils ; Hematopoietic Stem Cell Mobilization ; *Heterocyclic Compounds ; Bone Marrow ; Immunity ; },
abstract = {INTRODUCTION: MISTRG mice have been genetically modified to allow development of a human myeloid compartment from engrafted human CD34+ haemopoietic stem cells, making them particularly suited to study the human innate immune system in vivo. Here, we characterized the human neutrophil population in these mice to establish a model that can be used to study the biology and contribution in immune processes of these cells in vivo.<br><br>METHODS AND RESULTS: We could isolate human bone marrow neutrophils from humanized MISTRG mice and confirmed that all neutrophil maturation stages from promyelocytes (CD11b-CD16-) to end-stage segmented cells (CD11b+CD16+) were present. We documented that these cells possessed normal functional properties, including degranulation, reactive oxygen species production, adhesion, and antibody-dependent cellular cytotoxicity towards antibody-opsonized tumor cells ex vivo. The acquisition of functional capacities positively correlated with the maturation state of the cell. We found that human neutrophils were retained in the bone marrow of humanized MISTRG mice during steady state. However, the mature segmented CD11b+CD16+ human neutrophils were released from the bone marrow in response to two well-established neutrophil-mobilizing agents (i.e., G-CSF and/or CXCR4 antagonist Plerixafor). Moreover, the neutrophil population in the humanized MISTRG mice actively reacted to thioglycolate-induced peritonitis and could infiltrate implanted human tumors, as shown by flow cytometry and fluorescent microscopy.<br><br>DISCUSSION: These results show that functional human neutrophils are generated and can be studied in vivo using the humanized MISTRG mice, providing a model to study the various functions of neutrophils in inflammation and in tumors.},
}
@article {pmid36967168,
year = {2022},
author = {Prentice, RL and Pettinger, M and Zheng, C and Neuhouser, ML and Raftery, D and Gowda, GAN and Huang, Y and Tinker, LF and Howard, BV and Manson, JE and Van Horn, L and Wallace, R and Mossavar-Rahmani, Y and Johnson, KC and Snetselaar, L and Lampe, JW},
title = {Biomarkers for Components of Dietary Protein and Carbohydrate with Application to Chronic Disease Risk in Postmenopausal Women.},
journal = {The Journal of nutrition},
volume = {152},
number = {4},
pages = {1107-1117},
doi = {10.1093/jn/nxac004},
pmid = {36967168},
issn = {1541-6100},
mesh = {Humans ; Female ; Prospective Studies ; Postmenopause ; Biomarkers ; Dietary Carbohydrates ; Dietary Proteins ; *Diabetes Mellitus ; Chronic Disease ; *Cardiovascular Diseases/epidemiology ; *Neoplasms ; Risk Factors ; },
abstract = {BACKGROUND: We recently developed protein and carbohydrate intake biomarkers using metabolomics profiles in serum and urine, and used them to correct self-reported dietary data for measurement error. Biomarker-calibrated carbohydrate density was inversely associated with chronic disease risk, whereas protein density associations were mixed.<br><br>OBJECTIVES: To elucidate and extend this earlier work through biomarker development for protein and carbohydrate components, including animal protein and fiber.<br><br>METHODS: Prospective disease association analyses were undertaken in Women's Health Initiative (WHI) cohorts of postmenopausal US women, aged 50-79 y when enrolled at 40 US clinical centers. Biomarkers were developed using an embedded human feeding study (n = 153). Calibration equations for protein and carbohydrate components were developed using a WHI nutritional biomarker study (n = 436). Calibrated intakes were associated with chronic disease incidence in WHI cohorts (n = 81,954) over a 20-y (median) follow-up period, using HR regression methods.<br><br>RESULTS: Previously reported elevations in cardiovascular disease (CVD) with higher-protein diets tended to be explained by animal protein density. For example, for coronary heart disease a 20% increment in animal protein density had an HR of 1.20 (95% CI: 1.02, 1.42) relative to the HR for total protein density. In comparison, cancer and diabetes risk showed little association with animal protein density beyond that attributable to total protein density. Inverse carbohydrate density associations with total CVD were mostly attributable to fiber density, with a 20% increment HR factor of 0.89 (95% CI: 0.83, 0.94). Cancer risk showed little association with fiber density, whereas diabetes risk had a 20% increment HR of 0.93 (95% CI: 0.88, 0.98) relative to the HRs for total carbohydrate density.<br><br>CONCLUSIONS: In a population of postmenopausal US women, CVD risk was associated with high-animal-protein and low-fiber diets, cancer risk was associated with low-carbohydrate diets, and diabetes risk was associated with low-fiber/low-carbohydrate diets.},
}
@article {pmid36967167,
year = {2022},
author = {Cheng, TD and Ilozumba, MN and Balavarca, Y and Neuhouser, ML and Miller, JW and Beresford, SAA and Zheng, Y and Song, X and Duggan, DJ and Toriola, AT and Bailey, LB and Green, R and Caudill, MA and Ulrich, CM},
title = {Associations between Genetic Variants and Blood Biomarkers of One-Carbon Metabolism in Postmenopausal Women from the Women's Health Initiative Observational Study.},
journal = {The Journal of nutrition},
volume = {152},
number = {4},
pages = {1099-1106},
doi = {10.1093/jn/nxab444},
pmid = {36967167},
issn = {1541-6100},
mesh = {Female ; Humans ; *Cysteine ; *Postmenopause/genetics ; Folic Acid ; Women's Health ; Genotype ; Biomarkers ; Vitamin B 12 ; Vitamins ; Carbon/metabolism ; Methylenetetrahydrofolate Reductase (NADPH2)/genetics/metabolism ; Homocysteine ; Histocompatibility Antigens ; Histone-Lysine N-Methyltransferase/genetics ; },
abstract = {BACKGROUND: Genetic variation in one-carbon metabolism may affect nutrient concentrations and biological functions. However, data on genetic variants associated with blood biomarkers of one-carbon metabolism in US postmenopausal women are limited, and whether these associations were affected by the nationwide folic acid (FA) fortification program is unclear.<br><br>OBJECTIVES: We investigated associations between genetic variants and biomarkers of one-carbon metabolism using data from the Women's Health Initiative Observational Study.<br><br>METHODS: In 1573 non-Hispanic White (NHW) and 282 Black/African American, American Indian/Alaska Native, Asian/Pacific Islander, and Hispanic/Latino women aged 50-79 y, 288 nonsynonymous and tagging single-nucleotide variants (SNVs) were genotyped. RBC folate, plasma folate, pyridoxal-5'-phosphate (PLP), vitamin B-12, homocysteine, and cysteine concentrations were determined in 12-h fasting blood. Multivariable linear regression tested associations per variant allele and for an aggregated genetic risk score. Effect modifications before, during, and after nationwide FA fortification were examined.<br><br>RESULTS: After correction for multiple comparisons, among NHW women, 5,10-methylenetetrahydrofolate reductase (MTHFR) rs1801133 (677C&#x2192;T) variant T was associated with lower plasma folate (-13.0%; 95% CI: -17.3%, -8.6%) and higher plasma homocysteine (3.5%; 95% CI: 1.7%, 5.3%) concentrations. Other associations for nonsynonymous SNVs included DNMT3A rs11695471 (T&#x2192;A) with plasma PLP; EHMT2 rs535586 (G&#x2192;A), TCN2 rs1131603 (L349S A&#x2192;G), and TCN2 rs35838082 (R188W G&#x2192;A) with plasma vitamin B-12; CBS rs2851391 (G&#x2192;A) with plasma homocysteine; and MTHFD1 rs2236224 (G&#x2192;A) and rs2236225 (R653Q G&#x2192;A) with plasma cysteine. The influence of FA fortification on the associations was limited. Highest compared with lowest quartiles of aggregated genetic risk scores from SNVs in MTHFR and MTRR were associated with 14.8% to 18.9% lower RBC folate concentrations. Gene-biomarker associations were similar in women of other races/ethnicities.<br><br>CONCLUSIONS: Our findings on genetic variants associated with several one-carbon metabolism biomarkers may help elucidate mechanisms of maintaining B vitamin status in postmenopausal women.},
}
@article {pmid36966871,
year = {2023},
author = {Hall, AG and Winestone, LE and Sullivan, EM and Wu, Q and Lamble, AJ and Walters, MC and Aguayo-Hiraldo, P and Conde, LB and Coker, TR and Dornsife, D and Keating, AK and Merino, DM and Ramsey, B and Park, JR and Agrawal, AK},
title = {Access to CAR T-cell Clinical Trials in Underrepresented Populations: a Multicenter Cohort Study of Pediatric and Young Adult ALL Patients.},
journal = {Transplantation and cellular therapy},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jtct.2023.03.022},
pmid = {36966871},
issn = {2666-6367},
abstract = {BACKGROUND: Chimeric antigen receptor (CAR) T-cell therapy is a promising approach to improve survival for children and adults with relapsed/refractory (r/r) B-ALL, but these clinical trials may not be equally accessible to patients with low socioeconomic status or to patients from racial or ethnic minority groups.<br><br>OBJECTIVE: We sought to describe the sociodemographic characteristics of pediatric and AYA patients enrolled in CAR T-cell clinical trials and to compare these characteristics to other patients with r/r B-ALL.<br><br>STUDY DESIGN: We conducted a multicenter retrospective cohort study at five pediatric consortium sites to compare the sociodemographic characteristics of patients treated and enrolled in CAR T-cell trials at their home institution, other patients with r/r B-ALL treated at these sites, and patients referred from an external hospital for CAR T-cell trials. Patients were age 0-27 years with r/r B-ALL treated at one of the consortium sites between 2012-2018. Clinical and demographic data were collected from the electronic health record. We calculated distance from home to treating institution and assigned socioeconomic status scores based on census tract.<br><br>RESULTS: Among 337 patients treated for r/r B-ALL, 112 were referred from an external hospital to a consortium site and enrolled in a CAR T-cell trial; 225 were treated primarily at a consortium site, with 34% enrolled in a CAR T-cell trial. Patients treated primarily at a consortium site had similar characteristics, regardless of trial enrollment. A lower proportion of Hispanic patients (37% vs. 56%, p=0.03), patients whose preferred language was Spanish (8% vs. 22%, p=0.006), and publicly insured patients (38% vs. 65%, p=0.001) were referred from an external hospital compared to patients treated primarily at a consortium site and enrolled in a CAR T-cell trial.<br><br>CONCLUSIONS: Patients who are Hispanic, Spanish-speaking, or publicly insured are underrepresented in referrals from external hospitals to CAR T-cell centers. External provider implicit bias may also influence referral of these patients. Establishing partnerships between CAR T-cell centers and external hospital sites may improve provider familiarity, patient referral, and patient access to CAR T-cell clinical trials.},
}
@article {pmid36965799,
year = {2022},
author = {Moolgavkar, SH and Chang, ET and Luebeck, EG},
title = {Multistage carcinogenesis: Impact of age, genetic, and environmental factors on the incidence of malignant mesothelioma.},
journal = {Environmental research},
volume = {},
number = {},
pages = {114582},
doi = {10.1016/j.envres.2022.114582},
pmid = {36965799},
issn = {1096-0953},
abstract = {The current paradigm of carcinogenesis as a cellular evolutionary process driven by mutations of a few critical driver genes has immediate logical implications for the epidemiology of cancer. These include the impact of age on cancer risk, the role played by inherited tumor predisposition syndromes, and the interaction of genetics and environmental exposures on cancer risk. In this paper, we explore the following logical epidemiological consequences of carcinogenesis as a clonal process of mutation accumulation, with special emphasis on asbestos-related cancers, specifically malignant mesothelioma.},
}
@article {pmid36964402,
year = {2023},
author = {Dec, E and Clement, J and Cheng, K and Church, GM and Fossel, MB and Rehkopf, DH and Rosero-Bixby, L and Kobor, MS and Lin, DT and Lu, AT and Fei, Z and Guo, W and Chew, YC and Yang, X and Putra, SED and Reiner, AP and Correa, A and Vilalta, A and Pirazzini, C and Passarino, G and Monti, D and Arosio, B and Garagnani, P and Franceschi, C and Horvath, S},
title = {Centenarian clocks: epigenetic clocks for validating claims of exceptional longevity.},
journal = {GeroScience},
volume = {},
number = {},
pages = {},
pmid = {36964402},
issn = {2509-2723},
support = {U01AG060908/AG/NIA NIH HHS/United States ; },
abstract = {Claims surrounding exceptional longevity are sometimes disputed or dismissed for lack of credible evidence. Here, we present three DNA methylation-based age estimators (epigenetic clocks) for verifying age claims of centenarians. The three centenarian clocks were developed based on n = 7039 blood and saliva samples from individuals older than 40, including n = 184 samples from centenarians, 122 samples from semi-supercentenarians (aged 105 +), and 25 samples from supercentenarians (aged 110 +). The oldest individual was 115 years old. Our most accurate centenarian clock resulted from applying a neural network model to a training set composed of individuals older than 40. An epigenome-wide association study of age in different age groups revealed that age effects in young individuals (age < 40) are correlated (r = 0.55) with age effects in old individuals (age > 90). We present a chromatin state analysis of age effects in centenarians. The centenarian clocks are expected to be useful for validating claims surrounding exceptional old age.},
}
@article {pmid36964041,
year = {2023},
author = {Guo, C and Figueiredo, I and Gurel, B and Neeb, A and Seed, G and Crespo, M and Carreira, S and Rekowski, J and Buroni, L and Welti, J and Bogdan, D and Gallagher, L and Sharp, A and de la Maza, MDF and Rescigno, P and Westaby, D and Chandran, K and Riisnaes, R and Ferreira, A and Miranda, S and Calì, B and Alimonti, A and Bressan, S and Nguyen, AHT and Shen, MM and Hawley, JE and Obradovic, A and Drake, CG and Bertan, C and Baker, C and Tunariu, N and Yuan, W and de Bono, JS},
title = {Erratum to "B7-H3 as a Therapeutic Target in Advanced Prostate Cancer" [Eur Urol 2023;83(3):224-38].},
journal = {European urology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.eururo.2023.03.005},
pmid = {36964041},
issn = {1873-7560},
}
@article {pmid36963200,
year = {2023},
author = {Dotan, E and Catalano, P and Lenchik, L and Boutin, R and Yao, X and Marques, HS and Ioffe, D and Zhen, DB and Li, D and Wagner, LI and Simon, MA and Wong, TZ and O'Dwyer, PJ},
title = {The GIANT trial (ECOG-ACRIN EA2186) methods paper: A randomized phase II study of gemcitabine and nab-paclitaxel compared with 5-fluorouracil, leucovorin, and liposomal irinotecan in older patients with treatment-naïve metastatic pancreatic cancer - defining a new treatment option for older vulnerable patients.},
journal = {Journal of geriatric oncology},
volume = {14},
number = {3},
pages = {101474},
doi = {10.1016/j.jgo.2023.101474},
pmid = {36963200},
issn = {1879-4076},
abstract = {INTRODUCTION: Pancreatic cancer is the fourth leading cause of cancer-related death in the US with an increasing incidence in older adults (OA) over age 70. There are currently no treatment guidelines for OA with metastatic pancreatic cancer (mPCA) and selecting a chemotherapy regimen for these patients is subjective, based largely on chronologic age and performance status (PS). Geriatric screening tools provide a more objective and accurate evaluation of a patient's overall health but have not yet been validated in patient selection for mPCA treatment. This study aims to elucidate the optimal chemotherapy treatment of vulnerable OA with mPCA and understand the geriatric factors that affect outcomes in this population.<br><br>METHODS/DESIGN: The GIANT (ECOG-ACRIN EA2186) study is multicenter, randomized phase II trial enrolling patients over age 70 with newly diagnosed mPCA. This study utilizes a screening geriatric assessment (GA) which characterizes patients as fit, vulnerable, or frail. Patients with mild abnormalities in functional status and/or cognition, moderate comorbidities, or over age 80 are considered vulnerable. Enrolled patients are randomized to one of two dose-reduced treatment regimens (gemcitabine/nab-paclitaxel every other week, or dose-reduced 5-fluoruracil (5FU)/ liposomal irinotecan (nal-IRI) every other week). GA and quality of life (QoL) evaluations are completed prior to treatment initiation and at each disease evaluation. Overall survival (OS) is the primary endpoint, with secondary endpoints including progression free survival (PFS) and objective response rate (ORR). Enrolled patients will be stratified by age (70-74 vs &#x2265;75) and ECOG PS (0-1 vs 2). Additional endpoints of interest for OA include evaluation of risk factors identified through GA, QoL evaluation, and toxicities of interest for older adults. Correlative studies include assessment of pro-inflammatory biomarkers of aging in the blood (IL-6, CRP) and imaging evaluation of sarcopenia as predictors of treatment tolerance.<br><br>DISCUSSION: The GIANT study is the first randomized, prospective national trial evaluating vulnerable OA with mPCA aimed at developing a tailored treatment approach for this patient population. This trial has the potential to establish a new way of objectively selecting vulnerable OA with mPCA for modified treatment and to establish a new standard of care in this growing patient population.<br><br>TRIAL REGISTRATION: This trial is registered with ClinicalTrial.gov Identifier NCT04233866.},
}
@article {pmid36962933,
year = {2023},
author = {Cyrus, E and Lama, JR and Sanchez, J and Sullivan, DS and Leon, S and Villaran, MV and Vagenas, P and Vu, D and Coudray, M and Altice, FL},
title = {Substance use and other correlates of HIV infection among transwomen and men who have sex with men in Perú: Implications for targeted HIV prevention strategies for transwomen.},
journal = {PLOS global public health},
volume = {3},
number = {1},
pages = {e0001464},
pmid = {36962933},
issn = {2767-3375},
abstract = {Characterization of HIV risk factors among transwomen and men who have sex with men (MSM) should be assessed separately and independently. However, due to several constraints, these populations continue to be conflated in clinical research and data. There are limited datasets globally powered to make such comparisons. The study aimed to use one of the largest surveys of transwomen and MSM in Latin America to determine differences in HIV risk and related correlates between the two populations. Secondary data analysis was completed using a cross-sectional biobehavioral survey of 4413 MSM and 714 transwomen living in Perú. Chi Square analysis of selected HIV correlates was conducted to examine differences between transwomen and MSM. Additionally, stratified binary logistic regression was used to split data for further comparative analyses of correlates associated with transwomen and MSM separately. HIV prevalence among transwomen was two-fold greater than among MSM (14.9% vs. 7.0%, p<0.001). Transwomen had a higher prevalence of most HIV risk factors assessed, including presence of alcohol dependence (16.4% vs. 19.0%; p < .001) and drug use in the past 3 months (17.0% vs. 14.9%). MSM were more likely to use marijuana (68.0% vs. 50.0%, p < .001), and transwomen were more likely to engage in inhaled cocaine use (70.0% vs. 51.1%, p < .001). The regression exposed differences in correlates driving sub-epidemics in transwomen vs. MSM, with a trend of substance use increasing HIV risk for transwomen only. Transwomen were more likely to be HIV-infected and had different risk factors from MSM. Targeted prevention strategies are needed for transwomen that are at highest risk. Additionally, further research is needed to determine if these observations in Perú regarding substance use patterns and the role of substance use in HIV risk relate to other trans populations globally.},
}
@article {pmid36962150,
year = {2022},
author = {Mesic, A and Jackson, EK and Lalika, M and Koelle, DM and Patel, RC},
title = {Interferon-based agents for current and future viral respiratory infections: A scoping literature review of human studies.},
journal = {PLOS global public health},
volume = {2},
number = {4},
pages = {e0000231},
pmid = {36962150},
issn = {2767-3375},
abstract = {The interferon (IFN) system is a potent line of defense against viral infections. IFN-based agents already tested may be of use in COVID-19 or future viral respiratory outbreaks. Here we review the comparative efficacy, safety/tolerability, and future potential of IFN-based therapeutics. We reviewed human studies in which IFN or IFN pathway-interacting agents were used for viral respiratory infections. We identified 977 articles, of which 194 were included for full-text review. Of these, we deemed 35 articles to be relevant. The use of IFN-based agents for pre-exposure prophylaxis (n = 19) and treatment (n = 15) were most common, with intranasal (n = 22) as the most common route. We found IFN-α (n = 23) was used most often, and rhinovirus (n = 14) was the most common causative agent. Studies demonstrated mixed efficacy but generally positive safety and tolerability. Host-directed therapies, such as IFN or IFN inducers, are worthy of additional research to target viral respiratory infections lacking direct-acting antivirals.},
}
@article {pmid36961012,
year = {2023},
author = {Peehl, DM and Badea, CT and Chenevert, TL and Daldrup-Link, HE and Ding, L and Dobrolecki, LE and Houghton, AM and Kinahan, PE and Kurhanewicz, J and Lewis, MT and Li, S and Luker, GD and Ma, CX and Manning, HC and Mowery, YM and O'Dwyer, PJ and Pautler, RG and Rosen, MA and Roudi, R and Ross, BD and Shoghi, KI and Sriram, R and Talpaz, M and Wahl, RL and Zhou, R},
title = {Animal Models and Their Role in Imaging-Assisted Co-Clinical Trials.},
journal = {Tomography (Ann Arbor, Mich.)},
volume = {9},
number = {2},
pages = {657-680},
pmid = {36961012},
issn = {2379-139X},
support = {U24CA253377/NH/NIH HHS/United States ; P41EB013598/NH/NIH HHS/United States ; RO1CA215694/NH/NIH HHS/United States ; R35CA197701/NH/NIH HHS/United States ; U24CA237683/NH/NIH HHS/United States ; R01CA238023/NH/NIH HHS/United States ; U24CA231858/NH/NIH HHS/United States ; U24CA264044/NH/NIH HHS/United States ; P50CA228944/NH/NIH HHS/United States ; U24CA220245/NH/NIH HHS/United States ; U24CA226110/NH/NIH HHS/United States ; U24CA264298/NH/NIH HHS/United States ; U24CA209837/NH/NIH HHS/United States ; U24CA253531/NH/NIH HHS/United States ; P50CA236733/NH/NIH HHS/United States ; U24CA220325/NH/NIH HHS/United States ; 5P30CA125123/NH/NIH HHS/United States ; },
mesh = {Animals ; Mice ; Humans ; *Neoplasms/diagnostic imaging/therapy/pathology ; Disease Models, Animal ; Diagnostic Imaging ; },
abstract = {The availability of high-fidelity animal models for oncology research has grown enormously in recent years, enabling preclinical studies relevant to prevention, diagnosis, and treatment of cancer to be undertaken. This has led to increased opportunities to conduct co-clinical trials, which are studies on patients that are carried out parallel to or sequentially with animal models of cancer that mirror the biology of the patients' tumors. Patient-derived xenografts (PDX) and genetically engineered mouse models (GEMM) are considered to be the models that best represent human disease and have high translational value. Notably, one element of co-clinical trials that still needs significant optimization is quantitative imaging. The National Cancer Institute has organized a Co-Clinical Imaging Resource Program (CIRP) network to establish best practices for co-clinical imaging and to optimize translational quantitative imaging methodologies. This overview describes the ten co-clinical trials of investigators from eleven institutions who are currently supported by the CIRP initiative and are members of the Animal Models and Co-clinical Trials (AMCT) Working Group. Each team describes their corresponding clinical trial, type of cancer targeted, rationale for choice of animal models, therapy, and imaging modalities. The strengths and weaknesses of the co-clinical trial design and the challenges encountered are considered. The rich research resources generated by the members of the AMCT Working Group will benefit the broad research community and improve the quality and translational impact of imaging in co-clinical trials.},
}
@article {pmid36960942,
year = {2023},
author = {Ameen, R and Titus, R and Geo, JA and Al Shemmari, S and Geraghty, DE and Pyo, CW and Askar, M},
title = {KIR genotype and haplotype repertoire in Kuwaiti healthy donors, hematopoietic cell transplant recipients and healthy family members.},
journal = {HLA},
volume = {},
number = {},
pages = {},
doi = {10.1111/tan.15029},
pmid = {36960942},
issn = {2059-2310},
abstract = {The gene complex located on chromosome 19q13.4 encodes the Killer-cell Immunoglobulin-like Receptors (KIRs), which exhibit remarkable polymorphism in both gene content and sequences. Further, the repertoire of KIR genes varies within and between populations, creating a diverse pool of KIR genotypes. This study was carried out to characterize KIR genotypes and haplotypes among 379 Arab Kuwaiti individuals including 60 subjects from 20 trio families, 49 hematopoietic cell transplantation (HCT) recipients and 270 healthy Kuwaiti volunteer HCT donors. KIR Genotyping was performed by a combination of reverse sequence specific oligonucleotide probes (rSSO) and/or Real Time PCR. The frequencies of KIR genes in 270 healthy Kuwaiti volunteer donors were compared to previously reported frequencies in other populations. In addition, we compared the differences in KIR repertoire of patients and healthy donors to investigate the reproducibility of previously reported significant differences between patients with hematological malignancies and healthy donors. The observed frequencies in our cohort volunteer HCT donors was comparable to those reported in neighboring Arab populations. The activating genes KIR2DS1, KIR2DS5 and KIR3DS1 and the inhibitory gene KIR2DL5 were significantly more frequent in patients compared to healthy donors, however, none of the previously reported differences were reproducible in our Kuwaiti cohort. This report is the first description of KIR gene carrier frequency and haplotype characterization in a fairly large cohort of the Kuwaiti population, which may have implications in KIR based HCT donor selection strategies.},
}
@article {pmid36960714,
year = {2023},
author = {Seyerle, AA and Laurie, CA and Coombes, BJ and Jain, D and Conomos, MP and Brody, J and Chen, MH and Gogarten, SM and Beutel, KM and Gupta, N and Heckbert, SR and Jackson, RD and Johnson, AD and Ko, D and Manson, JE and McKnight, B and Metcalf, GA and Morrison, AC and Reiner, AP and Sofer, T and Tang, W and Wiggins, KL and , and Boerwinkle, E and Andrade, M and Gabriel, SB and Gibbs, RA and Laurie, CC and Psaty, BM and Vasan, RS and Rice, K and Kooperberg, C and Pankow, JS and Smith, NL and Pankratz, N},
title = {Whole Genome Analysis of Venous Thromboembolism: the Trans-Omics for Precision Medicine Program.},
journal = {Circulation. Genomic and precision medicine},
volume = {},
number = {},
pages = {e003532},
doi = {10.1161/CIRCGEN.121.003532},
pmid = {36960714},
issn = {2574-8300},
abstract = {Background Risk for venous thromboembolism has a strong genetic component. Whole genome sequencingfrom the Trans-Omics for Precision Medicine program allowed us to look for new associations, particularly rare variants missed by standard genome-wide association studies. Methods The 3793 cases and 7834 controls (11.6% of cases were Black, Hispanic/Latino, or Asian American) were analyzed using a single variant approach and an aggregate gene-based approach using our primary filter (included only loss-of-function and missense variants predicted to be deleterious) and our secondary filter (included all missense variants). Results Single variant analyses identified associations at 5 known loci. Aggregate gene-based analyses identified only PROC (odds ratio, 6.2 for carriers of rare variants; P=7.4×10[-14]) when using our primary filter. Employing our secondary variant filter led to a smaller effect size at PROC (odds ratio, 3.8; P=1.6×10[-14]), while excluding variants found only in rare isoforms led to a larger one (odds ratio, 7.5). Different filtering strategies improved the signal for 2 other known genes: PROS1 became significant (minimum P=1.8×10[-6] with the secondary filter), while SERPINC1 did not (minimum P=4.4×10[-5] with minor allele frequency <0.0005). Results were largely the same when restricting the analyses to include only unprovoked cases; however, one novel gene, MS4A1, became significant (P=4.4×10[-7] using all missense variants with minor allele frequency <0.0005). Conclusions Here, we have demonstrated the importance of using multiple variant filtering strategies, as we detected additional genes when filtering variants based on their predicted deleteriousness, frequency, and presence on the most expressed isoforms. Our primary analyses did not identify new candidate loci; thus larger follow-up studies are needed to replicate the novel MS4A1 locus and to identify additional rare variation associated with venous thromboembolism.},
}
@article {pmid36959278,
year = {2023},
author = {Nakamura, M and Hui, J and Stjepić, V and Parkhurst, SM},
title = {Scar/WAVE has Rac GTPase-independent functions during cell wound repair.},
journal = {Scientific reports},
volume = {13},
number = {1},
pages = {4763},
pmid = {36959278},
issn = {2045-2322},
support = {R01 HD095798/HD/NICHD NIH HHS/United States ; P30 CA015704/CA/NCI NIH HHS/United States ; },
abstract = {Rho family GTPases regulate both linear and branched actin dynamics by activating downstream effectors to facilitate the assembly and function of complex cellular structures such as lamellipodia and contractile actomyosin rings. Wiskott-Aldrich Syndrome (WAS) family proteins are downstream effectors of Rho family GTPases that usually function in a one-to-one correspondence to regulate branched actin nucleation. In particular, the WAS protein Scar/WAVE has been shown to exhibit one-to-one correspondence with Rac GTPase. Here we show that Rac and SCAR are recruited to cell wounds in the Drosophila repair model and are required for the proper formation and maintenance of the dynamic actomyosin ring formed at the wound periphery. Interestingly, we find that SCAR is recruited to wounds earlier than Rac and is still recruited to the wound periphery in the presence of a potent Rac inhibitor. We also show that while Rac is important for actin recruitment to the actomyosin ring, SCAR serves to organize the actomyosin ring and facilitate its anchoring to the overlying plasma membrane. These differing spatiotemporal recruitment patterns and wound repair phenotypes highlight the Rac-independent functions of SCAR and provide an exciting new context in which to investigate these newly uncovered SCAR functions.},
}
@article {pmid36959023,
year = {2023},
author = {Goodsell, KE and Sharib, JM and Pillarisetty, VG and Sham, JG},
title = {Leiomyosarcoma of the inferior vena cava: An uncommon malignancy requiring unique reconstructive approaches.},
journal = {American journal of surgery},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.amjsurg.2023.03.002},
pmid = {36959023},
issn = {1879-1883},
abstract = {Surgery is considered for patients without metastatic disease and with resectable primary tumor. Pre-operatively, high quality imaging is reviewed to determine the likely extent of resection, specifically including the need for potential en-bloc resection of adjacent organs. In cases where up-front surgical approach would expose the patient to excessive morbidity (such as bilateral nephrectomy, multi-visceral resection, or prohibitively high risk of positive margins), neoadjuvant chemotherapy and/or chemoradiotherapy is considered. Though data are sparse in LMS, a neoadjuvant regimen of doxorubicin and dacarbazine is typically considered for borderline resectable tumors at our institution; patients may be treated for up to 4 months with interval imaging every 2 months to evaluate for tumor response. Postoperatively, adjuvant systemic therapy or radiation may be considered for patients with positive surgical margins or high-grade tumors.},
}
@article {pmid36951943,
year = {2023},
author = {Arkatkar, T and Davé, VA and Cruz Talavera, I and Graham, JB and Swarts, JL and Hughes, SM and Bell, TA and Hock, P and Farrington, J and Shaw, GD and Kirby, AC and Fialkow, M and Huang, ML and Jerome, KR and Ferris, MT and Hladik, F and Schiffer, JT and Prlic, M and Lund, JM},
title = {Memory T cells possess an innate-like function in local protection from mucosal infection.},
journal = {The Journal of clinical investigation},
volume = {},
number = {},
pages = {},
doi = {10.1172/JCI162800},
pmid = {36951943},
issn = {1558-8238},
abstract = {Mucosal infections pose a significant global health burden. Antigen-specific tissue resident T cells are critical to maintaining barrier immunity. Previous studies in the context of systemic infection suggest that memory CD8 T cells may also provide innate-like protection against antigenically unrelated pathogens independent of TCR engagement. Whether "bystander T cell activation" is also an important defense mechanism in the mucosa is poorly understood. Here, we investigated if innate-like memory CD8 T cells could protect against a model mucosal virus infection, herpes simplex virus 2 (HSV-2). We found that immunization with an irrelevant antigen delayed disease progression from lethal HSV-2 challenge, suggesting that memory CD8 T cells may mediate protection despite the lack of antigen-specificity. Upon HSV-2 infection, we observed an early infiltration, rather than substantial local proliferation, of antigen-non-specific CD8 T cells, which became bystander-activated only within the infected mucosal tissue. Critically, we show that bystander-activated CD8 T cells are sufficient to reduce early viral burden after HSV-2 infection. Finally, local cytokine cues within the tissue microenvironment after infection were sufficient for bystander activation of mucosal tissue memory CD8 T cells from mice and humans. Altogether, our findings suggest that local bystander-activation of CD8 memory T cells contribute a fast and effective innate-like response to infection in mucosal tissue.},
}
@article {pmid36951833,
year = {2023},
author = {Disis, MLN},
title = {JAMA Oncology-The Year in Review, 2022.},
journal = {JAMA oncology},
volume = {},
number = {},
pages = {},
doi = {10.1001/jamaoncol.2023.0235},
pmid = {36951833},
issn = {2374-2445},
}
@article {pmid36949872,
year = {2023},
author = {Babu, TM and Srinivasan, S and Magaret, A and Proll, S and Karita, HS and Wallis, JM and Selke, S and Varon, D and Pholsena, T and Fredricks, D and Marrazzo, J and Wald, A and Johnston, C},
title = {Genital Herpes Simplex Virus Type 2 Suppression With Valacyclovir Is Not Associated With Changes in Nugent Score or Absolute Abundance of Key Vaginal Bacteria.},
journal = {Open forum infectious diseases},
volume = {10},
number = {3},
pages = {ofad099},
pmid = {36949872},
issn = {2328-8957},
abstract = {BACKGROUND: In women, genital herpes simplex virus type 2 (HSV-2) infection is associated with increased risk for recurrent bacterial vaginosis (BV), but causal relationships are unclear.<br><br>METHODS: Women with a self-reported history of BV and HSV-2 seropositivity self-collected vaginal and anogenital swabs for 2 nonconsecutive 28-day periods, in the absence or presence of valacyclovir suppressive therapy (500&#x2005;mg daily). HSV polymerase chain reaction was performed on anogenital swabs; vaginal swabs were used for assessment of BV by Nugent score and quantification of vaginal microbiota. Days with BV, defined by Nugent score &#x2265;7, were compared during the observational period and valacyclovir treatment.<br><br>RESULTS: Forty-one women collected swabs for a median of 28&#x2005;days (range, 20-32 days) each study period. The HSV-2 shedding rate decreased from 109 of 1126&#x2005;days (9.7%) presuppression to 6 of 1125&#x2005;days (0.05%) during valacyclovir (rate ratio [RR], 0.06 [95% confidence interval {CI},
.02-.13]). BV occurred on 343 of 1103&#x2005;days (31.1%) during observation and 302 of 1091&#x2005;days (27.7%) during valacyclovir (RR, 0.90 [95% CI, .68-1.20]). The median per-person Nugent score was 3.8 during observation and 4.0 during valacyclovir. Average log10 concentrations of vaginal bacterial species did not change significantly during valacyclovir treatment.<br><br>CONCLUSIONS: Short-term HSV-2 suppression with valacyclovir did not significantly affect the Nugent score or the vaginal microbiome despite potent suppression of HSV-2 shedding.},
}
@article {pmid36949413,
year = {2023},
author = {Johnson, DB and Atkins, MB and Hennessy, C and Wise-Draper, T and Heilman, H and Awosika, J and Bakouny, Z and Labaki, C and Saliby, RM and Hwang, C and Singh, SRK and Balanchivadze, N and Friese, CR and Fecher, LA and Yoon, JJ and Hayes-Lattin, B and Bilen, MA and Castellano, CA and Lyman, GH and Tachiki, L and Shah, SA and Glover, MJ and Flora, DB and Wulff-Burchfield, E and Kasi, A and Abbasi, SH and Farmakiotis, D and Viera, K and Klein, EJ and Weissman, LB and Jani, C and Puc, M and Fahey, CC and Reuben, DY and Mishra, S and Beeghly-Fadiel, A and French, B and Warner, JL and , },
title = {Impact of COVID-19 in patients on active melanoma therapy and with history of melanoma.},
journal = {BMC cancer},
volume = {23},
number = {1},
pages = {265},
pmid = {36949413},
issn = {1471-2407},
mesh = {Humans ; *COVID-19/therapy ; Multiple Organ Failure ; *Melanoma/complications/therapy ; Immunotherapy ; },
abstract = {INTRODUCTION: COVID-19 particularly impacted patients with co-morbid conditions, including cancer. Patients with melanoma have not been specifically studied in large numbers. Here, we sought to identify factors that associated with COVID-19 severity among patients with melanoma, particularly assessing outcomes of patients on active targeted or immune therapy.<br><br>METHODS: Using the COVID-19 and Cancer Consortium (CCC19) registry, we identified 307 patients with melanoma diagnosed with COVID-19. We used multivariable models to assess demographic, cancer-related, and treatment-related factors associated with COVID-19 severity on a 6-level ordinal severity scale. We assessed whether treatment was associated with increased cardiac or pulmonary dysfunction among hospitalized patients and assessed mortality among patients with a history of melanoma compared with other cancer survivors.<br><br>RESULTS: Of 307 patients, 52 received immunotherapy (17%), and 32 targeted therapy (10%) in the previous 3&#xa0;months. Using multivariable analyses, these treatments were not associated with COVID-19 severity (immunotherapy OR 0.51, 95% CI 0.19 - 1.39; targeted therapy OR 1.89, 95% CI 0.64 - 5.55). Among hospitalized patients, no signals of increased cardiac or pulmonary organ dysfunction, as measured by troponin, brain natriuretic peptide, and oxygenation were noted. Patients with a history of melanoma had similar 90-day mortality compared with other cancer survivors (OR 1.21, 95% CI 0.62 - 2.35).<br><br>CONCLUSIONS: Melanoma therapies did not appear to be associated with increased severity of COVID-19 or worsening organ dysfunction. Patients with history of melanoma had similar 90-day survival following COVID-19 compared with other cancer survivors.},
}
@article {pmid36949239,
year = {2023},
author = {Goffredo, P and Hart, AA and Tran, CG and Kahl, AR and Gao, X and Del Vecchio, NJ and Charlton, ME and Hassan, I},
title = {Patterns of Care and Outcomes of Rectal Cancer Patients from the Iowa Cancer Registry: Role of Hospital Volume and Tumor Location.},
journal = {Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract},
volume = {},
number = {},
pages = {},
pmid = {36949239},
issn = {1873-4626},
abstract = {BACKGROUND: Centralization of rectal cancer surgery has been associated with high-quality oncologic care. However, several patient, disease and system-related factors can impact where patients receive care. We hypothesized that patients with low rectal tumors would undergo treatment at high-volume centers and would be more likely to receive guideline-based multidisciplinary treatment.<br><br>METHODS: Adults who underwent proctectomy for stage II/III rectal cancer were included from the Iowa Cancer Registry and supplemented with tumor location data. Multinomial logistic regression was employed to analyze factors associated with receiving care in high-volume hospital, while logistic regression for those associated with&#x2009;&#x2265;&#x2009;12 lymph node yield, pre-operative chemoradiation and sphincter-preserving surgery.<br><br>RESULTS: Of 414 patients, 38%, 39%, and 22% had low, mid, and high rectal cancers, respectively. Thirty-two percent were&#x2009;>&#x2009;65&#xa0;years, 38% female, and 68% had stage III tumors. Older age and rural residence, but not tumor location, were associated with surgical treatment in low-volume hospitals. Higher tumor location, high-volume, and NCI-designated hospitals had higher nodal yield (&#x2265;&#x2009;12). Hospital-volume was not associated with neoadjuvant chemoradiation rates or circumferential resection margin status. Sphincter-sparing surgery was independently associated with high tumor location, female sex, and stage III cancer, but not hospital volume.<br><br>CONCLUSIONS: Low tumor location was not associated with care in high-volume hospitals. High-volume and NCI-designated hospitals had higher nodal yields, but not significantly higher neoadjuvant chemoradiation, negative circumferential margin, or sphincter preservation rates. Therefore, providing educational/quality improvement support in lower volume centers may be more pragmatic than attempting to centralize rectal cancer care among high-volume centers.},
}
@article {pmid36949233,
year = {2023},
author = {Berghuijs, KMVT and Kaddas, HK and Trujillo, G and Rouhani, G and Chevrier, A and Ose, J and Shibata, D and Toriola, AT and Figueiredo, JC and Peoples, AR and Li, CI and Hardikar, S and Siegel, EM and Gigic, B and Schneider, M and Ulrich, CM and Kirchhoff, AC},
title = {Age-related differences in employment, insurance, and financial hardship among colorectal cancer patients: a report from the ColoCare Study.},
journal = {Journal of cancer survivorship : research and practice},
volume = {},
number = {},
pages = {},
pmid = {36949233},
issn = {1932-2267},
support = {U01 CA206110/CA/NCI NIH HHS/United States ; U01 CA206110/CA/NCI NIH HHS/United States ; U01 CA206110/CA/NCI NIH HHS/United States ; U01 CA206110/CA/NCI NIH HHS/United States ; U01 CA206110/CA/NCI NIH HHS/United States ; U01 CA206110/CA/NCI NIH HHS/United States ; U01 CA206110/CA/NCI NIH HHS/United States ; },
abstract = {PURPOSE: Employment and financial hardships are common issues for working-age colorectal cancer patients. We surveyed colorectal cancer survivors to investigate employment, insurance, and financial outcomes by age at diagnosis.<br><br>METHODS: Cross-sectional survey of six ColoCare Study sites regarding employment, insurance, and financial hardship outcomes. Eligible participants were 1 to 5&#xa0;years from colorectal cancer diagnosis. Diagnosis age (18-49, 50-64, 65+&#x2009;years) with outcomes of interest were compared using chi-square and t-tests. Multivariable logistic and Poisson regressions were fit to examine association of demographic factors with any material/psychological hardship (yes/no) and the count of hardships.<br><br>RESULTS: N&#x2009;=&#x2009;202 participants completed the survey (age: 18-49 (n&#x2009;=&#x2009;42, 20.8%), 50-64 (n&#x2009;=&#x2009;79, 39.1%), 65+&#x2009;(n&#x2009;=&#x2009;81, 40.1%)). Most diagnosed age&#x2009;<&#x2009;65 worked at diagnosis (18-49: 83%; 50-64: 64%; 65+&#x2009;: 14%, p&#x2009;<&#x2009;0.001) and continued working after diagnosis (18-49: 76%; 50-64: 59%; 65+&#x2009;: 13%; p&#x2009;<&#x2009;0.001). Participants age 18-49 reported cancer-related difficulties with mental (81.3%) and physical (89%) tasks at work more than those working in the older age groups (45%-61%). In regression models, among those reporting any hardship, the rates of material and psychological hardships were higher among those age 18-64 (Incidence Rate Ratios (IRR) range 1.5-2.3 vs. age 65+) and for those with&#x2009;<&#x2009;college (IRR range 1.3-1.6 vs. college&#x2009;+).<br><br>CONCLUSIONS: Younger colorectal cancer patients are more likely to work after a cancer diagnosis and during cancer treatment, but report higher levels of financial hardship than older patients.<br><br>Younger colorectal cancer patients may encounter financial hardship, thus may feel a need to work during and after treatment.},
}
@article {pmid36949088,
year = {2023},
author = {Wahid, KA and Lin, D and Sahin, O and Cislo, M and Nelms, BE and He, R and Naser, MA and Duke, S and Sherer, MV and Christodouleas, JP and Mohamed, ASR and Murphy, JD and Fuller, CD and Gillespie, EF},
title = {Large scale crowdsourced radiotherapy segmentations across a variety of cancer anatomic sites.},
journal = {Scientific data},
volume = {10},
number = {1},
pages = {161},
pmid = {36949088},
issn = {2052-4463},
mesh = {Humans ; Female ; *Radiation Oncology ; *Crowdsourcing ; *Neoplasms/diagnostic imaging/radiotherapy ; Tomography, X-Ray Computed ; Radiotherapy Planning, Computer-Assisted/methods ; Image Processing, Computer-Assisted/methods ; },
abstract = {Clinician generated segmentation of tumor and healthy tissue regions of interest (ROIs) on medical images is crucial for radiotherapy. However, interobserver segmentation variability has long been considered a significant detriment to the implementation of high-quality and consistent radiotherapy dose delivery. This has prompted the increasing development of automated segmentation approaches. However, extant segmentation datasets typically only provide segmentations generated by a limited number of annotators with varying, and often unspecified, levels of expertise. In this data descriptor, numerous clinician annotators manually generated segmentations for ROIs on computed tomography images across a variety of cancer sites (breast, sarcoma, head and neck, gynecologic, gastrointestinal; one patient per cancer site) for the Contouring Collaborative for Consensus in Radiation Oncology challenge. In total, over 200 annotators (experts and non-experts) contributed using a standardized annotation platform (ProKnow). Subsequently, we converted Digital Imaging and Communications in Medicine data into Neuroimaging Informatics Technology Initiative format with standardized nomenclature for ease of use. In addition, we generated consensus segmentations for experts and non-experts using the Simultaneous Truth and Performance Level Estimation method. These standardized, structured, and easily accessible data are a valuable resource for systematically studying variability in segmentation applications.},
}
@article {pmid36949083,
year = {2023},
author = {Fong, Y and Huang, Y and Benkeser, D and Carpp, LN and Áñez, G and Woo, W and McGarry, A and Dunkle, LM and Cho, I and Houchens, CR and Martins, K and Jayashankar, L and Castellino, F and Petropoulos, CJ and Leith, A and Haugaard, D and Webb, B and Lu, Y and Yu, C and Borate, B and van der Laan, LWP and Hejazi, NS and Randhawa, AK and Andrasik, MP and Kublin, JG and Hutter, J and Keshtkar-Jahromi, M and Beresnev, TH and Corey, L and Neuzil, KM and Follmann, D and Ake, JA and Gay, CL and Kotloff, KL and Koup, RA and Donis, RO and Gilbert, PB and , and , and , },
title = {Publisher Correction: Immune correlates analysis of the PREVENT-19 COVID-19 vaccine efficacy clinical trial.},
journal = {Nature communications},
volume = {14},
number = {1},
pages = {1581},
doi = {10.1038/s41467-023-37367-2},
pmid = {36949083},
issn = {2041-1723},
}
@article {pmid36948922,
year = {2023},
author = {Lim, EA and Schweizer, MT and Chi, KN and Aggarwal, R and Agarwal, N and Gulley, J and Attiyeh, E and Greger, J and Wu, S and Jaiprasart, P and Loffredo, J and Bandyopadhyay, N and Xie, H and Hansen, AR},
title = {Phase 1 Study of Safety and Preliminary Clinical Activity of JNJ-63898081, a PSMA and CD3 Bispecific Antibody, for Metastatic Castration-Resistant Prostate Cancer.},
journal = {Clinical genitourinary cancer},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.clgc.2023.02.010},
pmid = {36948922},
issn = {1938-0682},
abstract = {INTRODUCTION: Cancer immunotherapies have limited efficacy in prostate cancer due to the immunosuppressive prostate microenvironment. Prostate specific membrane antigen (PSMA) expression is prevalent in prostate cancer, preserved during malignant transformation, and increases in response to anti-androgen therapies, making it a commonly targeted tumor associated antigen for prostate cancer. JNJ-63898081 (JNJ-081) is a bispecific antibody targeting PSMA-expressing tumor cells and CD3-expressing T cells, aiming to overcome immunosuppression and promoting antitumor activity.<br><br>PATIENTS AND METHODS: We conducted a phase 1 dose escalation study of JNJ-081 in patients with metastatic castration-resistance prostate cancer (mCRPC). Eligible patients included those receiving &#x2265;1 prior line treatment with either novel androgen receptor targeted therapy or taxane for mCRPC. Safety, pharmacokinetics, and pharmacodynamics of JNJ-081, and preliminary antitumor response to treatment were evaluated. JNJ-081 was administered initially by intravenous (IV) then by subcutaneous (SC) route.<br><br>RESULTS: Thirty-nine patients in 10 dosing cohorts received JNJ-081 ranging from 0.3 &#xb5;g/kg to 3.0 &#xb5;g/kg IV and 3.0 &#xb5;g/kg to 60 &#xb5;g/kg SC (with step-up priming used at higher SC doses). All 39 patients experienced &#x2265;1 treatment-emergent AE, and no treatment-related deaths were reported. Dose-limiting toxicities were observed in 4 patients. Cytokine release syndrome (CRS) was observed at higher doses with JNJ-081 IV or SC; however, CRS and infusion-related reaction (IRR) were reduced with SC dosing and step-up priming at higher doses. Treatment doses >30 &#xb5;g/kg SC led to transient PSA decreases. No radiographic responses were observed. Anti-drug antibody responses were observed in 19 patients receiving JNJ-081 IV or SC.<br><br>CONCLUSION: JNJ-081 dosing led to transient declines in PSA in patients with mCRPC. CRS and IRR could be partially mitigated by SC dosing, step-up priming, and a combination of both strategies. T cell redirection for prostate cancer is feasible and PSMA is a potential therapeutic target for T cell redirection in prostate cancer.},
}
@article {pmid36948887,
year = {2023},
author = {Köbel, M and Kang, EY and Weir, A and Rambau, PF and Lee, CH and Nelson, GS and Ghatage, P and Meagher, NS and Riggan, MJ and Alsop, J and Anglesio, MS and Beckmann, MW and Bisinotto, C and Boisen, M and Boros, J and Brand, AH and Brooks-Wilson, A and Carney, ME and Coulson, P and Courtney-Brooks, M and Cushing-Haugen, KL and Cybulski, C and Deen, S and El-Bahrawy, MA and Elishaev, E and Erber, R and Fereday, S and , and Fischer, A and Gayther, SA and Barquin-Garcia, A and Gentry-Maharaj, A and Gilks, CB and Gronwald, H and Grube, M and Harnett, PR and Harris, HR and Hartkopf, AD and Hartmann, A and Hein, A and Hendley, J and Hernandez, BY and Huang, Y and Jakubowska, A and Jimenez-Linan, M and Jones, ME and Kennedy, CJ and Kluz, T and Koziak, JM and Lesnock, J and Lester, J and Lubiński, J and Longacre, TA and Lycke, M and Mateoiu, C and McCauley, BM and McGuire, V and Ney, B and Olawaiye, A and Orsulic, S and Osorio, A and Paz-Ares, L and Ramón Y Cajal, T and Rothstein, JH and Ruebner, M and Schoemaker, MJ and Shah, M and Sharma, R and Sherman, ME and Shvetsov, YB and Singh, N and Steed, H and Storr, SJ and Talhouk, A and Traficante, N and Wang, C and Whittemore, AS and Widschwendter, M and Wilkens, LR and Winham, SJ and Benitez, J and Berchuck, A and Bowtell, DD and Candido Dos Reis, FJ and Campbell, I and Cook, LS and DeFazio, A and Doherty, JA and Fasching, PA and Fortner, RT and García, MJ and Goodman, MT and Goode, EL and Gronwald, J and Huntsman, DG and Karlan, BY and Kelemen, LE and Kommoss, S and Le, ND and Martin, SG and Menon, U and Modugno, F and Pharoah, PD and Schildkraut, JM and Sieh, W and Staebler, A and Sundfeldt, K and Swerdlow, AJ and Ramus, SJ and Brenton, JD},
title = {p53 and ovarian carcinoma survival: an Ovarian Tumor Tissue Analysis consortium study.},
journal = {The journal of pathology. Clinical research},
volume = {},
number = {},
pages = {},
doi = {10.1002/cjp2.311},
pmid = {36948887},
issn = {2056-4538},
support = {/BBC_/Breast Cancer Now/United Kingdom ; R01 CA087538/CA/NCI NIH HHS/United States ; R01 CA112523/CA/NCI NIH HHS/United States ; R01 CA168758/CA/NCI NIH HHS/United States ; UL1TR000124/TR/NCATS NIH HHS/United States ; P50-CA136393/NH/NIH HHS/United States ; P30-CA15083/NH/NIH HHS/United States ; R01-CA243483/NH/NIH HHS/United States ; R01-CA122443/NH/NIH HHS/United States ; C490/A16561/CRUK_/Cancer Research UK/United Kingdom ; MOP-86727/CAPMC/CIHR/Canada ; },
abstract = {Our objective was to test whether p53 expression status is associated with survival for women diagnosed with the most common ovarian carcinoma histotypes (high-grade serous carcinoma [HGSC], endometrioid carcinoma [EC], and clear cell carcinoma [CCC]) using a large multi-institutional cohort from the Ovarian Tumor Tissue Analysis (OTTA) consortium. p53 expression was assessed on 6,678 cases represented on tissue microarrays from 25 participating OTTA study sites using a previously validated immunohistochemical (IHC) assay as a surrogate for the presence and functional effect of TP53 mutations. Three abnormal expression patterns (overexpression, complete absence, and cytoplasmic) and the normal (wild type) pattern were recorded. Survival analyses were performed by histotype. The frequency of abnormal p53 expression was 93.4% (4,630/4,957) in HGSC compared to 11.9% (116/973) in EC and 11.5% (86/748) in CCC. In HGSC, there were no differences in overall survival across the abnormal p53 expression patterns. However, in EC and CCC, abnormal p53 expression was associated with an increased risk of death for women diagnosed with EC in multivariate analysis compared to normal p53 as the reference (hazard ratio [HR] = 2.18, 95% confidence interval [CI] 1.36-3.47, p = 0.0011) and with CCC (HR = 1.57, 95% CI 1.11-2.22, p = 0.012). Abnormal p53 was also associated with shorter overall survival in The International Federation of Gynecology and Obstetrics stage I/II EC and CCC. Our study provides further evidence that functional groups of TP53 mutations assessed by abnormal surrogate p53 IHC patterns are not associated with survival in HGSC. In contrast, we validate that abnormal p53 IHC is a strong independent prognostic marker for EC and demonstrate for the first time an independent prognostic association of abnormal p53 IHC with overall survival in patients with CCC.},
}
@article {pmid36948505,
year = {2023},
author = {Autio, KA and Higano, CS and Nordquist, L and Appleman, LJ and Zhang, T and Zhu, XH and Babiker, H and Vogelzang, NJ and Prasad, SM and Schweizer, MT and Madan, RA and Billotte, S and Cavazos, N and Bogg, O and Li, R and Chan, K and Cho, H and Kaneda, M and Wang, IM and Zheng, J and Tang, SY and Hollingsworth, R and Kern, KA and Petrylak, DP},
title = {First-in-human, phase 1 study of PF-06753512, a vaccine-based immunotherapy regimen (VBIR), in non-metastatic hormone-sensitive biochemical recurrence and metastatic castration-resistant prostate cancer (mCRPC).},
journal = {Journal for immunotherapy of cancer},
volume = {11},
number = {3},
pages = {},
doi = {10.1136/jitc-2022-005702},
pmid = {36948505},
issn = {2051-1426},
abstract = {BACKGROUND: This phase 1 study evaluated PF-06753512, a vaccine-based immunotherapy regimen (PrCa VBIR), in two clinical states of prostate cancer (PC), metastatic castration-resistant PC (mCRPC) and biochemical recurrence (BCR).<br><br>METHODS: For dose escalation, patients with mCRPC received intramuscular PrCa VBIR (adenovirus vector and plasmid DNA expressing prostate-specific membrane antigen (PSMA), prostate-specific antigen (PSA), and prostate stem cell antigen (PSCA)) with or without immune checkpoint inhibitors (ICIs, tremelimumab 40 or 80 mg with or without sasanlimab 130 or 300 mg, both subcutaneous). For dose expansion, patients with mCRPC received recommended phase 2 dose (RP2D) of PrCa VBIR plus tremelimumab 80 mg and sasanlimab 300 mg; patients with BCR received PrCa VBIR plus tremelimumab 80 mg (Cohort 1B-BCR) or tremelimumab 80 mg plus sasanlimab 130 mg (Cohort 5B-BCR) without androgen deprivation therapy (ADT). The primary endpoint was safety.<br><br>RESULTS: Ninety-one patients were treated in dose escalation (mCRPC=38) and expansion (BCR=35, mCRPC=18). Overall, treatment-related and immune-related adverse events occurred in 64 (70.3%) and 39 (42.9%) patients, with fatigue (40.7%), influenza-like illness (30.8%), diarrhea (23.1%), and immune-related thyroid dysfunction (19.8%) and rash (15.4%), as the most common. In patients with mCRPC, the objective response rate (ORR, 95% CI) was 5.6% (1.2% to 15.4%) and the median radiographic progression-free survival (rPFS) was 5.6 (3.5 to not estimable) months for all; the ORR was 16.7% (3.6% to 41.4%) and 6-month rPFS rate was 45.5% (24.9% to 64.1%) for those who received RP2D with measurable disease (n=18). 7.4% of patients with mCRPC achieved a &#x2265;50% decline in baseline PSA (PSA-50), with a median duration of 4.6 (1.2-45.2) months. In patients with BCR, 9 (25.7%) achieved PSA-50; the median duration of PSA response was 3.9 (1.9-4.2) and 10.1 (6.9-28.8) months for Cohorts 5B-BCR and 1B-BCR. Overall, antigen specific T-cell response was 88.0% to PSMA, 84.0% to PSA, and 80.0% to PSCA.<br><br>CONCLUSIONS: PrCa VBIR overall demonstrated safety signals similar to other ICI combination trials; significant side effects were seen in some patients with BCR. It stimulated antigen-specific immunity across all cohorts and resulted in modest antitumor activity in patients with BCR without using ADT.<br><br>TRIAL REGISTRATION NUMBER: NCT02616185.},
}
@article {pmid36948424,
year = {2023},
author = {Zauber, AG and Winawer, SJ and O'Brien, MJ and Mills, GM and Allen, JI and Feld, AD and Jordan, PA and Fleisher, M and Orlow, I and Meester, RGS and Lansdorp-Vogelaar, I and Rutter, CM and Knudsen, AB and Mandelson, M and Shaukat, A and Mendelsohn, RB and Hahn, AI and Lobaugh, SM and Palmer, BS and Serrano, V and Kumar, JR and Fischer, SE and Chen, JC and Bayuga-Miller, S and Kuk, D and O'Connell, K and Church, TR},
title = {Randomized Trial of Facilitated Adherence to Screening-Colonoscopy Versus Sequential Fecal-Based Blood Test.},
journal = {Gastroenterology},
volume = {},
number = {},
pages = {},
doi = {10.1053/j.gastro.2023.03.206},
pmid = {36948424},
issn = {1528-0012},
abstract = {BACKGROUND AND AIMS: Colorectal cancer (CRC) screening guidelines include screening-colonoscopy and sequential high sensitivity fecal occult blood testing (HSgFOBT), with expectation of similar effectiveness based on the assumption of similar high adherence. However, adherence to screening-colonoscopy compared to sequential HSgFOBT has not been reported. In this randomized clinical trial, we assessed adherence and pathology findings for a single screening-colonoscopy versus sequential and non-sequential HSgFOBT.<br><br>METHODS: Participants aged 40-69 were enrolled in three centers, which represented different clinical settings. Participants were randomized into a single screening-colonoscopy arm versus sequential HSgFOBT arm comprised of 4-7 rounds. Initial adherence to screening-colonoscopy and sequential adherence to HSgFOBT, follow-up colonoscopy for positive HSgFOBT tests, crossover to colonoscopy, and detection of advanced neoplasia or large serrated lesions (ADN-SER) were measured.<br><br>RESULTS: 3,523 participants were included in the trial with 1761 and 1762 participants randomized to the screening-colonoscopy and HSgFOBT arms, respectively. Adherence was 1473 (83.6%) for the screening-colonoscopy arm versus 1288 (73.1%) for the HSgFOBT arm after one round (RR=1.14, [95% CI 1.10-1.19] P &#x2264;0.001), but only 674 (38.3%) over four sequential HSgFOBT rounds (RR=2.19, [95% CI 2.05-2.33]). Overall adherence to any screening increased to 1558 (88.5%) in the screening-colonoscopy arm during the entire study period and 1493 in the HSgFOBT arm (84.7%) (RR=1.04, [95% CI 1.02-1.07]). 436 (24.7%) participants crossed over to screening-colonoscopy over the first four rounds. ADN-SER were detected in 121 (8.2%) of the 1473 participants in the colonoscopy arm who were adherent to protocol in the first 12 months of the study, whereas the detection of ADN-SER among those who were not sequentially adherent (N=709) to HSgFOBT was subpar (0.6%) (RR=14.72, [95% CI 5.46-39.67]) when compared to those who were sequentially adherent (3.3%) (N=647) (RR=2.52, [95% CI 1.61-3.98]) to HSgFOBT in the first four rounds. When including colonoscopies from HSgFOBT patients who were never positive yet crossed over (N=1483), 5.5% of ADN-SER were detected (RR=1.50, [95% CI 1.15-1.96]) in the first four rounds.<br><br>CONCLUSIONS: Observed adherence to sequential rounds of HSgFOBT was suboptimal when compared to a single screening-colonoscopy. The detection of ADN-SER was inferior when non-sequential HSgFOBT adherence was compared to sequential adherence. However, the greatest number of ADN-SER was detected among those who crossed over to colonoscopy and opted to receive a colonoscopy. The effectiveness of a HSgFOBT screening program may be enhanced if crossover to screening-colonoscopy is permitted.},
}
@article {pmid36948020,
year = {2023},
author = {Zhang, Z and Hong, W and Wu, Q and Tsavachidis, S and Li, JR and Amos, CI and Cheng, C and Sartain, SE and Afshar-Kharghan, V and Dong, JF and Bhatraju, P and Martin, PJ and Makar, RS and Bendapudi, PK and Li, A},
title = {Pathway-driven rare germline variants associated with transplant-associated thrombotic microangiopathy (TA-TMA).},
journal = {Thrombosis research},
volume = {225},
number = {},
pages = {39-46},
doi = {10.1016/j.thromres.2023.03.001},
pmid = {36948020},
issn = {1879-2472},
abstract = {The significance of rare germline mutations in transplant-associated thrombotic microangiopathy (TA-TMA) is not well studied. We performed a genetic association study in 100 adult TA-TMA patients vs. 98 post-transplant controls after matching by race, sex, and year. We focused on 5 pathways in complement, von Willebrand factor (VWF) function and related proteins, VWF clearance, ADAMTS13 function and related proteins, and endothelial activation (3641variants in 52 genes). In the primary analysis focused on 189 functional rare variants, no differential variant enrichment was observed in any of the pathways; specifically, 29 % TA-TMA and 33 % controls had at least 1 rare complement mutation. In the secondary analysis focused on 37 rare variants predicted to be pathogenic or likely pathogenic by ClinVar, Complement Database, or REVEL in-silico prediction tool, rare variants in the VWF clearance pathway were found to be significantly associated with TA-TMA (p = 0.008). On the gene level, LRP1 was the only one with significantly increased variants in TA-TMA in both analyses (p = 0.025 and 0.015). In conclusion, we did not find a significant association between rare variants in the complement pathway and TA-TMA; however, we discovered a new signal in the VWF clearance pathway driven by the gene LRP1 among likely pathogenic variants.},
}
@article {pmid36947201,
year = {2023},
author = {DeZern, AE and Goll, JB and Lindsley, RC and Bejar, R and Wilson, SH and Hebert, D and Deeg, HJ and Zhang, L and Gore, SD and Al Baghdadi, T and Maciejewski, JP and Liu, JJ and Padron, E and Komrokji, RS and Saber, W and Abel, GA and Kroft, SH and Harrington, AM and Grimes, T and Reed, HHV and Fulton, RS and DiFronzo, NL and Gillis, N and Sekeres, MA and Walter, MJ},
title = {Utility of Targeted Gene Sequencing to Differentiate Myeloid Malignancies from other Cytopenic Conditions.},
journal = {Blood advances},
volume = {},
number = {},
pages = {},
doi = {10.1182/bloodadvances.2022008578},
pmid = {36947201},
issn = {2473-9537},
abstract = {The National Heart, Lung, and Blood Institute National MDS Natural History Study (NCT02775383) is a prospective cohort study enrolling cytopenic patients with suspected myelodysplastic syndromes (MDS) to evaluate factors associated with disease. Here, we sequenced 53 genes in bone marrow samples harvested from 1,298 patients diagnosed with myeloid malignancy, including MDS and non-MDS myeloid malignancy, or alternative marrow conditions with cytopenia based on concordance between independent histopathologic reviews (local, centralized, and tertiary to adjudicate disagreements when needed). We developed a novel two-stage diagnostic classifier based on mutational profiles in 18 of 53 sequenced genes that were sufficient to best (1) predict a diagnosis of myeloid malignancy and (2) within those with a predicted myeloid malignancy, predict whether they had MDS. The classifier achieved a PPV of 0.84 and NPV of 0.8 with an AUROC of 0.85 when classifying patients as myeloid vs. no myeloid malignancy based on VAFs in 17 genes and a PPV of 0.71 and NPV of 0.64 with an AUROC of 0.73 when classifying patients as MDS vs. non-MDS malignancy based on VAFs in 10 genes. We next assessed how this approach could complement histopathology to improve diagnostic accuracy. For 99 of 139 (71%) patients (PPV of 0.83 and NPV of 0.65) with local and centralized histopathologic disagreement in myeloid vs. no myeloid malignancy, the classifier-predicted diagnosis agreed with the tertiary pathology review (considered the internal gold standard). An online version of the classifier that can be used with either VAFs or binary mutation profiles is available at https://thenationalmdsstudy.net.},
}
@article {pmid36946421,
year = {2023},
author = {Lu, W and Fan, M and Ji, W and Tse, J and You, I and Ficarro, SB and Tavares, I and Che, J and Kim, AY and Zhu, X and Boghossian, A and Rees, MG and Ronan, MM and Roth, JA and Hinshaw, SM and Nabet, B and Corsello, SM and Kwiatkowski, N and Marto, JA and Zhang, T and Gray, NS},
title = {Structure-Based Design of Y-Shaped Covalent TEAD Inhibitors.},
journal = {Journal of medicinal chemistry},
volume = {},
number = {},
pages = {},
doi = {10.1021/acs.jmedchem.2c01548},
pmid = {36946421},
issn = {1520-4804},
abstract = {Transcriptional enhanced associate domain (TEAD) proteins together with their transcriptional coactivator yes-associated protein (YAP) and transcriptional coactivator with the PDZ-binding motif (TAZ) are important transcription factors and cofactors that regulate gene expression in the Hippo pathway. In mammals, the TEAD families have four homologues: TEAD1 (TEF-1), TEAD2 (TEF-4), TEAD3 (TEF-5), and TEAD4 (TEF-3). Aberrant expression and hyperactivation of TEAD/YAP signaling have been implicated in a variety of malignancies. Recently, TEADs were recognized as being palmitoylated in cells, and the lipophilic palmitate pocket has been successfully targeted by both covalent and noncovalent ligands. In this report, we present the medicinal chemistry effort to develop MYF-03-176 (compound 22) as a selective, cysteine-covalent TEAD inhibitor. MYF-03-176 (compound 22) significantly inhibits TEAD-regulated gene expression and proliferation of the cell lines with TEAD dependence including those derived from mesothelioma and liposarcoma.},
}
@article {pmid36946291,
year = {2023},
author = {Unger, JM and Till, C and Hwang, JP and Arnold, KB and Leblanc, M and Hershman, DL and Ramsey, SD},
title = {Risk Prediction of Hepatitis B or C or HIV Among Newly Diagnosed Cancer Patients.},
journal = {Journal of the National Cancer Institute},
volume = {},
number = {},
pages = {},
doi = {10.1093/jnci/djad053},
pmid = {36946291},
issn = {1460-2105},
abstract = {BACKGROUND: Screening for viral infection in cancer patients is inconsistent. A mechanism to readily identify cancer patients at increased risk of existing or prior viral infection could enhance screening efforts while reducing costs.<br><br>METHODS: We identified factors associated with increased risk of past or chronic HBV, HCV, or HIV infection prior to initiation of systemic cancer therapy. Data were from a multicenter prospective cohort study of 3,051 patients with newly diagnosed cancer (SWOG-S1204) enrolled between 2013-2017. Patients completed a survey with questions pertaining to personal history, behavioral, socioeconomic, and demographic risk factors for viral hepatitis or HIV. We derived a risk model to predict the presence of viral infection in a random set of 60% of participants using best subset selection. The derived model was validated in the remaining 40% of participants. Logistic regression was used.<br><br>RESULTS: A model with 7 risk factors was identified, and a risk score with 4 levels was constructed. In the validation cohort, each increase in risk level was associated with nearly a threefold increased risk of viral positivity (OR&#x2009;=&#x2009;2.85, 95%-CI, 2.26-3.60, p<0.001). Consistent findings were observed for individual viruses. Participants in the highest risk group (with &#x2265;3 risk factors), comprised of 13.4% of participants, were 18 times more likely to be viral positive compared to participants with no risk factors (OR&#x2009;=&#x2009;18.18, 95%-CI, 8.00-41.3, p<0.001).<br><br>CONCLUSIONS AND RELEVANCE: A risk-stratified screening approach using a limited set of questions could serve as an effective strategy to streamline screening for individuals at increased risk of viral infection.},
}
@article {pmid36944964,
year = {2023},
author = {Ausenhus, C and Gold, JM and Perry, CK and Kozak, AT and Wang, ML and Jang, SH and Leong, J and Rodriguez, E and Duggan, C and Ko, LK},
title = {Publisher Correction: Factors impacting implementation of nutrition and physical activity policies in rural schools.},
journal = {BMC public health},
volume = {23},
number = {1},
pages = {538},
doi = {10.1186/s12889-023-15401-8},
pmid = {36944964},
issn = {1471-2458},
}
@article {pmid36943831,
year = {2023},
author = {Wagner, AD and Njuguna, IN and Neary, J and Lawley, KA and Louden, DKN and Tiwari, R and Jiang, W and Kalu, N and Burke, RM and Mangale, D and Obermeyer, C and Escudero, JN and Bulterys, MA and Waters, C and Mollo, B and Han, H and Barr-DiChiara, M and Baggaley, R and Jamil, MS and Shah, P and Wong, VJ and Drake, AL and Johnson, CC},
title = {Demand creation for HIV testing services: A systematic review and meta-analysis.},
journal = {PLoS medicine},
volume = {20},
number = {3},
pages = {e1004169},
pmid = {36943831},
issn = {1549-1676},
mesh = {Humans ; Americas ; *HIV Infections/diagnosis/epidemiology ; HIV Testing ; },
abstract = {BACKGROUND: HIV testing services (HTS) are the first steps in reaching the UNAIDS 95-95-95 goals to achieve and maintain low HIV incidence. Evaluating the effectiveness of different demand creation interventions to increase uptake of efficient and effective HTS is useful to prioritize limited programmatic resources. This review was undertaken to inform World Health Organization (WHO) 2019 HIV testing guidelines and assessed the research question, "Which demand creation strategies are effective for enhancing uptake of HTS?" focused on populations globally.<br><br>METHODS AND FINDINGS: The following electronic databases were searched through September 28, 2021: PubMed, PsycInfo, Cochrane CENTRAL, CINAHL Complete, Web of Science Core Collection, EMBASE, and Global Health Database; we searched IAS and AIDS conferences. We systematically searched for randomized controlled trials (RCTs) that compared any demand creation intervention (incentives, mobilization, counseling, tailoring, and digital interventions) to either a control or other demand creation intervention and reported HTS uptake. We pooled trials to evaluate categories of demand creation interventions using random-effects models for meta-analysis and assessed study quality with Cochrane's risk of bias 1 tool. This study was funded by the WHO and registered in Prospero with ID CRD42022296947. We screened 10,583 records and 507 conference abstracts, reviewed 952 full texts, and included 124 RCTs for data extraction. The majority of studies were from the African (N = 53) and Americas (N = 54) regions. We found that mobilization (relative risk [RR]: 2.01, 95% confidence interval [CI]: [1.30, 3.09], p < 0.05; risk difference [RD]: 0.29, 95% CI [0.16, 0.43], p < 0.05, N = 4 RCTs), couple-oriented counseling (RR: 1.98, 95% CI [1.02, 3.86], p < 0.05; RD: 0.12, 95% CI [0.03, 0.21], p < 0.05, N = 4 RCTs), peer-led interventions (RR: 1.57, 95% CI [1.15, 2.15], p < 0.05; RD: 0.18, 95% CI [0.06, 0.31], p < 0.05, N = 10 RCTs), motivation-oriented counseling (RR: 1.53, 95% CI [1.07, 2.20], p < 0.05; RD: 0.17, 95% CI [0.00, 0.34], p < 0.05, N = 4 RCTs), short message service (SMS) (RR: 1.53, 95% CI [1.09, 2.16], p < 0.05; RD: 0.11, 95% CI [0.03, 0.19], p < 0.05, N = 5 RCTs), and conditional fixed value incentives (RR: 1.52, 95% CI [1.21, 1.91], p < 0.05; RD: 0.15, 95% CI [0.07, 0.22], p < 0.05, N = 11 RCTs) all significantly and importantly (&#x2265;50% relative increase) increased HTS uptake and had medium risk of bias. Lottery-based incentives and audio-based interventions less importantly (25% to 49% increase) but not significantly increased HTS uptake (medium risk of bias). Personal invitation letters and personalized message content significantly but not importantly (<25% increase) increased HTS uptake (medium risk of bias). Reduced duration counseling had comparable performance to standard duration counseling (low risk of bias) and video-based interventions were comparable or better than in-person counseling (medium risk of bias). Heterogeneity of effect among pooled studies was high. This study was limited in that we restricted to randomized trials, which may be systematically less readily available for key populations; additionally, we compare only pooled estimates for interventions with multiple studies rather than single study estimates, and there was evidence of publication bias for several interventions.<br><br>CONCLUSIONS: Mobilization, couple- and motivation-oriented counseling, peer-led interventions, conditional fixed value incentives, and SMS are high-impact demand creation interventions and should be prioritized for programmatic consideration. Reduced duration counseling and video-based interventions are an efficient and effective alternative to address staffing shortages. Investment in demand creation activities should prioritize those with undiagnosed HIV or ongoing HIV exposure. Selection of demand creation interventions must consider risks and benefits, context-specific factors, feasibility and sustainability, country ownership, and universal health coverage across disease areas.},
}
@article {pmid36943219,
year = {2023},
author = {Chlebowski, RT and Aragaki, AK},
title = {Hormone Therapy for the Prevention of Chronic Conditions in Postmenopausal Persons.},
journal = {JAMA},
volume = {329},
number = {11},
pages = {942},
doi = {10.1001/jama.2023.0186},
pmid = {36943219},
issn = {1538-3598},
mesh = {Humans ; Female ; *Postmenopause ; Estrogen Replacement Therapy/adverse effects ; Chronic Disease ; Hormones ; *Osteoporosis, Postmenopausal ; Hormone Replacement Therapy/adverse effects ; },
}
@article {pmid36711972,
year = {2023},
author = {Arora, S and Szulzewsky, F and Jensen, M and Nuechterlein, N and Pattwell, SS and Holland, EC},
title = {An RNA seq-based reference landscape of human normal and neoplastic brain.},
journal = {Research square},
volume = {},
number = {},
pages = {},
pmid = {36711972},
abstract = {In order to better understand the relationship between normal and neoplastic brain, we combined five publicly available large-scale datasets, correcting for batch effects and applying Uniform Manifold Approximation and Projection (UMAP) to RNA-seq data. We assembled a reference Brain-UMAP including 702 adult gliomas, 802 pediatric tumors and 1409 healthy normal brain samples, which can be utilized to investigate the wealth of information obtained from combining several publicly available datasets to study a single organ site. Normal brain regions and tumor types create distinct clusters and because the landscape is generated by RNA seq, comparative gene expression profiles and gene ontology patterns are readily evident. To our knowledge, this is the first meta-analysis that allows for comparison of gene expression and pathways of interest across adult gliomas, pediatric brain tumors, and normal brain regions. We provide access to this resource via the open source, interactive online tool Oncoscape, where the scientific community can readily visualize clinical metadata, gene expression patterns, gene fusions, mutations, and copy number patterns for individual genes and pathway over this reference landscape.},
}
@article {pmid36711910,
year = {2023},
author = {Arora, S and Szulzewsky, F and Jensen, M and Nuechterlein, N and Pattwell, SS and Holland, EC},
title = {An RNA seq-based reference landscape of human normal and neoplastic brain.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {36711910},
abstract = {In order to better understand the relationship between normal and neoplastic brain, we combined five publicly available large-scale datasets, correcting for batch effects and applying Uniform Manifold Approximation and Projection (UMAP) to RNA-seq data. We assembled a reference Brain-UMAP including 702 adult gliomas, 802 pediatric tumors and 1409 healthy normal brain samples, which can be utilized to investigate the wealth of information obtained from combining several publicly available datasets to study a single organ site. Normal brain regions and tumor types create distinct clusters and because the landscape is generated by RNA seq, comparative gene expression profiles and gene ontology patterns are readily evident. To our knowledge, this is the first meta-analysis that allows for comparison of gene expression and pathways of interest across adult gliomas, pediatric brain tumors, and normal brain regions. We provide access to this resource via the open source, interactive online tool Oncoscape, where the scientific community can readily visualize clinical metadata, gene expression patterns, gene fusions, mutations, and copy number patterns for individual genes and pathway over this reference landscape.},
}
@article {pmid36548957,
year = {2023},
author = {Kopmar, NE and Cassaday, RD},
title = {How I prevent and treat central nervous system disease in adults with acute lymphoblastic leukemia.},
journal = {Blood},
volume = {141},
number = {12},
pages = {1379-1388},
doi = {10.1182/blood.2022017035},
pmid = {36548957},
issn = {1528-0020},
abstract = {The central nervous system (CNS) is the most important site of extramedullary disease in adults with acute lymphoblastic leukemia (ALL). Although CNS disease is identified only in a minority of patients at the time of diagnosis, subsequent CNS relapses (either isolated or concurrent with other sites) occur in some patients even after the delivery of prophylactic therapy targeted to the CNS. Historically, prophylaxis against CNS disease has included intrathecal (IT) chemotherapy and radiotherapy (RT), although the latter is being used with decreasing frequency. Treatment of a CNS relapse usually involves intensive systemic therapy and cranial or craniospinal RT along with IT therapy and consideration of allogeneic hematopoietic cell transplant. However, short- and long-term toxicities can make these interventions prohibitively risky, particularly for older adults. As new antibody-based immunotherapy agents have been approved for relapsed/refractory B-cell ALL, their use specifically for patients with CNS disease is an area of keen interest not only because of the potential for efficacy but also concerns of unique toxicity to the CNS. In this review, we discuss data-driven approaches for these common and challenging clinical scenarios as well as highlight how recent findings potentially support the use of novel immunotherapeutic strategies for CNS disease.},
}
@article {pmid36943218,
year = {2023},
author = {Anderson, GL},
title = {Hormone Therapy for the Prevention of Chronic Conditions in Postmenopausal Persons.},
journal = {JAMA},
volume = {329},
number = {11},
pages = {941},
doi = {10.1001/jama.2023.0189},
pmid = {36943218},
issn = {1538-3598},
}
@article {pmid36943212,
year = {2023},
author = {Shadman, M},
title = {Diagnosis and Treatment of Chronic Lymphocytic Leukemia: A Review.},
journal = {JAMA},
volume = {329},
number = {11},
pages = {918-932},
doi = {10.1001/jama.2023.1946},
pmid = {36943212},
issn = {1538-3598},
abstract = {IMPORTANCE: Chronic lymphocytic leukemia (CLL), defined by a minimum of 5 × 109/L monoclonal B cells in the blood, affects more than 200 000 people and is associated with approximately 4410 deaths in the US annually. CLL is associated with an immunocompromised state and an increased rate of complications from infections.<br><br>OBSERVATIONS: At the time of diagnosis, the median age of patients with CLL is 70 years, and an estimated 95% of patients have at least 1 medical comorbidity. Approximately 70% to 80% of patients with CLL are asymptomatic at the time of diagnosis, and one-third will never require treatment for CLL. Prognostic models have been developed to estimate the time to first treatment and the overall survival, but for patients who are asymptomatic, irrespective of disease risk category, clinical observation is the standard of care. Patients with symptomatic disease who have bulky or progressive lymphadenopathy or hepatosplenomegaly and those with a low neutrophil count, anemia, or thrombocytopenia and/or symptoms of fever, drenching night sweats, and weight loss (B symptoms) should be offered treatment. For these patients, first-line treatment consists of a regimen containing either a covalent Bruton tyrosine kinase (BTK) inhibitor (acalabrutinib, zanubrutinib, or ibrutinib) or a B-cell leukemia/lymphoma 2 (BCL2) inhibitor (venetoclax). There is no evidence that starting either class before the other improves outcomes. The covalent BTK inhibitors are typically used indefinitely. Survival rates are approximately 88% at 4 years for acalabrutinib, 94% at 2 years for zanubrutinib, and 78% at 7 years for ibrutinib. Venetoclax is prescribed in combination with obinutuzumab, a monoclonal anti-CD20 antibody, in first-line treatment for 1 year (overall survival, 82% at 5-year follow-up). A noncovalent BTK inhibitor, pitobrutinib, has shown an overall response rate of more than 70% after failure of covalent BTK inhibitors and venetoclax. Phosphoinositide 3'-kinase (PI3K) inhibitors (idelalisib and duvelisib) can be prescribed for disease that progresses with BTK inhibitors and venetoclax, but patients require close monitoring for adverse events such as autoimmune conditions and infections. In patients with multiple relapses, chimeric antigen receptor T-cell (CAR-T) therapy with lisocabtagene maraleucel was associated with a 45% complete response rate. The only potential cure for CLL is allogeneic hematopoietic cell transplant, which remains an option after use of targeted agents.<br><br>CONCLUSIONS AND RELEVANCE: More than 200&#x202f;000 people in the US are living with a CLL diagnosis, and CLL causes approximately 4410 deaths each year in the US. Approximately two-thirds of patients eventually need treatment. Highly effective novel targeted agents include BTK inhibitors such as acalabrutinib, zanubrutinib, ibrutinib, and pirtobrutinib or BCL2 inhibitors such as venetoclax.},
}
@article {pmid36943134,
year = {2023},
author = {Oishi, K and Blanco-Melo, D and Kurland, AP and Johnson, JR and tenOever, BR},
title = {Archaeal Kink-Turn Binding Protein Mediates Inhibition of Orthomyxovirus Splicing Biology.},
journal = {Journal of virology},
volume = {},
number = {},
pages = {e0181322},
doi = {10.1128/jvi.01813-22},
pmid = {36943134},
issn = {1098-5514},
abstract = {Despite lacking a DNA intermediate, orthomyxoviruses complete their replication cycle in the nucleus and generate multiple transcripts by usurping the host splicing machinery. This biology results in dynamic changes of relative viral transcripts over time and dictates the replicative phase of the infection. Here, we demonstrate that the family of archaeal L7Ae proteins uniquely inhibit the splicing biology of influenza A virus, influenza B virus, and Salmon isavirus, revealing a common strategy utilized by Orthomyxoviridae members to achieve this dynamic. L7Ae-mediated inhibition of virus biology was lost with the generation of a splicing-independent strain of influenza A virus and attempts to select for an escape mutant resulted in variants that conformed to host splicing biology at significant cost to their overall fitness. As L7Ae recognizes conventional kink turns in various RNAs, these data implicate the formation of a similar structure as a shared strategy adopted by this virus family to coordinate their replication cycle. IMPORTANCE Here, we demonstrate that a family of proteins from archaea specifically inhibit this splicing biology of all tested members of the Orthomyxoviridae family. We show that this inhibition extends to influenza A virus, influenza B virus, and isavirus genera, while having no significant impact on the mammalian transcriptome or proteome. Attempts to generate an escape mutant against L7Ae-mediated inhibition resulted in mutations surrounding the viral splice sites and a significant loss of viral fitness. Together, these findings reveal a unique biology shared among diverse members of the Orthomyxoviridae family that may serve as a means to generate future universal therapeutics.},
}
@article {pmid36941881,
year = {2023},
author = {Lopedote, P and Shadman, M},
title = {Targeted Treatment of Relapsed or Refractory Follicular Lymphoma: Focus on the Therapeutic Potential of Mosunetuzumab.},
journal = {Cancer management and research},
volume = {15},
number = {},
pages = {257-264},
pmid = {36941881},
issn = {1179-1322},
abstract = {Follicular lymphoma is the most common indolent non-Hodgkin's lymphoma, and because of the incurable nature of this disorder, new therapies are constantly needed. The recently approved T-cell-dependent bispecific antibody mosunetuzumab showed promising results and manageable toxicities for patients with relapsed or refractory follicular lymphoma. Namely, as opposed to cellular immunotherapy options, this agent has the potential of being effective in patients with unfavorable features with a tolerable rate and severity of cytokine release syndrome, immune effector cell-associated neurotoxicity, and infectious complications. Given the recent withdrawal from the market of PI3K inhibitors and the practical challenges in utilizing with chimeric antigen receptor T-cells (CAR-T) for some patients, mosunetuzumab represents a "breath of fresh air" for both patients and hemato-oncologists. More data are required to better define the real potential of this molecule, either alone or in combination with other agents, including antibody drug conjugates, immunomodulators, and checkpoint inhibitors. Future studies will also shed light on the efficacy of mosunetuzumab compared with CAR-T, in well-designed registries or ideally in randomized controlled trials.},
}
@article {pmid36941441,
year = {2023},
author = {Hou, K and Ding, Y and Xu, Z and Wu, Y and Bhattacharya, A and Mester, R and Belbin, GM and Buyske, S and Conti, DV and Darst, BF and Fornage, M and Gignoux, C and Guo, X and Haiman, C and Kenny, EE and Kim, M and Kooperberg, C and Lange, L and Manichaikul, A and North, KE and Peters, U and Rasmussen-Torvik, LJ and Rich, SS and Rotter, JI and Wheeler, HE and Wojcik, GL and Zhou, Y and Sankararaman, S and Pasaniuc, B},
title = {Causal effects on complex traits are similar for common variants across segments of different continental ancestries within admixed individuals.},
journal = {Nature genetics},
volume = {},
number = {},
pages = {},
pmid = {36941441},
issn = {1546-1718},
abstract = {Individuals of admixed ancestries (for example, African Americans) inherit a mosaic of ancestry segments (local ancestry) originating from multiple continental ancestral populations. This offers the unique opportunity of investigating the similarity of genetic effects on traits across ancestries within the same population. Here we introduce an approach to estimate correlation of causal genetic effects (radmix) across local ancestries and analyze 38 complex traits in African-European admixed individuals (N = 53,001) to observe very high correlations (meta-analysis radmix = 0.95, 95% credible interval 0.93-0.97), much higher than correlation of causal effects across continental ancestries. We replicate our results using regression-based methods from marginal genome-wide association study summary statistics. We also report realistic scenarios where regression-based methods yield inflated heterogeneity-by-ancestry due to ancestry-specific tagging of causal effects, and/or polygenicity. Our results motivate genetic analyses that assume minimal heterogeneity in causal effects by ancestry, with implications for the inclusion of ancestry-diverse individuals in studies.},
}
@article {pmid36941332,
year = {2023},
author = {Watanabe, K and Wilmanski, T and Diener, C and Earls, JC and Zimmer, A and Lincoln, B and Hadlock, JJ and Lovejoy, JC and Gibbons, SM and Magis, AT and Hood, L and Price, ND and Rappaport, N},
title = {Multiomic signatures of body mass index identify heterogeneous health phenotypes and responses to a lifestyle intervention.},
journal = {Nature medicine},
volume = {},
number = {},
pages = {},
pmid = {36941332},
issn = {1546-170X},
abstract = {Multiomic profiling can reveal population heterogeneity for both health and disease states. Obesity drives a myriad of metabolic perturbations and is a risk factor for multiple chronic diseases. Here we report an atlas of cross-sectional and longitudinal changes in 1,111 blood analytes associated with variation in body mass index (BMI), as well as multiomic associations with host polygenic risk scores and gut microbiome composition, from a cohort of 1,277 individuals enrolled in a wellness program (Arivale). Machine learning model predictions of BMI from blood multiomics captured heterogeneous phenotypic states of host metabolism and gut microbiome composition better than BMI, which was also validated in an external cohort (TwinsUK). Moreover, longitudinal analyses identified variable BMI trajectories for different omics measures in response to a healthy lifestyle intervention; metabolomics-inferred BMI decreased to a greater extent than actual BMI, whereas proteomics-inferred BMI exhibited greater resistance to change. Our analyses further identified blood analyte-analyte associations that were modified by metabolomics-inferred BMI and partially reversed in individuals with metabolic obesity during the intervention. Taken together, our findings provide a blood atlas of the molecular perturbations associated with changes in obesity status, serving as a resource to quantify metabolic health for predictive and preventive medicine.},
}
@article {pmid36940410,
year = {2023},
author = {Gagelmann, N and Badbaran, A and Salit, RB and Schroeder, T and Gurnari, C and Pagliuca, S and Panagiota, V and Rautenberg, C and Cassinat, B and Thol, FR and Wolschke, C and Robin, M and Heuser, M and Rubio, MT and Maciejewski, JP and Reinhardt, HC and Scott, BL and Kröger, N},
title = {Impact of TP53 on outcome of patients with myelofibrosis undergoing hematopoietic stem cell transplantation.},
journal = {Blood},
volume = {},
number = {},
pages = {},
doi = {10.1182/blood.2023019630},
pmid = {36940410},
issn = {1528-0020},
abstract = {TP53 mutations (TP53MT) have been associated with poor outcomes in various hematologic malignancies, but no data exist on its role in patients with myelofibrosis undergoing hematopoietic stem cell transplantation (HSCT). Here, we took advantage of a large international multicenter cohort to evaluate the role of TP53MTin this setting. Among 349 included patients, 49 (13%) had detectable TP53MT, of whom 30 showed a multi-hit configuration. Median variant allele frequency was 20.3%. Cytogenetic risk was favorable (71%), unfavorable (23%), and very high (6%), with complex karyotype present in 36 patients (10%). Median survival of TP53MT patients was 1.5 years vs 13.5 years for the TP53WT group (P<0.001). Outcome was driven by multi-hit TP53MT constellation (P<0.001), showing 6-year survival of 56% for single-hit vs 25% for multi-hit TP53MT carriers vs 64% for TP53WT. Outcome was independent of current transplant-specific risk factors and conditioning intensity. Similarly, cumulative incidence of relapse was 17% for single-hit vs 52% for multi-hit vs 21% for TP53WT. Ten patients with TP53MT (20%) presented as leukemic transformation vs only 7 (2%) in the TP53WT group (P<0.001). Out of the 10 patients with TP53MT, 8 showed multi-hit constellation. Median time to leukemic transformation was shorter for multi-and single-hit TP53MT (0.7 and 0.5 years, respectively) vs 2.5 years for TP53WT. In summary, multi-hit TP53MT represents a very high-risk group in myelofibrosis patients undergoing HSCT, whereas single-hit TP53MTalone showed similar outcome to non-mutated patients, informing prognostication for survival and relapse together with current transplant-specific tools.},
}
@article {pmid36940409,
year = {2023},
author = {Miller, SJ and Sly, JR and Alcaraz, KI and Ashing, K and Christy, SM and Gonzalez, B and Lu, Q and Newton, RL and Redmond, M and Shen, M and Thomas-Purcell, K and Yi, J and Veinot, T and Meade, CD},
title = {Equity and behavioral digital health interventions: Strategies to improve benefit and reach.},
journal = {Translational behavioral medicine},
volume = {},
number = {},
pages = {},
doi = {10.1093/tbm/ibad010},
pmid = {36940409},
issn = {1613-9860},
support = {K01HL135472/NH/NIH HHS/United States ; },
abstract = {BACKGROUND: Behavioral digital health interventions (e.g., mobile apps, websites, wearables) have been applied widely to improve health outcomes. However, many groups (e.g., people with low income levels, people who are geographically isolated, older adults) may face obstacles to technology access and use. In addition, research has found that biases and stereotypes can be embedded within digital health interventions. As such, behavioral digital health interventions that intend to improve overall population health may unintentionally widen health-related inequities.<br><br>PURPOSE: This commentary offers guidance and strategies to mitigate these risks when using technology as a means for delivering a behavioral health intervention.<br><br>METHODS: A collaborative working group from Society of Behavioral Medicine's Health Equity Special Interest Group developed a framework to center equity in the development, testing and dissemination of behavioral digital health interventions.<br><br>RESULTS: We introduce Partner, Identify, Demonstrate, Access, Report (PIDAR), a 5-point framework to avoid the creation, perpetuation, and/or widening of health inequities in behavioral digital health work.<br><br>CONCLUSIONS: It is critically important to prioritize equity when conducting digital health research. The PIDAR framework can serve as a guide for behavioral scientists, clinicians and developers.},
}
@article {pmid36940224,
year = {2023},
author = {Romeis, E and Lieberman, NAP and Molini, B and Tantalo, LC and Chung, B and Phung, Q and Avendaño, C and Vorobieva, A and Greninger, AL and Giacani, L},
title = {Treponema pallidum subsp. pallidum with an Artificially impaired TprK antigenic variation system is attenuated in the Rabbit model of syphilis.},
journal = {PLoS pathogens},
volume = {19},
number = {3},
pages = {e1011259},
doi = {10.1371/journal.ppat.1011259},
pmid = {36940224},
issn = {1553-7374},
abstract = {BACKGROUND: The TprK protein of the syphilis agent, Treponema pallidum subsp. pallidum (T. pallidum), undergoes antigenic variation in seven discrete variable (V) regions via non-reciprocal segmental gene conversion. These recombination events transfer information from a repertoire of 53 silent chromosomal donor cassettes (DCs) into the single tprK expression site to continually generate TprK variants. Several lines of research developed over the last two decades support the theory that this mechanism is central to T. pallidum's ability for immune avoidance and persistence in the host. Structural and modeling data, for example, identify TprK as an integral outer membrane porin with the V regions exposed on the pathogen's surface. Furthermore, infection-induced antibodies preferentially target the V regions rather than the predicted β-barrel scaffolding, and sequence variation abrogates the binding of antibodies elicited by antigenically different V regions. Here, we engineered a T. pallidum strain to impair its ability to vary TprK and assessed its virulence in the rabbit model of syphilis.<br><br>PRINCIPAL FINDINGS: A suicide vector was transformed into the wild-type (WT) SS14 T. pallidum isolate to eliminate 96% of its tprK DCs. The resulting SS14-DCKO strain exhibited an in vitro growth rate identical to the untransformed strain, supporting that the elimination of the DCs did not affect strain viability in absence of immune pressure. In rabbits injected intradermally with the SS14-DCKO strain, generation of new TprK sequences was impaired, and the animals developed attenuated lesions with a significantly reduced treponemal burden compared to control animals. During infection, clearance of V region variants originally in the inoculum mirrored the generation of antibodies to these variants, although no new variants were generated in the SS14-DCKO strain to overcome immune pressure. Na&#xef;ve rabbits that received lymph node extracts from animals infected with the SS14-DCKO strain remained uninfected.<br><br>CONCLUSION: These data further support the critical role of TprK in T. pallidum virulence and persistence during infection.},
}
@article {pmid36939690,
year = {2023},
author = {Smith, JW and O'Meally, RN and Burke, SM and Ng, DK and Chen, JG and Kensler, TW and Groopman, JD and Cole, RN},
title = {Global Discovery and Temporal Changes of Human Albumin Modifications by Pan-Protein Adductomics: Initial Application to Air Pollution Exposure.},
journal = {Journal of the American Society for Mass Spectrometry},
volume = {},
number = {},
pages = {},
doi = {10.1021/jasms.2c00314},
pmid = {36939690},
issn = {1879-1123},
abstract = {Assessing personal exposure to environmental toxicants is a critical challenge for predicting disease risk. Previously, using human serum albumin (HSA)-based biomonitoring, we reported dosimetric relationships between adducts at HSA Cys[34] and ambient air pollutant levels (Smith et al., Chem. Res. Toxicol. 2021, 34, 1183). These results provided the foundation to explore modifications at other sites in HSA to reveal novel adducts of complex exposures. Thus, the Pan-Protein Adductomics (PPA) technology reported here is the next step toward an unbiased, comprehensive characterization of the HSA adductome. The PPA workflow requires <2 μL serum/plasma and uses nanoflow-liquid chromatography, gas-phase fractionation, and overlapping-window data-independent acquisition high-resolution tandem mass spectrometry. PPA analysis of albumin from nonsmoking women exposed to high levels of air pollution uncovered 68 unique location-specific modifications (LSMs) across 21 HSA residues. While nearly half were located at Cys[34] (33 LSMs), 35 were detected on other residues, including Lys, His, Tyr, Ser, Met, and Arg. HSA adduct relative abundances spanned a ∼400 000-fold range and included putative products of exogenous (SO2, benzene, phycoerythrobilin) and endogenous (oxidation, lipid peroxidation, glycation, carbamylation) origin, as well as 24 modifications without annotations. PPA quantification revealed statistically significant changes in LSM levels across the 84 days of monitoring (∼3 HSA lifetimes) in the following putative adducts: Cys[34] trioxidation, β-methylthiolation, benzaldehyde, and benzene diol epoxide; Met[329] oxidation; Arg[145] dioxidation; and unannotated Cys[34] and His[146] adducts. Notably, the PPA workflow can be extended to any protein. Pan-Protein Adductomics is a novel and powerful strategy for untargeted global exploration of protein modifications.},
}
@article {pmid36938892,
year = {2023},
author = {Cassaday, RD and Zarling, LC and Garcia, KA and Sala-Torra, O and Stevenson, PA and Martino, CH and Liu, YJ and Fang, M and Percival, MM and Halpern, AB and Becker, PS and Oehler, VG and Shustov, AR and Cooper, JP and Orozco, JJ and Hendrie, PC and Walter, RB and Radich, JP and Soma, LA and Estey, EH},
title = {Phase II study of dose-adjusted EPOCH as initial therapy for adults with high-risk acute lymphoblastic leukemia.},
journal = {Leukemia &amp; lymphoma},
volume = {},
number = {},
pages = {1-11},
doi = {10.1080/10428194.2023.2189803},
pmid = {36938892},
issn = {1029-2403},
abstract = {Treatments for adults with newly-diagnosed acute lymphoblastic leukemia (ALL) may be prohibitively toxic and/or resource-intense. To address this, we performed a phase II study of dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin (DA-EPOCH). Imatinib or dasatinib was added for Ph + disease; rituximab was added when CD20+. Fifty-three patients were evaluable: 28 with Ph + disease, and 25 with Ph-. All patients had ≥1 high-risk clinical feature. Measurable residual disease-negativity by multiparameter flow cytometry within 4 cycles was achieved in 71% in patients with Ph + ALL and 64% in Ph - ALL. Median overall survival (OS) was 49 months, with a 2-year OS of 71%. Median relapse-free survival (RFS) in the 47 patients that attained morphologic remission was 24 months, with a 2-year RFS of 57%. Early mortality was 2%. In summary, DA-EPOCH yields deep and durable remissions in adults with ALL comparable to some resource-intense strategies but with a low rate of treatment-related death.},
}
@article {pmid36937899,
year = {2023},
author = {Sun, Y and Heng, F and Lee, U and Gilbert, PB},
title = {Estimation of conditional cumulative incidence functions under generalized semiparametric regression models with missing covariates, with application to analysis of biomarker correlates in vaccine trials.},
journal = {The Canadian journal of statistics = Revue canadienne de statistique},
volume = {51},
number = {1},
pages = {235-257},
pmid = {36937899},
issn = {0319-5724},
support = {R37 AI054165/AI/NIAID NIH HHS/United States ; T32 CA090301/CA/NCI NIH HHS/United States ; },
abstract = {This article studies generalized semiparametric regression models for conditional cumulative incidence functions with competing risks data when covariates are missing by sampling design or happenstance. A doubly-robust augmented inverse probability weighted complete-case (AIPW) approach to estimation and inference is investigated. This approach modifies IPW complete-case estimating equations by exploiting the key features in the relationship between the missing covariates and the phase-one data to improve efficiency. An iterative numerical procedure is derived to solve the nonlinear estimating equations. The asymptotic properties of the proposed estimators are established. A simulation study examining the finite-sample performances of the proposed estimators shows that the AIPW estimators are more efficient than the IPW estimators. The developed method is applied to the RV144 HIV-1 vaccine efficacy trial to investigate vaccine-induced IgG binding antibodies to HIV-1 as correlates of acquisition of HIV-1 infection while taking account of whether the HIV-1 sequences are near or far from the HIV-1 sequences represented in the vaccine construct.},
}
@article {pmid36937401,
year = {2023},
author = {Whitehouse, JP and Hii, H and Mayoh, C and Wong, M and Ajuyah, P and Barahona, P and Cui, L and Dholaria, H and White, CL and Buntine, MK and Byrne, J and Rodrigues da Silva, K and Howlett, M and Girard, EJ and Tsoli, M and Ziegler, DS and Dyke, JM and Lee, S and Ekert, PG and Cowley, MJ and Gottardo, NG and Endersby, R},
title = {In vivo loss of tumorigenicity in a patient-derived orthotopic xenograft mouse model of ependymoma.},
journal = {Frontiers in oncology},
volume = {13},
number = {},
pages = {1123492},
pmid = {36937401},
issn = {2234-943X},
abstract = {INTRODUCTION: Ependymomas (EPN) are the third most common malignant brain cancer in children. Treatment strategies for pediatric EPN have remained unchanged over recent decades, with 10-year survival rates stagnating at just 67% for children aged 0-14 years. Moreover, a proportion of patients who survive treatment often suffer long-term neurological side effects as a result of therapy. It is evident that there is a need for safer, more effective treatments for pediatric EPN patients. There are ten distinct subgroups of EPN, each with their own molecular and prognostic features. To identify and facilitate the testing of new treatments for EPN, in vivo laboratory models representative of the diverse molecular subtypes are required. Here, we describe the establishment of a patient-derived orthotopic xenograft (PDOX) model of posterior fossa A (PFA) EPN, derived from a metastatic cranial lesion.<br><br>METHODS: Patient and PDOX tumors were analyzed using immunohistochemistry, DNA methylation profiling, whole genome sequencing (WGS) and RNA sequencing.<br><br>RESULTS: Both patient and PDOX tumors classified as PFA EPN by methylation profiling, and shared similar histological features consistent with this molecular subgroup. RNA sequencing revealed that gene expression patterns were maintained across the primary and metastatic tumors, as well as the PDOX. Copy number profiling revealed gains of chromosomes 7, 8 and 19, and loss of chromosomes 2q and 6q in the PDOX and matched patient tumor. No clinically significant single nucleotide variants were identified, consistent with the low mutation rates observed in PFA EPN. Overexpression of EZHIP RNA and protein, a common feature of PFA EPN, was also observed. Despite the aggressive nature of the tumor in the patient, this PDOX was unable to be maintained past two passages in vivo.<br><br>DISCUSSION: Others who have successfully developed PDOX models report some of the lowest success rates for EPN compared to other pediatric brain cancer types attempted, with loss of tumorigenicity not uncommon, highlighting the challenges of propagating these tumors in the laboratory. Here, we discuss our collective experiences with PFA EPN PDOX model generation and propose potential approaches to improve future success in establishing preclinical EPN models.},
}
@article {pmid36935289,
year = {2023},
author = {Ma, J and Shao, L and Fuksenko, T and Liu, H and Shi, R and Dinh, A and Highfill, SL and Zhang, N and Panch, SR and Somerville, RP and Stroncek, DF and Jin, P},
title = {Reference gene selection for clinical chimeric antigen receptor T-cell product vector copy number assays.},
journal = {Cytotherapy},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jcyt.2023.02.010},
pmid = {36935289},
issn = {1477-2566},
abstract = {BACKGROUND AIMS: Reference genes are an essential part of clinical assays such as droplet digital polymerase chain reaction (ddPCR), which measure the number of copies of vector integrated into genetically engineered cells and the loss of plasmids in reprogrammed cells used in clinical cell therapies. Care should be taken to select reference genes, because it has been discovered that there may be thousands of variations in copy number from genomic segments among different individuals. In addition, within the same person in the context of cancer and other proliferative disorders, substantial parts of the genome also can differ in copy number between cells from diseased and healthy people. The purpose of this study was to identify reference genes that could be used for copy number variation analysis of transduced chimeric antigen receptor T cells and for plasmid loss analysis in induced pluripotent stem cells using ddPCR.<br><br>METHODS: We used The Cancer Genome Atlas (TCGA) to evaluate candidate reference genes. If TCGA found a candidate gene to have low copy number variance in cancer, ddPCR was used to measure the copy numbers of the potential reference gene in cells from healthy subjects, cancer cell lines and patients with acute lymphocytic leukemia, lymphoma, multiple myeloma and human papillomavirus-associated cancers.<br><br>RESULTS: In addition to the rPP30 gene, which we have has been using in our copy number assays, three other candidate reference genes were evaluated using TCGA, and this analysis found that none of the four gene regions (AGO1, AP3B1, MKL2 and rPP30) were amplified or deleted in all of the cancer cell types that are currently being treated with cellular therapies by our facility. The number of copies of the genes AP3B1, AGO1, rPP30 and MKL2 measured by ddPCR was similar among cells from healthy subjects. We found that AGO1 had copy number alteration in some of the clinical samples, and the number of copies of the genes AP3B1, MKL2 and rPP30 measured by ddPCR was similar among cells from patients with the cancer cell types that are currently being treated with genetically engineered T-cell therapies by our facility.<br><br>CONCLUSIONS: Based on our current results, the three genes, AP3B1, MKL2 and rPP30, are suitable for use as reference genes for assays measuring vector copy number in chimeric antigen receptor T cells produced from patients with acute leukemia, lymphoma, multiple myeloma and human papillomavirus-associated cancers. We will continue to evaluate AGO1 on our future samples.},
}
@article {pmid36935288,
year = {2023},
author = {Wilson, GJ and Rodriguez, B and Li, SS and Allen, M and Frank, I and Rudnicki, E and Trahey, M and Kalams, S and Hannaman, D and Clarke, DK and Xu, R and Egan, M and Eldridge, J and Pensiero, M and Latham, T and Ferrari, G and Montefiori, DC and Tomaras, GD and De Rosa, SC and Jacobson, JM and Miner, MD and Elizaga, M and , },
title = {Cellular and humoral responses to an HIV DNA prime by electroporation boosted with recombinant vesicular stomatitis virus expressing HIV subtype C Env in a randomized controlled clinical trial.},
journal = {Vaccine},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.vaccine.2023.03.015},
pmid = {36935288},
issn = {1873-2518},
abstract = {BACKGROUND: HIV subtypes B and C together account for around 60% of HIV-1 cases worldwide. We evaluated the safety and immunogenicity of a subtype B DNA vaccine prime followed by a subtype C viral vector boost.<br><br>METHODS: Fourteen healthy adults received DNA plasmid encoding HIV-1 subtype B nef/tat/vif and env (n&#xa0;=&#xa0;11) or placebo (n&#xa0;=&#xa0;3) intramuscularly (IM) via electroporation (EP) at 0, 1, and 3&#xa0;months, followed by IM injection of recombinant vesicular stomatitis virus encoding subtype C Env or placebo at 6 and 9&#xa0;months. Participants were assessed for safety, tolerability of EP, and Env-specific T-cell and antibody responses.<br><br>RESULTS: EP was generally well tolerated, although some device-related adverse events did occur, and vaccine reactogenicity was mild to moderate. The vaccine stimulated Env-specific CD4&#xa0;+&#xa0;T-cell responses in&#xa0;greater than&#xa0;80% of recipients, and CD8&#xa0;+&#xa0;T-cell responses in 30%. Subtype C Env-specific IgG binding antibodies (bAb) were elicited in all vaccine recipients, and antibody-dependent cell-mediated cytotoxicity (ADCC) responses to vaccine-matched subtype C targets in 80%. Negligible V1/V2 and neutralizing antibody (nAb) responses were detected.<br><br>CONCLUSIONS: This prime/boost regimen was safe and tolerable, with some device-related events, and immunogenic. Although immunogenicity missed targets for an HIV vaccine, the DNA/rVSV platform may be useful for other applications.<br><br>CLINICALTRIALS: gov: NCT02654080.},
}
@article {pmid36938334,
year = {2020},
author = {Janes, H and Zhu, Y and Brown, ER},
title = {Designing HIV Vaccine Efficacy Trials in the Context of Highly Effective Non-vaccine Prevention Modalities.},
journal = {Statistics in biosciences},
volume = {12},
number = {3},
pages = {468-494},
pmid = {36938334},
issn = {1867-1764},
support = {R56 AI143418/AI/NIAID NIH HHS/United States ; UM1 AI068635/AI/NIAID NIH HHS/United States ; },
abstract = {The evolving HIV prevention landscape poses challenges to the statistical design of future trials of candidate HIV vaccines. Study designs must address the anticipated reduction in HIV incidence due to adding new prevention modalities to the standard prevention package provided to trial participants, and must also accommodate individual choices of participants with regard to the use of these modalities. We explore four potential trial designs that address these challenges, with a focus on accommodating the newest addition to the prevention package-antiretroviral-based oral pre-exposure prophylaxis (PrEP). The designs differ with respect to how individuals who take up oral PrEP at screening are handled. An All-Comers Design enrolls and randomizes all eligible individuals, a Decliners Design enrolls and randomizes only those who decline PrEP at screening, and Single and Multi-Stage Run-In Designs enroll all but randomize only those who decline PrEP or show inadequate adherence to PrEP after one or multiple run-in periods. We compare these designs with respect to required sample sizes, study duration, and resource requirements, using a simulation model that incorporates data on HIV risk and PrEP uptake and adherence among men who have sex with men (MSM) in the Americas. We advocate considering Run-In Designs for some future contexts, and identify their advantages and tradeoffs relative to the other designs. The design concepts apply beyond HIV vaccines to other prevention modalities being developed with the aim to achieve further reductions in HIV incidence.},
}
@article {pmid36934994,
year = {2023},
author = {Banerjee, R and Kelkar, AH and Durani, U and Anagnostou, T and Nishitani, M and Mallhi, K and Majhail, NS and Logan, AC},
title = {Demographics, motivations, and experiences of participants in transplantation or cellular therapy fellowships.},
journal = {Transplantation and cellular therapy},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jtct.2023.03.011},
pmid = {36934994},
issn = {2666-6367},
abstract = {BACKGROUND: Recent ASTCT guidelines have sought to establish clinical and research expectations for participants in blood and marrow transplantation (BMT) and cellular therapy (CT) fellowships. However, little is known about participants in BMT/CT fellowships and the value they find from this additional training.<br><br>OBJECTIVES: To characterize the demographics, motivations, and experiences of recent participants in BMT/CT fellowships.<br><br>METHODS: We developed a 27-item online survey addressing backgrounds, application processes, training experiences, and perceived benefits among physicians who had started a clinical US-based BMT/CT fellowship between 2012-2021. Anonymous responses were solicited through program director outreach, society website postings, targeted emails, and social media.<br><br>RESULTS: Of 105 respondents (44% pediatric trainees), 4% were underrepresented minorities (URM) and 39% were non-US international medical graduates (IMGs). The most important motivations for applying were comfort with allogeneic BMT, improved career prospects, and opportunities for research and publication. Almost all respondents (92%) attended donor selection meetings, while smaller proportions visited cell processing facilities (65%), HLA labs (57%), or GMP facilities (22%). Most respondents reported &#x2265;1 publication (26% reported 4+) based on research or experiences during their fellowship. Respondents reported improved post-fellowship comfort with all queried BMT/CT-related competencies. Seventy percent of respondents stated that they would recommend their fellowship highly to others; this corresponded to a Net Promoter Score of +65%, consistent with a strongly positive experience. Most respondents reported currently being in clinical practice (89% at academic centers), with a median of 70% of time currently spent caring for BMT/CT recipients.<br><br>CONCLUSIONS: While limited by recruitment methods and recall bias, our study demonstrated that BMT/CT fellowships are effective at increasing comfort with BMT/CT management and that most participants would highly recommend this BMT/CT training to others. Nevertheless, our study identified substantial heterogeneity in clinical responsibilities and BMT/CT-related laboratory exposure. The high representation of non-US IMGs underscores the distinct role of BMT/CT fellowships for this group, while improved URM recruitment remains an important future direction for the field. Whether advanced fellowships will ever become required for the future BMT/CT workforce, analogous to the additional training required for solid organ transplantation in other medical and pediatric subspecialties, remains uncertain.},
}
@article {pmid36934308,
year = {2023},
author = {Brasky, TM and Hade, EM and Cohn, DE and Newton, AM and Petruzella, S and O'Connell, K and Bertrand, KA and Cook, LS and De Vivo, I and Du, M and Freudenheim, JL and Friedenreich, CM and Goodman, MT and Gorzelitz, J and Ibiebele, TI and Krogh, V and Liao, LM and Lipworth, L and Lu, L and McCann, S and O'Mara, TA and Palmer, JR and Ponte, J and Prizment, A and Risch, H and Sandin, S and Schouten, LJ and Setiawan, VW and Shu, XO and Trabert, B and van den Brandt, PA and Webb, PM and Wentzensen, N and Wilkens, LR and Wolk, A and Yu, H and Neuhouser, ML},
title = {Dietary omega-3 fatty acids and endometrial cancer risk in the Epidemiology of Endometrial Cancer Consortium: An individual-participant meta-analysis.},
journal = {Gynecologic oncology},
volume = {169},
number = {},
pages = {137-146},
pmid = {36934308},
issn = {1095-6859},
abstract = {BACKGROUND: Limited data from prospective studies suggest that higher dietary intake of long-chain omega-3 polyunsaturated fatty acids (LCn3PUFA), which hold anti-inflammatory properties, may reduce endometrial cancer risk; particularly among certain subgroups characterized by body mass and tumor pathology.<br><br>MATERIALS AND METHODS: Data from 12 prospective cohort studies participating in the Epidemiology of Endometrial Cancer Consortium were harmonized as nested case-control studies, including 7268 endometrial cancer cases and 26,133 controls. Habitual diet was assessed by food frequency questionnaire, from which fatty acid intakes were estimated. Two-stage individual-participant data mixed effects meta-analysis estimated adjusted odds ratios (OR) and 95% confidence intervals (CI) through logistic regression for associations between study-specific energy-adjusted quartiles of LCn3PUFA and endometrial cancer risk.<br><br>RESULTS: Women with the highest versus lowest estimated dietary intakes of docosahexaenoic acid, the most abundant LCn3PUFA in diet, had a 9% increased endometrial cancer risk (Quartile 4 vs. Quartile 1: OR 1.09, 95% CI: 1.01-1.19; P trend = 0.04). Similar elevated risks were observed for the summary measure of total LCn3PUFA (OR 1.07, 95% CI: 0.99-1.16; P trend = 0.06). Stratified by body mass index, higher intakes of LCn3PUFA were associated with 12-19% increased endometrial cancer risk among overweight/obese women and no increased risk among normal-weight women. Higher associations appeared restricted to White women. The results did not differ by cancer grade.<br><br>CONCLUSION: Higher dietary intakes of LCn3PUFA are unlikely to reduce endometrial cancer incidence; rather, they may be associated with small to moderate increases in risk in some subgroups of women, particularly overweight/obese women.},
}
@article {pmid36933659,
year = {2023},
author = {Reyes, KR and Huang, CY and Lo, M and Arora, S and Chung, A and Wong, SW and Wolf, J and Olin, RL and Martin, T and Shah, N and Banerjee, R},
title = {Safety and efficacy of BCMA CAR-T cell therapy in older patients with multiple myeloma.},
journal = {Transplantation and cellular therapy},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jtct.2023.03.012},
pmid = {36933659},
issn = {2666-6367},
abstract = {BACKGROUND: Risks of B-cell maturation antigen (BCMA) chimeric antigen receptor T-cell (CAR-T) therapy for patients with multiple myeloma (MM) include cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), cytopenias, and infections. The efficacy and safety of BCMA CAR-T therapy in the geriatric setting, including complications such as falls and delirium which may be more prevalent in older patients, have not been fully analyzed.<br><br>OBJECTIVES: To analyze the efficacy and safety of BCMA CAR-T therapy among older patients (age &#x2265;70 at infusion) versus younger patients with MM.<br><br>STUDY DESIGN: We analyzed all patients with MM who received any autologous BCMA CAR-T therapy over a 5-year period at our institution. Key endpoints included CRS, ICANS incidence, days to absolute neutrophil count (ANC) recovery, incidence of hypogammaglobulinemia (IgG < 400 mg/dL), infections within 6 months, progression-free survival (PFS), and overall survival (OS).<br><br>RESULTS: Of 83 analyzed patients (age range 33-77), 22 (27%) were aged &#x2265;70 at infusion. The older cohort had lower creatinine clearances (median 67.3 vs 91.9 mL/min, p<0.001) and a higher proportion of patients with performance status &#x2265;1 (59% vs 30%, p=0.02) but were otherwise similar. Rates of any-grade CRS, any-grade ICANS, and days to ANC recovery were similar between groups. Rates of baseline hypogammaglobulinemia were 36% in older patients and 30% in younger patients (p=0.60), while post-infusion hypogammaglobulinemia occurred in 82% vs 72% respectively (p=0.57). Infections occurred in 36% (n=8) of the older cohort versus 52% (n=32) of the younger cohort (p=0.22). There were no statistically significant differences between the older and younger cohorts in terms of documented falls (9% vs 15%, p=0.72) or non-ICANS delirium (5% vs 7%, p=1.0). Median PFS was 13.1 months in older patients (95% CI 9.2-not reached [NR]) vs 12.5 months in younger patients (95% CI 11.3-22.5, p=0.42. Median OS was not reached in the older cohort (95% CI: NR-NR) vs 31.4 months in the younger cohort (95% CI 24.8-NR) with p=0.04. However, age &#x2265;70 was not a significant predictor of OS after adjusting for high-risk cytogenetics, triple-class refractoriness, extramedullary disease, and bone marrow plasma cell burden.<br><br>CONCLUSIONS: While limited by small sample size and unmeasured confounders, our retrospective analysis did not demonstrate significant increases in CAR-T toxicity among older patients. This included toxicities associated with geriatric populations such as falls and delirium. Our paradoxical finding of borderline better OS among patients aged &#x2265;70, which was not significant in regression modeling, may have been due to selection bias in favor of disproportionately healthy CAR-T candidates in the geriatric population. Overall, BCMA CAR-T remains a safe and effective option for older patients with MM.},
}
@article {pmid36933003,
year = {2023},
author = {Fjeldstad, HE and Jacobsen, DP and Johnsen, GM and Sugulle, M and Chae, A and Kanaan, SB and Gammill, HS and Staff, AC},
title = {Markers of placental function correlate with prevalence and quantity of nucleated fetal cells in maternal circulation in normotensive term pregnancies.},
journal = {Acta obstetricia et gynecologica Scandinavica},
volume = {},
number = {},
pages = {},
doi = {10.1111/aogs.14547},
pmid = {36933003},
issn = {1600-0412},
abstract = {INTRODUCTION: Transplacental fetal cell transfer results in the engraftment of fetal-origin cells in the pregnant woman's body, a phenomenon termed fetal microchimerism. Increased fetal microchimerism measured decades postpartum is implicated in maternal inflammatory disease. Understanding which factors cause increased fetal microchimerism is therefore important. During pregnancy, circulating fetal microchimerism and placental dysfunction increase with increasing gestational age, particularly towards term. Placental dysfunction is reflected by changes in circulating placenta-associated markers, specifically placental growth factor (PlGF), decreased by several 100 pg/mL, soluble fms-like tyrosine kinase-1 (sFlt-1), increased by several 1000 pg/mL, and the sFlt-1/PlGF ratio, increased by several 10 (pg/mL)/(pg/mL). We investigated whether such alterations in placenta-associated markers correlate with an increase in circulating fetal-origin cells.<br><br>MATERIAL AND METHODS: We included 118 normotensive, clinically uncomplicated pregnancies (gestational age 37+1 up to 42+2&#x2009;weeks' gestation) pre-delivery. PlGF and sFlt-1 (pg/mL) were measured by Elecsys&#xae; Immunoassays. We extracted DNA from maternal and fetal samples and genotyped four human leukocyte antigen loci and 17 other autosomal loci. Paternally inherited, unique fetal alleles served as polymerase chain reaction (PCR) targets for detecting fetal-origin cells in maternal buffy coat. Fetal-origin cell prevalence was assessed by logistic regression, and quantity by negative binomial regression. Statistical exposures included gestational age (weeks), PlGF (100 pg/mL), sFlt-1 (1000&#x2009;pg/mL) and the sFlt-1/PlGF ratio (10 (pg/mL)/(pg/mL)). Regression models were adjusted for clinical confounders and PCR-related competing exposures.<br><br>RESULTS: Gestational age was positively correlated with fetal-origin cell quantity (DRR = 2.2, P = 0.003) and PlGF was negatively correlated with fetal-origin cell prevalence (odds ratio [OR]100 = 0.6, P = 0.003) and quantity (DRR100 = 0.7, P = 0.001). The sFlt-1 and the sFlt-1/PlGF ratios were positively correlated with fetal-origin cell prevalence (OR1000 = 1.3, P = 0.014 and OR10 = 1.2, P = 0.038, respectively), but not quantity (DRR1000 = 1.1, P = 0.600; DRR10 = 1.1, P = 0.112, respectively).<br><br>CONCLUSIONS: Our results suggest that placental dysfunction as evidenced by placenta-associated marker changes, may increase fetal cell transfer. The magnitudes of change tested were based on ranges in PlGF, sFlt-1 and the sFlt-1/PlGF ratio previously demonstrated in pregnancies near and post-term, lending clinical significance to our findings. Our results were statistically significant after adjusting for confounders including gestational age, supporting our novel hypothesis that underlying placental dysfunction potentially is a driver of increased fetal microchimerism.},
}
@article {pmid36932663,
year = {2023},
author = {Crisp, AM and Halloran, ME and Longini, IM and Vazquez-Prokopec, G and Dean, NE},
title = {Covariate-constrained randomization with cluster selection and substitution.},
journal = {Clinical trials (London, England)},
volume = {},
number = {},
pages = {17407745231160556},
doi = {10.1177/17407745231160556},
pmid = {36932663},
issn = {1740-7753},
abstract = {BACKGROUND: An ongoing cluster-randomized trial for the prevention of arboviral diseases utilizes covariate-constrained randomization to balance two treatment arms across four specified covariates and geographic sector. Each cluster is within a census tract of the city of Mérida, Mexico, and there were 133 eligible tracts from which to select 50. As some selected clusters may have been subsequently found unsuitable in the field, we desired a strategy to substitute new clusters while maintaining covariate balance.<br><br>METHODS: We developed an algorithm that successfully identified a subset of clusters that maximized the average minimum pairwise distance between clusters in order to reduce contamination and balanced the specified covariates both before and after substitutions were made.<br><br>SIMULATIONS: Simulations were performed to explore some limitations of this algorithm. The number of selected clusters and eligible clusters were varied along with the method of selecting the final allocation pattern.<br><br>CONCLUSION: The algorithm is presented here as a series of optional steps that can be added to the standard covariate-constrained randomization process in order to achieve spatial dispersion, cluster subsampling, and cluster substitution. Simulation results indicate that these extensions can be used without loss of statistical validity, given a sufficient number of clusters included in the trial.},
}
@article {pmid36931981,
year = {2023},
author = {Diamantopoulos, LN and Makrakis, D and Korentzelos, D and Alevizakos, M and Wright, JL and Grivas, P and Bountziouka, V and Vadikolias, K and Lambropoulou, M and Tripsianis, G},
title = {Development and validation of a prognostic nomogram for overall and disease-specific survival in patients with sarcomatoid urothelial carcinoma.},
journal = {Urologic oncology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.urolonc.2023.01.019},
pmid = {36931981},
issn = {1873-2496},
abstract = {INTRODUCTION: Sarcomatoid urothelial carcinoma (SUC) is a rare and aggressive variant of bladder cancer with limited data guiding prognosis. In this study, we present the first prognostic nomograms in the literature for 3- and 5-year overall survival (OS) and disease-specific survival (DSS), for patients with SUC derived from the surveillance, epidemiology and end results database (SEER).<br><br>MATERIALS AND METHODS: Patients with SUC were identified by using the ICD-10 topography codes C67.0-C67.9 (bladder cancer), and the morphologic code 8122 (SUC). Patients were randomly divided into a training cohort (TC) and a validation cohort (VC) (7:3 ratio). Variables significantly associated with OS and DSS were identified with multivariate Cox regression and were used to build the nomograms. Harrel's C-statistic with bootstrap resampling and calibration curves were used for internal (TC) and external (VC) validation. Clinical utility of the nomograms was assessed with the decision curve analysis (DCA). Goodness of fit between the nomograms and the AJCC 8th edition staging system was compared with the likelihood ratio test.<br><br>RESULTS: A total of 741 patients with SUC were included (507 TC, 234 VC). No statistically significant differences in baseline characteristics were identified between the 2 cohorts. Sex, SEER stage, radical cystectomy and chemotherapy were common variables for the OS and the DSS nomograms with the addition of age in the former. Optimism-corrected C-statistic for the nomograms was 0.68 and 0.67 for OS and DSS respectively. In comparison, C-statistic for AJCC was 0.59 for OS and 0.60 for DSS (P < 0.001). Calibration curves constructed for the nomograms showed appropriate consistency between predicted and actual survival. The nomograms demonstrated optimal clinical utility in the DCA, outperforming the AJCC staging system, by maintaining a higher clinical net benefits than treat all, treat none and AJCC curves, across threshold probabilities.<br><br>CONCLUSION: We present the first prognostic nomograms developed in patients with SUC. Our models demonstrated superior prognostic performance to the AJCC system, by utilizing a set of variables readily available in daily practice and may serve as useful tools for the individualized risk assessment of these patients.},
}
@article {pmid36931276,
year = {2023},
author = {Tripathi, P and Bender, MF and Lei, H and Da Silva Pereira, L and Shen, CH and Bonilla, B and Dillon, M and Ou, L and Pancera, M and Wang, LT and Zhang, B and Batista, FD and Idris, AH and Seder, RA and Kwong, PD},
title = {Cryo-EM structures of anti-malarial antibody L9 with circumsporozoite protein reveal trimeric L9 association and complete 27-residue epitope.},
journal = {Structure (London, England : 1993)},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.str.2023.02.009},
pmid = {36931276},
issn = {1878-4186},
abstract = {Monoclonal antibody L9 recognizes the Plasmodium falciparum circumsporozoite protein (PfCSP) and is highly protective following controlled human malaria challenge. To gain insight into its function, we determined cryoelectron microscopy (cryo-EM) structures of L9 in complex with full-length PfCSP and assessed how this recognition influenced protection by wild-type and mutant L9s. Cryo-EM reconstructions at 3.6- and 3.7-Å resolution revealed L9 to recognize PfCSP as an atypical trimer. Each of the three L9s in the trimer directly recognized an Asn-Pro-Asn-Val (NPNV) tetrapeptide on PfCSP and interacted homotypically to facilitate L9-trimer assembly. We analyzed peptides containing different repeat tetrapeptides for binding to wild-type and mutant L9s to delineate epitope and homotypic components of L9 recognition; we found both components necessary for potent malaria protection. Last, we found the 27-residue stretch recognized by L9 to be highly conserved in P. falciparum isolates, suggesting the newly revealed complete L9 epitope to be an attractive vaccine target.},
}
@article {pmid36930136,
year = {2023},
author = {Haring, B and Hunt, RP and Shadyab, AH and Eaton, C and Kaplan, R and Martin, LW and Panjrath, G and Kuller, LH and Assimes, T and Kooperberg, C and Wassertheil-Smoller, S},
title = {Cardiovascular Disease and Mortality in Black Women Carrying the Amyloidogenic V122I Transthyretin Gene Variant.},
journal = {JACC. Heart failure},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jchf.2023.02.003},
pmid = {36930136},
issn = {2213-1787},
abstract = {BACKGROUND: Long-term data on cardiovascular disease (CVD) and mortality in female carriers of the transthyretin (TTR) V122I (pV142I) variant, one of the most common variants of hereditary transthyretin cardiac amyloidosis, are sparse and the effects of blood pressure, heart rate, body mass index, and physical activity on CVD outcomes remain largely unknown.<br><br>OBJECTIVES: The aim was to first examine the relationship of TTR V122I (pV142I) carrier status with CVD and mortality and second to investigate the effects of blood pressure, heart rate, body mass index, and physical activity in a large cohort of postmenopausal women.<br><br>METHODS: The study population consisted of 9,862 non-Hispanic Black/African American women, 9,529 noncarriers&#xa0;and 333 TTR V122I carriers, enrolled in the Women's Health Initiative at 40 centers in the United States.&#xa0;Women were generally healthy and postmenopausal at the time of enrollment (1993-1998). CVD was defined&#xa0;as a composite endpoint consisting of coronary heart disease, stroke, acute heart failure or CVD death, and all-cause mortality. CVD cases were based on self-reported annual mailed health updates. All information was centrally adjudicated by trained physicians. HRs and 95%&#xa0;CIs were obtained from adjusted Cox proportional hazards models.<br><br>RESULTS: Among 9,862 Black female participants (mean age: 62 years [IQR: 56-67 years]), the population frequency of the TTR V122I variant was 3.4% (333 variant carriers and 9,529 noncarriers). During a mean follow-up of 16.1 years (IQR: 9.7-22.2 years), incident CVD occurred in 2,229 noncarriers and 96 carriers, whereas 2,689 noncarriers and 108 carriers died. In adjusted models including demographic, lifestyle, and medical history covariates, TTR V122I carriers were at higher risk of the composite endpoint CVD (HR: 1.52; 95%&#xa0;CI: 1.22-1.88), acute heart failure (HR: 2.21; 95%&#xa0;CI: 1.53-3.18), coronary heart disease (HR: 1.80; 95%&#xa0;CI: 1.30-2.47), CVD death (HR: 1.70; 95%&#xa0;CI: 1.26-2.30), and all-cause mortality (HR: 1.28; 95%&#xa0;CI: 1.04-1.56). The authors found a significant interaction by age but not by blood pressure, heart rate, body mass index, or physical activity.<br><br>CONCLUSIONS: Black female TTR V122I (pV142I) carriers have a higher CVD and all-cause mortality risk compared to noncarriers. In case of clinical suspicion of amyloidosis, they should be screened for TTR V122I (pV142I) carrier status to ensure early treatment onset.},
}
@article {pmid36929942,
year = {2023},
author = {Lindström, S and Wang, L and Feng, H and Majumdar, A and Huo, S and Macdonald, J and Harrison, T and Turman, C and Chen, H and Mancuso, N and Bammler, T and , and Gallinger, S and Gruber, SB and Gunter, MJ and Le Marchand, L and Moreno, V and Offit, K and , and de Vivo, I and O'Mara, TA and Spurdle, AB and Tomlinson, I and , and Fitzgerald, R and Gharahkhani, P and Gockel, I and Jankowski, J and Macgregor, S and Schumacher, J and Barnholtz-Sloan, J and Bondy, ML and Houlston, RS and Jenkins, RB and Melin, B and Wrensch, M and Brennan, P and Christiani, D and Johansson, M and Mckay, J and Aldrich, MC and Amos, CI and Landi, MT and Tardon, A and , and Bishop, DT and Demenais, F and Goldstein, AM and Iles, MM and Kanetsky, PA and Law, MH and , and Amundadottir, LT and Stolzenberg-Solomon, R and Wolpin, BM and , and Klein, A and Petersen, G and Risch, H and , and , and Chanock, SJ and Purdue, MP and Scelo, G and Pharoah, P and Kar, S and Hung, RJ and Pasaniuc, B and Kraft, P},
title = {Genome-Wide Analyses Characterize Shared Heritability Among Cancers and Identify Novel Cancer Susceptibility Regions.},
journal = {Journal of the National Cancer Institute},
volume = {},
number = {},
pages = {},
doi = {10.1093/jnci/djad043},
pmid = {36929942},
issn = {1460-2105},
abstract = {BACKGROUND: The shared inherited genetic contribution to risk of different cancers is not fully known. In this study, we leverage results from twelve cancer genome-wide association studies (GWAS) to quantify pair-wise genome-wide genetic correlations across cancers and identify novel cancer susceptibility loci.<br><br>METHODS: We collected GWAS summary statistics for twelve solid cancers based on 376,759 cancer cases and 532,864 controls of European ancestry. The included cancer types were breast, colorectal, endometrial, esophageal, glioma, head and neck, lung, melanoma, ovarian, pancreatic, prostate, and renal cancers. We conducted cross-cancer GWAS and transcriptome-wide association studies (TWAS) to discover novel cancer susceptibility loci. Finally, we assessed the extent of variant-specific pleiotropy among cancers at known and newly identified cancer susceptibility loci.<br><br>RESULTS: We observed wide-spread but modest genome-wide genetic correlations across cancers. In cross-cancer GWAS and TWAS, we identified 15 novel cancer susceptibility loci. Additionally, we identified multiple variants at 77 distinct loci with strong evidence of being associated with at least two cancer types by testing for pleiotropy at known cancer susceptibility loci.<br><br>CONCLUSIONS: Overall, these results suggest that some genetic risk variants are shared among cancers, though much of cancer heritability is cancer- and thus tissue-specific. The increase in statistical power associated with larger sample sizes in cross-disease analysis allows for the identification of novel susceptibility regions. Future studies incorporating data on multiple cancer types are likely to identify additional regions associated with the risk of multiple cancer types.},
}
@article {pmid36929319,
year = {2023},
author = {Malahleha, M and Laher, F and Dilraj, A and Smith, P and Gray, GE and Grove, D and Odhiambo, JA and Andrasik, MP and Grunenberg, NA and Moodie, Z and Huang, Y and Borate, BR and Gillespie, KM and Allen, M and Atujuna, M and Singh, N and Kalonji, D and Meintjes, G and Kotze, P and Bekker, LG and Janes, H},
title = {Risk Factors Associated with HIV Acquisition in Males Participating in HIV Vaccine Efficacy Trials in South Africa.},
journal = {AIDS and behavior},
volume = {},
number = {},
pages = {},
pmid = {36929319},
issn = {1573-3254},
abstract = {In South Africa, HIV acquisition risk has been studied less in people assigned male at birth. We studied the associations between risk behaviors, clinical features and HIV incidence amongst males in two South African HIV preventive vaccine efficacy trials. We used Cox proportional hazards models to test for associations between demographics, sexual behaviors, clinical variables and HIV acquisition among males followed in the HVTN 503 (n = 219) and HVTN 702 (n = 1611) trials. Most males reported no male sexual partners (99.09% in HVTN 503) or identified as heterosexual (88.08% in HVTN 702). Annual HIV incidence was 1.39% in HVTN 503 (95% CI 0.76-2.32%) and 1.33% in HVTN 702 (95% CI 0.80-2.07%). Increased HIV acquisition was significantly associated with anal sex (HR 6.32, 95% CI 3.44-11.62), transactional sex (HR 3.42, 95% CI 1.80-6.50), and non-heterosexual identity (HR 16.23, 95%CI 8.13-32.41) in univariate analyses and non-heterosexual identity (HR 14.99, 95% CI 4.99-45.04; p < 0.01) in multivariate analysis. It is appropriate that prevention efforts in South Africa, although focused on the severe epidemic in young women, also encompass key male populations, including men who have sex with men, but also men who engage in anal or transactional sex.},
}
@article {pmid36929166,
year = {2023},
author = {Jiao, B and Johnson, KM and Ramsey, SD and Bender, MA and Devine, B and Basu, A},
title = {Long-Term Survival with Sickle Cell Disease: A Nationwide Cohort Study of Medicare and Medicaid Beneficiaries.},
journal = {Blood advances},
volume = {},
number = {},
pages = {},
doi = {10.1182/bloodadvances.2022009202},
pmid = {36929166},
issn = {2473-9537},
abstract = {We report the first population-based period life table, the expected lifetime survival for Medicare and Medicaid beneficiaries with Sickle Cell Disease (SCD), and the disparities in survival by insurance types in the United States. We constructed a retrospective cohort of individuals with diagnosed SCD receiving Common Care (any real-world patterns of care except transplant) based on nationwide Medicare and Medicaid claims data (2008-2016), covering beneficiaries in all 50 states. We analyzed lifetime survival probabilities using Kaplan-Meier curves and projected life expectancies at various ages for all and stratified by sex and insurance types. Our analysis included 94,616 individuals with SCD that have not undergone any transplant. Life expectancy at birth was 52.6 years (95% CI: 51.9, 53.4). Compared to the adults covered by Medicaid only, those covered by Medicare for disabilities or end-stage renal disease and those dually insured by Medicare and Medicaid had significantly worse life expectancy. Similarly, for beneficiaries aged ≥65 years, these two insurance types were associated with significantly shorter life expectancy than those enrolled in Medicare old age and survivor's insurance. Our study underscores the persistent life expectancy shortfall for SCD patients, the burden of premature mortality during adulthood, and survival disparities by insurance status.},
}
@article {pmid36929133,
year = {2023},
author = {Balgansuren, G and Sprague, M and Peterson, P and Shenavar, Y and Ng, A and Regen, L and Shelton, N and Petersdorf, E},
title = {HLA-B leader genotypes in a clinical population.},
journal = {HLA},
volume = {},
number = {},
pages = {},
doi = {10.1111/tan.15022},
pmid = {36929133},
issn = {2059-2310},
abstract = {The -21 dimorphism in the leader sequences of HLA-B exon 1 is associated with risk of graft-versus-host disease (GVHD), relapse and overall survival after unrelated donor hematopoietic cell transplantation (HCT), haploidentical HCT and cord blood transplantation. Consideration of the leader dimorphism in the prospective selection of allogeneic donors for HCT may help to lower risks for patients, but requires understanding of the frequencies of the leader in patients and candidate transplant donors. We defined the frequencies of the HLA-B leader, and its association to HLA-B Bw4/Bw6 and C1/C2 KIR epitopes. Sequence variants of rs1050458 of exon 1 position -21 for 11,126 haplotypes were analyzed from high resolution HLA typing of over 5500 study subjects. HLA typing was performed by TruSight/AlloSeq NGS and analyzed using TruSight/AlloSeq Assign software. HLA-B Bw4/Bw6 and C1/C2 KIR epitopes were defined based on established sequence alignments and nomenclature. Alleles at rs1050458 of HLA-B exon 1 were validated as dimorphic: rs1050458-C or -T variants encoding threonine (T) or methionine (M) at anchor position 2 (P2) of nonameric HLA-B leader peptides, respectfully. No additional variants were observed. Among study subjects, 70% of HLA-B haplotypes encoded T-leader and 30% encoded M-leader sequences. The genotype frequencies of TT, MT, and MM were consistent among patient, related, and unrelated donor groups. The associations of M/T leader, Bw4/Bw6, and C1/C2 enhanced understanding of the Class I features involved in the innate immune response. A population of patients and transplant donors confirms the rs1050458 leader dimorphism and its association with HLA-B Bw4/Bw6 and C1/C2 KIR features.},
}
@article {pmid36928836,
year = {2023},
author = {Goswami, H and Alsumali, A and Jiang, Y and Schindler, M and Duke, ER and Cohen, J and Briggs, A and Puenpatom, A},
title = {Correction to: Cost-Effectiveness Analysis of Molnupiravir Versus Best Supportive Care for the Treatment of Outpatient COVID-19 in Adults in the US.},
journal = {PharmacoEconomics},
volume = {},
number = {},
pages = {1},
doi = {10.1007/s40273-023-01263-w},
pmid = {36928836},
issn = {1179-2027},
}
@article {pmid36927800,
year = {2023},
author = {Pogosova-Agadjanyan, EL and Hua, X and Othus, M and Appelbaum, FR and Chauncey, TR and Erba, HP and Fitzgibbon, MP and Jenkins, IC and Fang, M and Lee, SC and Moseley, A and Naru, J and Radich, JP and Smith, JL and Willborg, BE and Willman, CL and Wu, F and Meshinchi, S and Stirewalt, DL},
title = {Verification of prognostic expression biomarkers is improved by examining enriched leukemic blasts rather than mononuclear cells from acute myeloid leukemia patients.},
journal = {Biomarker research},
volume = {11},
number = {1},
pages = {31},
pmid = {36927800},
issn = {2050-7771},
support = {R01CA160872/NH/NIH HHS/United States ; R01CA160872/NH/NIH HHS/United States ; R01CA160872/NH/NIH HHS/United States ; },
abstract = {BACKGROUND: Studies have not systematically compared the ability to verify performance of prognostic transcripts in paired bulk mononuclear cells versus viable CD34-expressing leukemic blasts from patients with acute myeloid leukemia. We hypothesized that examining the homogenous leukemic blasts will yield different biological information and may improve prognostic performance of expression biomarkers.<br><br>METHODS: To assess the impact of cellular heterogeneity on expression biomarkers in acute myeloid leukemia, we systematically examined paired mononuclear cells and viable CD34-expressing leukemic blasts from SWOG diagnostic specimens. After enrichment, patients were assigned into discovery and validation cohorts based on availability of extracted RNA. Analyses of RNA sequencing data examined how enrichment impacted differentially expressed genes associated with pre-analytic variables, patient characteristics, and clinical outcomes.<br><br>RESULTS: Blast enrichment yielded significantly different expression profiles and biological pathways associated with clinical characteristics (e.g., cytogenetics). Although numerous differentially expressed genes were associated with clinical outcomes, most lost their prognostic significance in the mononuclear cells and blasts after adjusting for age and ELN&#xa0;risk, with only 11 genes remaining significant for overall survival in both cell populations (CEP70, COMMD7, DNMT3B, ECE1, LNX2, NEGR1, PIK3C2B, SEMA4D, SMAD2, TAF8, ZNF444). To examine the impact of enrichment on biomarker verification, these 11 candidate biomarkers were examined by quantitative RT/PCR in the validation cohort. After adjusting for ELN&#xa0;risk and age, expression of 4 genes (CEP70, DNMT3B, ECE1, and PIK3CB) remained significantly associated with overall survival in the blasts, while none met statistical significance in mononuclear cells.<br><br>CONCLUSIONS: This study provides insights into biological information gained/lost by examining viable CD34-expressing leukemic blasts versus mononuclear cells from the same patient and shows an improved verification rate for expression biomarkers in blasts.},
}
@article {pmid36924931,
year = {2023},
author = {Auletta, JJ and Kou, J and Chen, M and Bolon, YT and Broglie, L and Bupp, C and Christianson, D and Cusatis, RN and Devine, SM and Eapen, M and Flynn, KE and Hamadani, M and Hengen, M and Lee, SJ and Moskop, A and Page, KM and Pasquini, MC and Perez, WS and Phelan, R and Riches, ML and Rizzo, JD and Saber, W and Spellman, SR and Stefanski, HE and Steinert, P and Tuschl, E and Yusuf, R and Zhang, MJ and Shaw, BE},
title = {Real-world data showing trends and outcomes by race and ethnicity in allogeneic hematopoietic cell transplantation: a report from the Center for International Blood and Marrow Transplant Research.},
journal = {Transplantation and cellular therapy},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jtct.2023.03.007},
pmid = {36924931},
issn = {2666-6367},
abstract = {BACKGROUND: Use of human leukocyte antigen (HLA)-mismatched donors could enable more patients with ethnically diverse backgrounds to receive allogeneic hematopoietic cell transplantation (HCT) in the United States. However, real-world trends and outcomes following mismatched donor HCT for diverse patients remain largely undefined.<br><br>OBJECTIVE: To determine whether mismatched donor platforms have increased access to allogeneic HCT for ethnically diverse patients, particularly through the application of novel graft-versus-host disease (GvHD) prophylaxis regimens, and if outcomes for diverse patients were comparable to those of non-Hispanic White patients.<br><br>DESIGN: Observational cross-sectional study using real-world data from the Center for International Blood and Marrow Transplant Research (CIBMTR) registry. All patients receiving their first allogeneic HCT in the U.S. from 2009-2020 with focus on transplants performed in 2020 were included. Data from patients receiving allogeneic HCT using bone marrow, peripheral blood or cord blood from HLA-matched or mismatched related and unrelated donors was analyzed. Specifically, relative proportions of allogeneic HCT were generated as percent of total for donor type and for patient age, disease indication, GvHD prophylaxis, and race and ethnicity. Causes of death were summarized using frequencies, and the Kaplan-Meier estimator was used for estimating overall survival.<br><br>RESULTS: Compared to matched related donor and matched unrelated donor HCT, more ethnically diverse patients received mismatched unrelated donor, haploidentical donor, and cord blood HCT. Matched unrelated donor remains the most common donor type, but use of haploidentical donors has increased significantly over the last 5 years. Paralleling the increase in haploidentical HCT is the increased use of post-transplant cyclophosphamide (PTCy) as GvHD prophylaxis. Relative to older transplant eras, the most contemporary transplant era associates with the highest survival rates following allogeneic HCT irrespective of patient race and ethnicity. However, disease relapse remains the primary cause of death for both adult and pediatric allogeneic HCT recipients by donor type and across all patient race and ethnicity groups.<br><br>CONCLUSIONS: Ethnically diverse patients are undergoing allogeneic HCTs at higher rates largely through the use of alternative donor platforms incorporating PTCy. Maintaining access to potential life-saving allogeneic HCT using alternative donors and novel GvHD prophylaxis strategies and improving HCT outcomes, particularly disease relapse, are urgent clinical needs.},
}
@article {pmid36923305,
year = {2022},
author = {Andtbacka, RHI and Wang, Y and Pierce, RH and Campbell, JS and Yushak, M and Milhem, M and Ross, M and Niland, K and Arbeit, RD and Parasuraman, S and Bickley, K and Yeung, CC and Aicher, LD and Smythe, KS and Gan, L},
title = {Mavorixafor, an Orally Bioavailable CXCR4 Antagonist, Increases Immune Cell Infiltration and Inflammatory Status of Tumor Microenvironment in Patients with Melanoma.},
journal = {Cancer research communications},
volume = {2},
number = {8},
pages = {904-913},
pmid = {36923305},
issn = {2767-9764},
abstract = {PURPOSE: Mavorixafor is an oral, selective inhibitor of the CXCR4 chemokine receptor that modulates immune cell trafficking. A biomarker-driven phase Ib study (NCT02823405) was conducted in 16 patients with melanoma to investigate the hypothesis that mavorixafor favorably modulates immune cell profiles in the tumor microenvironment (TME) and to evaluate the safety of mavorixafor alone and in combination with pembrolizumab.<br><br>EXPERIMENTAL DESIGN: Serial biopsies of melanoma lesions were assessed after 3 weeks of mavorixafor monotherapy and after 6 weeks of combination treatment for immune cell markers by NanoString analysis for gene expression and by multiplexed immunofluorescent staining for in situ protein expression. Serum samples taken at biopsy timepoints were evaluated for key chemokine and cytokine alterations using the Myriad Rules Based Medicine multiplex immunoassays.<br><br>RESULTS: Within the TME, mavorixafor alone increased CD8[+] T-cell infiltration, granzyme B signal, antigen presentation machinery, and both tumor inflammatory signature (TIS) and IFN&#x3b3;&#xa0;gene expression signature scores. Increases in the key serum cytokines CXCL9 and CXCL10 were further enhanced when mavorixafor was combined with pembrolizumab. Adverse events (AE), as assessed by the investigator according to NCI Common Terminology Criteria for Adverse Events (v4.03), related to either mavorixafor or pembrolizumab (&#x2265;15%) were diarrhea, fatigue, maculopapular rash, and dry eye. Reported AEs were all &#x2264; grade 3.<br><br>CONCLUSION/DISCUSSION: Treatment with single-agent mavorixafor resulted in enhanced immune cell infiltration and activation in the TME, leading to increases in TIS and IFN&#x3b3; gene signatures. Mavorixafor as a single agent, and in combination with pembrolizumab, has an acceptable safety profile. These data support further investigation of the use of mavorixafor for patients unresponsive to checkpoint inhibitors.<br><br>SIGNIFICANCE: Despite survival improvements in patients with melanoma treated with checkpoint inhibitor therapy, a significant unmet medical need exists for therapies that enhance effectiveness. We propose that mavorixafor sensitizes the melanoma tumor microenvironment and enhances the activity of checkpoint inhibitors, and thereby may translate to a promising treatment for broader patient populations.},
}
@article {pmid36922886,
year = {2023},
author = {Sager, JE and El-Zailik, A and Passarell, J and Roepcke, S and Li, X and Aldinger, M and Nader, A and Skingsley, A and Alexander, EL and Yeh, WW and Mogalian, E and Garner, C and Peppercorn, A and Shapiro, AE and Reyes, M},
title = {Population pharmacokinetics and exposure-response analysis of a single dose of sotrovimab in the early treatment of patients with mild to moderate COVID-19.},
journal = {CPT: pharmacometrics &amp; systems pharmacology},
volume = {},
number = {},
pages = {},
doi = {10.1002/psp4.12958},
pmid = {36922886},
issn = {2163-8306},
abstract = {Sotrovimab is a recombinant human monoclonal antibody that has been shown to prevent progression to hospitalization or death in non-hospitalized high-risk patients with mild-to-moderate COVID-19 following either intravenous (IV) or intramuscular (IM) administration. Population pharmacokinetic (popPK) and exposure-response (ER) analyses were performed to characterize single dose sotrovimab PK and the relationship between exposure and response (probability of progression), as well as covariates that may contribute to between-participant variability in sotrovimab PK and efficacy following IV or IM administration. Sotrovimab PK was described by a two-compartment model with linear elimination; IM absorption was characterized by a sigmoid absorption model. PopPK covariate analysis led to the addition of the effect of body weight on systemic clearance and peripheral volume of distribution, sex on IM bioavailability and first-order absorption rate (KA), and body mass index on KA. However, the magnitude of covariate effect was not pronounced and was therefore not expected to be clinically relevant based on available data to date. For ER analysis, sotrovimab exposure measures were predicted using the final popPK model. An ER model was developed using the exposure measure of sotrovimab concentration at 168 hours that described the relationship between exposure and probability of progression within the ER dataset for COMET-TAIL. The number of risk factors (≤1 vs >1) was incorporated as an additive shift on the model-estimated placebo response but had no impact on overall drug response. Limitations in the ER model may prevent generalization of these results to describe the sotrovimab exposure-progression relationship across SARS-COV-2 variants.},
}
@article {pmid36921918,
year = {2023},
author = {Okamoto, S and Iida, M and Hamad, N and Duarte, FB and Sureda, A and Srivastava, A and Galeano, S and Chao, N and Rondelli, D and Flowers, ME},
title = {American Society of Transplantation and Cellular Therapy International Affair Committee: Report of 3[rd] Workshop on Global Perspective to Access to Transplantation at the 2022 Tandem Meeting.},
journal = {Transplantation and cellular therapy},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jtct.2023.02.024},
pmid = {36921918},
issn = {2666-6367},
}
@article {pmid36921916,
year = {2023},
author = {Rashid, N and Arora, M and Jurdi, NE and Onstad, L and Pidala, JA and Flowers, ME and Lee, SJ},
title = {Frailty in Patients with Chronic Graft-versus-Host Disease.},
journal = {Transplantation and cellular therapy},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jtct.2023.03.010},
pmid = {36921916},
issn = {2666-6367},
abstract = {BACKGROUND: Frailty is an increasingly recognized clinical diagnosis associated with high risk of disability and mortality. Frailty in patients after hematopoietic cell transplantation (HCT) is associated with increased non-relapse mortality (NRM) and decreased overall survival (OS). Frailty has not been extensively studied in patients with chronic graft-versus-host disease (cGVHD).<br><br>OBJECTIVES: The objectives of this study were to assess the prevalence and clinical correlates of frailty and the association of frailty with NRM and OS in patients enrolled in the Chronic GVHD Consortium. Patients were characterized as frail if they met Fried's definition: &#x2265;3 of the following criteria at enrollment: unintentional weight loss, exhaustion, slow walking speed, low physical activity, and weakness. Frailty was assessed retrospectively and used surrogate measures for the 5 domains of frailty. Frailty, chronic GVHD organ scores, and patient-reported outcomes were measured at the time of enrollment.<br><br>RESULTS: This study included 399 patients from 9 centers in the United States with 32% characterized as frail and 68% as not frail. The median follow-up time from enrollment was 9 years (interquartile range 7 - 11 years). Frail patients were more likely to be older (p=0.004), have lower Karnofsky performance score (p<0.001), have severe cGVHD (p<0.001), and have GI (p<0.001), liver (p=0.04), or lung cGVHD (p=0.002). In a multivariable analysis, older age, increased cGVHD global severity, and thrombocytopenia were statically associated with frailty when cGVHD organ involvement was excluded. A separate analysis excluding cGVHD severity and including organ involvement showed that lung and liver cGVHD, and older age were associated with frailty. Neither corticosteroid usage at the time of enrollment nor the maximum recorded dose of corticosteroids prior to enrollment were associated with frailty. Frail patients had higher NRM than not frail patients (p<0.001) with 10-year cumulative incidences of 41% (95% CI 32-49%) vs 22% (95% CI 17-28%), respectively. Reciprocally, frailty was also associated with a significantly lower OS (p<0.001) with 10-year OS of 43% (95% CI 35-53%) in frail patients vs 63% (95% CI 57-69%) in not frail patients. In multivariable analysis that included the individual domains of frailty, weakness, low physical activity, and slow walking speed were associated with survival. Frail patients also had worse scores on various measures of patient reported outcomes including SF-36, Lee Symptom Scale, and the trial outcome of the FACT-BMT index score.<br><br>CONCLUSIONS: Frail patients with cGVHD have significantly worse outcomes compared to not frail patients. Clinical features such as older age and lung and liver cGVHD are associated with frailty. Earlier clinical recognition of frailty in cGVHD patients may prompt interventions to counteract frailty that could be beneficial to this population.},
}
@article {pmid36921904,
year = {2023},
author = {Peterson, LM and Lee, H and Huybrechts, I and Biessy, C and Neuhouser, ML and Haaland, B and Krick, B and Gunter, M and Schulze, MB and Jannasch, F and Coletta, AM and Hardikar, S and Chaix, A and Bauer, CX and Xiao, Q and Playdon, MC},
title = {Reliability estimates for assessing meal timing derived from longitudinal repeated 24-hour dietary recalls.},
journal = {The American journal of clinical nutrition},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.ajcnut.2023.02.026},
pmid = {36921904},
issn = {1938-3207},
abstract = {BACKGROUND: Regulating meal timing may have efficacy for improving metabolic health for preventing or managing chronic disease. However, the reliability of measuring meal timing with commonly used dietary assessment tools needs characterization prior to investigating meal timing and health outcomes in epidemiologic studies.<br><br>OBJECTIVE: To evaluate the reliability of estimating meal timing parameters including overnight fasting duration, midpoint of overnight fasting time, number of daily eating episodes, period with largest percentage of daily caloric intake, and late last eating episode (>9pm) from repeated 24-hour dietary recalls (24HR).<br><br>DESIGN: Intraclass correlation coefficients, Light's kappa estimates and 95% confidence intervals (CIs) were calculated from repeated 24HR administered in three epidemiologic studies: United States-based IDATA study (n=996, six 24HR collected over 12-months), German EPIC-Potsdam Validation Study (n=134, twelve 24HR collected over 12-months) and EPIC-Potsdam BMBF-II Study (n=725, four 24HR collected over 36-months).<br><br>RESULTS: Measurement reliability of overnight fasting duration based on a single 24HR was "poor" in all studies (ICC range 0.27, 95% CI 0.23, 0.32 to 0.46, 95% CI 0.43, 0.50). Reliability was "moderate" with three 24HR (ICC range: 0.53, 95% CI 0.47, 0.58 in IDATA, 0.62, 95% CI 0.52, 0.69 in the EPIC-Potsdam Validation Study, and 0.72, 95% CI 0.70-0.75 in the EPIC-Potsdam BMBF-II Study). Results were similar for midpoint of overnight fasting time and number of eating episodes. Reliability of measuring late eating was "fair" in IDATA (Light's Kappa 0.30, 95% CI 0.21, 0.39) and "slight" in the EPIC-Potsdam Validation study and the EPIC-Potsdam BMBF-II study (Light's Kappa 0.19, 95% CI 0.15, 0.25 and 0.09, 95% CI 0.06, 0.12, respectively). Reliability estimates differed by sex, body mass index, and weekday and season of 24HR administration in some studies.<br><br>CONCLUSIONS: Our result show that at least three 24HR over a 1-3-year period are required for reliable estimates of meal timing variables.},
}
@article {pmid36921601,
year = {2023},
author = {Du, M and Gu, D and Xin, J and Peters, U and Song, M and Cai, G and Li, S and Ben, S and Meng, Y and Chu, H and Chen, L and Wang, Q and Zhu, L and Fu, Z and Zhang, Z and Wang, M},
title = {Integrated multi-omics approach to distinct molecular characterization and classification of early-onset colorectal cancer.},
journal = {Cell reports. Medicine},
volume = {},
number = {},
pages = {100974},
doi = {10.1016/j.xcrm.2023.100974},
pmid = {36921601},
issn = {2666-3791},
abstract = {Incidence of early-onset colorectal cancer (EOCRC), defined by a diagnosed age under 50 years, is increasing, but its heterogeneous etiologies that differ from general CRC remain undetermined. We initially characterize the genome, epigenome, transcriptome, and proteome of tumors from 79 patients in a Chinese CRC cohort. Data for an additional 126 EOCRC subjects are obtained from the International Cancer Genome Consortium Chinese cohort and The Cancer Genome Atlas European cohort. We observe that early-onset tumors have a high tumor mutation burden; increased DNA repair features by mutational signature 3 and multi-layer pathway enrichments; strong perturbations at effects of DNA methylation and somatic copy-number alteration on gene expression; and upregulated immune infiltration as hot tumors underlying immunophenotypes. Notably, LMTK3 exhibits ancestral mutation disparity, potentially being a functional modulator and biomarker that drives molecular alterations in EOCRC development and immunotherapies. This integrative omics study provides valuable knowledge for precision oncology of CRC.},
}
@article {pmid36920244,
year = {2023},
author = {Hulverson, MA and Choi, R and Schaefer, DA and Betzer, DP and McCloskey, MC and Whitman, GR and Huang, W and Lee, S and Pranata, A and McLeod, MD and Marsh, KC and Kempf, DJ and LeRoy, BE and Zafiratos, MT and Bielinski, AL and Hackman, RC and Ojo, KK and Arnold, SLM and Barrett, LK and Tzipori, S and Riggs, MW and Fan, E and Van Voorhis, WC},
title = {Comparison of Toxicities among Different Bumped Kinase Inhibitor Analogs for Treatment of Cryptosporidiosis.},
journal = {Antimicrobial agents and chemotherapy},
volume = {},
number = {},
pages = {e0142522},
doi = {10.1128/aac.01425-22},
pmid = {36920244},
issn = {1098-6596},
abstract = {Recent advances on the development of bumped kinase inhibitors for treatment of cryptosporidiosis have focused on the 5-aminopyrazole-4-carboxamide scaffold, due to analogs that have less hERG inhibition, superior efficacy, and strong in vitro safety profiles. Three compounds, BKI-1770, -1841, and -1708, showed strong efficacy in C. parvum infected mice. Both BKI-1770 and BKI-1841 had efficacy in the C. parvum newborn calf model, reducing diarrhea and oocyst excretion. However, both compounds caused hyperflexion of the limbs seen as dropped pasterns. Toxicity experiments in rats and calves dosed with BKI-1770 showed enlargement of the epiphyseal growth plate at doses only slightly higher than the efficacious dose. Mice were used as a screen to check for bone toxicity, by changes to the tibia epiphyseal growth plate, or neurological causes, by use of a locomotor activity box. These results showed neurological effects from both BKI-1770 and BKI-1841 and bone toxicity in mice from BKI-1770, indicating one or both effects may be contributing to toxicity. However, BKI-1708 remains a viable treatment candidate for further evaluation as it showed no signs of bone toxicity or neurological effects in mice.},
}
@article {pmid36918656,
year = {2023},
author = {Arora, S and Szulzewsky, F and Jensen, M and Nuechterlein, N and Pattwell, SS and Holland, EC},
title = {Visualizing genomic characteristics across an RNA-Seq based reference landscape of normal and neoplastic brain.},
journal = {Scientific reports},
volume = {13},
number = {1},
pages = {4228},
pmid = {36918656},
issn = {2045-2322},
support = {U54 CA193461/GF/NIH HHS/United States ; R01 CA195718/NH/NIH HHS/United States ; },
mesh = {Adult ; Child ; Humans ; RNA-Seq ; *Brain Neoplasms/genetics ; Brain ; *Glioma ; Genomics ; },
abstract = {In order to better understand the relationship between normal and neoplastic brain, we combined five publicly available large-scale datasets, correcting for batch effects and applying Uniform Manifold Approximation and Projection (UMAP) to RNA-Seq data. We assembled a reference Brain-UMAP including 702 adult gliomas, 802 pediatric tumors and 1409 healthy normal brain samples, which can be utilized to investigate the wealth of information obtained from combining several publicly available datasets to study a single organ site. Normal brain regions and tumor types create distinct clusters and because the landscape is generated by RNA-Seq, comparative gene expression profiles and gene ontology patterns are readily evident. To our knowledge, this is the first meta-analysis that allows for comparison of gene expression and pathways of interest across adult gliomas, pediatric brain tumors, and normal brain regions. We provide access to this resource via the open source, interactive online tool Oncoscape, where the scientific community can readily visualize clinical metadata, gene expression patterns, gene fusions, mutations, and copy number patterns for individual genes and pathway over this reference landscape.},
}
@article {pmid36918541,
year = {2023},
author = {Young, WJ and Haessler, J and Benjamins, JW and Repetto, L and Yao, J and Isaacs, A and Harper, AR and Ramirez, J and Garnier, S and van Duijvenboden, S and Baldassari, AR and Concas, MP and Duong, T and Foco, L and Isaksen, JL and Mei, H and Noordam, R and Nursyifa, C and Richmond, A and Santolalla, ML and Sitlani, CM and Soroush, N and Thériault, S and Trompet, S and Aeschbacher, S and Ahmadizar, F and Alonso, A and Brody, JA and Campbell, A and Correa, A and Darbar, D and De Luca, A and Deleuze, JF and Ellervik, C and Fuchsberger, C and Goel, A and Grace, C and Guo, X and Hansen, T and Heckbert, SR and Jackson, RD and Kors, JA and Lima-Costa, MF and Linneberg, A and Macfarlane, PW and Morrison, AC and Navarro, P and Porteous, DJ and Pramstaller, PP and Reiner, AP and Risch, L and Schotten, U and Shen, X and Sinagra, G and Soliman, EZ and Stoll, M and Tarazona-Santos, E and Tinker, A and Trajanoska, K and Villard, E and Warren, HR and Whitsel, EA and Wiggins, KL and Arking, DE and Avery, CL and Conen, D and Girotto, G and Grarup, N and Hayward, C and Jukema, JW and Mook-Kanamori, DO and Olesen, MS and Padmanabhan, S and Psaty, BM and Pattaro, C and Ribeiro, ALP and Rotter, JI and Stricker, BH and van der Harst, P and van Duijn, CM and Verweij, N and Wilson, JG and Orini, M and Charron, P and Watkins, H and Kooperberg, C and Lin, HJ and Wilson, JF and Kanters, JK and Sotoodehnia, N and Mifsud, B and Lambiase, PD and Tereshchenko, LG and Munroe, PB},
title = {Genetic architecture of spatial electrical biomarkers for cardiac arrhythmia and relationship with cardiovascular disease.},
journal = {Nature communications},
volume = {14},
number = {1},
pages = {1411},
pmid = {36918541},
issn = {2041-1723},
support = {R01 HL118277/HL/NHLBI NIH HHS/United States ; R56 HL118277/HL/NHLBI NIH HHS/United States ; },
mesh = {Humans ; *Cardiovascular Diseases/genetics ; *Atrioventricular Block ; Genome-Wide Association Study ; Risk Factors ; Arrhythmias, Cardiac/genetics ; Electrocardiography/methods ; Biomarkers ; },
abstract = {The 3-dimensional spatial and 2-dimensional frontal QRS-T angles are measures derived from the vectorcardiogram. They are independent risk predictors for arrhythmia, but the underlying biology is unknown. Using multi-ancestry genome-wide association studies we identify 61 (58 previously unreported) loci for the spatial QRS-T angle (N = 118,780) and 11 for the frontal QRS-T angle (N = 159,715). Seven out of the 61 spatial QRS-T angle loci have not been reported for other electrocardiographic measures. Enrichments are observed in pathways related to cardiac and vascular development, muscle contraction, and hypertrophy. Pairwise genome-wide association studies with classical ECG traits identify shared genetic influences with PR interval and QRS duration. Phenome-wide scanning indicate associations with atrial fibrillation, atrioventricular block and arterial embolism and genetically determined QRS-T angle measures are associated with fascicular and bundle branch block (and also atrioventricular block for the frontal QRS-T angle). We identify potential biology involved in the QRS-T angle and their genetic relationships with cardiovascular traits and diseases, may inform future research and risk prediction.},
}
@article {pmid36898367,
year = {2023},
author = {Shields, PG and Bierut, L and Arenberg, D and Balis, D and Cinciripini, PM and Davis, J and Edmondson, D and Feliciano, J and Hitsman, B and Hudmon, KS and Jaklitsch, MT and Leone, FT and Ling, P and McCarthy, DE and Ong, MK and Park, ER and Prochaska, J and Sandoval, AJ and Sheffer, CE and Spencer, S and Studts, JL and Tanvetyanon, T and Tindle, HA and Tong, E and Triplette, M and Urbanic, J and Videtic, G and Warner, D and Whitlock, CW and McCullough, B and Darlow, S},
title = {Smoking Cessation, Version 3.2022, NCCN Clinical Practice Guidelines in Oncology.},
journal = {Journal of the National Comprehensive Cancer Network : JNCCN},
volume = {21},
number = {3},
pages = {297-322},
doi = {10.6004/jnccn.2023.0013},
pmid = {36898367},
issn = {1540-1413},
mesh = {Humans ; *Smoking Cessation ; Smoking ; *Tobacco Products ; Medical Oncology ; *Neoplasms ; },
abstract = {Although the harmful effects of smoking after a cancer diagnosis have been clearly demonstrated, many patients continue to smoke cigarettes during treatment and beyond. The NCCN Guidelines for Smoking Cessation emphasize the importance of smoking cessation in all patients with cancer and seek to establish evidence-based recommendations tailored to the unique needs and concerns of patients with cancer. The recommendations contained herein describe interventions for cessation of all combustible tobacco products (eg, cigarettes, cigars, hookah), including smokeless tobacco products. However, recommendations are based on studies of cigarette smoking. The NCCN Smoking Cessation Panel recommends that treatment plans for all patients with cancer who smoke include the following 3 tenets that should be done concurrently: (1) evidence-based motivational strategies and behavior therapy (counseling), which can be brief; (2) evidence-based pharmacotherapy; and (3) close follow-up with retreatment as needed.},
}
@article {pmid36898362,
year = {2023},
author = {Moses, KA and Sprenkle, PC and Bahler, C and Box, G and Carlsson, SV and Catalona, WJ and Dahl, DM and Dall'Era, M and Davis, JW and Drake, BF and Epstein, JI and Etzioni, RB and Farrington, TA and Garraway, IP and Jarrard, D and Kauffman, E and Kaye, D and Kibel, AS and LaGrange, CA and Maroni, P and Ponsky, L and Reys, B and Salami, SS and Sanchez, A and Seibert, TM and Shaneyfelt, TM and Smaldone, MC and Sonn, G and Tyson, MD and Vapiwala, N and Wake, R and Washington, S and Yu, A and Yuh, B and Berardi, RA and Freedman-Cass, DA},
title = {NCCN Guidelines® Insights: Prostate Cancer Early Detection, Version 1.2023.},
journal = {Journal of the National Comprehensive Cancer Network : JNCCN},
volume = {21},
number = {3},
pages = {236-246},
doi = {10.6004/jnccn.2023.0014},
pmid = {36898362},
issn = {1540-1413},
mesh = {Male ; Humans ; *Early Detection of Cancer/methods ; Prostate ; *Prostatic Neoplasms/diagnosis ; Biopsy ; },
abstract = {The NCCN Guidelines for Prostate Cancer Early Detection provide recommendations for individuals with a prostate who opt to participate in an early detection program after receiving the appropriate counseling on the pros and cons. These NCCN Guidelines Insights provide a summary of recent updates to the NCCN Guidelines with regard to the testing protocol, use of multiparametric MRI, and management of negative biopsy results to optimize the detection of clinically significant prostate cancer and minimize the detection of indolent disease.},
}
@article {pmid36914876,
year = {2023},
author = {Rahmioglu, N and Mortlock, S and Ghiasi, M and Møller, PL and Stefansdottir, L and Galarneau, G and Turman, C and Danning, R and Law, MH and Sapkota, Y and Christofidou, P and Skarp, S and Giri, A and Banasik, K and Krassowski, M and Lepamets, M and Marciniak, B and Nõukas, M and Perro, D and Sliz, E and Sobalska-Kwapis, M and Thorleifsson, G and Topbas-Selcuki, NF and Vitonis, A and Westergaard, D and Arnadottir, R and Burgdorf, KS and Campbell, A and Cheuk, CSK and Clementi, C and Cook, J and De Vivo, I and DiVasta, A and Dorien, O and Donoghue, JF and Edwards, T and Fontanillas, P and Fung, JN and Geirsson, RT and Girling, JE and Harkki, P and Harris, HR and Healey, M and Heikinheimo, O and Holdsworth-Carson, S and Hostettler, IC and Houlden, H and Houshdaran, S and Irwin, JC and Jarvelin, MR and Kamatani, Y and Kennedy, SH and Kepka, E and Kettunen, J and Kubo, M and Kulig, B and Kurra, V and Laivuori, H and Laufer, MR and Lindgren, CM and MacGregor, S and Mangino, M and Martin, NG and Matalliotaki, C and Matalliotakis, M and Murray, AD and Ndungu, A and Nezhat, C and Olsen, CM and Opoku-Anane, J and Padmanabhan, S and Paranjpe, M and Peters, M and Polak, G and Porteous, DJ and Rabban, J and Rexrode, KM and Romanowicz, H and Saare, M and Saavalainen, L and Schork, AJ and Sen, S and Shafrir, AL and Siewierska-Górska, A and Słomka, M and Smith, BH and Smolarz, B and Szaflik, T and Szyłło, K and Takahashi, A and Terry, KL and Tomassetti, C and Treloar, SA and Vanhie, A and Vincent, K and Vo, KC and Werring, DJ and Zeggini, E and Zervou, MI and , and , and , and , and , and Adachi, S and Buring, JE and Ridker, PM and D'Hooghe, T and Goulielmos, GN and Hapangama, DK and Hayward, C and Horne, AW and Low, SK and Martikainen, H and Chasman, DI and Rogers, PAW and Saunders, PT and Sirota, M and Spector, T and Strapagiel, D and Tung, JY and Whiteman, DC and Giudice, LC and Velez-Edwards, DR and Uimari, O and Kraft, P and Salumets, A and Nyholt, DR and Mägi, R and Stefansson, K and Becker, CM and Yurttas-Beim, P and Steinthorsdottir, V and Nyegaard, M and Missmer, SA and Montgomery, GW and Morris, AP and Zondervan, KT},
title = {The genetic basis of endometriosis and comorbidity with other pain and inflammatory conditions.},
journal = {Nature genetics},
volume = {55},
number = {3},
pages = {423-436},
pmid = {36914876},
issn = {1546-1718},
mesh = {Female ; Humans ; *Endometriosis/genetics/metabolism ; Genetic Predisposition to Disease ; Genome-Wide Association Study ; Pain ; Comorbidity ; },
abstract = {Endometriosis is a common condition associated with debilitating pelvic pain and infertility. A genome-wide association study meta-analysis, including 60,674 cases and 701,926 controls of European and East Asian descent, identified 42 genome-wide significant loci comprising 49 distinct association signals. Effect sizes were largest for stage 3/4 disease, driven by ovarian endometriosis. Identified signals explained up to 5.01% of disease variance and regulated expression or methylation of genes in endometrium and blood, many of which were associated with pain perception/maintenance (SRP14/BMF, GDAP1, MLLT10, BSN and NGF). We observed significant genetic correlations between endometriosis and 11 pain conditions, including migraine, back and multisite chronic pain (MCP), as well as inflammatory conditions, including asthma and osteoarthritis. Multitrait genetic analyses identified substantial sharing of variants associated with endometriosis and MCP/migraine. Targeted investigations of genetically regulated mechanisms shared between endometriosis and other pain conditions are needed to aid the development of new treatments and facilitate early symptomatic intervention.},
}
@article {pmid36913789,
year = {2023},
author = {Drain, PK and Dalmat, RR and Hao, L and Bemer, MJ and Budiawan, E and Morton, JF and Ireton, RC and Hsiang, TY and Marfatia, Z and Prabhu, R and Woosley, C and Gichamo, A and Rechkina, E and Hamilton, D and Montaño, M and Cantera, JL and Ball, AS and Golez, I and Smith, E and Greninger, AL and McElrath, MJ and Thompson, M and Grant, BD and Meisner, A and Gottlieb, GS and Gale, MJ},
title = {Duration of viral infectiousness and correlation with symptoms and diagnostic testing in non-hospitalized adults during acute SARS-CoV-2 infection: A longitudinal cohort study.},
journal = {Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology},
volume = {161},
number = {},
pages = {105420},
pmid = {36913789},
issn = {1873-5967},
abstract = {BACKGROUND: Guidelines for SARS-CoV-2 have relied on limited data on duration of viral infectiousness and correlation with COVID-19 symptoms and diagnostic testing.<br><br>METHODS: We enrolled ambulatory adults with acute SARS-CoV-2 infection and performed serial measurements of COVID-19 symptoms, nasal swab viral RNA, nucleocapsid (N) and spike (S) antigens, and replication-competent SARS-CoV-2 by viral growth in culture. We determined average time from symptom onset to a first negative test result and estimated risk of infectiousness, as defined by positive viral growth in culture.<br><br>RESULTS: Among 95 adults, median [interquartile range] time from symptom onset to first negative test result was 9 [5] days, 13 [6] days, 11 [4] days, and >19 days for S antigen, N antigen, culture growth, and viral RNA by RT-PCR, respectively. Beyond two weeks, virus growth and N antigen titers were rarely positive, while viral RNA remained detectable among half (26/51) of participants tested 21-30 days after symptom onset. Between 6-10 days from symptom onset, N antigen was strongly associated with culture positivity (relative risk=7.61, 95% CI: 3.01-19.22), whereas neither viral RNA nor symptoms were associated with culture positivity. During the 14 days following symptom onset, the presence of N antigen remained strongly associated (adjusted relative risk=7.66, 95% CI: 3.96-14.82) with culture positivity, regardless of COVID-19 symptoms.<br><br>CONCLUSIONS: Most adults have replication-competent SARS-CoV-2 for 10-14 after symptom onset. N antigen testing is a strong predictor of viral infectiousness and may be a more suitable biomarker, rather than absence of symptoms or viral RNA, to discontinue isolation within two weeks from symptom onset.},
}
@article {pmid36913694,
year = {2023},
author = {Lynch, RC and Ujjani, CS and Poh, C and Warren, EH and Smith, SD and Shadman, M and Till, BG and Raghunathan, V and Alig, S and Alizadeh, AA and Gulhane, A and Chen, D and Tseng, Y and Coye, H and Shelby, M and Ottemiller, S and Keo, S and Verni, K and Du, H and Vandermeer, J and Gaston, A and Rasmussen, H and Martin, P and Marzbani, E and Voutsinas, JM and Gopal, AK},
title = {Concurrent pembrolizumab with AVD for untreated classical Hodgkin lymphoma.},
journal = {Blood},
volume = {},
number = {},
pages = {},
doi = {10.1182/blood.2022019254},
pmid = {36913694},
issn = {1528-0020},
abstract = {Concurrent administration pembrolizumab with chemotherapy in untreated classical Hodgkin lymphoma (CHL) has not previously been studied. To investigate this combination, we conducted a single arm study of concurrent pembrolizumab with AVD (APVD) for untreated CHL. We enrolled 30 patients (6 early favorable, 6 early unfavorable, and 18 advanced stage, median age 33 years (range 18-69 years)) and met the primary safety endpoint with no observed significant treatment delays in the first two cycles. Twelve patients experienced grade 3-4 non-hematologic adverse events (AEs) most commonly febrile neutropenia (5, 17%) and infection/sepsis (3, 10%). Grade 3-4 immune-related AEs were seen in 3 patients, including ALT elevation (3, 10%) and AST elevation (1, 3%). One patient experienced an episode of grade 2 colitis and arthritis. Six (20%) patients missed at least one dose of pembrolizumab due to adverse events, primarily grade 2 or higher transaminitis (5, 17%). Among 29 response-evaluable patients, the best overall response rate was 100% and CR rate of 90%. With median follow up of 2.1 years, 2-year progression-free survival (PFS) and overall survival were 97% and 100%, respectively. To date, no patient who withheld or discontinued pembrolizumab due to toxicity has progressed. Clearance of ctDNA was associated with superior PFS when measured after cycle 2 (p=0.025) and at end of treatment (EOT, p=0.0016). None of the 4 patients with persistent disease by FDG-PET at EOT yet negative ctDNA have relapsed to date. Concurrent APVD shows promising safety and efficacy, but may yield spurious PET findings in some patients. Trial Registration Number: NCT03331341.},
}
@article {pmid36912284,
year = {2023},
author = {Nguyen, HT and Tang, W and Webster, ALH and Whiteaker, JR and Chandler, CM and Errazquin, R and Roohollahi, K and Fritzke, M and Hoskins, EE and Jonlin, E and Wakefield, L and Sullivan, LB and Chen, EY and Dorsman, J and Brakenhoff, R and Paulovich, AG and Grompe, M and Garcia-Escudero, R and Wells, SI and Smogorzewska, A and Monnat, RJ},
title = {Fanconi anemia-isogenic head and neck cancer cell line pairs - a basic and translational science resource.},
journal = {International journal of cancer},
volume = {},
number = {},
pages = {},
doi = {10.1002/ijc.34506},
pmid = {36912284},
issn = {1097-0215},
abstract = {Fanconi anemia (FA) is a heritable malformation, bone marrow failure and cancer predisposition syndrome that confers an exceptionally high risk of squamous carcinomas. These carcinomas originate in epithelia lining the mouth, proximal esophagus, vulva and anus: their origins are not understood, and no effective ways have been identified to prevent or delay their appearance. Many FA-associated carcinomas are also therapeutically challenging: they may be multi-focal and stage-advanced at diagnosis, and most individuals with FA cannot tolerate standard-of-care systemic therapies such as DNA cross-linking drugs or ionizing radiation due to constitutional DNA damage hypersensitivity. We developed the Fanconi Anemia Cancer Cell Line Resource (FA-CCLR) to foster new work on the origins, treatment and prevention of FA-associated carcinomas. The FA-CCLR consists of Fanconi-isogenic head and neck squamous cell carcinoma (HNSCC) cell line pairs generated from 5 individuals with FA-associated HNSCC, and 5 individuals with sporadic HNSCC. Sporadic, isogenic HNSCC cell line pairs were generated in parallel with FA patient-derived isogenic cell line pairs to provide comparable experimental material to use to identify cell and molecular phenotypes driven by germline or somatic loss of Fanconi pathway function, and the subset of these FA-dependent phenotypes that can be modified, complemented or suppressed. All ten FANC-isogenic cell line pairs are available to academic, non-profit and industry investigators via the 'Fanconi Anemia Research Materials' Resource and Repository at Oregon Health &amp; Sciences University, Portland OR. This article is protected by copyright. All rights reserved.},
}
@article {pmid36908449,
year = {2023},
author = {Kiptinness, C and Naik, P and Thuo, N and Malen, RC and Dettinger, JC and Pintye, J and Rafferty, M and Jomo, E and Nyamasyo, N and Wood, T and Isabelli, P and Morris, S and Hattery, D and Stergachis, A and Were, D and Sharma, M and Ngure, K and Mugambi, ML and Ortblad, KF},
title = {Online HIV prophylaxis delivery: Protocol for the ePrEP Kenya pilot study.},
journal = {Frontiers in public health},
volume = {11},
number = {},
pages = {1054559},
pmid = {36908449},
issn = {2296-2565},
mesh = {Humans ; *HIV Infections/prevention &amp; control ; Pilot Projects ; Kenya ; *Pre-Exposure Prophylaxis/methods ; },
abstract = {BACKGROUND: Online pharmacies in Kenya provide sexual and reproductive health products (e.g., HIV self-testing, contraception) and could be leveraged to increase the reach of HIV pre-exposure and post-exposure prophylaxis (PrEP/PEP) to populations who do not frequently attend health facilities. To date, evidence is limited for operationalizing online PrEP/PEP delivery and the type of populations reached with this differential service delivery model.<br><br>METHODS: The ePrEP Kenya Pilot will deliver daily oral PrEP and PEP via MYDAWA, a private online pharmacy retailer, to clients in Nairobi for 18 months. Potential clients will obtain information about PrEP/PEP on MYDAWA's sexual wellness page and self-screen for HIV risk. Individuals &#x2265;18 years, identified as at HIV risk, and willing to pay for a blood-based HIV self-test and PrEP/PEP delivery will be eligible for enrollment. To continue with online PrEP/PEP initiation, eligible clients will purchase a blood-based HIV self-test for 250 KES (~USD 2) [delivered to their setting of choice for 99 KES (~USD 1)], upload an image of their self-test result, and attend a telemedicine visit with a MYDAWA provider. During the telemedicine visit, providers will screen clients for PrEP/PEP eligibility, including clinical concerns (e.g., kidney disease), discuss self-test results, and complete counseling on PrEP/PEP use and safety. Providers will refer clients who self-test HIV positive or report any existing medical conditions to the appropriate services at healthcare facilities that meet their preferences. Eligible clients will be prescribed PrEP (30-day PrEP supply at initiation; 90-day PrEP supply at follow-up visits) or PEP (28-day supply) for free and have it delivered for 99 KES (~USD 1). We will measure PrEP and PEP initiation among eligible clients, PEP-to-PrEP transition, PrEP continuation, and implementation outcomes (e.g., feasibility, acceptability, and costs).<br><br>DISCUSSION: Establishing pathways to increase PrEP and PEP access is crucial to help curb new HIV infections in settings with high HIV prevalence. The findings from this study will provide evidence on the implementation of online pharmacy PrEP and PEP service delivery that can help inform guidelines in Kenya and similar settings.},
}
@article {pmid36907443,
year = {2023},
author = {Takata, Y and Yang, JJ and Yu, D and Smith-Warner, SA and Blot, WJ and White, E and Robien, K and Prizment, A and Wu, K and Sawada, N and Lan, Q and Park, Y and Gao, YT and Cai, Q and Song, M and Zhang, X and Pan, K and Agudo, A and Panico, S and Liao, LM and Tsugane, S and Chlebowski, RT and Nøst, TH and Schulze, MB and Johannson, M and Zheng, W and Shu, XO},
title = {Calcium intake and lung cancer risk: a pooled analysis of 12 prospective cohort studies.},
journal = {The Journal of nutrition},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.tjnut.2023.03.011},
pmid = {36907443},
issn = {1541-6100},
abstract = {BACKGROUND: Previous studies on calcium intake and lung cancer risk reported inconsistent associations, possibly due to differences in intake amounts and contributing sources of calcium and smoking prevalence.<br><br>OBJECTIVE: We investigated associations of lung cancer risk with intakes of calcium from foods and/or supplements and major calcium-rich foods in 12 studies.<br><br>METHODS: Data from 12 prospective cohort studies conducted in the US, Europe, and Asia were pooled and harmonized. We applied Dietary Reference Intake to categorize calcium intake based on the recommendations and quintile distribution to categorize calcium-rich food intakes. We ran multivariable Cox regression by each cohort and pooled risk estimates to compute overall hazard ratios (HR) (95% confidence intervals [CI]).<br><br>RESULTS: Among 1,624,244 adult men and women, 21,513 incident lung cancer cases were ascertained during a mean follow-up of 9.9 years. Overall, dietary calcium intake was not significantly associated with lung cancer risk; the HRs (95% CI) were 1.08 (0.98-1.18) for higher (>1,500 [men] or >1,800 [women] mg/d) and1.01 (0.95-1.07) for lower intake (&#x2264;500 [men] or &#x2264;600 [women] mg/d) comparing with recommended intake (800-1,200 mg/d). Milk and soy food intake was positively or inversely associated with lung cancer risk (HR [95% CI]=1.07 [1.02-1.12] and 0.92 [0.84-1.00]), respectively. The positive association with milk intake was significant only in European and US studies (P-interaction for region=0.04). No significant association was observed for calcium supplements.<br><br>CONCLUSIONS: In this largest prospective investigation, overall, calcium intake was not associated with risk of lung cancer, but milk intake was associated with a higher risk. Our findings underscore the importance of considering food sources of calcium in studies of calcium intake.},
}
@article {pmid36906275,
year = {2023},
author = {Hines, MR and Knight, TE and McNerney, KO and Leick, MB and Jain, T and Ahmed, S and Frigault, MJ and Hill, JA and Jain, MD and Johnson, WT and Lin, Y and Mahadeo, KM and Maron, GM and Marsh, RA and Neelapu, SS and Nikiforow, S and Ombrello, AK and Shah, NN and Talleur, AC and Turicek, D and Vatsayan, A and Wong, SW and Maus, MV and Komanduri, KV and Berliner, N and Henter, JI and Perales, MA and Frey, NV and Teachey, DT and Frank, MJ and Shah, NN},
title = {Immune Effector Cell associated Hemophagocytic Lymphohistiocytosis-like Syndrome (IEC-HS).},
journal = {Transplantation and cellular therapy},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jtct.2023.03.006},
pmid = {36906275},
issn = {2666-6367},
abstract = {BACKGROUND: T cell mediated hyperinflammatory responses such as cytokine release syndrome (CRS) and immune effector cell associated neurotoxicity syndrome (ICANS) are now well-established toxicities of chimeric antigen receptor (CAR) T cells. As the field of CAR T cells advances, however, there is increasing recognition that hemophagocytic lymphohistiocytosis (HLH)-like toxicities following CAR T cell infusions are occurring broadly across patient populations and CAR T cell constructs. Importantly, these HLH-like toxicities are often not as directly associated with CRS and/or its severity as initially described. This emergent toxicity, however ill-defined, is associated with life-threatening complications, creating an urgent need for improved identification and optimal management.<br><br>OBJECTIVES: With the goal to improve patient outcomes and formulate a framework to characterize and study this HLH-like syndrome, we established an American Society for Transplantation and Cellular Therapy (ASTCT) panel comprised of experts in primary and secondary HLH, pediatric and adult HLH, infectious disease, rheumatology and hematology, oncology, and cellular therapy.<br><br>RESULTS: Through this effort, we provide an overview of the underlying biology of classical primary and secondary HLH, its relationship with similar manifestations following CAR T cell infusions and propose the term "immune effector cell (IEC) associated HLH-like syndrome (IEC-HS)" to describe this emergent toxicity. Further, we delineate a framework for identification of IEC-HS and put forward a grading schema which can be used to assess severity and facilitate cross-trial comparisons. Additionally, given the critical need to optimize outcomes for patients experiencing IEC-HS, we provide insights into potential treatment approaches, strategies to optimize supportive care and delineate alternate etiologies which should be considered in a patient presenting with IEC-HS.<br><br>CONCLUSION: By collectively defining IEC-HS as a hyperinflammatory toxicity we can now embark on further study of the pathophysiology underlying this toxicity profile and make strides towards a more comprehensive assessment and treatment approach.},
}
@article {pmid36906080,
year = {2023},
author = {van den Puttelaar, R and Meester, RGS and Peterse, EEP and Zauber, AG and Zheng, J and Hayes, RB and Su, YR and Lee, JK and Thomas, M and Sakoda, LC and Li, Y and Corley, DA and Peters, U and Hsu, L and Lansdorp-Vogelaar, I},
title = {Risk-stratified screening for colorectal cancer using genetic and environmental risk factors: A cost-effectiveness analysis based on real-world data.},
journal = {Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.cgh.2023.03.003},
pmid = {36906080},
issn = {1542-7714},
abstract = {BACKGROUND AND AIMS: Previous studies on the cost-effectiveness of personalized colorectal cancer (CRC) screening were based on hypothetical performance of CRC risk prediction and did not consider the association with competing causes of death. In this study, we estimated the cost-effectiveness of risk-stratified screening using real-world data for CRC risk and competing causes of death.<br><br>METHODS: Risk predictions for CRC and competing causes of death, from a large community-based cohort, were used to stratify individuals into risk groups. A microsimulation model was used to optimize colonoscopy screening for each risk group by varying the start age (40-60 years), end age (70-85 years), and screening interval (5-15 years). The outcomes included personalized screening ages and intervals, and cost-effectiveness compared to uniform colonoscopy screening (ages 45-75, every 10 years). Key assumptions were varied in sensitivity analyses.<br><br>RESULTS: Risk-stratified screening resulted in substantially different screening recommendations, ranging from a one-time colonoscopy at age 60 for low-risk individuals to a colonoscopy every five years from ages 40-85 for high-risk individuals. Nevertheless, on a population-level, risk-stratified screening would increase net quality adjusted life years gained (QALYG) by only 0.7% at equal costs to uniform screening, or, reduce average costs by 1.2% for equal QALYG. The benefit of risk-stratified screening improved when it was assumed to increase participation or costs less per genetic test.<br><br>CONCLUSIONS: Personalized screening for CRC, accounting for competing causes of death risk, could result in highly tailored individual screening programs. However, average improvements across the population in QALYG and cost-effectiveness compared with uniform screening are small.},
}
@article {pmid36902377,
year = {2023},
author = {Murakami, K and Furuya, H and Hokutan, K and Goodison, S and Pagano, I and Chen, R and Shen, CH and Chan, MWY and Ng, CF and Kobayashi, T and Ogawa, O and Miyake, M and Thornquist, M and Shimizu, Y and Hayashi, K and Wang, Z and Yu, H and Rosser, CJ},
title = {Association of SNPs in the PAI1 Gene with Disease Recurrence and Clinical Outcome in Bladder Cancer.},
journal = {International journal of molecular sciences},
volume = {24},
number = {5},
pages = {},
pmid = {36902377},
issn = {1422-0067},
support = {R01CA198887/CA/NCI NIH HHS/United States ; UH3CA271377/CA/NCI NIH HHS/United States ; R21CA263230/CA/NCI NIH HHS/United States ; },
mesh = {Humans ; Neoplasm Recurrence, Local ; *Plasminogen Activator Inhibitor 1/genetics ; *Polymorphism, Single Nucleotide ; *Urinary Bladder Neoplasms/genetics ; },
abstract = {PURPOSE: Bladder cancer (BCa) is one of the most common cancer types worldwide and is characterized by a high rate of recurrence. In previous studies, we and others have described the functional influence of plasminogen activator inhibitor-1 (PAI1) in bladder cancer development. While polymorphisms in PAI1 have been associated with increased risk and worsened prognosis in some cancers, the mutational status of PAI1 in human bladder tumors has not been well defined.<br><br>METHODS: In this study, we evaluated the mutational status of PAI1 in a series of independent cohorts, comprised of a total of 660 subjects.<br><br>RESULTS: Sequencing analyses identified two clinically relevant 3' untranslated region (UTR) single nucleotide polymorphisms (SNPs) in PAI1 (rs7242; rs1050813). Somatic SNP rs7242 was present in human BCa cohorts (overall incidence of 72%; 62% in Caucasians and 72% in Asians). In contrast, the overall incidence of germline SNP rs1050813 was 18% (39% in Caucasians and 6% in Asians). Furthermore, Caucasian patients with at least one of the described SNPs had worse recurrence-free survival and overall survival (p = 0.03 and p = 0.03, respectively). In vitro functional studies demonstrated that SNP rs7242 increased the anti-apoptotic effect of PAI1, and SNP rs1050813 was related to a loss of contact inhibition associated with cellular proliferation when compared to wild type.<br><br>CONCLUSION: Further investigation of the prevalence and potential downstream influence of these SNPs in bladder cancer is warranted.},
}
@article {pmid36899395,
year = {2023},
author = {Dong, J and Buradagunta, CS and Zhang, T and Spellman, S and Bolon, YT and DeZern, AE and Gadalla, SM and Deeg, HJ and Nazha, A and Cutler, C and Cheng, C and Urrutia, R and Auer, P and Saber, W},
title = {Prognostic landscape of mitochondrial genome in myelodysplastic syndrome after stem-cell transplantation.},
journal = {Journal of hematology &amp; oncology},
volume = {16},
number = {1},
pages = {21},
pmid = {36899395},
issn = {1756-8722},
mesh = {Humans ; Prognosis ; *Genome, Mitochondrial ; *Hematopoietic Stem Cell Transplantation ; *Myelodysplastic Syndromes/genetics ; Transplantation Conditioning ; DNA, Mitochondrial ; Retrospective Studies ; },
abstract = {Despite mitochondrial DNA (mtDNA) mutations are common events in cancer, their global frequency and clinical impact have not been comprehensively characterized in patients with myelodysplastic neoplasia (also known as myelodysplastic syndromes, MDS). Here we performed whole-genome sequencing (WGS) on samples obtained before allogenic hematopoietic cell transplantation (allo-HCT) from 494 patients with MDS who were enrolled in the Center for International Blood and Marrow Transplant Research. We evaluated the impact of mtDNA mutations on transplantation outcomes, including overall survival (OS), relapse, relapse-free survival (RFS), and transplant-related mortality (TRM). A random survival forest algorithm was applied to evaluate the prognostic performance of models that include mtDNA mutations alone and combined with MDS- and HCT-related clinical factors. A total of 2666 mtDNA mutations were identified, including 411 potential pathogenic variants. We found that overall, an increased number of mtDNA mutations was associated with inferior transplantation outcomes. Mutations in several frequently mutated mtDNA genes (e.g., MT-CYB and MT-ND5) were identified as independent predictors of OS, RFS, relapse and/or TRM after allo-HCT. Integration of mtDNA mutations into the models based on the Revised International Prognostic Scores (IPSS-R) and clinical factors related to MDS and allo-HCT could capture more prognostic information and significantly improve the prognostic stratification efforts. Our study represents the first WGS effort in MDS receiving allo-HCT and shows that there may be clinical utility of mtDNA variants to predict allo-HCT outcomes in combination with more standard clinical parameters.},
}
@article {pmid36899062,
year = {2023},
author = {Benkeser, D and Fong, Y and Janes, HE and Kelly, EJ and Hirsch, I and Sproule, S and Stanley, AM and Maaske, J and Villafana, T and Houchens, CR and Martins, K and Jayashankar, L and Castellino, F and Ayala, V and Petropoulos, CJ and Leith, A and Haugaard, D and Webb, B and Lu, Y and Yu, C and Borate, B and van der Laan, LWP and Hejazi, NS and Carpp, LN and Randhawa, AK and Andrasik, MP and Kublin, JG and Isaacs, MB and Makhene, M and Tong, T and Robb, ML and Corey, L and Neuzil, KM and Follmann, D and Hoffman, C and Falsey, AR and Sobieszczyk, M and Koup, RA and Donis, RO and Gilbert, PB and , and , and , },
title = {Immune correlates analysis of a phase 3 trial of the AZD1222 (ChAdOx1 nCoV-19) vaccine.},
journal = {NPJ vaccines},
volume = {8},
number = {1},
pages = {36},
pmid = {36899062},
issn = {2059-0105},
abstract = {In the phase 3 trial of the AZD1222 (ChAdOx1 nCoV-19) vaccine conducted in the U.S., Chile, and Peru, anti-spike binding IgG concentration (spike IgG) and pseudovirus 50% neutralizing antibody titer (nAb ID50) measured four weeks after two doses were assessed as correlates of risk and protection against PCR-confirmed symptomatic SARS-CoV-2 infection (COVID-19). These analyses of SARS-CoV-2 negative participants were based on case-cohort sampling of vaccine recipients (33 COVID-19 cases by 4 months post dose two, 463 non-cases). The adjusted hazard ratio of COVID-19 was 0.32 (95% CI: 0.14, 0.76) per 10-fold increase in spike IgG concentration and 0.28 (0.10, 0.77) per 10-fold increase in nAb ID50 titer. At nAb ID50 below the limit of detection (< 2.612 IU50/ml), 10, 100, and 270 IU50/ml, vaccine efficacy was -5.8% (-651%, 75.6%), 64.9% (56.4%, 86.9%), 90.0% (55.8%, 97.6%) and 94.2% (69.4%, 99.1%). These findings provide further evidence towards defining an immune marker correlate of protection to help guide regulatory/approval decisions for COVID-19 vaccines.},
}
@article {pmid36898381,
year = {2023},
author = {Nava Lauson, CB and Tiberti, S and Corsetto, PA and Conte, F and Tyagi, P and Machwirth, M and Ebert, S and Loffreda, A and Scheller, L and Sheta, D and Mokhtari, Z and Peters, T and Raman, AT and Greco, F and Rizzo, AM and Beilhack, A and Signore, G and Tumino, N and Vacca, P and McDonnell, LA and Raimondi, A and Greenberg, PD and Huppa, JB and Cardaci, S and Caruana, I and Rodighiero, S and Nezi, L and Manzo, T},
title = {Linoleic acid potentiates CD8[+] T cell metabolic fitness and antitumor immunity.},
journal = {Cell metabolism},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.cmet.2023.02.013},
pmid = {36898381},
issn = {1932-7420},
abstract = {The metabolic state represents a major hurdle for an effective adoptive T cell therapy (ACT). Indeed, specific lipids can harm CD8[+] T cell (CTL) mitochondrial integrity, leading to defective antitumor responses. However, the extent to which lipids can affect the CTL functions and fate remains unexplored. Here, we show that linoleic acid (LA) is a major positive regulator of CTL activity by improving metabolic fitness, preventing exhaustion, and stimulating a memory-like phenotype with superior effector functions. We report that LA treatment enhances the formation of ER-mitochondria contacts (MERC), which in turn promotes calcium (Ca[2+]) signaling, mitochondrial energetics, and CTL effector functions. As a direct consequence, the antitumor potency of LA-instructed CD8 T cells is superior in vitro and in vivo. We thus propose LA treatment as an ACT potentiator in tumor therapy.},
}
@article {pmid36897025,
year = {2023},
author = {Kato, I and Larson, JC},
title = {Reply to: Comments on "Association of calcium and vitamin D supplementation with cancer incidence and cause-specific mortality in Black women: extended follow-up of the Women's Health Initiative calcium-vitamin D trial".},
journal = {International journal of cancer},
volume = {},
number = {},
pages = {},
doi = {10.1002/ijc.34501},
pmid = {36897025},
issn = {1097-0215},
}
@article {pmid36896478,
year = {2023},
author = {Kopmar, NE and Gooley, T and Curley, N and Russell, K and Shaw, C and Schonhoff, K and Lim, J and Halpern, AB and Walter, RB and Scott, BL and Appelbaum, J and Hendrie, PC and Estey, EH and Percival, MM},
title = {Results from a phase I study of continuous infusion cladribine, high-dose cytarabine, and mitoxantrone for relapsed/refractory high-grade myeloid neoplasms.},
journal = {Leukemia &amp; lymphoma},
volume = {},
number = {},
pages = {1-3},
doi = {10.1080/10428194.2023.2185087},
pmid = {36896478},
issn = {1029-2403},
}
@article {pmid36895838,
year = {2023},
author = {Wright, CE and Enquobahrie, DA and Prager, S and Painter, I and Kooperberg, C and Wild, RA and Park, K and Sealy-Jefferson, S and Kernic, MA},
title = {Pregnancy loss and risk of incident CVD within 5 years: Findings from the Women's Health Initiative.},
journal = {Frontiers in cardiovascular medicine},
volume = {10},
number = {},
pages = {1108286},
pmid = {36895838},
issn = {2297-055X},
abstract = {BACKGROUND: Previous studies have demonstrated an increased risk of cardiovascular disease (CVD) in women with a history of pregnancy loss. Less is known about whether pregnancy loss is associated with age at the onset of CVD, but this is a question of interest, as a demonstrated association of pregnancy loss with early-onset CVD may provide clues to the biological basis of the association, as well as having implications for clinical care. We conducted an age-stratified analysis of pregnancy loss history and incident CVD in a large cohort of postmenopausal women aged 50-79 years old.<br><br>METHODS: Associations between a history of pregnancy loss and incident CVD were examined among participants in the Women's Health Initiative Observational Study. Exposures were any history of pregnancy loss (miscarriage and/or stillbirth), recurrent (2+) loss, and a history of stillbirth. Logistic regression analyses were used to examine associations between pregnancy loss and incident CVD within 5 years of study entry in three age strata (50-59, 69-69, and 70-79). Outcomes of interest were total CVD, coronary heart disease (CHD), congestive heart failure, and stroke. To assess the risk of early onset CVD, Cox proportional hazard regression was used to examine incident CVD before the age of 60 in a subset of subjects aged 50-59 at study entry.<br><br>RESULTS: After adjustment for cardiovascular risk factors, a history of stillbirth was associated with an elevated risk of all cardiovascular outcomes in the study cohort within 5 years of study entry. Interactions between age and pregnancy loss exposures were not significant for any cardiovascular outcome; however, age-stratified analyses demonstrated an association between a history of stillbirth and risk of incident CVD within 5 years in all age groups, with the highest point estimate seen in women aged 50-59 (OR 1.99; 95% CI, 1.16-3.43). Additionally, stillbirth was associated with incident CHD among women aged 50-59 (OR 3.12; 95% CI, 1.33-7.29) and 60-69 (OR 2.06; 95% CI, 1.24-3.43) and with incident heart failure and stroke among women aged 70-79. Among women aged 50-59 with a history of stillbirth, a non-significantly elevated hazard ratio was observed for heart failure before the age of 60 (HR 2.93, 95% CI, 0.96-6.64).<br><br>CONCLUSIONS: History of stillbirth was strongly associated with a risk of cardiovascular outcomes within 5 years of baseline in a cohort of postmenopausal women aged 50-79. History of pregnancy loss, and of stillbirth in particular, might be a clinically useful marker of cardiovascular disease risk in women.},
}
@article {pmid36895656,
year = {2023},
author = {Nakambale, HN and Roche, SD and Mogere, P and Omollo, V and Kuo, AP and Stergachis, A and Baeten, JM and Bukusi, E and Ngure, K and Mugambi, ML and Ortblad, KF},
title = {Barriers to and strategies for early implementation of pharmacy-delivered HIV PrEP services in Kenya: An analysis of routine data.},
journal = {Frontiers in reproductive health},
volume = {5},
number = {},
pages = {1023568},
pmid = {36895656},
issn = {2673-3153},
abstract = {BACKGROUND: For individuals who face challenges accessing clinic-based HIV pre-exposure prophylaxis (PrEP), differentiated service delivery models are needed to expand access and reach. During a pilot study testing a novel pharmacy-delivered oral PrEP model in Kenya, we used routine programmatic data to identify early implementation barriers and actions that providers and study staff took in response to the barriers.<br><br>METHODS: We trained pharmacy providers at five private pharmacies in Kisumu and Kiambu Counties to initiate and continue clients at risk of HIV acquisition on PrEP for a fee of 300 KES per visit (&#x223c;$3 USD) using a prescribing checklist with remote clinician oversight. Research assistants stationed at the pharmacies completed weekly observation reports of pharmacy-delivered PrEP services using a structured template. We analyzed reports from the first 6 month of implementation using content analysis and identified multi-level early implementation barriers and actions taken to address these. We then organized the identified barriers and actions according to the Consolidated Framework for Implementation Research (CFIR).<br><br>RESULTS: From November 2020 to May 2021, research assistants completed 74 observation reports (&#x223c;18/pharmacy). During this period, pharmacy providers screened 496 potential PrEP clients, identified 425 as eligible for pharmacy-delivered PrEP services, and initiated 230 (54%) on PrEP; 125 of 197 (63%) clients eligible for PrEP continuation refilled PrEP. We identified the following early implementation barriers to pharmacy-delivered PrEP services (by CFIR domain): high costs to clients (intervention characteristics), client discomfort discussing sexual behaviors and HIV testing with providers (outer setting), provider frustrations that PrEP delivery was time-consuming and disruptive to their workflow (inner setting), and provider hesitancy to deliver PrEP due to concerns about encouraging sexual promiscuity (characteristics of individuals). To help address these, pharmacy providers implemented a self-screening option for behavioral HIV risk assessment for prospective PrEP clients, allowed flexible appointment scheduling, and conducted pharmacy PrEP trainings for newly hired staff.<br><br>CONCLUSION: Our study provides insight into early barriers to implementing pharmacy-delivered PrEP services in Kenya and potential actions to mitigate these barriers. It also demonstrates how routine programmatic data can be used to understand the early implementation process.},
}
@article {pmid36895286,
year = {2023},
author = {Follmann, D and Janes, HE and Chu, E and Jayashankar, L and Petropoulos, CJ and Serebryannyy, L and Carroll, R and Jean-Baptiste, N and Narpala, S and Lin, BC and McDermott, A and Novak, RM and Graciaa, DS and Rolsma, S and Magaret, CA and Doria-Rose, N and Corey, L and Neuzil, KM and Pajon, R and Miller, JM and Donis, RO and Koup, RA and Baden, LR and El Sahly, HM},
title = {Kinetics of the Antibody Response to Symptomatic SARS-CoV-2 Infection in Vaccinated and Unvaccinated Individuals in the Blinded Phase of the mRNA-1273 COVID-19 Vaccine Efficacy Trial.},
journal = {Open forum infectious diseases},
volume = {10},
number = {3},
pages = {ofad069},
pmid = {36895286},
issn = {2328-8957},
abstract = {BACKGROUND: Hybrid immunity is associated with more durable protection against coronavirus disease 2019 (COVID-19). We describe the antibody responses following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in vaccinated and unvaccinated individuals.<br><br>METHODS: The 55 vaccine arm COVID-19 cases diagnosed during the blinded phase of the Coronavirus Efficacy trial were matched with 55 placebo arm COVID-19 cases. Pseudovirus neutralizing antibody (nAb) activity to the ancestral strain and binding antibody (bAb) responses to nucleocapsid and spike antigens (ancestral and variants of concern [VOCs]) were assessed on disease day 1 (DD1) and 28&#x2005;days later (DD29).<br><br>RESULTS: The primary analysis set was 46 vaccine cases and 49 placebo cases with COVID-19 at least 57 days post-first dose. For vaccine group cases, there was a 1.88-fold rise in ancestral antispike bAbs 1 month post-disease onset, although 47% had no increase. The vaccine-to-placebo geometric mean ratios for DD29 antispike and antinucleocapsid bAbs were 6.9 and 0.04, respectively. DD29 mean bAb levels were higher for vaccine vs placebo cases for all VOCs. DD1 nasal viral load positively correlated with bAb levels in the vaccine group.<br><br>CONCLUSIONS: Following COVID-19, vaccinated participants had higher levels and greater breadth of antispike bAbs and higher nAb titers than unvaccinated participants. These were largely attributable to the primary immunization series.},
}
@article {pmid36895169,
year = {2023},
author = {Brasky, TM and Ray, RM and Newton, AM and Navarro, SL and Schenk, JM and Loomans-Kropp, HA and Arthur, RS and Snetselaar, LG and Hays, J and Neuhouser, ML},
title = {Supplemental B-Vitamins and Risk of Upper Gastrointestinal Cancers in the Women's Health Initiative.},
journal = {Nutrition and cancer},
volume = {},
number = {},
pages = {1-6},
doi = {10.1080/01635581.2023.2186258},
pmid = {36895169},
issn = {1532-7914},
abstract = {B-vitamins contribute to DNA synthesis, maintenance, and regulation. Few studies have examined associations of supplemental sources of B-vitamins with the incidence of upper gastrointestinal (GI) cancers [including gastric (GCA) and esophageal (ECA) cancers]; the only prior study to comprehensively examine such intakes reported potential elevated risks of ECA. We examined 159,401 postmenopausal women, ages 50-79 years at baseline, including 302 incident GCA and 183 incident ECA cases, over 19 years of follow-up within the Women's Health Initiative observational study and clinic trials. Adjusted Cox regression models estimated hazard ratios (HR) and 95% confidence intervals (CI) for associations of supplemental B-vitamins [riboflavin (B2), pyridoxine (B6), folic acid (B9), or cobalamin (B12)] with GCA and ECA risk, respectively. Although HRs were generally below 1.0, we observed no statistically significant associations between supplemental intakes of any of the evaluated B-vitamins with the risk of GCA or ECA. As the first prospective study to comprehensively assess these associations, our findings do not corroborate prior research indicating potential harm from supplemental B-vitamin intake for upper GI cancer risk. This study adds evidence that supplemental intakes of B-vitamins may be used by postmenopausal women without regard to their relationship with upper GI cancer risk.},
}
@article {pmid36894662,
year = {2023},
author = {Lewinsohn, MA and Bedford, T and Müller, NF and Feder, AF},
title = {State-dependent evolutionary models reveal modes of solid tumour growth.},
journal = {Nature ecology &amp; evolution},
volume = {},
number = {},
pages = {},
pmid = {36894662},
issn = {2397-334X},
abstract = {Spatial properties of tumour growth have profound implications for cancer progression, therapeutic resistance and metastasis. Yet, how spatial position governs tumour cell division remains difficult to evaluate in clinical tumours. Here, we demonstrate that faster division on the tumour periphery leaves characteristic genetic patterns, which become evident when a phylogenetic tree is reconstructed from spatially sampled cells. Namely, rapidly dividing peripheral lineages branch more extensively and acquire more mutations than slower-dividing centre lineages. We develop a Bayesian state-dependent evolutionary phylodynamic model (SDevo) that quantifies these patterns to infer the differential division rates between peripheral and central cells. We demonstrate that this approach accurately infers spatially varying birth rates of simulated tumours across a range of growth conditions and sampling strategies. We then show that SDevo outperforms state-of-the-art, non-cancer multi-state phylodynamic methods that ignore differential sequence evolution. Finally, we apply SDevo to single-time-point, multi-region sequencing data from clinical hepatocellular carcinomas and find evidence of a three- to six-times-higher division rate on the tumour edge. With the increasing availability of high-resolution, multi-region sequencing, we anticipate that SDevo will be useful in interrogating spatial growth restrictions and could be extended to model non-spatial factors that influence tumour progression.},
}
@article {pmid36891630,
year = {2023},
author = {Zhang, MY and Othus, M and Shaw, C and Schonhoff, KG and Halpern, AB and Appelbaum, J and Hendrie, PC and Walter, RB and Estey, EH and Percival, MM},
title = {Poor post-induction outcomes in patients with acute myeloid leukemia previously treated with hypomethylating agents.},
journal = {Leukemia &amp; lymphoma},
volume = {},
number = {},
pages = {1-7},
doi = {10.1080/10428194.2023.2186732},
pmid = {36891630},
issn = {1029-2403},
abstract = {Patients with acute myeloid leukemia (AML) who have failed hypomethylating agents (HMA) have a poor prognosis. We examined whether high intensity induction chemotherapy could abrogate negative outcomes in 270 patients with AML or other high-grade myeloid neoplasms. Prior HMA therapy was significantly associated with a lower overall survival (OS) as compared to a reference group of patients with secondary disease without prior HMA therapy (median 7.2 vs 13.1 months). In patients with prior HMA therapy, high intensity induction was associated with a non-significant trend toward longer OS (median 8.2 vs 4.8 months) and decreased rates of treatment failure (39% vs 64%). These results redemonstrate poor outcomes in patients with prior HMA and suggest possible benefit of high intensity induction that should be evaluated in future studies.},
}
@article {pmid36890020,
year = {2023},
author = {Johnson, ML and Strauss, J and Patel, MR and Garon, EB and Eaton, KD and Neskorik, T and Morin, J and Chao, R and Halmos, B},
title = {Mocetinostat in Combination With Durvalumab for Patients With Advanced NSCLC: Results From a Phase I/II Study.},
journal = {Clinical lung cancer},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.cllc.2023.01.013},
pmid = {36890020},
issn = {1938-0690},
abstract = {BACKGROUND: Histone deacetylase (HDAC) inhibitors have potential to augment the effectiveness of immune checkpoint inhibitors and overcome treatment resistance. This dose-escalation/expansion study (NCT02805660) investigated mocetinostat (class I/IV HDAC inhibitor) plus durvalumab in patients with advanced non-small cell lung cancer (NSCLC) across cohorts defined by tumor programmed death-ligand 1 (PD-L1) expression and prior experience with anti-programmed cell death protein-1 (anti-PD-1) or anti-PD-L1 regimens.<br><br>PATIENTS AND METHODS: Sequential cohorts of patients with solid tumors received mocetinostat (starting dose: 50 mg TIW) plus durvalumab at a standard dose (1500 mg Q4W) to determine the recommended phase II dose (RP2D: phase I primary endpoint), based on the observed safety profile. RP2D was administered to patients with advanced NSCLC across 4 cohorts grouped by tumor PD-L1 expression (none or low/high) and prior experience with anti-PD-L1 /anti-PD-1 agents (na&#xef;ve, clinical benefit: yes/no). The phase II primary endpoint was objective response rate (ORR, RECIST v1.1).<br><br>RESULTS: Eighty-three patients were enrolled (phase I [n&#xa0;=&#xa0;20], phase II [n&#xa0;=&#xa0;63]). RP2D was mocetinostat 70 mg TIW plus durvalumab. ORR was 11.5% across the phase II cohorts, and responses were durable (median 329 days). Clinical activity was observed in NSCLC patients with disease refractory to prior checkpoint inhibitor treatment: ORR 23.1%. Across all patients, fatigue (41%), nausea (40%), and diarrhea (31%) were the most frequent treatment-related adverse events.<br><br>CONCLUSION: Mocetinostat 70 mg TIW plus durvalumab at the standard dose was generally well tolerated. Clinical activity was observed in patients with NSCLC unresponsive to prior anti-PD-(L)1 therapy.},
}
@article {pmid36889914,
year = {2023},
author = {Delany-Moretlwe, S and Mgodi, N and Bekker, LG and Baeten, JM and Li, C and Donnell, D and Agyei, Y and Lennon, D and Rose, SM and Mokgatle, M and Kassim, S and Mukaka, S and Adeyeye, A and Celum, C},
title = {High prevalence and incidence of gonorrhoea and chlamydia in young women eligible for HIV pre-exposure prophylaxis in South Africa and Zimbabwe: results from the HPTN 082 trial.},
journal = {Sexually transmitted infections},
volume = {},
number = {},
pages = {},
doi = {10.1136/sextrans-2022-055696},
pmid = {36889914},
issn = {1472-3263},
abstract = {INTRODUCTION: We investigated the prevalence, incidence and factors associated with sexually transmitted infections (STIs) among young African women seeking HIV pre-exposure prophylaxis (PrEP).<br><br>METHODS: HPTN 082 was a prospective, open-label PrEP study enrolling HIV-negative sexually active women aged 16-25 years in Cape Town and Johannesburg, South Africa, and Harare, Zimbabwe. Endocervical swabs from enrolment, months 6 and 12 were tested for Neisseria gonorrhoeae (GC) and Chlamydia trachomatis (CT) by nucleic acid amplification, and Trichomonas vaginalis (TV) by a rapid test. Intracellular tenofovir-diphosphate (TFV-DP) concentrations in dried blood spots were measured at months 6 and 12. Associations between risk characteristics and STI outcomes were assessed using Poisson regression.<br><br>RESULTS: Of 451 enrolled participants, 55% had an STI detected at least once. CT incidence was 27.8 per 100 person-years (py) (95%&#x2009;CI 23.1, 33.2), GC incidence was 11.4 per 100 py (95% CI 8.5, 15.0) and TV incidence was 6.7 per 100 py (95%&#x2009;CI 4.5, 9.5). 66% of incident infections were diagnosed in women uninfected at baseline. Baseline cervical infection (GC or CT) risk was highest in Cape Town (relative risk (RR) 2.38, 95%&#x2009;CI 1.35, 4.19) and in those not living with family (RR 1.87, 95% 1.13, 3.08); condom use was protective (RR 0.67, 95%&#x2009;CI 0.45, 0.99). Incident CT was associated with baseline CT (RR 2.01; 95%&#x2009;CI 1.28, 3.15) and increasing depression score (RR 1.05; 95%&#x2009;CI 1.01, 1.09). Incident GC was higher in Cape Town (RR 2.40; 95%&#x2009;CI 1.18, 4.90) and in participants with high PrEP adherence (TFV-DP concentrations &#x2265;700&#x2009;fmol/punch) (RR 2.04 95%&#x2009;CI 1.02, 4.08).<br><br>CONCLUSION: Adolescent girls and young women seeking PrEP have a high prevalence and incidence of curable STIs. Alternatives to syndromic management for diagnosis and treatment are needed to reduce the burden of STIs in this population.<br><br>TRIAL REGISTRATION NUMBER: NCT02732730.},
}
@article {pmid36889672,
year = {2023},
author = {Prentice, RL and Aragaki, AK and Manson, JE and Schoeller, DA and Tinker, LF and Mossavar-Rahmani, Y and Wallace, RB and LaMonte, MJ and Tooze, JA and Johnson, KC and Lampe, JW and Neuhouser, ML},
title = {Total energy expenditure as assessed by doubly-labeled water and all-cause mortality in a cohort of postmenopausal females.},
journal = {The American journal of clinical nutrition},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.ajcnut.2023.02.023},
pmid = {36889672},
issn = {1938-3207},
abstract = {BACKGROUND: The association of total energy expenditure with all-cause mortality is uncertain, as is the dependence of this association on age.<br><br>OBJECTIVE: To examine the association between total energy expenditure and all-cause mortality, and its age interaction, in a Women's Health Initiative (WHI) cohort of postmenopausal U.S. females (1992-present).<br><br>DESIGN: A cohort of 1,131 WHI participants having Doubly-Labeled Water (DLW) total energy expenditure (TEE) assessment about 10.0 years (median) following WHI enrollment with about 13.7 years (median) of subsequent follow-up, was used to study energy expenditure associations with all-cause mortality. To enhance the comparability of TEE and total energy intake, key analyses excluded participants having more than 5% weight change between WHI enrollment and DLW assessment. The influence of participant age on mortality associations was examined, as was the ability of concurrent and earlier weight and height measures to explain results.<br><br>RESULTS: There were 308 deaths following TEE assessment through 2021. TEE was unrelated to mortality (P=0.83) overall in this cohort of generally healthy, older (mean 71 years at TEE assessment) U.S. females. However, this potential association varied with age (P=0.003). Higher TEE was associated with higher mortality rate at age 60 and lower mortality rate at age 80. Within the weight stable subset (532 participants, 129 deaths), TEE was weakly positively related to mortality overall (P=0.08). This association also varied with age (P=0.03), with mortality HRs (95% CIs) for a 20% increment in TEE of 2.33 (1.24, 4.36) at age 60, 1.49 (1.10, 2.02) at age 70, and 0.96 (0.66, 1.38) at age 80. This pattern remained, though was somewhat attenuated, following control for baseline weight and weight changes between WHI enrollment and TEE assessment.<br><br>CONCLUSIONS: Higher energy expenditure is associated with higher all-cause mortality among younger postmenopausal females, only partially explained by weight and weight change. This study is registered with clinicaltrials.gov identifier: NCT00000611.},
}
@article {pmid36884323,
year = {2023},
author = {Gounder, M and Ratan, R and Alcindor, T and Schöffski, P and van der Graaf, WT and Wilky, BA and Riedel, RF and Lim, A and Smith, LM and Moody, S and Attia, S and Chawla, S and D'Amato, G and Federman, N and Merriam, P and Van Tine, BA and Vincenzi, B and Benson, C and Bui, NQ and Chugh, R and Tinoco, G and Charlson, J and Dileo, P and Hartner, L and Lapeire, L and Mazzeo, F and Palmerini, E and Reichardt, P and Stacchiotti, S and Bailey, HH and Burgess, MA and Cote, GM and Davis, LE and Deshpande, H and Gelderblom, H and Grignani, G and Loggers, E and Philip, T and Pressey, JG and Kummar, S and Kasper, B},
title = {Nirogacestat, a γ-Secretase Inhibitor for Desmoid Tumors.},
journal = {The New England journal of medicine},
volume = {388},
number = {10},
pages = {898-912},
doi = {10.1056/NEJMoa2210140},
pmid = {36884323},
issn = {1533-4406},
mesh = {Adult ; Humans ; Female ; *Amyloid Precursor Protein Secretases ; *Fibromatosis, Aggressive/drug therapy ; Quality of Life ; Progression-Free Survival ; Double-Blind Method ; },
abstract = {BACKGROUND: Desmoid tumors are rare, locally aggressive, highly recurrent soft-tissue tumors without approved treatments.<br><br>METHODS: We conducted a phase 3, international, double-blind, randomized, placebo-controlled trial of nirogacestat in adults with progressing desmoid tumors according to the Response Evaluation Criteria in Solid Tumors, version 1.1. Patients were assigned in a 1:1 ratio to receive the oral &#x3b3;-secretase inhibitor nirogacestat (150 mg) or placebo twice daily. The primary end point was progression-free survival.<br><br>RESULTS: From May 2019 through August 2020, a total of 70 patients were assigned to receive nirogacestat and 72 to receive placebo. Nirogacestat had a significant progression-free survival benefit over placebo (hazard ratio for disease progression or death, 0.29; 95% confidence interval, 0.15 to 0.55; P<0.001); the likelihood of being event-free at 2 years was 76% with nirogacestat and 44% with placebo. Between-group differences in progression-free survival were consistent across prespecified subgroups. The percentage of patients who had an objective response was significantly higher with nirogacestat than with placebo (41% vs. 8%; P<0.001), with a median time to response of 5.6 months and 11.1 months, respectively; the percentage of patients with a complete response was 7% and 0%, respectively. Significant between-group differences in secondary patient-reported outcomes, including pain, symptom burden, physical or role functioning, and health-related quality of life, were observed (P&#x2264;0.01). Frequent adverse events with nirogacestat included diarrhea (in 84% of the patients), nausea (in 54%), fatigue (in 51%), hypophosphatemia (in 42%), and maculopapular rash (in 32%); 95% of adverse events were of grade 1 or 2. Among women of childbearing potential receiving nirogacestat, 27 of 36 (75%) had adverse events consistent with ovarian dysfunction, which resolved in 20 women (74%).<br><br>CONCLUSIONS: Nirogacestat was associated with significant benefits with respect to progression-free survival, objective response, pain, symptom burden, physical functioning, role functioning, and health-related quality of life in adults with progressing desmoid tumors. Adverse events with nirogacestat were frequent but mostly low grade. (Funded by SpringWorks Therapeutics; DeFi ClinicalTrials.gov number, NCT03785964.).},
}
@article {pmid36884224,
year = {2023},
author = {Baumrin, E and Baker, LX and Byrne, M and Martin, PJ and Flowers, ME and Onstad, L and El Jurdi, N and Chen, H and Beeghly-Fadiel, A and Lee, SJ and Tkaczyk, ER},
title = {Prognostic Value of Cutaneous Disease Severity Estimates on Survival Outcomes in Patients With Chronic Graft-vs-Host Disease.},
journal = {JAMA dermatology},
volume = {},
number = {},
pages = {},
pmid = {36884224},
issn = {2168-6084},
abstract = {IMPORTANCE: Prior studies have demonstrated an association between cutaneous chronic graft-vs-host disease (cGVHD) and mortality. Assessment of the prognostic value of different measures of disease severity would assist in risk stratification.<br><br>OBJECTIVE: To compare the prognostic value of body surface area (BSA) and National Institutes of Health (NIH) Skin Score on survival outcomes stratified by erythema and sclerosis subtypes of cGVHD.<br><br>Multicenter prospective cohort study from the Chronic Graft-vs-Host Disease Consortium including 9 medical centers in the US, enrolled from 2007 through 2012 and followed until 2018. Participants were adults and children with a diagnosis of cGVHD requiring systemic immunosuppression and with skin involvement during the study period, who had longitudinal follow-up. Data analysis was performed from April 2019 to April 2022.<br><br>EXPOSURES: Patients underwent continuous BSA estimation and categorical NIH Skin Score grading of cutaneous cGVHD at enrollment and every 3 to 6 months thereafter.<br><br>MAIN OUTCOMES AND MEASURES: Nonrelapse mortality (NRM) and overall survival (OS), compared between BSA and NIH Skin Score longitudinal prognostic models, adjusted for age, race, conditioning intensity, patient sex, and donor sex.<br><br>RESULTS: Of 469 patients with cGVHD, 267 (57%) (105 female [39%]; mean [SD] age, 51 [12] years) had cutaneous cGVHD at enrollment, and 89 (19%) developed skin involvement subsequently. Erythema-type disease had earlier onset and was more responsive to treatment compared with sclerosis-type disease. Most cases (77 of 112 [69%]) of sclerotic disease occurred without prior erythema. Erythema-type cGVHD at first follow-up visit was associated with NRM (hazard ratio, 1.33 per 10% BSA increase; 95% CI, 1.19-1.48; P&#x2009;<&#x2009;.001) and OS (hazard ratio, 1.28 per 10% BSA increase; 95% CI, 1.14-1.44; P&#x2009;<&#x2009;.001), while sclerosis-type cGVHD had no significant association with mortality. The model with erythema BSA collected at baseline and first follow-up visits retained 75% of the total prognostic information (from all covariates including BSA and NIH Skin Score) for NRM and 73% for OS, with no statistical difference between prognostic models (likelihood ratio test &#x3c7;2, 5.9; P&#x2009;=&#x2009;.05). Conversely, NIH Skin Score collected at the same intervals lost significant prognostic information (likelihood ratio test &#x3c7;2, 14.7; P&#x2009;<&#x2009;.001). The model incorporating NIH Skin Score instead of erythema BSA accounted for only 38% of the total information for NRM and 58% for OS.<br><br>CONCLUSIONS AND RELEVANCE: In this prospective cohort study, erythema-type cutaneous cGVHD was associated with increased risk of mortality. Erythema BSA collected at baseline and follow-up predicted survival more accurately than the NIH Skin Score in patients requiring immunosuppression. Accurate assessment of erythema BSA may assist in identifying patients with cutaneous cGVHD at high risk for mortality.},
}
@article {pmid36883907,
year = {2023},
author = {Bannick, MS and Gao, F and Brown, ER and Janes, HE},
title = {Retrospective, Observational Studies for Estimating Vaccine Effects on the Secondary Attack Rate of SARS-CoV-2.},
journal = {American journal of epidemiology},
volume = {},
number = {},
pages = {},
doi = {10.1093/aje/kwad046},
pmid = {36883907},
issn = {1476-6256},
abstract = {COVID-19 vaccines are highly efficacious at preventing symptomatic infection, severe disease, and death. Most of the evidence that COVID-19 vaccines also reduce transmission of SARS-CoV-2 is based on retrospective, observational studies. Specifically, an increasing number of studies are evaluating vaccine effectiveness against the secondary attack rate of SARS-CoV-2 using data available in existing healthcare databases or contact tracing databases. Since these types of databases were designed for clinical diagnosis or management of COVID-19, they are limited in their ability to provide accurate information on infection, infection timing, and transmission events. In this manuscript, we highlight challenges with using existing databases to identify transmission units and confirm potential SARS-CoV-2 transmission events. We discuss the impact of common diagnostic testing strategies including event-prompted and infrequent testing and illustrate their potential biases in estimating vaccine effectiveness against the secondary attack rate of SARS-CoV-2. We articulate the need for prospective observational studies of vaccine effectiveness against the SARS-CoV-2 SAR, and we provide design and reporting considerations for studies using retrospective databases.},
}
@article {pmid36883850,
year = {2023},
author = {Fitzpatrick, KS and Degefu, HN and Poljakov, K and Bibby, MG and Remington, AJ and Searles, TG and Gray, MD and Boonyaratanakornkit, J and Rosato, PC and Taylor, JJ},
title = {Validation of Ligand Tetramers for the Detection of Antigen-Specific Lymphocytes.},
journal = {Journal of immunology (Baltimore, Md. : 1950)},
volume = {},
number = {},
pages = {},
doi = {10.4049/jimmunol.2200934},
pmid = {36883850},
issn = {1550-6606},
abstract = {The study of Ag-specific lymphocytes has been a key advancement in immunology over the past few decades. The development of multimerized probes containing Ags, peptide:MHC complexes, or other ligands was one innovation allowing the direct study of Ag-specific lymphocytes by flow cytometry. Although these types of study are now common and performed by thousands of laboratories, quality control and assessment of probe quality are often minimal. In fact, many of these types of probe are made in-house, and protocols vary between laboratories. Although peptide:MHC multimers can often be obtained from commercial sources or core facilities, few such services exist for Ag multimers. To ensure high quality and consistency with ligand probes, we have developed an easy and robust multiplexed approach using commercially available beads able to bind Abs specific for the ligand of interest. Using this assay, we have sensitively assessed the performance of peptide:MHC and Ag tetramers and have found considerable batch-to-batch variability in performance and stability over time more easily than using murine or human cell-based assays. This bead-based assay can also reveal common production errors such as miscalculation of Ag concentration. This work could set the stage for the development of standardized assays for all commonly used ligand probes to limit laboratory-to-laboratory technical variation and experimental failure caused by probe underperformance.},
}
@article {pmid36883551,
year = {2023},
author = {Hart, ML and Quon, E and Vigil, ABG and Engstrom, IA and Newsom, OJ and Davidsen, K and Hoellerbauer, P and Carlisle, SM and Sullivan, LB},
title = {Mitochondrial redox adaptations enable alternative aspartate synthesis in SDH-deficient cells.},
journal = {eLife},
volume = {12},
number = {},
pages = {},
doi = {10.7554/eLife.78654},
pmid = {36883551},
issn = {2050-084X},
support = {P30CA015704/CA/NCI NIH HHS/United States ; T32GM095421/GM/NIGMS NIH HHS/United States ; R00CA218679-03S1/CA/NCI NIH HHS/United States ; R00CA218679/CA/NCI NIH HHS/United States ; R35GM147118/GM/NIGMS NIH HHS/United States ; U54CA132381/CA/NCI NIH HHS/United States ; P30CA015704/CA/NCI NIH HHS/United States ; T32GM095421/GM/NIGMS NIH HHS/United States ; R00CA218679-03S1/CA/NCI NIH HHS/United States ; R00CA218679/CA/NCI NIH HHS/United States ; R35GM147118/GM/NIGMS NIH HHS/United States ; U54CA132381/CA/NCI NIH HHS/United States ; },
abstract = {The oxidative tricarboxylic acid (TCA) cycle is a central mitochondrial pathway integrating catabolic conversions of NAD+ to NADH and anabolic production of aspartate, a key amino acid for cell proliferation. Several TCA cycle components are implicated in tumorigenesis, including loss of function mutations in subunits of succinate dehydrogenase (SDH), also known as complex II of the electron transport chain (ETC), but mechanistic understanding of how proliferating cells tolerate the metabolic defects of SDH loss is still lacking. Here, we identify that SDH supports human cell proliferation through aspartate synthesis but, unlike other ETC impairments, the effects of SDH inhibition are not ameliorated by electron acceptor supplementation. Interestingly, we find aspartate production and cell proliferation are restored to SDH-impaired cells by concomitant inhibition of ETC complex I (CI). We determine that the benefits of CI inhibition in this context depend on decreasing mitochondrial NAD+/NADH, which drives SDH-independent aspartate production through pyruvate carboxylation and reductive carboxylation of glutamine. We also find that genetic loss or restoration of SDH selects for cells with concordant CI activity, establishing distinct modalities of mitochondrial metabolism for maintaining aspartate synthesis. These data therefore identify a metabolically beneficial mechanism for CI loss in proliferating cells and reveal how compartmentalized redox changes can impact cellular fitness.},
}
@article {pmid36882950,
year = {2023},
author = {Gowda, GAN and Pascua, V and Lusk, JA and Hong, NN and Guo, L and Dong, J and Sweet, IR and Raftery, D},
title = {Monitoring Live Mitochondrial Metabolism in Real-Time Using NMR Spectroscopy.},
journal = {Magnetic resonance in chemistry : MRC},
volume = {},
number = {},
pages = {},
doi = {10.1002/mrc.5341},
pmid = {36882950},
issn = {1097-458X},
abstract = {Investigation of mitochondrial metabolism is gaining increased interest owing to the growing recognition of the role of mitochondria in health and numerous diseases. Studies of isolated mitochondria promise novel insights into the metabolism devoid of confounding effects from other cellular organelles such as cytoplasm. This study describes the isolation of mitochondria from mouse skeletal myoblast cells (C2C12) and the investigation of live mitochondrial metabolism in real time using isotope tracer-based NMR spectroscopy. [3-[13] C1 ]pyruvate was used as the substrate to monitor the dynamic changes of the downstream metabolites in mitochondria. The results demonstrate an intriguing phenomenon, in which lactate is produced from pyruvate inside the mitochondria and the results were confirmed by treating mitochondria with an inhibitor of mitochondrial pyruvate carrier (UK5099). Lactate is associated with health and numerous diseases including cancer and, to date, it is known to occur only in the cytoplasm. The insight that lactate is also produced inside mitochondria opens avenues for exploring new pathways of lactate metabolism. Further, experiments performed using inhibitors of the mitochondrial respiratory chain, FCCP and rotenone, show that [2-[13] C1 ]acetyl coenzyme A, which is produced from [3-[13] C1 ]pyruvate and acts as a primary substrate for the tricarboxylic acid cycle in mitochondria, exhibits a remarkable sensitivity to the inhibitors. These results offer a direct approach to visualize mitochondrial respiration through altered levels of the associated metabolites.},
}
@article {pmid36263061,
year = {2022},
author = {Dadonaite, B and Crawford, KHD and Radford, CE and Farrell, AG and Yu, TC and Hannon, WW and Zhou, P and Andrabi, R and Burton, DR and Liu, L and Ho, DD and Neher, RA and Bloom, JD},
title = {A pseudovirus system enables deep mutational scanning of the full SARS-CoV-2 spike.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {36263061},
abstract = {A major challenge in understanding SARS-CoV-2 evolution is interpreting the antigenic and functional effects of emerging mutations in the viral spike protein. Here we describe a new deep mutational scanning platform based on non-replicative pseudotyped lentiviruses that directly quantifies how large numbers of spike mutations impact antibody neutralization and pseudovirus infection. We demonstrate this new platform by making libraries of the Omicron BA.1 and Delta spikes. These libraries each contain ~7000 distinct amino-acid mutations in the context of up to ~135,000 unique mutation combinations. We use these libraries to map escape mutations from neutralizing antibodies targeting the receptor binding domain, N-terminal domain, and S2 subunit of spike. Overall, this work establishes a high-throughput and safe approach to measure how ~10 [5] combinations of mutations affect antibody neutralization and spike-mediated infection. Notably, the platform described here can be extended to the entry proteins of many other viruses.},
}
@article {pmid36882941,
year = {2023},
author = {Peters, BA and Qi, Q and Usyk, M and Daviglus, ML and Cai, J and Franceschini, N and Lash, JP and Gellman, MD and Yu, B and Boerwinkle, E and Knight, R and Burk, RD and Kaplan, RC},
title = {Association of the gut microbiome with kidney function and damage in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL).},
journal = {Gut microbes},
volume = {15},
number = {1},
pages = {2186685},
doi = {10.1080/19490976.2023.2186685},
pmid = {36882941},
issn = {1949-0984},
abstract = {BACKGROUND: The gut microbiome is altered in chronic kidney disease (CKD), potentially contributing to CKD progression and co-morbidities, but population-based studies of the gut microbiome across a wide range of kidney function and damage are lacking.<br><br>METHODS: In the Hispanic Community Health Study/Study of Latinos, gut microbiome was assessed by shotgun sequencing of stool (n&#x2009;=&#x2009;2,438; 292 with suspected CKD). We examined cross-sectional associations of estimated glomerular filtration rate (eGFR), urinary albumin:creatinine (UAC) ratio, and CKD with gut microbiome features. Kidney trait-related microbiome features were interrogated for correlation with serum metabolites (n&#x2009;=&#x2009;700), and associations of microbiome-related serum metabolites with kidney trait progression were examined in a prospective analysis (n&#x2009;=&#x2009;3,635).<br><br>RESULTS: Higher eGFR was associated with overall gut microbiome composition, greater abundance of species from Prevotella, Faecalibacterium, Roseburia, and Eubacterium, and microbial functions related to synthesis of long-chain fatty acids and carbamoyl-phosphate. Higher UAC ratio and CKD were related to lower gut microbiome diversity and altered overall microbiome composition only in participants without diabetes. Microbiome features related to better kidney health were associated with many serum metabolites (e.g., higher indolepropionate, beta-cryptoxanthin; lower imidazole propionate, deoxycholic acids, p-cresol glucuronide). Imidazole propionate, deoxycholic acid metabolites, and p-cresol glucuronide were associated with prospective reductions in eGFR and/or increases in UAC ratio over ~6&#x2009;y.<br><br>CONCLUSIONS: Kidney function is a significant correlate of the gut microbiome, while the relationship of kidney damage with the gut microbiome depends on diabetes status. Gut microbiome metabolites may contribute to CKD progression.},
}
@article {pmid36882916,
year = {2023},
author = {Hurwitz, MD and Chundury, A and Goodman, CR and Jones, J and Lo, SS and Saeed, H and Small, W and Schechter, NR},
title = {ACR-ARS Practice Parameter on Informed Consent Radiation Oncology.},
journal = {American journal of clinical oncology},
volume = {},
number = {},
pages = {},
doi = {10.1097/COC.0000000000000994},
pmid = {36882916},
issn = {1537-453X},
abstract = {OBJECTIVES: Consent is a communication process between the patient and a health care provider, in which both parties have the opportunity to ask questions and exchange information relevant to the patient's diagnosis and treatment. The process of informed consent is designed to protect a patient's autonomy in their medical decision-making in the context of an asymmetric relationship with the health care system. A proper consent process assures a patient's individual autonomy, reduces the opportunity for abusive conduct or conflicts of interest, and raises trust levels among participants. This document was developed as an educational tool to facilitate these goals.<br><br>METHODS: This practice parameter was produced according to the process described under the heading "The Process for Developing ACR Practice Parameters and Technical Standards" on the ACR website (https://www.acr.org/Clinical-Resources/Practice-Parameters-and-Technical-Standards) by the Committee on Practice Parameters-Radiation Oncology of the ACR Commission on Radiation Oncology in collaboration with the ARS. Committee members were charged with reviewing the prior version of the informed consent practice parameter published in 2017 and recommending additions, modifications, or deletions. The committee met through remote access and subsequently through an online exchange to facilitate the development of the revised document. Focus was given on identifying new considerations and challenges with informed consent given the evolution of the practice of radiation oncology in part driven by the COVID-19 pandemic and other external factors.<br><br>RESULTS: A review of the practice parameter published in 2017 confirmed the ongoing relevance of recommendations made at that time. In addition, the evolution of the practice of radiation oncology since the publication of the prior document resulted in the need for new topics to be addressed. These topics include remote consent either through telehealth or telephone and with the patient or their health care proxy.<br><br>CONCLUSIONS: Informed consent is an essential process in the care of radiation oncology patients. This practice parameter serves as an educational tool designed to assist practitioners in optimizing this process for the benefit of all involved parties.},
}
@article {pmid36881439,
year = {2023},
author = {Tordoff, DM and Minalga, B and Perry, NL and Gross, B and Khosropour, CM and Glick, SN and Barbee, LA and Duerr, A and , },
title = {Heterogeneity in HIV/STI Prevalence and Prevention Among the Partners of Transgender and Nonbinary People.},
journal = {Sexually transmitted diseases},
volume = {},
number = {},
pages = {},
doi = {10.1097/OLQ.0000000000001796},
pmid = {36881439},
issn = {1537-4521},
abstract = {BACKGROUND: Transgender and nonbinary (TNB) people are diverse in their sexual orientation and partnerships. We describe the epidemiology of HIV/STI prevalence and prevention utilization among the partners of TNB people in Washington State.<br><br>METHODS: We pooled data from five 2017-2021 cross-sectional HIV surveillance data sources to generate a large sample of TNB people and cisgender people who had a TNB partner in the past year. We describe characteristics of recent partners of trans women, trans men, and nonbinary people and use Poisson regression to assess if having a TNB partner was associated with self-reported HIV/STIs prevalence, testing, and PrEP use.<br><br>RESULTS: Our analysis included 360 trans women, 316 trans men, 963 nonbinary people, 2896 cis women, and 7540 cis men. Overall, 9% of sexual minority cis men, 13% of sexual minority cis women, and 36% of TNB participants reported having any TNB partners. There was significant heterogeneity in HIV/STI prevalence, testing, and PrEP use among the partners of TNB people by study participant gender and the gender of their sex partners. In regression models, having a TNB partner was associated with a higher likelihood of HIV/STI testing and PrEP use but was not associated with higher HIV prevalence.<br><br>CONCLUSIONS: We observed significant heterogeneity in HIV/STI prevalence and preventative behaviors among the partners of TNB people. Given that TNB people are diverse in their sexual partnerships, there is a need to better understand individual-, dyad-, and structural-level factors that facilitate HIV/STI prevention across these diverse partnerships.},
}
@article {pmid36878897,
year = {2023},
author = {Sagawa, ZK and Goman, C and Frevol, A and Blazevic, A and Tennant, J and Fisher, B and Day, T and Jackson, S and Lemiale, F and Toussaint, L and Kalisz, I and Jiang, J and Ondrejcek, L and Mohamath, R and Vergara, J and Lew, A and Beckmann, AM and Casper, C and Hoft, DF and Fox, CB},
title = {Safety and immunogenicity of a thermostable ID93 + GLA-SE tuberculosis vaccine candidate in healthy adults.},
journal = {Nature communications},
volume = {14},
number = {1},
pages = {1138},
pmid = {36878897},
issn = {2041-1723},
support = {HHSN272201400041C/AI/NIAID NIH HHS/United States ; },
mesh = {Humans ; Adult ; *Tuberculosis Vaccines/adverse effects ; Leukocytes, Mononuclear ; Antibodies ; Adjuvants, Immunologic ; Antibody-Producing Cells ; },
abstract = {Adjuvant-containing subunit vaccines represent a promising approach for protection against tuberculosis (TB), but current candidates require refrigerated storage. Here we present results from a randomized, double-blinded Phase 1 clinical trial (NCT03722472) evaluating the safety, tolerability, and immunogenicity of a thermostable lyophilized single-vial presentation of the ID93 + GLA-SE vaccine candidate compared to the non-thermostable two-vial vaccine presentation in healthy adults. Participants were monitored for primary, secondary, and exploratory endpoints following intramuscular administration of two vaccine doses 56 days apart. Primary endpoints included local and systemic reactogenicity and adverse events. Secondary endpoints included antigen-specific antibody (IgG) and cellular immune responses (cytokine-producing peripheral blood mononuclear cells and T cells). Both vaccine presentations are safe and well tolerated and elicit robust antigen-specific serum antibody and Th1-type cellular immune responses. Compared to the non-thermostable presentation, the thermostable vaccine formulation generates greater serum antibody responses (p < 0.05) and more antibody-secreting cells (p < 0.05). In this work, we show the thermostable ID93 + GLA-SE vaccine candidate is safe and immunogenic in healthy adults.},
}
@article {pmid36878433,
year = {2023},
author = {Larson, JH and Jin, S and Loschi, M and Wagers, SB and Thangavelu, G and Zaiken, MC and McDonald-Hyman, C and Saha, A and Aguilar, EG and Koehn, B and Osborn, MJ and Panoskaltsis-Mortari, A and Macdonald, KPA and Hill, GR and Murphy, WJ and Serody, JS and Maillard, I and Kean, LS and Kim, SV and Littman, DR and Blazar, BR},
title = {Enforced gut homing of murine regulatory T cells reduces early graft-versus-host disease severity.},
journal = {American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.ajt.2023.01.030},
pmid = {36878433},
issn = {1600-6143},
abstract = {Damage to the gastrointestinal tract following allogeneic hematopoietic stem cell transplantation is a significant contributor to the severity and perpetuation of graft-versus-host disease. In preclinical models and clinical trials, we showed that infusing high numbers of regulatory T-cells reduces graft-versus-host disease incidence. Despite no change in in vitro suppressive function, transfer of ex vivo expanded regulatory T-cells transduced to overexpress G-protein coupled receptor 15 or C-C Motif Chemokine Receptor 9, specific homing receptors for colon or small intestine, respectively, lessened graft-versus-host disease severity in mice. Increased regulatory T-cell frequency and retention within the gastrointestinal tissues of mice that received gut homing T-cells correlated with lower inflammation and gut damage early post-transplant, decreased graft-versus-host disease severity and prolonged survival compared to those receiving control transduced regulatory T-cells. These data provide evidence that enforced targeting of ex vivo expanded regulatory T-cells to the gastrointestinal tract diminishes gut injury and is associated with decreased graft-versus-host disease severity.},
}
@article {pmid36877894,
year = {2023},
author = {Yao, Y and Fong Ng, J and Park, WD and Samur, MK and Morelli, E and Encinas, J and Chyra, Z and Xu, Y and Derebail, S and Epstein, CB and Nabet, B and Chesi, M and Gray, NS and Young, R and Kwiatkowski, N and Mitsiades, CS and Anderson, KC and Lin, CY and Munshi, NC and Fulciniti, M},
title = {CDK7 controls E2F- and MYC-driven proliferative and metabolic vulnerabilities in multiple myeloma.},
journal = {Blood},
volume = {},
number = {},
pages = {},
doi = {10.1182/blood.2022018885},
pmid = {36877894},
issn = {1528-0020},
abstract = {Therapeutic targeting of CDK7 has proven beneficial in pre-clinical studies, yet the off-target effects of currently available CDK7 inhibitors make it difficult to pinpoint the exact mechanisms behind MM cell death mediated by CDK7 inhibition. Here, we show that CDK7 expression positively correlates with E2F and MYC transcriptional programs in multiple myeloma (MM) patient cells; and its selective targeting counteracts E2F activity via perturbation of the CDKs/Rb axis and impairs MYC-regulated metabolic gene signatures translating into defects in glycolysis and reduced levels of lactate production in MM cells. CDK7 inhibition using the covalent small molecule inhibitor YKL-5-124 elicits a strong therapeutic response with minimal effects on normal cells, and causes in vivo tumor regression increasing survival in several MM mouse models including a genetically engineered mouse model of MYC-dependent MM. Through its role as a critical cofactor and regulator of MYC and E2F activity, CDK7 is therefore a master regulator of oncogenic cellular programs supporting MM growth and survival, and a valuable therapeutic target providing rationale for development of YKL-5-124 for clinical use.},
}
@article {pmid36877661,
year = {2023},
author = {Barata, A and Abrams, HR and Meyer, CL and Mau, LW and Mattila, D and Burns, LJ and Ullrich, CK and Murthy, HS and Wood, WA and Petersdorf, EW and LeBlanc, TW and El-Jawahri, A},
title = {What Do Patients Think about Palliative Care? A National Survey of Hematopoietic Stem Cell Transplant Recipients.},
journal = {Blood advances},
volume = {},
number = {},
pages = {},
doi = {10.1182/bloodadvances.2023009712},
pmid = {36877661},
issn = {2473-9537},
abstract = {Palliative care (PC) benefits patients undergoing hematopoietic stem cell transplantation (HSCT) but remains under-utilized. Whereas transplant physicians report concerns regarding how patients perceive PC, HSCT recipients' perceptions about PC remain unaddressed. We conducted a multi-site cross-sectional survey of autologous and allogeneic HSCT recipients 3-12 months post-transplant to assess their familiarity, knowledge, and perception of PC, as well as their unmet PC needs. We computed a composite score of patients' perceptions of PC and used a generalized linear regression model to examine factors associated with these perceptions. We enrolled 69.6% (250/359) of potential participants (Median age = 58.1; 63.1% autologous HSCT). Overall, 44.3.8% (109/249) reported limited knowledge about PC and 52% (127/245) endorsed familiarity with PC. Most patients felt hopeful (54%) and reassured (50%) when they heard the term PC; 83% saw referral as a sign their doctor cared about what was happening to them. In multivariate analyses, patients who were more knowledgeable about PC were more likely to have positive perceptions of PC (B = 7.54, SE=1.61, P < 0.001). Patients' demographics, HSCT features, quality of life, and symptom burden were not significantly associated with perceptions of PC. HSCT recipients have positive perceptions of PC, though many have limited knowledge about its role. Patients who were more knowledgeable about PC were more likely to have positive perceptions of PC. These data do not support transplant physicians' negative concerns about how patients perceive PC and underscore the need to further educate patients and transplant physicians about PC.},
}
@article {pmid36877518,
year = {2023},
author = {Santos, LG and Buzdnitskaya, T and Rolf, BA and Souza, W and Sienko, M and Ruiz-Bonilla, JA and Shah, B and Jewell, P and Jensen, L and Horike-Pyne, M and Elrod, JA and Crews, J and Laurino, M and Weeks, KA and Dubard-Gault, ME},
title = {Assessment of a Peer Physician Coaching Partnership Between a Designated Cancer Center Genetics Service and a Community Cancer Network Hospital.},
journal = {JAMA network open},
volume = {6},
number = {3},
pages = {e231723},
pmid = {36877518},
issn = {2574-3805},
mesh = {Male ; Humans ; Female ; Aged ; Community Networks ; *Mentoring ; Prospective Studies ; Precision Medicine ; Genetic Services ; Hospitals, Community ; *Pancreatic Neoplasms ; *Physicians ; *Ovarian Neoplasms ; },
abstract = {BACKGROUND: Patients with cancer seen in rural and underserved areas disproportionately face barriers to access genetic services. Genetic testing is critical to inform treatment decisions, for early detection of another cancer, and to identify at-risk family members who may benefit from screening and prevention.<br><br>OBJECTIVE: To examine medical oncologists' genetic testing ordering trends for patients with cancer.<br><br>This prospective quality improvement study was performed in 2 phases over 6 months between August 1, 2020, and January 31, 2021, at a community network hospital. Phase 1 focused on observation of clinic processes. Phase 2 incorporated peer coaching from cancer genetics experts for medical oncologists at the community network hospital. The follow-up period lasted 9 months.<br><br>MAIN OUTCOMES AND MEASURES: The number of genetic tests ordered was compared between phases.<br><br>RESULTS: The study included 634 patients (mean [SD] age, 71.0 [10.8] years [range, 39-90 years]; 409 women [64.5%]; 585 White [92.3%]); 353 (55.7%) had breast cancer, 184 (29.0%) had prostate cancer, and 218 (34.4%) had a family history of cancer. Of the 634 patients with cancer, 29 of 415 (7.0%) received genetic testing in phase 1, and 25 of 219 (11.4%) received genetic testing in phase 2. Of the 29 patients who received testing in phase 1, 20 (69.0%) had germline genetic testing; 23 of 25 patients (92.0%) had germline genetic testing in phase 2. Uptake of germline genetic testing increased by 23.0% between phases, but the difference was not statistically significant (P&#x2009;=&#x2009;.06). Uptake of germline genetic testing was highest among patients with pancreatic cancer (4 of 19 [21.1%]) and ovarian cancer (6 of 35 [17.1%]); the National Comprehensive Cancer Network (NCCN) recommends offering genetic testing to all patients with pancreatic cancer and ovarian cancer.<br><br>CONCLUSIONS AND RELEVANCE: This study suggests that peer coaching from cancer genetics experts was associated with an increase in ordering of genetic testing by medical oncologists. Efforts made to (1) standardize gathering of personal and family history of cancer, (2) review biomarker data suggestive of a hereditary cancer syndrome, (3) facilitate ordering tumor and/or germline genetic testing every time NCCN criteria are met, (4) encourage data sharing between institutions, and (5) advocate for universal coverage for genetic testing may help realize the benefits associated with precision oncology for patients and their families seeking care at community cancer centers.},
}
@article {pmid36877164,
year = {2023},
author = {Li, M and Liu, M and Han, W and Wang, Z and Han, D and Patalano, S and Macoska, JA and Balk, SP and He, HH and Corey, E and Gao, S and Cai, C},
title = {LSD1 inhibition disrupts super-enhancer driven oncogenic transcriptional programs in castration-resistant prostate cancer.},
journal = {Cancer research},
volume = {},
number = {},
pages = {},
doi = {10.1158/0008-5472.CAN-22-2433},
pmid = {36877164},
issn = {1538-7445},
abstract = {The lysine demethylase LSD1 (also called KDM1A) plays important roles in promoting multiple malignancies including both hematologic cancers and solid tumors. LSD1 targets histone and non-histone proteins and can function as a transcriptional corepressor and coactivator. LSD1 has been reported to act as a coactivator of androgen receptor (AR) in prostate cancer (PCa) and to regulate the AR cistrome via demethylation of its pioneer factor FOXA1. A deeper understanding of the key oncogenic programs targeted by LSD1 could help stratify PCa patients for treatment with LSD1 inhibitors, which are currently under clinical investigation. In this study, we performed transcriptomic profiling in an array of castration-resistant PCa (CRPC) xenograft models that are sensitive to LSD1 inhibitor treatment. Impaired tumor growth by LSD1 inhibition was attributed to significantly decreased MYC signaling, and MYC was found to be a consistent target of LSD1. Moreover, LSD1 formed a network with BRD4 and FOXA1 and was enriched at super-enhancer (SE) regions exhibiting liquid-liquid phase separation. Combining LSD1 inhibitors with BET inhibitors exhibited strong synergy in disrupting the activities of multiple drivers in CRPC, thereby inducing significant growth repression of tumors. Importantly, the combination treatment showed superior effects than either inhibitor alone in disrupting a subset of newly identified CRPC-specific SEs. These results provide mechanistic and therapeutic insights for co-targeting two key epigenetic factors and could be rapidly translated in the clinic for CRPC patients.},
}
@article {pmid36876486,
year = {2023},
author = {Grivas, P and Veeranki, P and Chiu, K and Pawar, V and Chang, J and Bharmal, M},
title = {Preferences for first-line treatment of advanced urothelial carcinoma among US practicing oncologists and patients.},
journal = {Future oncology (London, England)},
volume = {},
number = {},
pages = {},
doi = {10.2217/fon-2022-0767},
pmid = {36876486},
issn = {1744-8301},
abstract = {Aim: Investigate oncologist and patient preferences for the first-line treatment of advanced urothelial carcinoma. Materials &amp; methods: A discrete-choice experiment was used to elicit treatment attribute preferences, including patient treatment experience (number and duration of treatments and grade 3/4 treatment-related adverse events), overall survival and treatment administration frequency. Results: The study included 151 eligible medical oncologists and 150 patients with urothelial carcinoma. Both physicians and patients appeared to prefer treatment attributes related to overall survival, treatment-related adverse events and the number and duration of the medications in a regimen over frequency of administration. Overall survival had the most influence in driving oncologists' treatment preferences, followed by the patient's treatment experience. Patients found the treatment experience the most important attribute when considering options, followed by overall survival. Conclusion: Patient preferences were based on treatment experience, while oncologists preferred treatments that prolong overall survival. These results help to direct clinical conversations, treatment recommendations and clinical guideline development.},
}
@article {pmid36875691,
year = {2023},
author = {VoPham, T and Jones, RR},
title = {State of the science on outdoor air pollution exposure and liver cancer risk.},
journal = {Environmental advances},
volume = {11},
number = {},
pages = {},
pmid = {36875691},
issn = {2666-7657},
support = {K01 DK125612/DK/NIDDK NIH HHS/United States ; L30 ES027668/ES/NIEHS NIH HHS/United States ; },
abstract = {BACKGROUND: There is emerging evidence that air pollution exposure increases the risk of developing liver cancer. To date, there have been four epidemiologic studies conducted in the United States, Taiwan, and Europe showing generally consistent positive associations between ambient exposure to air pollutants, including particulate matter <2.5 μm in aerodynamic diameter (PM2.5) and nitrogen dioxide (NO2), and liver cancer risk. There are several research gaps and thus valuable opportunities for future work to continue building on this expanding body of literature. The objectives of this paper are to narratively synthesize existing epidemiologic literature on the association between air pollution exposure and liver cancer incidence and describe future research directions to advance the science of understanding the role of air pollution exposure in liver cancer development.<br><br>FUTURE RESEARCH DIRECTIONS: include 1) accounting for potential confounding by established risk factors for the predominant histological subtype, hepatocellular carcinoma (HCC); 2) examination of incident primary liver cancer outcomes with consideration of potential differential associations according to histology; 3) air pollution exposure assessments considering early-life and/or historical exposures, residential histories, residual confounding from other sources of air pollution (e.g., tobacco smoking), and integration of geospatial ambient exposure modeling with novel biomarker technologies; 4) examination of air pollution mixtures experienced in the exposome; 5) consideration of increased opportunities for exposure to outdoor air pollution due to climate change (e.g., wildfires); and 6) consideration of modifying factors for air pollution exposure, such as socioeconomic status, that may contribute to disparities in liver cancer incidence.<br><br>CONCLUSIONS: In light of mounting evidence demonstrating that higher levels of air pollution exposure increase the risk for developing liver cancer, methodological considerations primarily concerning residual confounding and improved exposure assessment are warranted to robustly demonstrate an independent association for air pollution as a hepatocarcinogen.},
}
@article {pmid36874241,
year = {2023},
author = {Radtke, S},
title = {The unknown impact of conditioning on HSC engraftment and clonal dynamics.},
journal = {Molecular therapy. Methods &amp; clinical development},
volume = {28},
number = {},
pages = {385-386},
pmid = {36874241},
issn = {2329-0501},
}
@article {pmid36874058,
year = {2023},
author = {Ghezelayagh, TS and Wu, ES and Barber, EL and Dao, MD and Zsiros, E and Urban, RR and Gray, HJ and Goff, BA and Shah, CA and Neubauer, NL and Dai, JY and Tanyi, JL and Liao, JB},
title = {Timing and duration of bevacizumab treatment and survival in patients with recurrent ovarian, fallopian tube, and peritoneal cancer: a multi-institution study.},
journal = {European journal of gynaecological oncology},
volume = {44},
number = {1},
pages = {17-25},
pmid = {36874058},
issn = {0392-2936},
abstract = {Bevacizumab has demonstrated significant benefit in recurrent ovarian, fallopian tube and peritoneal cancer (OC), but its optimal position within the sequence of systemic therapies remains controversial. Since rebound progression after bevacizumab has been observed in other cancers, and because bevacizumab is incorporated in several regimens used in the recurrent setting, the duration of treatment may impact survival. We sought to identify whether earlier bevacizumab exposure is associated with prolonged bevacizumab therapy and survival by conducting a multi-institution retrospective study of recurrent OC patients treated with bevacizumab from 2004-2014. Multivariate logistic regression identified factors associated with receiving more than six bevacizumab cycles. Overall survival by duration and ordinal sequence of bevacizumab therapy were evaluated using logrank testing and Cox regression. In total, 318 patients were identified. 89.1% had stage III or IV disease; 36% had primary platinum resistance; 40.5% received two or fewer prior chemotherapy regimens. Multivariate logistic regression demonstrated that primary platinum sensitivity (Odds Ratio (OR) 2.34, p = 0.001) or initiating bevacizumab at the first or second recurrence (OR 2.73, p < 0.001) were independently associated with receiving more than six cycles of bevacizumab. Receiving more cycles of bevacizumab was associated with improved overall survival whether measured from time of diagnosis (logrank p < 0.001), bevacizumab initiation (logrank p < 0.001), or bevacizumab discontinuation (logrank p = 0.017). Waiting one additional recurrence to initiate bevacizumab resulted in a 27% increased hazard of death (Hazard Ratio (HR) 1.27, p < 0.001) by multivariate analysis. In conclusion, patients with primary platinum sensitive disease who received fewer prior lines of chemotherapy were able to receive more cycles of bevacizumab, which was associated with improved overall survival. Survival worsened when bevacizumab was initiated later in the ordinal sequence of therapies.},
}
@article {pmid36872133,
year = {2023},
author = {Chen, F and Madduri, RK and Rodriguez, AA and Darst, BF and Chou, A and Sheng, X and Wang, A and Shen, J and Saunders, EJ and Rhie, SK and Bensen, JT and Ingles, SA and Kittles, RA and Strom, SS and Rybicki, BA and Nemesure, B and Isaacs, WB and Stanford, JL and Zheng, W and Sanderson, M and John, EM and Park, JY and Xu, J and Wang, Y and Berndt, SI and Huff, CD and Yeboah, ED and Tettey, Y and Lachance, J and Tang, W and Rentsch, CT and Cho, K and Mcmahon, BH and Biritwum, RB and Adjei, AA and Tay, E and Truelove, A and Niwa, S and Sellers, TA and Yamoah, K and Murphy, AB and Crawford, DC and Patel, AV and Bush, WS and Aldrich, MC and Cussenot, O and Petrovics, G and Cullen, J and Neslund-Dudas, CM and Stern, MC and Kote-Jarai, Z and Govindasami, K and Cook, MB and Chokkalingam, AP and Hsing, AW and Goodman, PJ and Hoffmann, TJ and Drake, BF and Hu, JJ and Keaton, JM and Hellwege, JN and Clark, PE and Jalloh, M and Gueye, SM and Niang, L and Ogunbiyi, O and Idowu, MO and Popoola, O and Adebiyi, AO and Aisuodionoe-Shadrach, OI and Ajibola, HO and Jamda, MA and Oluwole, OP and Nwegbu, M and Adusei, B and Mante, S and Darkwa-Abrahams, A and Mensah, JE and Diop, H and Van Den Eeden, SK and Blanchet, P and Fowke, JH and Casey, G and Hennis, AJ and Lubwama, A and Thompson, IM and Leach, R and Easton, DF and Preuss, MH and Loos, RJ and Gundell, SM and Wan, P and Mohler, JL and Fontham, ET and Smith, GJ and Taylor, JA and Srivastava, S and Eeles, RA and Carpten, JD and Kibel, AS and Multigner, L and Parent, M&#xc9; and Menegaux, F and Cancel-Tassin, G and Klein, EA and Andrews, C and Rebbeck, TR and Brureau, L and Ambs, S and Edwards, TL and Watya, S and Chanock, SJ and Witte, JS and Blot, WJ and Michael Gaziano, J and Justice, AC and Conti, DV and Haiman, CA},
title = {Evidence of Novel Susceptibility Variants for Prostate Cancer and a Multiancestry Polygenic Risk Score Associated with Aggressive Disease in Men of African Ancestry.},
journal = {European urology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.eururo.2023.01.022},
pmid = {36872133},
issn = {1873-7560},
abstract = {BACKGROUND: Genetic factors play an important role in prostate cancer (PCa) susceptibility.<br><br>OBJECTIVE: To discover common genetic variants contributing to the risk of PCa in men of African ancestry.<br><br>We conducted a meta-analysis of ten genome-wide association studies consisting of 19378 cases and 61620 controls of African ancestry.<br><br>Common genotyped and imputed variants were tested for their association with PCa risk. Novel susceptibility loci were identified and incorporated into a multiancestry polygenic risk score (PRS). The PRS was evaluated for associations with PCa risk and disease aggressiveness.<br><br>RESULTS AND LIMITATIONS: Nine novel susceptibility loci for PCa were identified, of which seven were only found or substantially more common in men of African ancestry, including an African-specific stop-gain variant in the prostate-specific gene anoctamin 7 (ANO7). A multiancestry PRS of 278 risk variants conferred strong associations with PCa risk in African ancestry studies (odds ratios [ORs] >3 and >5 for men in the top PRS decile and percentile, respectively). More importantly, compared with men in the 40-60% PRS category, men in the top PRS decile had a significantly higher risk of aggressive PCa (OR = 1.23, 95% confidence interval = 1.10-1.38, p = 4.4 &#xd7; 10[-4]).<br><br>CONCLUSIONS: This study demonstrates the importance of large-scale genetic studies in men of African ancestry for a better understanding of PCa susceptibility in this high-risk population and suggests a potential clinical utility of PRS in differentiating between the risks of developing aggressive and nonaggressive disease in men of African ancestry.<br><br>PATIENT SUMMARY: In this large genetic study in men of African ancestry, we discovered nine novel prostate cancer (PCa) risk variants. We also showed that a multiancestry polygenic risk score was effective in stratifying PCa risk, and was able to differentiate risk of aggressive and nonaggressive disease.},
}
@article {pmid36872018,
year = {2023},
author = {Peters, BA and Xing, J and Chen, GC and Usyk, M and Wang, Z and McClain, AC and Thyagarajan, B and Daviglus, ML and Sotres-Alvarez, D and Hu, FB and Knight, R and Burk, RD and Kaplan, RC and Qi, Q},
title = {Healthy dietary patterns are associated with the gut microbiome in the Hispanic Community Health Study/Study of Latinos.},
journal = {The American journal of clinical nutrition},
volume = {117},
number = {3},
pages = {540-552},
doi = {10.1016/j.ajcnut.2022.11.020},
pmid = {36872018},
issn = {1938-3207},
abstract = {BACKGROUND: Dietary patterns high in healthy minimally processed plant foods play an important role in modulating the gut microbiome and promoting cardiometabolic health. Little is known on the diet-gut microbiome relationship in US Hispanics/Latinos, who have a high burden of obesity and diabetes.<br><br>OBJECTIVE: In a cross-sectional analysis, we sought to examine the relationships of 3 healthy dietary patterns-the alternate Mediterranean diet (aMED), the Healthy Eating Index (HEI)-2015, and the healthful plant-based diet index (hPDI)-with the gut microbiome in US Hispanic/Latino adults, and to study the association of diet-related species with cardiometabolic traits.<br><br>METHODS: The Hispanic Community Health Study/Study of Latinos is a multi-site community-based cohort. At baseline (2008-2011), diet was assessed by using 2, 24-hour recalls. Shotgun sequencing was performed on stool samples collected in 2014-17 (n = 2444). Analysis of Compositions of Microbiomes 2 (ANCOM2) was used to identify the associations of dietary pattern scores with gut microbiome species and functions, adjusting for sociodemographic, behavioral, and clinical covariates.<br><br>RESULTS: Better diet quality according to multiple healthy dietary patterns was associated with a higher abundance of species from class Clostridia, including [Eubacterium] eligens, Butyrivibrio crossotus, and Lachnospiraceae bacterium TF01-11, but functions related to better diet quality differed for the dietary patterns (e.g., aMED with pyruvate:ferredoxin oxidoreductase, hPDI with L-arabinose/lactose transport). Poorer diet quality was associated with a higher abundance of Acidaminococcus intestini and with functions of manganese/iron transport, adhesin protein transport, and nitrate reduction. Some healthy diet pattern-enriched Clostridia species were related to more favorable cardiometabolic traits such as lower triglycerides and waist-to-hip ratio.<br><br>CONCLUSIONS: Healthy dietary patterns in this population are associated with a higher abundance of fiber-fermenting Clostridia species in the gut microbiome, consistent with previous studies in other racial/ethnic groups. Gut microbiota may be involved in the beneficial effect of higher diet quality on cardiometabolic disease risk.},
}
@article {pmid36871221,
year = {2023},
author = {Rajendran, S and Hu, Y and Canella, A and Peterson, C and Gross, A and Cam, M and Nazzaro, M and Haffey, A and Serin-Harmanci, A and Distefano, R and Nigita, G and Wang, W and Kreatsoulas, D and Li, Z and Sepeda, JA and Sas, A and Hester, ME and Miller, KE and Elemento, O and Roberts, RD and Holland, EC and Rao, G and Mardis, ER and Rajappa, P},
title = {Single-cell RNA sequencing reveals immunosuppressive myeloid cell diversity during malignant progression in a murine model of glioma.},
journal = {Cell reports},
volume = {42},
number = {3},
pages = {112197},
doi = {10.1016/j.celrep.2023.112197},
pmid = {36871221},
issn = {2211-1247},
abstract = {Recent studies have shown the importance of the dynamic tumor microenvironment (TME) in high-grade gliomas (HGGs). In particular, myeloid cells are known to mediate immunosuppression in glioma; however, it is still unclear if myeloid cells play a role in low-grade glioma (LGG) malignant progression. Here, we investigate the cellular heterogeneity of the TME using single-cell RNA sequencing in a murine glioma model that recapitulates the malignant progression of LGG to HGG. LGGs show increased infiltrating CD4[+] and CD8[+] T cells and natural killer (NK) cells in the TME, whereas HGGs abrogate this infiltration. Our study identifies distinct macrophage clusters in the TME that show an immune-activated phenotype in LGG but then evolve to an immunosuppressive state in HGG. We identify CD74 and macrophage migration inhibition factor (MIF) as potential targets for these distinct macrophage populations. Targeting these intra-tumoral macrophages in the LGG stage may attenuate their immunosuppressive properties and impair malignant progression.},
}
@article {pmid36870388,
year = {2023},
author = {Chakraborty, R and Yi, J and Rybicki, L and Preussler, J and Deol, A and Loren, A and Savani, B and Jim, HSL and Cerny, J and Reynolds, J and Whitten, J and Wingard, JR and McGuirk, JP and Uberti, J and Khera, N and Stiff, P and Jaglowski, SM and Hashmi, S and Holtan, SG and Devine, S and Hahn, T and Whalen, VL and Saber, W and Wood, W and Baker, KS and Syrjala, K and Majhail, NS},
title = {Patient-Reported Outcomes in Long-Term Survivors of Autologous Hematopoietic Cell Transplantation in Multiple Myeloma.},
journal = {Transplantation and cellular therapy},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jtct.2023.02.011},
pmid = {36870388},
issn = {2666-6367},
abstract = {BACKGROUND: The overall survival in patients with transplant-eligible multiple myeloma has tripled in the past two decades, leading to a growing population of myeloma survivors. However, there is a paucity of data on health-related quality of life (HRQoL), distress, and health behaviors in long-term myeloma survivors who are in stable remission after autologous hematopoietic cell transplantation (AHCT).<br><br>METHODS: This is a cross-sectional study using data from two randomized controlled trials of survivorship care plans and internet based self-management intervention in transplant survivors. The primary objective of this study was to measure HRQoL (SF12v2), distress, and health behaviors of myeloma survivors in stable remission after AHCT. Distress were measured by Cancer and Treatment Related Distress (CTXD) instrument.<br><br>FINDINGS: A total of 345 patients at a median of 4 years (range, 1.4-11) post-AHCT were included. The mean Physical Component Summary (PCS) and Mental Component Summary (MCS) score was 45.5 (&#xb1;10.5) and 51.3 (&#xb1;10.1) respectively, compared to US population norm of 50 (&#xb1;10) (p<0.001 and p=0.021 for PCS and MCS comparisons, respectively), with neither reaching the threshold for minimal clinically important difference (5) Approximately one-third of patients had clinically significant distress based on CTXD total score, with the following proportion of patients reporting distress at each domain: Health Burden (53%), Uncertainty (46%), Finances (33%), Family Strain (31%), Identity (21%), and Medical Demands (15%). Preventative care guidelines were met by 81% of myeloma survivors. However, adherence to exercise and diet guideline were relatively low at 33% and 13% respectively.<br><br>INTERPRETATION: Myeloma AHCT survivors in stable remission have no clinically meaningful worsening in physical functioning compared to general population.. Survivorship programs should address ongoing distress due to health burden, uncertainty, and finances in myeloma survivors, along with targeted interventions for modifiable health behaviors such as nutrition and exercise.},
}
@article {pmid36870037,
year = {2023},
author = {Marchak, JG and Sadak, KT and Effinger, KE and Haardörfer, R and Escoffery, C and Kinahan, KE and Freyer, DR and Chow, EJ and Mertens, A},
title = {Transition practices for survivors of childhood cancer: a report from the Children's Oncology Group.},
journal = {Journal of cancer survivorship : research and practice},
volume = {},
number = {},
pages = {},
pmid = {36870037},
issn = {1932-2267},
abstract = {PURPOSE: Pediatric healthcare systems must support childhood cancer survivors to optimize their transition to adult care. This study aimed to assess the state of healthcare transition services provided by Children's Oncology Group (COG) institutions.<br><br>METHODS: A 190-question online survey was distributed to 209 COG institutions to assess survivor services, including transition practices, barriers, and implementation of services aligned with the six core elements of Health Care Transition 2.0 from the US Center for Health Care Transition Improvement.<br><br>RESULTS: Representatives from 137 COG sites reported on institutional transition practices. Two-thirds (66.4%) of site discharge survivors to another institution for cancer-related follow-up care in adulthood. Transfer to primary care (33.6%) was a commonly reported model of care for young adult-aged survivors. Site transfer at &#x2264; 18 years (8.0%), &#x2264; 21 years (13.1%), &#x2264; 25 years (7.3%), &#x2265; 26 years (12.4%), or when survivors are "ready" (25.5%). Few institutions reported offering services aligned with the structured transition process from the six core elements (Median = 1, Mean = 1.56, SD = 1.54, range: 0-5). The most prevalent barriers to transitioning survivors to adult care were perceived lack of late-effects knowledge among clinicians (39.6%) and perceived lack of survivor desire to transfer care (31.9%).<br><br>CONCLUSIONS: Most COG institutions transfer adult-aged survivors of childhood cancer elsewhere for survivor care, yet few programs report delivering recognized standards for quality healthcare transition programming to support survivors.<br><br>Development of best practices for survivor transition is needed to help promote increased early detection and treatment of late effects among adult survivors of childhood cancer.},
}
@article {pmid36868218,
year = {2023},
author = {Dadonaite, B and Crawford, KHD and Radford, CE and Farrell, AG and Yu, TC and Hannon, WW and Zhou, P and Andrabi, R and Burton, DR and Liu, L and Ho, DD and Chu, HY and Neher, RA and Bloom, JD},
title = {A pseudovirus system enables deep mutational scanning of the full SARS-CoV-2 spike.},
journal = {Cell},
volume = {},
number = {},
pages = {},
pmid = {36868218},
issn = {1097-4172},
abstract = {A major challenge in understanding SARS-CoV-2 evolution is interpreting the antigenic and functional effects of emerging mutations in the viral spike protein. Here, we describe a deep mutational scanning platform based on non-replicative pseudotyped lentiviruses that directly quantifies how large numbers of spike mutations impact antibody neutralization and pseudovirus infection. We apply this platform to produce libraries of the Omicron BA.1 and Delta spikes. These libraries each contain ∼7,000 distinct amino acid mutations in the context of up to ∼135,000 unique mutation combinations. We use these libraries to map escape mutations from neutralizing antibodies targeting the receptor-binding domain, N-terminal domain, and S2 subunit of spike. Overall, this work establishes a high-throughput and safe approach to measure how ∼10[5] combinations of mutations affect antibody neutralization and spike-mediated infection. Notably, the platform described here can be extended to the entry proteins of many other viruses.},
}
@article {pmid36867911,
year = {2023},
author = {Saini, J and Maes, D and Regmi, R and Fung, A and Bloch, C and Schwarz, M and Stacey, A and Chen, J and Rengan, R and Halasz, L},
title = {Improved lateral penumbra for proton ocular treatments on a general-purpose spot scanning beamline.},
journal = {Physica medica : PM : an international journal devoted to the applications of physics to medicine and biology : official journal of the Italian Association of Biomedical Physics (AIFB)},
volume = {107},
number = {},
pages = {102551},
doi = {10.1016/j.ejmp.2023.102551},
pmid = {36867911},
issn = {1724-191X},
abstract = {PURPOSE: An ocular applicator that fits a commercial proton snout with an upstream range shifter to allow for treatments with sharp lateral penumbra is described.<br><br>MATERIALS AND METHODS: The validation of the ocular applicator consisted of a comparison of range, depth doses (Bragg peaks and spread out Bragg peaks), point doses, and 2-D lateral profiles. Measurements were made for three field sizes, 1.5, 2, and 3&#xa0;cm, resulting in 15 beams. Distal and lateral penumbras were simulated in the treatment planning system for seven range-modulation combinations for beams typical of ocular treatments and a field size of 1.5&#xa0;cm, and penumbra values were compared to published literature.<br><br>RESULTS: All the range errors were within 0.5&#xa0;mm. The maximum averaged local dose differences for Bragg peaks and SOBPs were 2.6% and 1.1%, respectively. All the 30 measured point doses were within +/-3% of the calculated. The measured lateral profiles, analyzed through gamma index analysis and compared to the simulated, had pass rates&#xa0;greater than&#xa0;96% for all the planes. The lateral penumbra increased linearly with depth, from 1.4&#xa0;mm at 1&#xa0;cm depth to 2.5&#xa0;mm at 4&#xa0;cm depth. The distal penumbra ranged from 3.6 to 4.4&#xa0;mm and increased linearly with the range. The treatment time for a single 10&#xa0;Gy (RBE) fractional dose ranged from 30 to 120&#xa0;s, depending on the shape and size of the target.<br><br>CONCLUSIONS: The ocular applicator's modified design allows lateral penumbra similar to dedicated ocular beamlines while enabling planners to use modern treatment tools such as Monte Carlo and full CT-based planning with increased flexibility in beam placement.},
}
@article {pmid36649143,
year = {2023},
author = {Zouiouich, S and Byrd, DA and Hua, X and Karwa, S and Wan, Y and Shi, J and Humphrey, GC and Ackermann, GL and Knight, R and Abnet, CC and Vogtmann, E and Sinha, R},
title = {Stability of the Fecal and Oral Microbiome over 2 Years at -80°C for Multiple Collection Methods.},
journal = {Cancer epidemiology, biomarkers &amp; prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology},
volume = {32},
number = {3},
pages = {444-451},
doi = {10.1158/1055-9965.EPI-22-0883},
pmid = {36649143},
issn = {1538-7755},
abstract = {BACKGROUND: In prospective cohorts, biological samples are generally stored over long periods before an adequate number of cases have accrued. We investigated the impact of sample storage at -80°C for 2 years on the stability of the V4 region of the 16S rRNA gene across seven different collection methods (i.e., no additive, 95% ethanol, RNAlater stabilization solution, fecal occult blood test cards, and fecal immunochemical test tubes for feces; OMNIgene ORAL tubes and Scope mouthwash for saliva) among 51 healthy volunteers.<br><br>METHODS: Intraclass correlation coefficients (ICC) were calculated for the relative abundance of the top three phyla, the 20 most abundant genera, three alpha-diversity metrics, and the first principal coordinates of three beta-diversity matrices.<br><br>RESULTS: The subject variability was much higher than the variability introduced by the sample collection type, and storage time. For fecal samples, microbial stability over 2 years was high across collection methods (range, ICCs = 0.70-0.99), except for the samples collected with no additive (range, ICCs = 0.23-0.83). For oral samples, most microbiome diversity measures were stable over time with ICCs above 0.74; however, ICCs for the samples collected with Scope mouthwash were lower for two alpha-diversity measures, Faith's phylogenetic diversity (0.23) and the observed number of operational taxonomic units (0.23).<br><br>CONCLUSIONS: Fecal and oral samples in most used collection methods are stable for microbiome analyses after 2 years at -80&#xb0;C, except for fecal samples with no additive.<br><br>IMPACT: This study provides evidence that samples stored for an extended period from prospective studies are useful for microbiome analyses.},
}
@article {pmid36867557,
year = {2023},
author = {Iovino, L and Shadman, M},
title = {CAR T-cell therapy for CLL: a new addition to our treatment toolbox?.},
journal = {Clinical advances in hematology &amp; oncology : H&amp;O},
volume = {21},
number = {3},
pages = {134-141},
pmid = {36867557},
issn = {1543-0790},
abstract = {Treatment of high-risk chronic lymphocytic leukemia (CLL) has undergone a revolution in recent years with the introduction of novel agents. Bruton kinase inhibitors (BTK) inhibitors, such as ibrutinib, acalabrutinib, and zanubrutinib, are effective at controlling CLL in all lines of therapy, including in patients with high-risk features. BTK inhibitors can be used in sequence or in combination with the BCL2 inhibitor venetoclax. As a result, standard chemotherapy and allogeneic stem cell transplant (allo-SCT)-once major treatment approaches in high-risk patients-are used much less commonly in the current era. Despite the outstanding efficacy of these novel agents, a proportion of patients still experience disease progression. Chimeric antigen receptor (CAR) T-cell therapy has received regulatory approval for several B-cell malignancies in which it has shown efficacy, but it remains investigational for CLL. Several studies have shown the potential for long-term remission in CLL with CAR T-cell therapy, with a favorable safety profile compared with conventional approaches. This review focuses on selected literature on CAR T-cell therapy for CLL, including the interim results of key ongoing studies, with an emphasis on recent research.},
}
@article {pmid36865902,
year = {2022},
author = {Ostroff, JS and Banerjee, SC and Lynch, K and Shen, MJ and Williamson, TJ and Haque, N and Riley, K and Hamann, HA and Rigney, M and Park, B},
title = {Reducing stigma triggered by assessing smoking status among patients diagnosed with lung cancer: De-stigmatizing do and don't lessons learned from qualitative interviews.},
journal = {PEC innovation},
volume = {1},
number = {},
pages = {},
pmid = {36865902},
issn = {2772-6282},
support = {R21 CA202793/CA/NCI NIH HHS/United States ; P30 CA008748/CA/NCI NIH HHS/United States ; T32 CA009461/CA/NCI NIH HHS/United States ; K99 CA256351/CA/NCI NIH HHS/United States ; R03 CA193986/CA/NCI NIH HHS/United States ; K07 CA207580/CA/NCI NIH HHS/United States ; P30 CA023074/CA/NCI NIH HHS/United States ; },
abstract = {OBJECTIVE: To characterize lung cancer patients' reactions to cancer care providers' (CCPs) assessment of smoking behavior and to develop recommendations to reduce stigma and improve patient-clinician communication about smoking in the context of lung cancer care.<br><br>METHODS: Semi-structured interviews with 56 lung cancer patients (Study 1) and focus groups with 11 lung cancer patients (Study 2) were conducted and analyzed using thematic content analysis.<br><br>RESULTS: Three broad themes were identified: cursory questions about smoking history and current behavior; stigma triggered by assessment of smoking behavior; and recommended dos and don'ts for CCPs treating patients with lung cancer. CCP communication that contributed to patients' comfort included responding in an empathic manner and using supportive verbal and non-verbal communication skills. Blaming statements, doubting patients' self-reported smoking status, insinuating subpar care, nihilistic statements, and avoidant behaviors contributed to patients' discomfort.<br><br>CONCLUSIONS: Patients often experienced stigma in response to smoking-related discussions with their CCPs and identified several communication strategies that CCPs can use to improve patients' comfort within these clinical encounters.<br><br>INNOVATION: These patient perspectives advance the field by providing specific communication recommendations that CCPs can adopt to mitigate stigma and enhance lung cancer patients' comfort, particularly when taking a routine smoking history.},
}
@article {pmid36865544,
year = {2023},
author = {Wanjalla, CN and Gabriel, CL and Fuseini, H and Bailin, SS and Mashayekhi, M and Simmons, J and Warren, CM and Glass, DR and Oakes, J and Gangula, R and Wilfong, E and Priest, S and Temu, T and Newell, EW and Pakala, S and Kalams, SA and Gianella, S and Smith, D and Harrison, DG and Mallal, SA and Koethe, JR},
title = {CD4[+] T cells expressing CX3CR1, GPR56, with variable CD57 are associated with cardiometabolic diseases in persons with HIV.},
journal = {Frontiers in immunology},
volume = {14},
number = {},
pages = {1099356},
pmid = {36865544},
issn = {1664-3224},
abstract = {Persons with HIV (PWH) on long-term antiretroviral therapy (ART) have a higher incidence and prevalence of cardiometabolic diseases attributed, in part, to persistent inflammation despite viral suppression. In addition to traditional risk factors, immune responses to co-infections such as cytomegalovirus (CMV) may play an unappreciated role in cardiometabolic comorbidities and offer new potential therapeutic targets in a subgroup of individuals. We assessed the relationship of CX3CR1[+], GPR56[+], and CD57[+/-] T cells (termed CGC[+]) with comorbid conditions in a cohort of 134 PWH co-infected with CMV on long-term ART. We found that PWH with cardiometabolic diseases (non-alcoholic fatty liver disease, calcified coronary arteries, or diabetes) had higher circulating CGC[+]CD4[+] T cells compared to metabolically healthy PWH. The traditional risk factor most correlated with CGC[+]CD4[+] T cell frequency was fasting blood glucose, as well as starch/sucrose metabolites. While unstimulated CGC[+]CD4[+] T cells, like other memory T cells, depend on oxidative phosphorylation for energy, they exhibited higher expression of carnitine palmitoyl transferase 1A compared to other CD4[+] T cell subsets, suggesting a potentially greater capacity for fatty acid β-oxidation. Lastly, we show that CMV-specific T cells against multiple viral epitopes are predominantly CGC[+]. Together, this study suggests that among PWH, CGC[+] CD4[+] T cells are frequently CMV-specific and are associated with diabetes, coronary arterial calcium, and non-alcoholic fatty liver disease. Future studies should assess whether anti-CMV therapies could reduce cardiometabolic disease risk in some individuals.},
}
@article {pmid36862969,
year = {2023},
author = {Etzioni, R and Castle, PE},
title = {Shopping for New Cancer Screening Tests.},
journal = {Journal of clinical oncology : official journal of the American Society of Clinical Oncology},
volume = {},
number = {},
pages = {JCO2300240},
doi = {10.1200/JCO.23.00240},
pmid = {36862969},
issn = {1527-7755},
}
@article {pmid36862968,
year = {2023},
author = {Paulson, VA and Liu, YJ and Fang, H and Browd, SR and Hauptman, JS and Wright, J and Lockwood, CM and Leary, SES and Cole, BL},
title = {Infantile ZFTA Fusion-Positive Tumor of the Posterior Fossa: Molecular Tumor Board.},
journal = {JCO precision oncology},
volume = {7},
number = {},
pages = {e2200226},
doi = {10.1200/PO.22.00226},
pmid = {36862968},
issn = {2473-4284},
}
@article {pmid36862437,
year = {2023},
author = {Hill, GR and Koyama, M},
title = {A novel RIPK1 inhibitor attenuates GVHD.},
journal = {Blood},
volume = {141},
number = {9},
pages = {969-970},
doi = {10.1182/blood.2022019019},
pmid = {36862437},
issn = {1528-0020},
}
@article {pmid36860641,
year = {2023},
author = {Layan, M and Müller, NF and Dellicour, S and De Maio, N and Bourhy, H and Cauchemez, S and Baele, G},
title = {Impact and mitigation of sampling bias to determine viral spread: Evaluating discrete phylogeography through CTMC modeling and structured coalescent model approximations.},
journal = {Virus evolution},
volume = {9},
number = {1},
pages = {vead010},
pmid = {36860641},
issn = {2057-1577},
abstract = {Bayesian phylogeographic inference is a powerful tool in molecular epidemiological studies, which enables reconstruction of the origin and subsequent geographic spread of pathogens. Such inference is, however, potentially affected by geographic sampling bias. Here, we investigated the impact of sampling bias on the spatiotemporal reconstruction of viral epidemics using Bayesian discrete phylogeographic models and explored different operational strategies to mitigate this impact. We considered the continuous-time Markov chain (CTMC) model and two structured coalescent approximations (Bayesian structured coalescent approximation [BASTA] and marginal approximation of the structured coalescent [MASCOT]). For each approach, we compared the estimated and simulated spatiotemporal histories in biased and unbiased conditions based on the simulated epidemics of rabies virus (RABV) in dogs in Morocco. While the reconstructed spatiotemporal histories were impacted by sampling bias for the three approaches, BASTA and MASCOT reconstructions were also biased when employing unbiased samples. Increasing the number of analyzed genomes led to more robust estimates at low sampling bias for the CTMC model. Alternative sampling strategies that maximize the spatiotemporal coverage greatly improved the inference at intermediate sampling bias for the CTMC model, and to a lesser extent, for BASTA and MASCOT. In contrast, allowing for time-varying population sizes in MASCOT resulted in robust inference. We further applied these approaches to two empirical datasets: a RABV dataset from the Philippines and a SARS-CoV-2 dataset describing its early spread across the world. In conclusion, sampling biases are ubiquitous in phylogeographic analyses but may be accommodated by increasing the sample size, balancing spatial and temporal composition in the samples, and informing structured coalescent models with reliable case count data.},
}
@article {pmid36860137,
year = {2023},
author = {Herodes, M and Anderson, LJ and Shober, S and Schur, EA and Graf, SA and Ammer, N and Salas, R and Marcelli, M and Garcia, JM},
title = {Pilot clinical trial of macimorelin to assess safety and efficacy in patients with cancer cachexia.},
journal = {Journal of cachexia, sarcopenia and muscle},
volume = {},
number = {},
pages = {},
doi = {10.1002/jcsm.13191},
pmid = {36860137},
issn = {2190-6009},
support = {R01AG061558/NH/NIH HHS/United States ; R01CA239208/NH/NIH HHS/United States ; P30 DK017047/DK/NIDDK NIH HHS/United States ; },
abstract = {BACKGROUND: Cancer cachexia is associated with reduced body weight, appetite and quality of life (QOL) with no approved treatments. Growth hormone secretagogues like macimorelin have potential to mitigate these effects.<br><br>METHODS: This pilot study assessed the safety and efficacy of macimorelin for 1&#xa0;week. Efficacy was defined a priori as 1-week change in body weight (&#x2265;0.8&#xa0;kg), plasma insulin-like growth factor (IGF)-1 (&#x2265;50&#xa0;ng/mL) or QOL (&#x2265;15%). Secondary outcomes included food intake, appetite, functional performance, energy expenditure and safety laboratory parameters. Patients with cancer cachexia were randomized to 0.5 or 1.0&#xa0;mg/kg macimorelin or placebo; outcomes were assessed non-parametrically.<br><br>RESULTS: Participants receiving at least one of either macimorelin dose were combined (N&#xa0;=&#xa0;10; 100% male; median age&#xa0;=&#xa0;65.50&#xa0;&#xb1;&#xa0;2.12) and compared with placebo (N&#xa0;=&#xa0;5; 80% male; median age&#xa0;=&#xa0;68.00&#xa0;&#xb1;&#xa0;6.19). Efficacy criteria achieved: body weight (macimorelin N&#xa0;=&#xa0;2; placebo N&#xa0;=&#xa0;0; P&#xa0;=&#xa0;0.92); IGF-1 (macimorelin N&#xa0;=&#xa0;0; placebo N&#xa0;=&#xa0;0); QOL by Anderson Symptom Assessment Scale (macimorelin N&#xa0;=&#xa0;4; placebo N&#xa0;=&#xa0;1; P&#xa0;=&#xa0;1.00) or Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F; macimorelin N&#xa0;=&#xa0;3; placebo N&#xa0;=&#xa0;0; P&#xa0;=&#xa0;0.50). No related serious or non-serious adverse events were reported. In macimorelin recipients, change in FACIT-F was directly associated with change in body weight (r&#xa0;=&#xa0;0.92, P&#xa0;=&#xa0;0.001), IGF-1 (r&#xa0;=&#xa0;0.80, P&#xa0;=&#xa0;0.01), and caloric intake (r&#xa0;=&#xa0;0.83, P&#xa0;=&#xa0;0.005), and inversely associated with change in energy expenditure (r&#xa0;=&#xa0;-0.67, P&#xa0;=&#xa0;0.05).<br><br>CONCLUSIONS: Daily oral macimorelin for 1&#xa0;week was safe and numerically improved body weight and QOL in patients with cancer cachexia compared with placebo. Longer term administration should be evaluated for mitigation of cancer-induced reductions in body weight, appetite and QOL in larger studies.},
}
@article {pmid36856617,
year = {2023},
author = {Patel, SP and Othus, M and Chen, Y and Wright, GP and Yost, KJ and Hyngstrom, JR and Hu-Lieskovan, S and Lao, CD and Fecher, LA and Truong, TG and Eisenstein, JL and Chandra, S and Sosman, JA and Kendra, KL and Wu, RC and Devoe, CE and Deutsch, GB and Hegde, A and Khalil, M and Mangla, A and Reese, AM and Ross, MI and Poklepovic, AS and Phan, GQ and Onitilo, AA and Yasar, DG and Powers, BC and Doolittle, GC and In, GK and Kokot, N and Gibney, GT and Atkins, MB and Shaheen, M and Warneke, JA and Ikeguchi, A and Najera, JE and Chmielowski, B and Crompton, JG and Floyd, JD and Hsueh, E and Margolin, KA and Chow, WA and Grossmann, KF and Dietrich, E and Prieto, VG and Lowe, MC and Buchbinder, EI and Kirkwood, JM and Korde, L and Moon, J and Sharon, E and Sondak, VK and Ribas, A},
title = {Neoadjuvant-Adjuvant or Adjuvant-Only Pembrolizumab in Advanced Melanoma.},
journal = {The New England journal of medicine},
volume = {388},
number = {9},
pages = {813-823},
doi = {10.1056/NEJMoa2211437},
pmid = {36856617},
issn = {1533-4406},
support = {P30CA014089/CA/NCI NIH HHS/United States ; P30CA016042/CA/NCI NIH HHS/United States ; P30CA033572/CA/NCI NIH HHS/United States ; P30CA076292/CA/NCI NIH HHS/United States ; U10CA180819/CA/NCI NIH HHS/United States ; U10CA180820/CA/NCI NIH HHS/United States ; U10CA180821/CA/NCI NIH HHS/United States ; U10CA180868/CA/NCI NIH HHS/United States ; U10CA180888/CA/NCI NIH HHS/United States ; UG1CA180830/CA/NCI NIH HHS/United States ; UG1CA189821/CA/NCI NIH HHS/United States ; UG1CA189830/CA/NCI NIH HHS/United States ; UG1CA189850/CA/NCI NIH HHS/United States ; UG1CA189860/CA/NCI NIH HHS/United States ; UG1CA189869/CA/NCI NIH HHS/United States ; UG1CA189956/CA/NCI NIH HHS/United States ; UG1CA233160/CA/NCI NIH HHS/United States ; UG1CA233178/CA/NCI NIH HHS/United States ; UG1CA233180/CA/NCI NIH HHS/United States ; UG1CA233193/CA/NCI NIH HHS/United States ; UG1CA233234/CA/NCI NIH HHS/United States ; UG1CA233247/CA/NCI NIH HHS/United States ; UG1CA233320/CA/NCI NIH HHS/United States ; UG1CA233328/CA/NCI NIH HHS/United States ; UG1CA233329/CA/NCI NIH HHS/United States ; UG1CA233330/CA/NCI NIH HHS/United States ; UG1CA233331/CA/NCI NIH HHS/United States ; UG1CA239758/CA/NCI NIH HHS/United States ; UG1CA239767/CA/NCI NIH HHS/United States ; },
mesh = {Humans ; Adjuvants, Immunologic ; Disease Progression ; *Melanoma/drug therapy/pathology/surgery ; *Neoadjuvant Therapy ; *Skin Neoplasms/drug therapy/pathology/surgery ; *Antineoplastic Agents, Immunological/administration &amp; dosage/adverse effects/therapeutic use ; Chemotherapy, Adjuvant ; },
abstract = {BACKGROUND: Whether pembrolizumab given both before surgery (neoadjuvant therapy) and after surgery (adjuvant therapy), as compared with pembrolizumab given as adjuvant therapy alone, would increase event-free survival among patients with resectable stage III or IV melanoma is unknown.<br><br>METHODS: In a phase 2 trial, we randomly assigned patients with clinically detectable, measurable stage IIIB to IVC melanoma that was amenable to surgical resection to three doses of neoadjuvant pembrolizumab, surgery, and 15 doses of adjuvant pembrolizumab (neoadjuvant-adjuvant group) or to surgery followed by pembrolizumab (200 mg intravenously every 3 weeks for a total of 18 doses) for approximately 1 year or until disease recurred or unacceptable toxic effects developed (adjuvant-only group). The primary end point was event-free survival in the intention-to-treat population. Events were defined as disease progression or toxic effects that precluded surgery; the inability to resect all gross disease; disease progression, surgical complications, or toxic effects of treatment that precluded the initiation of adjuvant therapy within 84 days after surgery; recurrence of melanoma after surgery; or death from any cause. Safety was also evaluated.<br><br>RESULTS: At a median follow-up of 14.7 months, the neoadjuvant-adjuvant group (154 patients) had significantly longer event-free survival than the adjuvant-only group (159 patients) (P&#x2009;=&#x2009;0.004 by the log-rank test). In a landmark analysis, event-free survival at 2 years was 72% (95% confidence interval [CI], 64 to 80) in the neoadjuvant-adjuvant group and 49% (95% CI, 41 to 59) in the adjuvant-only group. The percentage of patients with treatment-related adverse events of grades 3 or higher during therapy was 12% in the neoadjuvant-adjuvant group and 14% in the adjuvant-only group.<br><br>CONCLUSIONS: Among patients with resectable stage III or IV melanoma, event-free survival was significantly longer among those who received pembrolizumab both before and after surgery than among those who received adjuvant pembrolizumab alone. No new toxic effects were identified. (Funded by the National Cancer Institute and Merck Sharp and Dohme; S1801 ClinicalTrials.gov number, NCT03698019.).},
}
@article {pmid36856462,
year = {2023},
author = {Mohanlal, R and Ogenstad, S and Lyman, GH and Huang, L and Blayney, DW},
title = {Grade 4 Neutropenia Frequency as a Binary Risk Predictor for Adverse Clinical Consequences of Chemotherapy‑Induced Neutropenia: A Meta-analysis.},
journal = {Cancer investigation},
volume = {},
number = {},
pages = {1-23},
doi = {10.1080/07357907.2023.2179064},
pmid = {36856462},
issn = {1532-4192},
abstract = {Neutropenia is the major toxicity of myelosuppressive cancer chemotherapy. Grade 4 neutropenia (Gr4N) is a measure of chemotherapy-induced neutropenia (CIN) severity.We conducted a meta-analysis of CIN data. Gr4N incidence was significantly correlated with febrile neutropenia (FN), days of severe neutropenia (DSN), and nadir absolute neutrophil count (ANC), which are all important predictors of morbidity. With a Gr4N threshold of 65%, both FN and DSN were below levels for low risk of adverse CIN outcomes. Gr4N was highly predictive for adverse CIN outcomes, and a 65% threshold demarcated low vs. high risk for FN and other adverse CIN outcomes.},
}
@article {pmid36854058,
year = {2023},
author = {Lee, AA and Wang, QL and Kim, J and Babic, A and Zhang, X and Perez, K and Ng, K and Nowak, J and Rifazzzzzzzzgi, N and Sesso, HD and Buring, JE and Anderson, GL and Wactawski-Wende, J and Wallace, R and Manson, JE and Giovannucci, EL and Stampfer, MJ and Kraft, P and Fuchs, CS and Yuan, C and Wolpin, BM},
title = {Helicobacter pylori Seropositivity, ABO Blood Type, and Pancreatic Cancer Risk from 5 Prospective Cohorts.},
journal = {Clinical and translational gastroenterology},
volume = {},
number = {},
pages = {},
doi = {10.14309/ctg.0000000000000573},
pmid = {36854058},
issn = {2155-384X},
abstract = {BACKGROUND: Helicobacter pylori infection may be a risk factor for pancreatic cancer, particularly infection by strains without the cytotoxin-associated gene A (CagA) virulence factor. Non-O blood type is a known risk factor for pancreatic cancer, and H. pylori gastric colonization occurs largely from bacterial adhesins binding to blood group antigens on gastric mucosa.<br><br>METHODS: We included 485 pancreatic cancer cases and 1,122 matched controls from 5 U.S. prospective cohorts. Prediagnostic plasma samples were assessed for H. pylori and CagA antibody titers. Conditional logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI) for pancreatic cancer. ABO blood type was assessed using genetic polymorphisms at the ABO gene locus or self-report.<br><br>RESULTS: Compared to H. pylori seronegative participants, those who were seropositive did not demonstrate an increased risk for pancreatic cancer (OR 0.83, 95% CI 0.65-1.06). This lack of association was similar among CagA seropositive (OR 0.75, 95% CI 0.53-1.04) and seronegative (OR 0.89, 95% CI 0.65-1.20) participants. The association was also similar when stratified by time between blood collection and cancer diagnosis (P-interaction=0.80). Consistent with prior studies, non-O blood type was associated with increased pancreatic cancer risk, but this increase in risk was similar regardless of H. pylori seropositivity (P-interaction=0.51).<br><br>DISCUSSION: In this nested case-control study, history of H. pylori infection as determined by H. pylori antibody serology was not associated with pancreatic cancer risk, regardless of CagA virulence factor status. The elevated risk associated with non-O blood type was consistent in those with or without H. pylori seropositivity.},
}
@article {pmid36853945,
year = {2023},
author = {Yamamoto, A and Huang, Y and Krajina, BA and McBirney, M and Doak, AE and Qu, S and Wang, CL and Haffner, MC and Cheung, KJ},
title = {Metastasis from the tumor interior and necrotic core formation are regulated by breast cancer-derived angiopoietin-like 7.},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
volume = {120},
number = {10},
pages = {e2214888120},
doi = {10.1073/pnas.2214888120},
pmid = {36853945},
issn = {1091-6490},
mesh = {Humans ; Animals ; Rats ; Female ; *Breast Neoplasms/genetics ; *Mammary Neoplasms, Animal ; *Neoplastic Cells, Circulating ; Necrosis ; Angiopoietins/genetics ; Angiopoietin-like Proteins ; Angiopoietin-Like Protein 7 ; },
abstract = {Necrosis in the tumor interior is a common feature of aggressive cancers that is associated with poor clinical prognosis and the development of metastasis. How the necrotic core promotes metastasis remains unclear. Here, we report that emergence of necrosis inside the tumor is correlated temporally with increased tumor dissemination in a rat breast cancer model and in human breast cancer patients. By performing spatially focused transcriptional profiling, we identified angiopoietin-like 7 (Angptl7) as a tumor-specific factor localized to the perinecrotic zone. Functional studies showed that Angptl7 loss normalizes central necrosis, perinecrotic dilated vessels, metastasis, and reduces circulating tumor cell counts to nearly zero. Mechanistically, Angptl7 promotes vascular permeability and supports vascular remodeling in the perinecrotic zone. Taken together, these findings show that breast tumors actively produce factors controlling central necrosis formation and metastatic dissemination from the tumor core.},
}
@article {pmid36853602,
year = {2023},
author = {Doll, MK and Waghmare, A and Heit, A and Levenson Shakoor, B and Kimball, LE and Ozbek, N and Blazevic, RL and Mose, L and Boonyaratanakornkit, J and Stevens-Ayers, TL and Cornell, K and Sheppard, BD and Hampson, E and Sharmin, F and Goodwin, B and Dan, JM and Archie, T and O'Connor, T and Heckerman, D and Schmitz, F and Boeckh, M and Crotty, S},
title = {Acute and Postacute COVID-19 Outcomes Among Immunologically Naive Adults During Delta vs Omicron Waves.},
journal = {JAMA network open},
volume = {6},
number = {2},
pages = {e231181},
pmid = {36853602},
issn = {2574-3805},
mesh = {Humans ; Adult ; Female ; Middle Aged ; Male ; *SARS-CoV-2 ; *COVID-19/epidemiology ; Cohort Studies ; Prospective Studies ; },
abstract = {IMPORTANCE: The US arrival of the Omicron variant led to a rapid increase in SARS-CoV-2 infections. While numerous studies report characteristics of Omicron infections among vaccinated individuals or persons with previous infection, comprehensive data describing infections among adults who are immunologically naive are lacking.<br><br>OBJECTIVES: To examine COVID-19 acute and postacute clinical outcomes among a well-characterized cohort of unvaccinated and previously uninfected adults who contracted SARS-CoV-2 during the Omicron (BA.1/BA.2) surge, and to compare outcomes with infections that occurred during the Delta wave.<br><br>This prospective multisite cohort study included community-dwelling adults undergoing high-resolution symptom and virologic monitoring in 8 US states between June 2021 and September 2022. Unvaccinated adults aged 30 to less than 65 years without an immunological history of SARS-CoV-2 who were at high risk of infection were recruited. Participants were followed for up to 48 weeks, submitting regular COVID-19 symptom surveys and nasal swabs for SARS-CoV-2 polymerase chain reaction (PCR) testing. Data were analyzed from May to October 2022.<br><br>EXPOSURES: Omicron (BA.1/BA.2 lineages) vs Delta SARS-CoV-2 infection, defined as a positive PCR test result that occurred during a period when the variant represented at least 50% of circulating SARS-CoV-2 variants in the participant's geographic region.<br><br>MAIN OUTCOMES AND MEASURE(S): The main outcomes examined were the prevalence and severity of acute (&#x2264;28 days after onset) and postacute (&#x2265;5 weeks after onset) symptoms.<br><br>RESULTS: Among 274 participants who were immunologically naive (mean [SD] age, 49 [9.7] years; 186 [68%] female; 19 [7%] Hispanic participants; 242 [88%] White participants), 166 (61%) contracted SARS-CoV-2. Of these, 137 infections (83%) occurred during the Omicron-predominant period and 29 infections (17%) occurred during the Delta-predominant period. Asymptomatic infections occurred among 7% (95% CI, 3%-12%) of Omicron-wave infections and 0% (95% CI, 0%-12%) of Delta-wave infections. Health care use among individuals with Omicron-wave infections was 79% (95% CI, 43%-92%) lower relative to individuals with Delta-wave infections (P&#x2009;=&#x2009;.001). Compared with individuals infected during the Delta wave, individuals infected during the Omicron wave also experienced a 56% (95% CI, 26%-74%, P&#x2009;=&#x2009;.004) relative reduction in the risk of postacute symptoms and a 79% (95% CI, 54%-91%, P&#x2009;<&#x2009;.001) relative reduction in the rate of postacute symptoms.<br><br>CONCLUSIONS AND RELEVANCE: These findings suggest that among adults who were previously immunologically naive, few Omicron-wave (BA.1/BA.2) and Delta-wave infections were asymptomatic. Compared with individuals with Delta-wave infections, individuals with Omicron-wave infections were less likely to seek health care and experience postacute symptoms.},
}
@article {pmid36851745,
year = {2023},
author = {Hao, L and Hsiang, TY and Dalmat, RR and Ireton, R and Morton, JF and Stokes, C and Netland, J and Hale, M and Thouvenel, C and Wald, A and Franko, NM and Huden, K and Chu, HY and Sigal, A and Greninger, AL and Tilles, S and Barrett, LK and Van Voorhis, WC and Munt, J and Scobey, T and Baric, RS and Rawlings, DJ and Pepper, M and Drain, PK and Gale, M},
title = {Dynamics of SARS-CoV-2 VOC Neutralization and Novel mAb Reveal Protection against Omicron.},
journal = {Viruses},
volume = {15},
number = {2},
pages = {},
pmid = {36851745},
issn = {1999-4915},
support = {AI100625/NH/NIH HHS/United States ; AI151698/NH/NIH HHS/United States ; },
mesh = {Humans ; *COVID-19/prevention &amp; control ; SARS-CoV-2/genetics ; Antibodies, Monoclonal ; Antiviral Agents ; },
abstract = {New variants of SARS-CoV-2 continue to emerge and evade immunity. We isolated SARS-CoV-2 temporally across the pandemic starting with the first emergence of the virus in the western hemisphere and evaluated the immune escape among variants. A clinic-to-lab viral isolation and characterization pipeline was established to rapidly isolate, sequence, and characterize SARS-CoV-2 variants. A virus neutralization assay was applied to quantitate humoral immunity from infection and/or vaccination. A panel of novel monoclonal antibodies was evaluated for antiviral efficacy. We directly compared all variants, showing that convalescence greater than 5 months post-symptom onset from ancestral virus provides little protection against SARS-CoV-2 variants. Vaccination enhances immunity against viral variants, except for Omicron BA.1, while a three-dose vaccine regimen provides over 50-fold enhanced protection against Omicron BA.1 compared to a two-dose. A novel Mab neutralizes Omicron BA.1 and BA.2 variants better than the clinically approved Mabs, although neither can neutralize Omicron BA.4 or BA.5. Thus, the need remains for continued vaccination-booster efforts, with innovation for vaccine and Mab improvement for broadly neutralizing activity. The usefulness of specific Mab applications links with the window of clinical opportunity when a cognate viral variant is present in the infected population.},
}
@article {pmid36851590,
year = {2023},
author = {Einav, T and Kosikova, M and Radvak, P and Kuo, YC and Kwon, HJ and Xie, H},
title = {Mapping the Antibody Repertoires in Ferrets with Repeated Influenza A/H3 Infections: Is Original Antigenic Sin Really "Sinful"?.},
journal = {Viruses},
volume = {15},
number = {2},
pages = {},
pmid = {36851590},
issn = {1999-4915},
support = {DRQ 01-20 (T. Einav)//Damon Runyon Cancer Research Foundation/United States ; },
mesh = {Animals ; Humans ; *Influenza, Human ; Ferrets ; Antibodies ; *Influenza Vaccines ; Broadly Neutralizing Antibodies ; },
abstract = {The influenza-specific antibody repertoire is continuously reshaped by infection and vaccination. The host immune response to contemporary viruses can be redirected to preferentially boost antibodies specific for viruses encountered early in life, a phenomenon called original antigenic sin (OAS) that is suggested to be responsible for diminished vaccine effectiveness after repeated seasonal vaccination. Using a new computational tool called Neutralization Landscapes, we tracked the progression of hemagglutination inhibition antibodies within ferret antisera elicited by repeated influenza A/H3 infections and deciphered the influence of prior exposures on the de novo antibody response to evolved viruses. The results indicate that a broadly neutralizing antibody signature can nevertheless be induced by repeated exposures despite OAS induction. Our study offers a new way to visualize how immune history shapes individual antibodies within a repertoire, which may help to inform future universal influenza vaccine design.},
}
@article {pmid36851349,
year = {2023},
author = {Michelo, CM and Fiore-Gartland, A and Dalel, JA and Hayes, P and Tang, J and McGowan, E and Kilembe, W and Fernandez, N and Gilmour, J and Hunter, E},
title = {Cohort-Specific Peptide Reagents Broaden Depth and Breadth Estimates of the CD8 T Cell Response to HIV-1 Gag Potential T Cell Epitopes.},
journal = {Vaccines},
volume = {11},
number = {2},
pages = {},
pmid = {36851349},
issn = {2076-393X},
support = {107752/Z/15/Z/WT_/Wellcome Trust/United Kingdom ; },
abstract = {An effective HIV vaccine will need to stimulate immune responses against the sequence diversity presented in circulating virus strains. In this study, we evaluate breadth and depth estimates of potential T-cell epitopes (PTEs) in transmitted founder virus sequence-derived cohort-specific peptide reagents against reagents representative of consensus and global sequences. CD8 T-cells from twenty-six HIV-1+ PBMC donor samples, obtained at 1-year post estimated date of infection, were evaluated. ELISpot assays compared responses to 15mer consensus (n = 121), multivalent-global (n = 320), and 10mer multivalent cohort-specific (n = 300) PTE peptides, all mapping to the Gag antigen. Responses to 38 consensus, 71 global, and 62 cohort-specific PTEs were confirmed, with sixty percent of common global and cohort-specific PTEs corresponding to consensus sequences. Both global and cohort-specific peptides exhibited broader epitope coverage compared to commonly used consensus reagents, with mean breadth estimates of 3.2 (global), 3.4 (cohort) and 2.2 (consensus) epitopes. Global or cohort peptides each identified unique epitope responses that would not be detected if these peptide pools were used alone. A peptide set designed around specific virologic and immunogenetic characteristics of a target cohort can expand the detection of CD8 T-cell responses to epitopes in circulating viruses, providing a novel way to better define the host response to HIV-1 with implications for vaccine development.},
}
@article {pmid36847573,
year = {2023},
author = {Vigdorovich, V and Patel, H and Watson, A and Raappana, A and Reynolds, L and Selman, W and Beeman, S and Edlefsen, PT and Kappe, SHI and Sather, DN},
title = {Coimmunization with Preerythrocytic Antigens alongside Circumsporozoite Protein Can Enhance Sterile Protection against Plasmodium Sporozoite Infection.},
journal = {Microbiology spectrum},
volume = {},
number = {},
pages = {e0379122},
doi = {10.1128/spectrum.03791-22},
pmid = {36847573},
issn = {2165-0497},
abstract = {Malaria-causing Plasmodium parasites have a complex life cycle and present numerous antigen targets that may contribute to protective immune responses. The currently recommended vaccine-RTS,S-functions by targeting the Plasmodium falciparum circumsporozoite protein (CSP), which is the most abundant surface protein of the sporozoite form responsible for initiating infection of the human host. Despite showing only moderate efficacy, RTS,S has established a strong foundation for the development of next-generation subunit vaccines. Our previous work characterizing the sporozoite surface proteome identified additional non-CSP antigens that may be useful as immunogens individually or in combination with CSP. In this study, we examined eight such antigens using the rodent malaria parasite Plasmodium yoelii as a model system. We demonstrate that despite conferring weak protection individually, coimmunizing each of several of these antigens alongside CSP could significantly enhance the sterile protection achieved by CSP immunization alone. Thus, our work provides compelling evidence that a multiantigen preerythrocytic vaccine approach may enhance protection compared to CSP-only vaccines. This lays the groundwork for further studies aimed at testing the identified antigen combinations in human vaccination trials that assess efficacy with controlled human malaria infection. IMPORTANCE The currently approved malaria vaccine targets a single parasite protein (CSP) and results in only partial protection. We tested several additional vaccine targets in combination with CSP to identify those that could enhance protection from infection upon challenge in the mouse malaria model. In identifying several such enhancing vaccine targets, our work indicates that a multiprotein immunization approach may be a promising avenue to achieving higher levels of protection from infection. Our work identified several candidate leads for follow-up in the models relevant for human malaria and provides an experimental framework for efficiently carrying out such screens for other combinations of vaccine targets.},
}
@article {pmid36845406,
year = {2023},
author = {Hill-Jarrett, TG and Ng, R and Cardenas-Iniguez, C and Akinsanya, J and Blanco, I and Borland, JM and Brown, JS and Clemons, T and Cushnie, AK and Garcia, J and George, B and Hassinan, CW and Hines, TJ and Landayan, D and McCorkle, TA and Meckel, KR and Metcalfe, M and Montoya, SA and Rose, DK and Warren, DR},
title = {A developmental approach to diversifying neuroscience through effective mentorship practices: perspectives on cross-identity mentorship and a critical call to action.},
journal = {Frontiers in integrative neuroscience},
volume = {17},
number = {},
pages = {1052418},
pmid = {36845406},
issn = {1662-5145},
abstract = {Many early-career neuroscientists with diverse identities may not have mentors who are more advanced in the neuroscience pipeline and have a congruent identity due to historic biases, laws, and policies impacting access to education. Cross-identity mentoring relationships pose challenges and power imbalances that impact the retention of diverse early career neuroscientists, but also hold the potential for a mutually enriching and collaborative relationship that fosters the mentee's success. Additionally, the barriers faced by diverse mentees and their mentorship needs may evolve with career progression and require developmental considerations. This article provides perspectives on factors that impact cross-identity mentorship from individuals participating in Diversifying the Community of Neuroscience (CNS)-a longitudinal, National Institute of Neurological Disorders and Stroke (NINDS) R25 neuroscience mentorship program developed to increase diversity in the neurosciences. Participants in Diversifying CNS were comprised of 14 graduate students, postdoctoral fellows, and early career faculty who completed an online qualitative survey on cross-identity mentorship practices that impact their experience in neuroscience fields. Qualitative survey data were analyzed using inductive thematic analysis and resulted in four themes across career levels: (1) approach to mentorship and interpersonal dynamics, (2) allyship and management of power imbalance, (3) academic sponsorship, and (4) institutional barriers impacting navigation of academia. These themes, along with identified mentorship needs by developmental stage, provide insights mentors can use to better support the success of their mentees with diverse intersectional identities. As highlighted in our discussion, a mentor's awareness of systemic barriers along with active allyship are foundational for their role.},
}
@article {pmid36844011,
year = {2023},
author = {Mitchell, KM and Boily, MC and Hanscom, B and Moore, M and Todd, J and Paz-Bailey, G and Wejnert, C and Liu, A and Donnell, DJ and Grinsztejn, B and Landovitz, RJ and Dimitrov, DT},
title = {Estimating the impact of HIV PrEP regimens containing long-acting injectable cabotegravir or daily oral tenofovir disoproxil fumarate/emtricitabine among men who have sex with men in the United States: a mathematical modelling study for HPTN 083.},
journal = {Lancet regional health. Americas},
volume = {18},
number = {},
pages = {100416},
pmid = {36844011},
issn = {2667-193X},
abstract = {BACKGROUND: The HPTN 083 trial demonstrated superiority of HIV pre-exposure prophylaxis (PrEP) containing long-acting injectable cabotegravir (CAB) to daily oral tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) among men who have sex with men (MSM). We compared the potential population-level impact of TDF/FTC and CAB among MSM in Atlanta, Georgia.<br><br>METHODS: An MSM HIV transmission model was calibrated to Atlanta-specific data on HIV prevalence and PrEP usage (percentage of uninfected MSM on PrEP), assuming only PrEP-indicated MSM used PrEP. CAB effectiveness (efficacy&#xa0;&#xd7;&#xa0;adherence) of 91% was estimated using data from HPTN 083 and previous TDF/FTC trials. We estimated HIV infections averted over 5/10 years if TDF/FTC use were maintained, or if all TDF/FTC users switched to CAB in January 2022 (vs. no PrEP or continued TDF/FTC use). CAB scenarios with 10%/20% more users were also considered. Progress towards Ending the HIV Epidemic (EHE) goals (75%/90% fewer HIV infections in 2025/2030 vs. 2017) was estimated.<br><br>FINDINGS: We predicted TDF/FTC at current usage (&#x223c;28%) would avert 36.3% of new HIV infections (95% credible interval 25.6-48.7%) among all Atlanta MSM over 2022-2026 vs. no PrEP. Switching to CAB with similar usage may prevent 44.6% (33.2-56.6%) infections vs. no PrEP and 11.9% (5.2-20.2%) infections vs. continued TDF/FTC. Increasing CAB usage 20% could increase the incremental impact over TDF/FTC to 30.0% over 2022-2026, getting &#x223c;60% towards reaching EHE goals (47%/54% fewer infections in 2025/2030). Reaching the 2030 EHE goal would require 93% CAB usage.<br><br>INTERPRETATION: If CAB effectiveness were like HPTN 083, CAB could prevent more infections than TDF/FTC at similar usage. Increased CAB usage could contribute substantially towards reaching EHE goals, but the usage required to meet EHE goals is unrealistic.<br><br>FUNDING: NIH, MRC.},
}
@article {pmid36843621,
year = {2023},
author = {Kassamali Escobar, Z and Bouchard, T and Buck, C and Sandhu, K and Bryson-Cahn, C},
title = {A single-centre experience rolling out an antibiotic stewardship intervention prior to and during the SARS-CoV-2 pandemic 2019-2022.},
journal = {Drugs in context},
volume = {12},
number = {},
pages = {},
pmid = {36843621},
issn = {1745-1981},
abstract = {BACKGROUND: Antibiotics are prescribed to nearly one-half of patients with viral respiratory tract infections (RTI) in outpatient settings. This use is ineffective and may cause undue harm and excess cost from unnecessary antibiotic exposure. We implemented a multifaceted intervention to address inappropriate antibiotic prescribing for viral RTI. Here, we discuss the impact over 4 years, before and during the SARS-CoV-2 pandemic.<br><br>METHODS: This observational study describes the implementation and initial impact of a multimodal stewardship intervention on inappropriate antibiotic prescribing for viral RTIs in outpatient care settings at a single centre. We tracked the rate of visits for viral RTI as well as antibiotic prescribing for viral RTIs in urgent care, primary care and the emergency department between January 2018 and March 2022. Data were collected 1 year prior to implementation and 3 years after implementation. The primary outcome - the rate of inappropriate antibiotics prescribed for viral RTIs - was described by calendar year (CY) to review changes after the stewardship intervention.<br><br>RESULTS: In CY2018, the year prior to implementation of targeted RTI antimicrobial stewardship, the rate of inappropriate RTI antibiotics prescribed was 10% in urgent care, 11% in primary care and 18% in the emergency department (ED). During the first CY of the intervention, rates were 8% in urgent care, 10% in primary care and 16% in the ED. In CY2020, the second year of the intervention, inappropriate RTI antibiotics were prescribed in 5% of urgent care and 3% primary care RTI visits and 15% of ED RTI visits. These rates were similar in CY2021 and the first 3 months of CY2022. Over 30,000 visits for RTIs were seen annually in CY2018 and CY2019. Annual RTI visits dropped to 20,222 in CY2020 and 14,172 in CY2021.<br><br>CONCLUSION: Although total visits for non-COVID RTIs decreased by approximately 50% during the first 2 years of the SARS-CoV-2 pandemic, an antimicrobial stewardship intervention was associated with decreases in inappropriate antibiotic prescribing for RTIs. This was maintained throughout 2 years of the pandemic.This article is part of the Antibiotic stewardship Special Issue: https://www.drugsincontext.com/special_issues/antimicrobial-stewardship-a-focus-on-the-need-for-moderation.},
}
@article {pmid36842087,
year = {2023},
author = {Kwan, EX and Alvino, GM and Lynch, KL and Levan, PF and Amemiya, HM and Wang, XS and Johnson, SA and Sanchez, JC and Miller, MA and Croy, M and Lee, SB and Naushab, M and Bedalov, A and Cuperus, JT and Brewer, BJ and Queitsch, C and Raghuraman, MK},
title = {Ribosomal DNA replication time coordinates completion of genome replication and anaphase in yeast.},
journal = {Cell reports},
volume = {42},
number = {3},
pages = {112161},
doi = {10.1016/j.celrep.2023.112161},
pmid = {36842087},
issn = {2211-1247},
abstract = {Timely completion of genome replication is a prerequisite for mitosis, genome integrity, and cell survival. A challenge to this timely completion comes from the need to replicate the hundreds of untranscribed copies of rDNA that organisms maintain in addition to the copies required for ribosome biogenesis. Replication of these rDNA arrays is relegated to late S phase despite their large size, repetitive nature, and essentiality. Here, we show that, in Saccharomyces cerevisiae, reducing the number of rDNA repeats leads to early rDNA replication, which results in delaying replication elsewhere in the genome. Moreover, cells with early-replicating rDNA arrays and delayed genome-wide replication aberrantly release the mitotic phosphatase Cdc14 from the nucleolus and enter anaphase prematurely. We propose that rDNA copy number determines the replication time of the rDNA locus and that the release of Cdc14 upon completion of rDNA replication is a signal for cell cycle progression.},
}
@article {pmid36839598,
year = {2023},
author = {Buchanan, AL and Katenka, N and Lee, Y and Wu, J and Pantavou, K and Friedman, SR and Halloran, ME and Marshall, BDL and Forastiere, L and Nikolopoulos, GK},
title = {Methods for Assessing Spillover in Network-Based Studies of HIV/AIDS Prevention among People Who Use Drugs.},
journal = {Pathogens (Basel, Switzerland)},
volume = {12},
number = {2},
pages = {},
pmid = {36839598},
issn = {2076-0817},
support = {DP2 DA046856/DA/NIDA NIH HHS/United States ; R01 AI085073/AI/NIAID NIH HHS/United States ; P30 DA011041/DA/NIDA NIH HHS/United States ; DP1 DA034989/DA/NIDA NIH HHS/United States ; },
abstract = {Human Immunodeficiency Virus (HIV) interventions among people who use drugs (PWUD) often have spillover, also known as interference or dissemination, which occurs when one participant's exposure affects another participant's outcome. PWUD are often members of networks defined by social, sexual, and drug-use partnerships and their receipt of interventions can affect other members in their network. For example, HIV interventions with possible spillover include educational training about HIV risk reduction, pre-exposure prophylaxis, or treatment as prevention. In turn, intervention effects frequently depend on the network structure, and intervention coverage levels and spillover can occur even if not measured in a study, possibly resulting in an underestimation of intervention effects. Recent methodological approaches were developed to assess spillover in the context of network-based studies. This tutorial provides an overview of different study designs for network-based studies and related methodological approaches for assessing spillover in each design. We also provide an overview of other important methodological issues in network studies, including causal influence in networks and missing data. Finally, we highlight applications of different designs and methods from studies of PWUD and conclude with an illustrative example from the Transmission Reduction Intervention Project (TRIP) in Athens, Greece.},
}
@article {pmid36832314,
year = {2023},
author = {Tham, SW and Law, EF and Palermo, TM and Kapos, FP and Mendoza, JA and Groenewald, CB},
title = {Household Food Insufficiency and Chronic Pain among Children in the US: A National Study.},
journal = {Children (Basel, Switzerland)},
volume = {10},
number = {2},
pages = {},
pmid = {36832314},
issn = {2227-9067},
abstract = {This study aimed to determine the prevalence of pediatric chronic pain by household food sufficiency status and examine whether food insufficiency would be associated with greater risk for chronic pain. We analyzed data from the 2019-2020 National Survey of Children's Health of 48,410 children (6-17 years) in the United States. Across the sample, 26.1% (95% CI: 25.2-27.0) experienced mild food insufficiency and 5.1% (95% CI: 4.6-5.7) moderate/severe food insufficiency. The prevalence of chronic pain was higher among children with mild (13.7%) and moderate/severe food insufficiency (20.6%) relative to children in food-sufficient households (6.7%, p < 0.001). After adjusting for a priori covariates (individual: age, sex, race/ethnicity, anxiety, depression, other health conditions, adverse childhood events; household: poverty, parent education, physical and mental health; community: region of residence), multivariable logistic regression revealed that children with mild food insufficiency had 1.6 times greater odds of having chronic pain (95% CI: 1.4-1.9, p < 0.0001) and those with moderate/severe food insufficiency, 1.9 higher odds (95% CI: 1.4-2.7, p < 0.0001) relative to food-sufficient children. The dose-response relationship between food insufficiency and childhood chronic pain highlights the importance of further research to identify underlying mechanisms and evaluate the impact of food insufficiency on the onset and persistence of chronic pain across the lifespan.},
}
@article {pmid36831606,
year = {2023},
author = {Cazzetta, V and Depierreux, D and Colucci, F and Mikulak, J and Mavilio, D},
title = {NKG2A Immune Checkpoint in Vδ2 T Cells: Emerging Application in Cancer Immunotherapy.},
journal = {Cancers},
volume = {15},
number = {4},
pages = {},
pmid = {36831606},
issn = {2072-6694},
abstract = {Immune regulation has revolutionized cancer treatment with the introduction of T-cell-targeted immune checkpoint inhibitors (ICIs). This successful immunotherapy has led to a more complete view of cancer that now considers not only the cancer cells to be targeted and destroyed but also the immune environment of the cancer cells. Current challenges associated with the enhancement of ICI effects are increasing the fraction of responding patients through personalized combinations of multiple ICIs and overcoming acquired resistance. This requires a complete overview of the anti-tumor immune response, which depends on a complex interplay between innate and adaptive immune cells with the tumor microenvironment. The NKG2A was revealed to be a key immune checkpoint for both Natural Killer (NK) cells and T cells. Monalizumab, a humanized anti-NKG2A antibody, enhances NK cell activity against various tumor cells and rescues CD8 αβ T cell function in combination with PD-1/PD-L1 blockade. In this review, we discuss the potential for targeting NKG2A expressed on tumor-sensing human γδ T cells, mostly on the specific Vδ2 T cell subset, in order to emphasize its importance and potential in the development of new ICI-based therapeutic approaches.},
}
@article {pmid36831502,
year = {2023},
author = {Pauleck, S and Sinnott, JA and Zheng, YL and Gadalla, SM and Viskochil, R and Haaland, B and Cawthon, RM and Hoffmeister, A and Hardikar, S},
title = {Association of Telomere Length with Colorectal Cancer Risk and Prognosis: A Systematic Review and Meta-Analysis.},
journal = {Cancers},
volume = {15},
number = {4},
pages = {},
pmid = {36831502},
issn = {2072-6694},
abstract = {(1) Background: Colorectal cancer risk and survival have previously been associated with telomere length in peripheral blood leukocytes and tumor tissue. A systematic review and meta-analysis of the literature was conducted. The PubMed, Embase, and Web of Science databases were searched through March 2022. (2) Methods: Relevant studies were identified through database searching following PRISMA guidelines. Risk estimates were extracted from identified studies; meta-analyses were conducted using random effects models. (3) Results: Fourteen studies were identified (eight on risk; six on survival) through systematic review. While no association was observed between circulating leukocyte telomere length and the risk of colorectal cancer [overall OR (95% CI) = 1.01 (0.82-1.24)], a worse survival for those with shorter telomeres in leukocytes and longer telomeres in tumor tissues was observed [Quartile1/Quartile2-4 overall HR (95% CI) = 1.41 (0.26-7.59) and 0.82 (0.69-0.98), respectively]. (4) Conclusions: Although there was no association with colorectal cancer risk, a poorer survival was observed among those with shorter leukocyte telomere length. Future larger studies evaluating a potentially non-linear relationship between telomeres and colorectal cancer are needed.},
}
@article {pmid36828152,
year = {2023},
author = {Elahy, V and Thomson, C and Neuhouser, ML and Jiang, L and Lee, S and Pan, K and Vitolins, M and Chlebowski, R and Lane, D and Odegaard, AO},
title = {Frequency of Consuming Breakfast Meals and After-Dinner Snacks Is not Associated with Postmenopausal Breast Cancer Risk: Women's Health Initiative Observational Study.},
journal = {The Journal of nutrition},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.tjnut.2023.02.003},
pmid = {36828152},
issn = {1541-6100},
abstract = {BACKGROUND: There has been little investigation into how the timing of meals and eating occasions associates with postmenopausal breast cancer risk.<br><br>OBJECTIVE: We examined the association between the frequency of consuming breakfast meals and after-dinner snacks with the risk for postmenopausal breast cancer.<br><br>METHODS: A prospective analysis of 74,825 postmenopausal women aged 49 to 81 y from the Women's Health Initiative Observational Study cohort. Breakfast and after-dinner snack intake were assessed at year 1 examination. Risk for invasive and in situ breast cancer diagnosed before 28 February 2020 was modeled with multivariable Cox proportional hazards regression models according to breakfast and after-dinner snack consumption frequencies. The models were adjusted for age, self-identified race/ethnicity, education, income, physical activity, smoking, alcohol intake, diet quality score (Healthy Eating Index 2015), energy intake, diabetic status, hormone therapy, and BMI.<br><br>RESULTS: During the follow-up period, 5313 participants were diagnosed with invasive breast cancer and 1197 participants with in situ breast cancer. Compared with participants who did not eat breakfast, those with daily breakfast consumption was not associated with invasive breast cancer (HR: 1.04; 95% CI: 0.9, 1.19) nor in situ (HR: 1.25; 95% CI: 0.91, 1.74) breast cancer. There were monotonic higher point estimates of in situ breast cancer for each higher category of breakfast intake from 0 to 7 times per week (P-trend = 0.04, Wald test). Compared with consumption of daily after-dinner snacks, avoidance of after-dinner snacks was not associated with invasive breast cancer (HR: 0.97; 95% CI: 0.87, 1.08) nor in situ (HR: 1.12; 95% CI: 0.89, 1.42) breast cancer.<br><br>CONCLUSIONS: There was no association between intake frequency of breakfast meals or after-dinner snack habits and with risk of breast cancer in postmenopausal women.},
}
@article {pmid36827681,
year = {2023},
author = {Ragon, BK and Shah, MV and D'Souza, A and Estrada-Merly, N and Gowda, L and George, G and DeLima, M and Hashmi, S and Kharfan-Dabaja, MA and Majhail, NS and Banerjee, R and Saad, A and Hildebrandt, GC and Mian, H and Abid, MB and Battiwalla, M and Lekakis, LJ and Patel, SS and Murthy, HS and Nieto, Y and Strouse, CS and Badawy, SM and Al Hadidi, SA and Dholaria, B and Aljurf, M and Vesole, DH and Lee, CH and Pawarode, A and Gergis, U and Miller, KC and Holmberg, LA and Afrough, A and Solh, MM and Munshi, P and Nishihori, T and Anderson, LD and Wirk, B and Kaur, G and Qazilbash, MH and Shah, N and Kumar, SK and Usmani, SZ},
title = {Impact of Second Primary Malignancy Post-Autologous Transplantation on Outcomes of Multiple Myeloma: A CIBMTR Analysis.},
journal = {Blood advances},
volume = {},
number = {},
pages = {},
doi = {10.1182/bloodadvances.2022009138},
pmid = {36827681},
issn = {2473-9537},
abstract = {The overall survival (OS) has improved significantly in multiple myeloma (MM) over the last decade with use of proteasome inhibitor and immunomodulatory drug-based combinations, followed by high-dose melphalan and autologous hematopoietic stem cell transplantation (auto-HSCT) and subsequent maintenance therapies in eligible newly diagnosed patients. However, clinical trials employing auto-HSCT followed by lenalidomide maintenance have shown an increased risk of second primary malignancies (SPM), including second hematological malignancies (SHM). We evaluated the impact of SPM and SHM on progression-free survival (PFS) and OS in MM patients following auto-HSCT using CIBMTR registry data. Adult MM patients who underwent first auto-HSCT in the United States with melphalan conditioning regimen from 2011 to 2018 and received maintenance therapy were included (n=3,948). At a median follow up of 37 months, 175 (4%) patients developed SPM, including 112 (64%) solid, 36 (20%) myeloid, 24 (14%) SHM, not otherwise specified, and 3 (2%) lymphoid malignancies. Multivariate analysis demonstrated that SPM and SHM were associated with an inferior PFS (HR 2.62, P<.001 and HR 5.01, P<.001, respectively) and OS (HR 3.85, P<.001 and HR 8.13, P<.001, respectively). In patients who developed SPM and SHM, MM remained the most frequent primary cause of death (42% versus 30% and 53% versus 18%, respectively). We conclude the development of SPM and SHM leads to a poor survival in MM patients and is an important survivorship challenge. Given the median survival for MM continues to improve, continued vigilance is needed to assess the risks of SPM and SHM with maintenance therapy post-auto-HSCT.},
}
@article {pmid36827440,
year = {2023},
author = {Beauchamp, G and Hosek, S and Donnell, DJ and Chan, KCG and Flaherty, BP and Anderson, PL and Dye, BJ and Mgodi, N and Bekker, LG and Delany-Moretlwe, S and Celum, C and , },
title = {Development of a tool to assess HIV prevention readiness of adolescent girls and young women in HPTN 082 study.},
journal = {PloS one},
volume = {18},
number = {2},
pages = {e0281728},
pmid = {36827440},
issn = {1932-6203},
abstract = {BACKGROUND: African adolescent girls and young women (AGYW) represent a large proportion of new HIV infections, a priority population for pre-exposure prophylaxis (PrEP), but adherence remains a challenge. A reliable, valid readiness tool would help identify AGYW motivated to take PrEP who need adherence support.<br><br>METHODS: In the HPTN 082 open-label PrEP study (2016-2019), South African and Zimbabwean women ages 16-25 were administered an HIV prevention readiness measure (HPRM). The 25 items in the HPRM included medication beliefs, connection with care, disclosure of PrEP use, social support, and housing stability using a 5-point Likert scale. Exploratory factor analysis (EFA) using polychoric correlations, scale reliability, and predictive validity were performed on data from 315 participants who responded to all items. We assessed the predictive value of HPRM scores with PrEP adherence, defined as tenofovir-diphosphate (TFV-DP) concentrations in dried blood spots, as a continuous measure and dichotomized as high PrEP adherence (&#x2265;700 fmol/punch).<br><br>RESULTS: EFA yielded 23 items with three subscales: self-efficacy (16 items), PrEP disclosure (4 items), and social support (3 items). Cronbach's &#x3b1; ranged from 0.71 to 0.92 for the overall scale and the subscales. The average overall scale and the subscales were predictive of 3-month PrEP adherence for TFV-DP concentrations: for each unit increase of the HPRM score, TFV-DP concentration increased by 103 fmol/punch (95% CI: 16, 189, p = 0.02); the highest HPRM score equated with 608 fmol/punch on average. For the self-efficacy subscale, TFV-DP increased by 90 fmol/punch (95% CI: 7, 172, p = 0.03); PrEP disclosure, 68 fmol/punch (95% CI: 19, 117 p = 0.01); and social support, 58fmol/punch (95% CI: 2, 113, p = 0.04). Higher PrEP disclosure suggests high adherence (OR 1.36, 95% CI: 1.00, 1.86, p = 0.05) and predicted persistent high adherence at both months three and six (OR: 1.50, 95% CI: 1.03, 2.21, p = 0.04).<br><br>CONCLUSIONS: The HPRM scale overall and the subscales individually demonstrated good internal consistency among African young women. PrEP disclosure subscale exhibiting significant association with persistent high PrEP adherence is an important finding for PrEP adherence support programs. Future work will assess replicability and expand self-efficacy and social-support subscales after item revision.<br><br>TRIAL REGISTRATION: ClinicalTrials.gov NCT02732730.},
}
@article {pmid36826816,
year = {2023},
author = {Hurwitz, LM and Webb, PM and Jordan, SJ and Doherty, JA and Harris, HR and Goodman, MT and Shvetsov, YB and Modugno, F and Moysich, KB and Schildkraut, JM and Berchuck, A and Anton-Culver, H and Ziogas, A and Menon, U and Ramus, SJ and Wu, AH and Pearce, CL and Wentzensen, N and Tworoger, SS and Pharoah, PDP and Trabert, B},
title = {Association of Frequent Aspirin Use With Ovarian Cancer Risk According to Genetic Susceptibility.},
journal = {JAMA network open},
volume = {6},
number = {2},
pages = {e230666},
doi = {10.1001/jamanetworkopen.2023.0666},
pmid = {36826816},
issn = {2574-3805},
abstract = {IMPORTANCE: Frequent aspirin use is associated with reduced ovarian cancer risk, but it is unknown whether genetic factors modify this association. Understanding effect modifiers is important given that any use of aspirin for ovarian cancer chemoprevention will likely need to focus on specific higher-risk subgroups.<br><br>OBJECTIVE: To evaluate whether the association between frequent aspirin use and ovarian cancer is modified by a polygenic score (PGS) for nonmucinous ovarian cancer.<br><br>We pooled individual-level data from 8 population-based case-control studies from the Ovarian Cancer Association Consortium conducted in the US, UK, and Australia between 1995 and 2009. We included case patients and control participants with both genetic data and data on frequent aspirin use. Case patients with mucinous ovarian cancer were excluded. Data were analyzed between November 1, 2021, and July 31, 2022.<br><br>EXPOSURES: Frequent aspirin use, defined as daily or almost daily use for 6 months or longer.<br><br>MAIN OUTCOMES AND MEASURES: The main outcome was nonmucinous epithelial ovarian cancer. We used logistic regression to estimate odds ratios (ORs) and 95% CIs and likelihood ratio tests to investigate effect modification by the PGS.<br><br>RESULTS: There were 4476 case patients with nonmucinous ovarian cancer and 6659 control participants included in this analysis. At study enrollment, the median (IQR) age was 58 (50-66) years for case patients and 57 (49-65) years for control participants. Case patients and control participants self-reported that they were Black (122 [3%] vs 218 [3%]), White (3995 [89%] vs 5851 [88%]), or of other race and ethnicity (348 [8%] vs 580 [9%]; race and ethnicity were unknown for 11 [0%] vs 10 [0%]). There were 575 case patients (13%) and 1030 control participants (15%) who reported frequent aspirin use. The 13% reduction in ovarian cancer risk associated with frequent aspirin use (OR, 0.87 [95% CI, 0.76-0.99]) was not modified by the PGS. Consistent ORs were observed among individuals with a PGS less than (0.85 [0.70-1.02]) and greater than (0.86 [0.74-1.01]) the median. Results were similar by histotype.<br><br>CONCLUSIONS AND RELEVANCE: The findings of this study suggest that genetic susceptibility to ovarian cancer based on currently identified common genetic variants does not appear to modify the protective association between frequent aspirin use and ovarian cancer risk. Future work should continue to explore the role of aspirin use for ovarian cancer prevention among individuals who are at higher risk for ovarian cancer.},
}
@article {pmid36822396,
year = {2023},
author = {Kaplan, RC and Williams-Nguyen, JS and Huang, Y and Mossavar-Rahmani, Y and Yu, B and Boerwinkle, E and Gellman, MD and Daviglus, M and Chilcoat, A and Van Horn, L and Faurot, K and Qi, Q and Greenlee, H},
title = {Identification of dietary supplements associated with blood metabolites in the Hispanic Community Health Study / Study of Latinos cohort study.},
journal = {The Journal of nutrition},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.tjnut.2023.02.021},
pmid = {36822396},
issn = {1541-6100},
abstract = {BACKGROUND: Metabolomics approaches have been widely used to define consumption of foods but have less often been used to study exposure to dietary supplements.<br><br>OBJECTIVE: To identify dietary supplements associated with metabolite levels, and to examine whether those metabolites predicted incident diabetes risk.<br><br>METHODS: We studied 3972 participants from a prospective cohort study of 18 to 74 year old Hispanic/Latino adults. At a baseline examination we ascertained use of dietary supplements using recall methods and concurrently, a serum metabolomic panel. After adjustment for potential confounders, we identified dietary supplements associated with metabolites. We then examined the association of these metabolites with incident diabetes at the six-year study examination.<br><br>RESULTS: We observed a total of 110 dietary supplement - metabolite associations that met criteria for statistical significance adjusted for age, sex, field center, Hispanic/Latino background, body mass index, diet, smoking, physical activity and number of medications (adjusted P < 0.05). This included 13 metabolites uniquely associated with only one dietary supplement ingredient. Vitamin C had the most associated metabolites (n=15), including positive associations with oxalate, tartronate, threonate and isocitrate which were each in turn protective for risk of incident diabetes. Vitamin C also was associated with higher N-acetylvaline level, which was an unfavorable diabetes risk factor. Other findings related to branched chain amino acid (BCAA) related compounds including alpha-hydroxyisovalerate and 2-hydroxy-3-methylvalerate, which were inversely associated with thiamin or riboflavin intake and also predicted higher diabetes risk. Vitamin B12 had an inverse association with gamma-glutamylvaline, levels of which were inversely associated with risk of diabetes.<br><br>CONCLUSIONS: Our data point to potential metabolite changes associated with Vitamin C and B vitamins which may have favorable metabolic effects. Knowledge of blood metabolites that can be modified by dietary supplement intake may aid understanding of health effects of dietary supplements and identify potential biological mediators.},
}
@article {pmid36821766,
year = {2023},
author = {Radtke, S and Enstrom, MR and Pande, D and Duke, ER and Cardozo Ojeda, EF and Madhu, R and Owen, S and Kanestrom, G and Cui, ML and Perez, AM and Schiffer, JT and Kiem, HP},
title = {Stochastic fate decisions of HSCs after transplantation: early contribution, symmetric expansion, and pool formation.},
journal = {Blood},
volume = {},
number = {},
pages = {},
doi = {10.1182/blood.2022018564},
pmid = {36821766},
issn = {1528-0020},
abstract = {Hematopoietic stem cells (HSCs) are assumed to be rare, infrequently dividing, long-lived, and not involved in immediate recovery after transplantation. Here we performed unprecedented high-density clonal tracking in nonhuman primates and found long-term persisting HSC clones to actively contribute during early neutrophil recovery and be the main source of blood production as early as 50 days post-transplant. Most surprisingly, we observed a rapid decline in the number of unique HSC clones, while persisting HSCs expanded undergoing symmetric divisions to create identical siblings and formed clonal pools ex vivo as well as in vivo. In contrast to the currently assumed model of hematopoietic reconstitution, we provide evidence for contribution of HSCs in short-term recovery as well as symmetric expansion of individual clones into pools. These findings provide novel insights into HSC biology informing the design of HSC transplantation and gene therapy studies.},
}
@article {pmid36821396,
year = {2023},
author = {Sayar, E and Patel, RA and Coleman, IM and Roudier, MP and Zhang, A and Mustafi, P and Low, JY and Hanratty, B and Ang, LS and Bhatia, V and Adil, M and Bakbak, H and Quigley, DA and Schweizer, MT and Hawley, JE and Kollath, L and True, LD and Feng, FY and Bander, NH and Corey, E and Lee, JK and Morrissey, C and Gulati, R and Nelson, PS and Haffner, MC},
title = {Reversible epigenetic alterations mediate PSMA expression heterogeneity in advanced metastatic prostate cancer.},
journal = {JCI insight},
volume = {},
number = {},
pages = {},
doi = {10.1172/jci.insight.162907},
pmid = {36821396},
issn = {2379-3708},
abstract = {Prostate-specific membrane antigen (PSMA) is an important cell surface target in prostate cancer. There are limited data on the heterogeneity of PSMA tissue expression in metastatic castration-resistant prostate cancer (mCRPC). Furthermore, the mechanisms regulating PSMA expression (encoded by the FOLH1 gene) are not well understood. Here, we demonstrate that PSMA expression is heterogeneous across different metastatic sites and molecular subtypes of mCRPC. In a rapid autopsy cohort in which multiple metastatic sites per patient were sampled, we found that 13/52 (25%) cases had no detectable PSMA and 23/52 (44%) showed heterogeneous PSMA expression across individual metastases with 33 (63%) cases harboring at least one PSMA-negative site. PSMA-negative tumors displayed distinct transcriptional profiles, including the expression of druggable targets such as MUC1. Loss of PSMA was associated with epigenetic changes of the FOLH1 locus, including gain of CpG methylation and loss of histone 3 lysine 27 (H3K27) acetylation. Treatment with histone deacetylase (HDAC) inhibitors reversed this epigenetic repression and restored PSMA expression in vitro and in vivo. Collectively, these data provide novel insights into the expression patterns and regulation of PSMA in mCRPC and suggest that epigenetic therapies, in particular HDAC inhibitors, can be used to augment PSMA levels.},
}
@article {pmid36818577,
year = {2021},
author = {Fahey, JW and Kensler, TW},
title = {Phytochemicals: Do They Belong on our Plate for Sustaining Healthspan?.},
journal = {Food frontiers},
volume = {2},
number = {3},
pages = {235-239},
pmid = {36818577},
issn = {2643-8429},
support = {R35 CA197222/CA/NCI NIH HHS/United States ; },
}
@article {pmid36817949,
year = {2023},
author = {Cole, A and Andrilla, CHA and Patterson, D and Davidson, S and Mendoza, J},
title = {Measuring the Impact of the COVID-19 Pandemic on Health Behaviors and Health Care Utilization in Rural and Urban Patients with Cancer and Cancer Survivors.},
journal = {Cancer research communications},
volume = {3},
number = {2},
pages = {215-222},
pmid = {36817949},
issn = {2767-9764},
support = {P30 CA015704/CA/NCI NIH HHS/United States ; },
abstract = {Healthcare access and health behaviors differ between those living in urban and rural communities and contribute to inequitable cancer health outcomes. The COVID-19 pandemic led to significant disruptions in daily life and healthcare delivery. This cross-sectional survey aimed to measure the impact of the COVID-19 pandemic on the health behaviors of cancer patients and survivors, comparing outcomes for urban and rural respondents. Survey was administered from January 2021-June 2021 to cancer patients or survivors (treated within the last 5 years) at one of six cancer centers in Washington and Idaho. Respondent ZIP code was used to assess rurality using Rural-Urban Commuting Area designation. 515 rural (43.5% of those contacted) and 146 urban (40% of those contacted) cancer patients and survivors participated. Few differences between urban and rural cancer patients and cancer survivors were noted. Rural residents were older (69.2 years vs. 66.9 years). Rural respondents had higher mean alcohol consumption than urban respondents (4.4 drinks per week vs. 2.7 drinks per week). 12.2% of those who reported drinking in the last 30 days also reported increased alcohol consumption since the start of the pandemic, with no difference in reported increased alcohol consumption in rural vs. urban respondents. 38.5% reported decreased physical activity. 20.5% reported cancelling or delaying cancer care due to the COVID-19 pandemic. Delays in cancer healthcare services and worsening health behaviors due to the COVID-19 pandemic may contribute to poorer health outcomes, with few differences between rural and urban cancer patients and cancer survivors.},
}
@article {pmid36815378,
year = {2023},
author = {Bertrums, EJM and Smith, JL and Harmon, L and Ries, RE and Wang, YJ and Alonzo, TA and Menssen, AJ and Chisholm, KM and Leonti, AR and Tarlock, K and Ostronoff, F and Pogosova-Agadjanyan, EL and Kaspers, GJL and Hasle, H and Dworzak, M and Walter, C and Muhlegger, N and Morerio, C and Pardo, L and Hirsch, B and Raimondi, S and Cooper, TM and Aplenc, R and Gamis, AS and Kolb, EA and Farrar, JE and Stirewalt, D and Ma, X and Shaw, TI and Furlan, SN and Brodersen, LE and Loken, MR and Van den Heuvel-Eibrink, MM and Zwaan, CM and Triche, TJ and Goemans, BF and Meshinchi, S},
title = {Comprehensive molecular and clinical characterization of NUP98 fusions in pediatric acute myeloid leukemia.},
journal = {Haematologica},
volume = {},
number = {},
pages = {},
doi = {10.3324/haematol.2022.281653},
pmid = {36815378},
issn = {1592-8721},
abstract = {NUP98 fusions c omprise a family o f rare r ecurrent a lterations i n A ML, associated w ith adverse outcomes. To define the underlying biology and clinical implications of this family of fusions, we performed comprehensive transcriptome, epigenome, and immunophenotypic profiling of 2,235 children and young adults with AML and identified 160 NUP98 rearrangements (7.2%), including 108 NUP98-NSD1 (4.8%), 32 NUP98-KDM5A (1.4%) and 20 NUP98-X cases (0.9%) with 13 different fusion partners. Fusion partners defined disease characteristics and biology; patients with NUP98-NSD1 or NUP98-KDM5A had distinct immunophenotypic, transcriptomic, and epigenomic profiles. Unlike the two most prevalent NUP98 fusions, NUP98-X variants are typically not cryptic. Furthermore, NUP98-X cases are associated with WT1 mutations, and have epigenomic profiles that resemble either NUP98- NSD1 or NUP98-KDM5A. Cooperating FLT3-ITD and WT1 mutations define NUP98-NSD1, and chromosome 13 aberrations are highly enriched in NUP98-KDM5A. Importantly, we demonstrate that NUP98 fusions portend dismal overall survival, with the noteworthy exception of patients bearing abnormal chr13.},
}
@article {pmid36814836,
year = {2023},
author = {Usyk, M and Peters, BA and Karthikeyan, S and McDonald, D and Sollecito, CC and Vazquez-Baeza, Y and Shaffer, JP and Gellman, MD and Talavera, GA and Daviglus, ML and Thyagarajan, B and Knight, R and Qi, Q and Kaplan, R and Burk, RD},
title = {Comprehensive evaluation of shotgun metagenomics, amplicon sequencing, and harmonization of these platforms for epidemiological studies.},
journal = {Cell reports methods},
volume = {3},
number = {1},
pages = {100391},
pmid = {36814836},
issn = {2667-2375},
abstract = {In a large cohort of 1,772 participants from the Hispanic Community Health Study/Study of Latinos with overlapping 16SV4 rRNA gene (bacterial amplicon), ITS1 (fungal amplicon), and shotgun sequencing data, we demonstrate that 16SV4 amplicon sequencing and shotgun metagenomics offer the same level of taxonomic accuracy for bacteria at the genus level even at shallow sequencing depths. In contrast, for fungal taxa, we did not observe meaningful agreements between shotgun and ITS1 amplicon results. Finally, we show that amplicon and shotgun data can be harmonized and pooled to yield larger microbiome datasets with excellent agreement (<1% effect size variance across three independent outcomes) using pooled amplicon/shotgun data compared to pure shotgun metagenomic analysis. Thus, there are multiple approaches to study the microbiome in epidemiological studies, and we provide a demonstration of a powerful pooling approach that will allow researchers to leverage the massive amount of amplicon sequencing data generated over the last two decades.},
}
@article {pmid36814251,
year = {2023},
author = {Rashidi, A and Koyama, M and Dey, N and McLean, JS and Hill, GR},
title = {Colonization resistance is dispensable for segregation of oral and gut microbiota.},
journal = {BMC medical genomics},
volume = {16},
number = {1},
pages = {31},
pmid = {36814251},
issn = {1755-8794},
abstract = {BACKGROUND: The oral and colonic microbiota are distinct in healthy individuals. However, this distinction is diminished in common diseases such as colon cancer and inflammatory bowel disease, suggesting a potential pathogenic role for oral bacteria when ectopically colonized in the gut. A key mechanism for the segregation of oral and colonic microbiota niches is thought to be microbiota-mediated colonization resistance whereby the commensal gut microbiota outcompete and eliminate the ingested oral bacteria.<br><br>METHODS: We tested this theory by analyzing exact amplicon sequence variants generated from concurrent fecal and oral samples from healthy volunteers exposed to a brief course of a single antibiotic (cohort 1), acute leukemia patients (cohort 2), and stem cell transplant recipients (cohort 3). Cohorts 2 and 3 represent extreme clinical scenarios with respect to antibiotic pressure and severity of gut microbiota injury.<br><br>RESULTS: While mild antibiotic exposure in cohort 1 was not sufficient for colonization of any oral bacteria in the gut, even with extreme antibiotic pressure and severe gut microbiota disruptions in cohorts 2 and 3, only one oral species in each cohort colonized the gut.<br><br>CONCLUSIONS: Colonization resistance is dispensable for segregation of oral and colonic microbiota in humans. This finding implies that the presence of oral bacteria in the distal gut in diseases such as colon cancer and inflammatory bowel disease is not driven by impaired colonization resistance.},
}
@article {pmid36813070,
year = {2023},
author = {Kulick, ER and Eliot, MN and Szpiro, AA and Coull, BA and Tinker, LF and Eaton, CB and Whitsel, EA and Stewart, JD and Kaufman, JD and Wellenius, GA},
title = {Long-term exposure to ambient particulate matter and stroke etiology: Results from the Women's Health Initiative.},
journal = {Environmental research},
volume = {},
number = {},
pages = {115519},
doi = {10.1016/j.envres.2023.115519},
pmid = {36813070},
issn = {1096-0953},
abstract = {BACKGROUND: Ambient particulate matter (PM) air pollution is a leading cause of global disability and accounts for an annual 2.9 million deaths globally. PM is established as an important risk factor for cardiovascular disease, however the evidence supporting a link specifically between long-term exposure to ambient PM and incident stroke is less clear. We sought to evaluate the association of long-term exposure to different size fractions of ambient PM with incident stroke (overall and by etiologic subtypes) and cerebrovascular deaths within the Women's Health Initiative, a large prospective study of older women in the US.<br><br>METHODS: We studied 155,410 postmenopausal women without previous cerebrovascular disease enrolled into the study between 1993 and 1998, with follow-up through 2010. We assessed geocoded participant address-specific concentrations of ambient PM (fine [PM2.5], respirable [PM10] and coarse [PM10-2.5]), as well as nitrogen dioxide [NO2]) using spatiotemporal models. We classified hospitalization events into ischemic, hemorrhagic, or other/unclassified stroke. Cerebrovascular mortality was defined as death from any stroke etiology. We used Cox proportional hazard models to calculate hazard ratios (HR) and 95% confidence intervals, adjusting for individual and neighborhood-level characteristics.<br><br>RESULTS: During a median follow-up time of 15 years, participants experienced 4556 cerebrovascular events. The hazard ratio for all cerebrovascular events was 2.14 (95% CI: 1.87, 2.44) comparing the top versus bottom quartiles of PM2.5. Similarly, there was a statistically significant increase in events comparing the top versus bottom quartiles of PM10 and NO2 (HR: 1.17; 95% CI: 1.03, 1.33 and HR:1.26; 95% CI: 1.12, 1.42). The strength of association did not vary substantially by stroke etiology. There was little evidence of an association between PMcoarse and incident cerebrovascular events.<br><br>CONCLUSIONS: Long-term exposure to fine (PM2.5) and respirable (PM10) particulate matter as well as NO2 was associated with a significant increase of cerebrovascular events among postmenopausal women. Strength of the associations were consistent by stroke etiology.},
}
@article {pmid36812131,
year = {2023},
author = {Hyde, ET and LaCroix, AZ and Evenson, KR and Howard, AG and Anuskiewicz, B and Di, C and Bellettiere, J and LaMonte, MJ and Manson, JE and Buring, JE and Shiroma, EJ and Lee, IM and Parada, H},
title = {Accelerometer-measured physical activity and postmenopausal breast cancer incidence in the Women's Health Accelerometry Collaboration.},
journal = {Cancer},
volume = {},
number = {},
pages = {},
doi = {10.1002/cncr.34699},
pmid = {36812131},
issn = {1097-0142},
support = {P30 AG059299/AG/NIA NIH HHS/United States ; U54 CA132379/CA/NCI NIH HHS/United States ; U54 CA132384/CA/NCI NIH HHS/United States ; 75N92021D00001/HL/NHLBI NIH HHS/United States ; 75N92021D00002/HL/NHLBI NIH HHS/United States ; 75N92021D00003/HL/NHLBI NIH HHS/United States ; 75N92021D00004/HL/NHLBI NIH HHS/United States ; 75N92021D00005/HL/NHLBI NIH HHS/United States ; HL130591/HL/NHLBI NIH HHS/United States ; HL150170/HL/NHLBI NIH HHS/United States ; HL151885/HL/NHLBI NIH HHS/United States ; HL153462/HL/NHLBI NIH HHS/United States ; R01HL105065/HL/NHLBI NIH HHS/United States ; T32HL079891/HL/NHLBI NIH HHS/United States ; CA047988/NH/NIH HHS/United States ; CA154647/NH/NIH HHS/United States ; CA182913/NH/NIH HHS/United States ; HL043851/NH/NIH HHS/United States ; HL080467/NH/NIH HHS/United States ; HL099355/NH/NIH HHS/United States ; 5R01CA227122/CA/NCI NIH HHS/United States ; K01 CA234317/CA/NCI NIH HHS/United States ; },
abstract = {BACKGROUND: Few studies have examined accelerometer-measured physical activity and incident breast cancer (BC). Thus, this study examined associations between accelerometer-measured vector magnitude counts per 15 seconds (VM/15s) and average daily minutes of light physical activity (LPA), moderate-to-vigorous PA (MVPA), and total PA (TPA) and BC risk among women in the Women's Health Accelerometry Collaboration (WHAC).<br><br>METHODS: The WHAC comprised 21,089 postmenopausal women (15,375 from the Women's Health Study [WHS]; 5714 from the Women's Health Initiative Objective Physical Activity and Cardiovascular Health Study [OPACH]). Women wore an ActiGraph GT3X+&#xa0;on the hip for &#x2265;4&#xa0;days and were followed for 7.4 average years to identify physician-adjudicated in situ (n&#xa0;=&#xa0;94) or invasive (n&#xa0;=&#xa0;546) BCs. Multivariable stratified Cox regression estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for tertiles of physical activity measures in association with incident BC overall and by cohort. Effect measure modification was&#xa0;examined&#xa0;by age, race/ethnicity, and body mass index (BMI).<br><br>RESULTS: In covariate-adjusted models, the highest (vs. lowest) tertiles of VM/15s, TPA, LPA, and MVPA were associated with BC HRs of 0.80 (95% CI, 0.64-0.99), 0.84 (95% CI,&#xa0;0.69-1.02), 0.89 (95% CI,&#xa0;0.73-1.08), and 0.81 (95% CI,&#xa0;0.64-1.01), respectively. Further adjustment for BMI or physical function attenuated these associations. Associations were more pronounced among OPACH than WHS women for VM/15s, MVPA, and TPA; younger than older women for MVPA; and women with BMI &#x2265;30 than <30&#xa0;kg/m[2] for LPA.<br><br>CONCLUSION: Greater levels of accelerometer-assessed PA were associated with lower BC risk. Associations varied by age and obesity and were not independent of BMI or physical function.},
}
@article {pmid36809468,
year = {2023},
author = {Zhao, LP and Cohen, S and Zhao, M and Madeleine, M and Payne, TH and Lybrand, TP and Geraghty, DE and Jerome, KR and Corey, L},
title = {Using Haplotype-Based Artificial Intelligence to Evaluate SARS-CoV-2 Novel Variants and Mutations.},
journal = {JAMA network open},
volume = {6},
number = {2},
pages = {e230191},
pmid = {36809468},
issn = {2574-3805},
abstract = {IMPORTANCE: Earlier detection of emerging novel SARS-COV-2 variants is important for public health surveillance of potential viral threats and for earlier prevention research. Artificial intelligence may facilitate early detection of SARS-CoV2 emerging novel variants based on variant-specific mutation haplotypes and, in turn, be associated with enhanced implementation of risk-stratified public health prevention strategies.<br><br>OBJECTIVE: To develop a haplotype-based artificial intelligence (HAI) model for identifying novel variants, including mixture variants (MVs) of known variants and new variants with novel mutations.<br><br>This cross-sectional study used serially observed viral genomic sequences globally (prior to March 14, 2022) to train and validate the HAI model and used it to identify variants arising from a prospective set of viruses from March 15 to May 18, 2022.<br><br>MAIN OUTCOMES AND MEASURES: Viral sequences, collection dates, and locations were subjected to statistical learning analysis to estimate variant-specific core mutations and haplotype frequencies, which were then used to construct an HAI model to identify novel variants.<br><br>RESULTS: Through training on more than 5 million viral sequences, an HAI model was built, and its identification performance was validated on an independent validation set of more than 5 million viruses. Its identification performance was assessed on a prospective set of 344&#x202f;901 viruses. In addition to achieving an accuracy of 92.8% (95% CI within 0.1%), the HAI model identified 4 Omicron MVs (Omicron-Alpha, Omicron-Delta, Omicron-Epsilon, and Omicron-Zeta), 2 Delta MVs (Delta-Kappa and Delta-Zeta), and 1 Alpha-Epsilon MV, among which Omicron-Epsilon MVs were most frequent (609/657 MVs [92.7%]). Furthermore, the HAI model found that 1699 Omicron viruses had unidentifiable variants given that these variants acquired novel mutations. Lastly, 524 variant-unassigned and variant-unidentifiable viruses carried 16 novel mutations, 8 of which were increasing in prevalence percentages as of May 2022.<br><br>CONCLUSIONS AND RELEVANCE: In this cross-sectional study, an HAI model found SARS-COV-2 viruses with MV or novel mutations in the global population, which may require closer examination and monitoring. These results suggest that HAI may complement phylogenic variant assignment, providing additional insights into emerging novel variants in the population.},
}
@article {pmid36807505,
year = {2023},
author = {Kinuthia, J and Dettinger, JC and Stern, J and Ngumbau, N and Ochieng, B and Gómez, L and Abuna, F and Watoyi, S and Marwa, M and Odinga, D and Wagner, AD and Richardson, BA and Pintye, J and Baeten, JM and John-Stewart, G},
title = {Risk-based versus universal PrEP delivery during pregnancy: a cluster randomized trial in Western Kenya from 2018 to 2019.},
journal = {Journal of the International AIDS Society},
volume = {26},
number = {2},
pages = {e26061},
pmid = {36807505},
issn = {1758-2652},
abstract = {INTRODUCTION: Integrating pre-exposure prophylaxis (PrEP) delivery for pregnant and postpartum women within maternal and child health (MCH) clinics is feasible and acceptable. It is unknown whether a risk-guided model would facilitate appropriate PrEP use among MCH attendees better than universally offering PrEP.<br><br>METHODS: The PrEP Implementation for Mothers in Antenatal Care (PrIMA) study was a cluster randomized trial to assess two models for PrEP delivery among pregnant women seeking routine MCH care at 20 public clinics in Kenya between January 2018 and July 2019 (NCT03070600). In the Universal arm, all participants received PrEP counselling and self-selected whether to initiate PrEP. In the Targeted arm, participants underwent an HIV risk assessment, including an objective risk-scoring tool and an offer of HIV self-tests for at-home partner testing; those determined to be at high risk received a PrEP offer. Participants were followed through 9 months postpartum. Primary outcomes included incident HIV and appropriate PrEP use (defined as PrEP uptake among those at high risk and no PrEP uptake for those not at risk). Outcomes were compared using intention-to-treat analyses, adjusting for baseline HIV risk and marital status.<br><br>RESULTS: Among 4447 women enrolled, the median age was 24.0 years (interquartile range [IQR]: 20.9, 28.3), and most were married (84.8%). The median gestational age at enrolment was 24 weeks (IQR: 20, 30). Women in the Targeted arm were more likely to be at high risk for HIV acquisition at baseline (51.6% vs. 33.3%). During 4638 person-years (p-yr) of follow-up, there were 16 maternal HIV infections with no difference in maternal HIV incidence between arms: 0.31/100 p-yr (95% CI: 0.15, 0.65) Targeted and 0.38/100p-yr (95% CI: 0.20, 0.73) Universal (adjusted relative risk [aRR]: 0.85 [CI: 0.28, 2.55]). There was no significant difference in the frequency of appropriate PrEP use between the arms (68.2% vs. 59.1% in Targeted vs. Universal, respectively) (aRR: 1.03 [CI: 0.96, 1.10]).<br><br>CONCLUSIONS: Given comparable maternal HIV incidence and PrEP uptake in Universal and Targeted approaches, and the simplicity that universal PrEP offers, our findings suggest that universal PrEP counselling is optimal for integrating PrEP in MCH systems.},
}
@article {pmid36806947,
year = {2023},
author = {Pan, C and Wu, QV and Voutsinas, J and Houlton, JJ and Barber, B and Rizvi, ZH and Marchiano, E and Futran, N and Laramore, GE and Liao, JJ and Parvathaneni, U and Martins, RG and Fromm, JR and Rodriguez, CP},
title = {Peripheral lymphocytes and lactate dehydrogenase correlate with response and survival in head and neck cancers treated with immune checkpoint inhibitors.},
journal = {Cancer medicine},
volume = {},
number = {},
pages = {},
doi = {10.1002/cam4.5697},
pmid = {36806947},
issn = {2045-7634},
support = {T32 DC000018/DC/NIDCD NIH HHS/United States ; },
abstract = {BACKGROUND: Little is known regarding associations between peripheral blood biomarkers (PBBMs) and survival, response, and toxicity in recurrent/metastatic head and neck squamous cell carcinomas (R/M HNSCC) treated with immune checkpoint inhibitors (ICIs).<br><br>METHODS: In this single-institution retrospective cohort study, a dataset of patients with R/M HNSCC treated with ICIs between 08/2012-03/2021 was established, including demographic and clinicopathologic characteristics. Pretreatment PBBMs were collected and evaluated for associations with grade &#x2265;3 adverse events (G&#x2009;&#x2265;&#x2009;3AE) by CTCAEv5, objective response (ORR) by RECIST 1.1, overall survival (OS), and progression-free survival (PFS). Multivariable models for each outcome were created using elastic net variable selection.<br><br>RESULTS: Our study included 186 patients, with 51 (27%) demonstrating complete or partial response to immunotherapy. Multivariable models adjusted for ECOG performance status (PS), p16, and smoking demonstrated that pretreatment higher LDH and absolute neutrophils, as well as lower percent lymphocytes correlated with worse OS and PFS. Higher LDH and lower % lymphocytes also correlated with worse ORR.<br><br>CONCLUSIONS: In the largest study to date examining PBBMs in ICI-treated R/M HNSCCs, our variable selection method revealed PBBMs prognostic for survival and response to immunotherapy. These biomarkers warrant further investigation in a prospective study along with validation with CPS biomarker.},
}
@article {pmid36806839,
year = {2023},
author = {Bullman, S},
title = {INVADEseq to study the intratumoural microbiota at host single-cell resolution.},
journal = {Nature reviews. Cancer},
volume = {},
number = {},
pages = {},
pmid = {36806839},
issn = {1474-1768},
}
@article {pmid36804933,
year = {2023},
author = {Rashidi, A and Huselton, EJ and Stefanski, HE and DeFor, TE and Shanley, R and Choi, J and DiPersio, JF and Juckett, M and Miller, JS and Weisdorf, DJ and Schroeder, MA},
title = {A multicenter phase 2 clinical trial of 10-day decitabine, dose-escalated donor lymphocyte infusion, and ruxolitinib for relapsed acute myeloid leukemia and myelodysplastic syndromes after allogeneic hematopoietic cell transplantation.},
journal = {Transplantation and cellular therapy},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jtct.2023.02.010},
pmid = {36804933},
issn = {2666-6367},
abstract = {Post-transplant relapse of acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) has a poor prognosis. Donor lymphocyte infusion (DLI) is one treatment approach. However, efficacy is limited and toxicity, mostly in the form of acute graft-versus-host disease (GVHD), is frequent OBJECTIVE: We tested a novel approach using 10-day decitabine, dose-escalated DLI, and ruxolitinib in a multicenter phase 2 trial to increase the efficacy of DLI and reduce its toxicity STUDY DESIGN: Up to four 28-day cycles were administered. The primary endpoint was 6-month overall survival (OS) RESULTS: Thirteen, 6, 1, and 0 of the 14 patients who started cycle 1 received 1, 2, 3, and 4 DLIs, respectively. Pre-planned interim analysis after enrolling 14 patients suggested futility and the trial was closed to accrual. Final analysis showed a 6-month OS of 36% (95% confidence interval: 18-72), 1-year PFS 7% (1-47), 6-month cumulative incidence of grade II-IV acute GVHD 57% (26-80), and 1-year NRM 14% (2-38) CONCLUSION: The combined-modality treatment studied in this trial was ineffective and did not reduce DLI toxicity.},
}
@article {pmid36804930,
year = {2023},
author = {Barreras, H and Copsel, SN and Bader, CS and Ding, Y and Wolf, D and Cash, C and Stacey, CJ and Benjamin, C and Seavey, MM and Wolf, J and Jasuja, RR and Pfeiffer, B and Hill, GR and Komanduri, KV and Jurecic, R and Malek, TR and Levy, RB},
title = {Treg amelioration of GVHD following allo/xeno-HSCT using mobilized mouse and human peripheral blood donors.},
journal = {Transplantation and cellular therapy},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jtct.2023.02.015},
pmid = {36804930},
issn = {2666-6367},
}
@article {pmid36804046,
year = {2023},
author = {Salloum, RG and Bricker, JB and Lee, JH and Theis, RP and Pluta, K and Williams, MP and Naous, J and Mulani, SR and Cogle, CR and Rubin, DA and Fahnlander, AM and Nordelo, B and Sullivan, BM and Bloodworth, S and Corbin, L and Siler, K and Willis, D and Carrasquillo, O and Dallery, J},
title = {Comparative effectiveness of mobile health smoking cessation approaches among underserved patients in primary care: Study protocol for the PROMOTE-UP trial.},
journal = {Contemporary clinical trials},
volume = {},
number = {},
pages = {107120},
doi = {10.1016/j.cct.2023.107120},
pmid = {36804046},
issn = {1559-2030},
abstract = {INTRODUCTION: Tobacco smoking is the leading cause of preventable disease, disability, and premature death in the United States. Recent advances have led to two efficacious mobile health (mHealth) treatments for smoking cessation: iCanQuit, an Acceptance and Commitment Therapy-based behavioral treatment promoting cessation through accepting triggers and committing to values; and Motiv8, a contingency management intervention promoting smoking cessation with financial incentives via biochemically verified abstinence. This study will evaluate the comparative effectiveness of the Florida Quitline, iCanQuit alone, and iCanQuit+Motiv8 in a pragmatic trial among patients who smoke in underserved primary care settings.<br><br>METHODS: The study will be an individually-randomized controlled trial with three arms (Florida Quitline, iCanQuit alone, iCanQuit+Motiv8 combined) conducted in multiple primary care practices affiliated with the OneFlorida+ Clinical Research Consortium. Adult patients who smoke will be randomized to one of the 3 study arms (n&#x202f;=&#x202f;444/arm), stratified by healthcare setting (academic vs. community). The primary outcome will be 7-day point prevalence smoking abstinence at 6&#x202f;months post-randomization. Secondary outcomes will be 12-month smoking abstinence, patient satisfaction with the interventions, and changes in patient quality of life and self-efficacy. The study will also assess how and for whom the interventions help sub-group patients in achieving smoking abstinence by measuring theory-derived factors that mediate smoking outcome-specific baseline moderators.<br><br>CONCLUSIONS: Results from this study will provide evidence for the comparative effectiveness of mHealth smoking cessation interventions in healthcare settings. Use of mHealth interventions can make smoking cessation resources more equitably accessible and have far-reaching impact on community and population health.<br><br>TRIAL REGISTRATION: ClinicalTrials.gov, NCT05415761, Registered 13 June 2022.},
}
@article {pmid36803543,
year = {2023},
author = {Moulana, A and Dupic, T and Phillips, AM and Chang, J and Roffler, AA and Greaney, AJ and Starr, T and Bloom, JD and Desai, MM},
title = {The landscape of antibody binding affinity in SARS-CoV-2 Omicron BA.1 evolution.},
journal = {eLife},
volume = {12},
number = {},
pages = {},
doi = {10.7554/eLife.83442},
pmid = {36803543},
issn = {2050-084X},
support = {Hanna H. Gray Postdoctoral Fellowship/HHMI/Howard Hughes Medical Institute/United States ; Harvard Quantitative Biology InitiativeGM104239/NH/NIH HHS/United States ; NIH/NIAID R01AI141707/NH/NIH HHS/United States ; },
abstract = {The Omicron BA.1 variant of SARS-CoV-2 escapes convalescent sera and monoclonal antibodies that are effective against earlier strains of the virus. This immune evasion is largely a consequence of mutations in the BA.1 receptor binding domain (RBD), the major antigenic target of SARS-CoV-2. Previous studies have identified several key RBD mutations leading to escape from most antibodies. However, little is known about how these escape mutations interact with each other and with other mutations in the RBD. Here, we systematically map these interactions by measuring the binding affinity of all possible combinations of these 15 RBD mutations (2[15] = 32,768 genotypes) to four monoclonal antibodies (LY-CoV016, LY-CoV555, REGN10987, and S309) with distinct epitopes. We find that BA.1 can lose affinity to diverse antibodies by acquiring a few large-effect mutations and can reduce affinity to others through several small-effect mutations. However, our results also reveal alternative pathways to antibody escape that do not include every large-effect mutation. Moreover, epistatic interactions are shown to constrain affinity decline in S309 but only modestly shape the affinity landscapes of other antibodies. Together with previous work on the ACE2 affinity landscape, our results suggest that escape of each antibody is mediated by distinct groups of mutations, whose deleterious effects on ACE2 affinity are compensated by another distinct group of mutations (most notably Q498R and N501Y).},
}
@article {pmid36802421,
year = {2023},
author = {Motmaen, A and Dauparas, J and Baek, M and Abedi, MH and Baker, D and Bradley, P},
title = {Peptide-binding specificity prediction using fine-tuned protein structure prediction networks.},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
volume = {120},
number = {9},
pages = {e2216697120},
doi = {10.1073/pnas.2216697120},
pmid = {36802421},
issn = {1091-6490},
abstract = {Peptide-binding proteins play key roles in biology, and predicting their binding specificity is a long-standing challenge. While considerable protein structural information is available, the most successful current methods use sequence information alone, in part because it has been a challenge to model the subtle structural changes accompanying sequence substitutions. Protein structure prediction networks such as AlphaFold model sequence-structure relationships very accurately, and we reasoned that if it were possible to specifically train such networks on binding data, more generalizable models could be created. We show that placing a classifier on top of the AlphaFold network and fine-tuning the combined network parameters for both classification and structure prediction accuracy leads to a model with strong generalizable performance on a wide range of Class I and Class II peptide-MHC interactions that approaches the overall performance of the state-of-the-art NetMHCpan sequence-based method. The peptide-MHC optimized model shows excellent performance in distinguishing binding and non-binding peptides to SH3 and PDZ domains. This ability to generalize well beyond the training set far exceeds that of sequence-only models and should be particularly powerful for systems where less experimental data are available.},
}
@article {pmid36800642,
year = {2023},
author = {Li, C and Georgakopoulou, A and Newby, GA and Chen, PJ and Everette, KA and Paschoudi, K and Vlachaki, E and Gil, S and Anderson, AK and Koob, T and Huang, L and Wang, H and Kiem, HP and Liu, DR and Yannaki, E and Lieber, A},
title = {In vivo HSC prime editing rescues Sickle Cell Disease in a mouse model.},
journal = {Blood},
volume = {},
number = {},
pages = {},
doi = {10.1182/blood.2022018252},
pmid = {36800642},
issn = {1528-0020},
abstract = {Sickle Cell Disease (SCD) is a monogenic disease caused by a nucleotide mutation in the β-globin gene. Current gene therapy studies are mainly focused on lentivirus vector-mediated gene addition or CRISPR/Cas9-mediated fetal globin reactivation, leaving the root cause unfixed. We developed a vectorized prime editing system that can directly repair the SCD mutation in hematopoietic stem cells (HSCs) in vivo in a SCD mouse model (CD46/Townes mice). Our approach involved a single intravenous injection of a non-integrating, prime editor-expressing virus vector into mobilized CD46/Townes mice and low-dose drug selection in vivo. This procedure resulted in the correction of ~40% of bS alleles in HSCs. On average 43% of HbS was replaced by HbA thereby greatly mitigating the SCD phenotypes. Transplantation in secondary recipients demonstrated that long-term repopulating HSCs were edited. Highly efficient target site editing was achieved with minimal generation of insertions and deletions and no detectable off-target editing. Because of its simplicity and portability, our in vivo prime editing approach has the potential for application in resource-poor countries where SCD is prevalent.},
}
@article {pmid36800564,
year = {2023},
author = {Sorror, ML},
title = {The Use of Prognostic Models in Allogeneic Transplants: A Perspective Guide for Clinicians and Investigators.},
journal = {Blood},
volume = {},
number = {},
pages = {},
doi = {10.1182/blood.2022017999},
pmid = {36800564},
issn = {1528-0020},
abstract = {Allogeneic hematopoietic cell transplantation (HCT) can cure many hematologic diseases, but it carries the potential risks of increased morbidity and mortality rates. Prognostic evaluation is a scientific entity at the core of care for potential recipients of HCT. It improves the decision-making process of transplant versus not and of which transplant strategy and allows for future trials targeting patients' intolerances to transplant; hence it ultimately improves transplant outcomes. Prognostic models are key for appropriate actuarial outcome estimates, which has been frequently shown to be better than physicians' subjective estimates. To make the most accurate prognostic evaluation for HCT, one should rely on more than one prognostic model. For relapse and relapse-related mortality risks, the refined disease risk index is currently the most informative model. It can be supplemented by disease-specific models that consider genetic mutations as predictors in addition to information on measurable residual disease. For non-relapse mortality and HCT-related morbidity risks, the HCT-comorbidity index and Karnofsky performance status have proven to be the most reliable and most accepted by physicians. These can be supplemented by gait speed as a measure of frailty. Some other global prognostic models might add additional prognostic information. Physicians' educated perceptions can then put all this information in context taking into consideration conditioning regimen and donor choices. The future of transplantation mandates 1) clinical investigators specifically trained in prognostication, 2) increased reliance on geriatric assessment, 3) the use of novel biomarkers such as genetic variants, and 4) successfully applying novel statistical methods such as machine-learning.},
}
@article {pmid36798090,
year = {2023},
author = {Rivers, Z and Roth, JA and Wright, W and Rim, SH and Richardson, LC and Thomas, CC and Townsend, JS and Ramsey, SD},
title = {Translating an Economic Analysis into a Tool for Public Health Resource Allocation in Cancer Survivorship.},
journal = {MDM policy &amp; practice},
volume = {8},
number = {1},
pages = {23814683231153378},
pmid = {36798090},
issn = {2381-4683},
abstract = {UNLABELLED: Background. The complexity of decision science models may prevent their use to assist in decision making. User-centered design (UCD) principles provide an opportunity to engage end users in model development and refinement, potentially reducing complexity and increasing model utilization in a practical setting. We report our experiences with UCD to develop a modeling tool for cancer control planners evaluating cancer survivorship interventions. Design. Using UCD principles (described in the article), we developed a dynamic cohort model of cancer survivorship for individuals with female breast, colorectal, lung, and prostate cancer over 10 y. Parameters were obtained from the National Program of Cancer Registries and peer-reviewed literature, with model outcomes captured in quality-adjusted life-years and net monetary benefit. Prototyping and iteration were conducted with structured focus groups involving state cancer control planners and staff from the Centers for Disease Control and Prevention and the American Public Health Association. Results. Initial feedback highlighted model complexity and unclear purpose as barriers to end user uptake. Revisions addressed complexity by simplifying model input requirements, providing clear examples of input types, and reducing complex language. Wording was added to the results page to explain the interpretation of results. After these updates, feedback demonstrated that end users more clearly understood how to use and apply the model for cancer survivorship resource allocation tasks. Conclusions. A UCD approach identified challenges faced by end users in integrating a decision aid into their workflow. This approach created collaboration between modelers and end users, tailoring revisions to meet the needs of the users. Future models developed for individuals without a decision science background could leverage UCD to ensure the model meets the needs of the intended audience.<br><br>HIGHLIGHTS: Model complexity and unclear purpose are 2 barriers that prevent lay users from integrating decision science tools into their workflow.Modelers could integrate the user-centered design framework when developing a model for lay users to reduce complexity and ensure the model meets the needs of the users.},
}
@article {pmid36797830,
year = {2023},
author = {Mandal, S and Kim, DH and Hua, X and Li, S and Shi, J},
title = {Estimating the overall fraction of phenotypic variance attributed to high-dimensional predictors measured with error.},
journal = {Biostatistics (Oxford, England)},
volume = {},
number = {},
pages = {},
doi = {10.1093/biostatistics/kxad001},
pmid = {36797830},
issn = {1468-4357},
abstract = {In prospective genomic studies (e.g., DNA methylation, metagenomics, and transcriptomics), it is crucial to estimate the overall fraction of phenotypic variance (OFPV) attributed to the high-dimensional genomic variables, a concept similar to heritability analyses in genome-wide association studies (GWAS). Unlike genetic variants in GWAS, these genomic variables are typically measured with error due to technical limitation and temporal instability. While the existing methods developed for GWAS can be used, ignoring measurement error may severely underestimate OFPV and mislead the design of future studies. Assuming that measurement error variances are distributed similarly between causal and noncausal variables, we show that the asymptotic attenuation factor equals to the average intraclass correlation coefficients of all genomic variables, which can be estimated based on a pilot study with repeated measurements. We illustrate the method by estimating the contribution of microbiome taxa to body mass index and multiple allergy traits in the American Gut Project. Finally, we show that measurement error does not cause meaningful bias when estimating the correlation of effect sizes for two traits.},
}
@article {pmid36797499,
year = {2023},
author = {Scherer, S and Oberle, SG and Kanev, K and Gerullis, AK and Wu, M and de Almeida, GP and Puleston, DJ and Baixauli, F and Aly, L and Greco, A and Nizharadze, T and Becker, NB and Hoesslin, MV and Donhauser, LV and Berner, J and Chu, T and McNamara, HA and Esencan, Z and Roelli, P and Wurmser, C and Kleiter, I and Vehreschild, MJGT and Mayer, CA and Knolle, P and Klingenspor, M and Fumagalli, V and Iannacone, M and Prlic, M and Korn, T and Pearce, EL and Höfer, T and Schulz, AM and Zehn, D},
title = {Pyrimidine de novo synthesis inhibition selectively blocks effector but not memory T cell development.},
journal = {Nature immunology},
volume = {},
number = {},
pages = {},
pmid = {36797499},
issn = {1529-2916},
abstract = {Blocking pyrimidine de novo synthesis by inhibiting dihydroorotate dehydrogenase is used to treat autoimmunity and prevent expansion of rapidly dividing cell populations including activated T cells. Here we show memory T cell precursors are resistant to pyrimidine starvation. Although the treatment effectively blocked effector T cells, the number, function and transcriptional profile of memory T cells and their precursors were unaffected. This effect occurred in a narrow time window in the early T cell expansion phase when developing effector, but not memory precursor, T cells are vulnerable to pyrimidine starvation. This vulnerability stems from a higher proliferative rate of early effector T cells as well as lower pyrimidine synthesis capacity when compared with memory precursors. This differential sensitivity is a drug-targetable checkpoint that efficiently diminishes effector T cells without affecting the memory compartment. This cell fate checkpoint might therefore lead to new methods to safely manipulate effector T cell responses.},
}
@article {pmid36796273,
year = {2023},
author = {Shirakawa, M and Yamada, K and Watase, H and Chu, B and Enomoto, Y and Kojima, T and Wakabayashi, K and Sun, J and Hippe, DS and Ferguson, MS and Balu, N and Yoshimura, S and Hatsukami, TS and Yuan, C},
title = {Atherosclerotic carotid plaque characteristics vary with time from ischemic event: A multicenter, prospective magnetic resonance vessel wall imaging registry study.},
journal = {Journal of the neurological sciences},
volume = {446},
number = {},
pages = {120582},
doi = {10.1016/j.jns.2023.120582},
pmid = {36796273},
issn = {1878-5883},
abstract = {Recent studies report that the rate of recurrent stroke is highest in the stages immediately following cerebral infarction and decreases over time in patients with atherosclerotic carotid stenosis. The purpose of this study was to identify temporal differences in early stage carotid plaque components from acute cerebrovascular ischemic events using carotid MRI. Carotid plaque images were obtained on 3 T MRI from 128 patients enrolled in MR-CAS. Among the 128 subjects, 53 were symptomatic and 75 asymptomatic. The symptomatic patients were classified into three groups based on interval from onset of symptoms to the date of the carotid MRI (Group <14 days; 15-30 days; and > 30 days). The volume of each plaque component was identified and quantified from MR images. The presence of juxtaluminal loose matrix/inflammation (LM/I) was identified as a possible indicator of inflammation on the luminal side. Plaque components were compared between groups using the Wilcoxon rank-sum or the Chi-square test. Patient characteristics and carotid plaque morphology were similar among all four groups. The median volume of LM/I in Group >30 days was significantly lower than in other groups (0 mm3 vs 12.3 mm3 and 18.1 mm3; p = 0.003). In addition, the prevalence of juxtaluminal LM/I decreased over time (ptrend = 0.002). There were no statistically significant differences in other plaque components between the symptomatic groups. The volume of LM/I was significantly smaller in Group >30 days and prevalence of juxtaluminal LM/I in the atherosclerotic carotid plaque was high in the early stages after events. This suggests that carotid plaques undergo rapid evolution after an acute cerebrovascular ischemic event.},
}
@article {pmid36795987,
year = {2023},
author = {Farrar, JE and Smith, JL and Othus, M and Huang, BJ and Wang, YC and Ries, R and Hylkema, T and Pogosova-Agadjanyan, EL and Challa, S and Leonti, A and Shaw, TI and Triche, TJ and Gamis, AS and Aplenc, R and Kolb, EA and Ma, X and Stirewalt, DL and Alonzo, TA and Meshinchi, S},
title = {Long Noncoding RNA Expression Independently Predicts Outcome in Pediatric Acute Myeloid Leukemia.},
journal = {Journal of clinical oncology : official journal of the American Society of Clinical Oncology},
volume = {},
number = {},
pages = {JCO2201114},
doi = {10.1200/JCO.22.01114},
pmid = {36795987},
issn = {1527-7755},
abstract = {PURPOSE: Optimized strategies for risk classification are essential to tailor therapy for patients with biologically distinctive disease. Risk classification in pediatric acute myeloid leukemia (pAML) relies on detection of translocations and gene mutations. Long noncoding RNA (lncRNA) transcripts have been shown to associate with and mediate malignant phenotypes in acute myeloid leukemia (AML) but have not been comprehensively evaluated in pAML.<br><br>METHODS: To identify lncRNA transcripts associated with outcomes, we evaluated the annotated lncRNA landscape by transcript sequencing of 1,298 pediatric and 96 adult AML specimens. Upregulated lncRNAs identified in the pAML training set were used to establish a regularized Cox regression model of event-free survival (EFS), yielding a 37 lncRNA signature (lncScore). Discretized lncScores were correlated with initial and postinduction treatment outcomes using Cox proportional hazards models in validation sets. Predictive model performance was compared with standard stratification methods by concordance analysis.<br><br>RESULTS: Training set cases with positive lncScores had 5-year EFS and overall survival rates of 26.7% and 42.7%, respectively, compared with 56.9% and 76.3% with negative lncScores (hazard ratio, 2.48 and 3.16; P < .001). Pediatric validation cohorts and an adult AML group yielded comparable results in magnitude and significance. lncScore remained independently prognostic in multivariable models, including key factors used in preinduction and postinduction risk stratification. Subgroup analysis suggested that lncScores provide additional outcome information in heterogeneous subgroups currently classified as indeterminate risk. Concordance analysis showed that lncScore adds to overall classification accuracy with at least comparable predictive performance to current stratification methods that rely on multiple assays.<br><br>CONCLUSION: Inclusion of the lncScore enhances predictive power of traditional cytogenetic and mutation-defined stratification in pAML with potential, as a single assay, to replace these complex stratification schemes with comparable predictive accuracy.},
}
@article {pmid36795981,
year = {2023},
author = {Wu, NL and Chen, Y and Dieffenbach, BV and Ehrhardt, MJ and Hingorani, S and Howell, RM and Jefferies, JL and Mulrooney, DA and Oeffinger, KC and Robison, LL and Weil, BR and Yuan, Y and Yasui, Y and Hudson, MM and Leisenring, WM and Armstrong, GT and Chow, EJ},
title = {Development and Validation of a Prediction Model for Kidney Failure in Long-Term Survivors of Childhood Cancer.},
journal = {Journal of clinical oncology : official journal of the American Society of Clinical Oncology},
volume = {},
number = {},
pages = {JCO2201926},
doi = {10.1200/JCO.22.01926},
pmid = {36795981},
issn = {1527-7755},
abstract = {PURPOSE: Kidney failure is a rare but serious late effect following treatment for childhood cancer. We developed a model using demographic and treatment characteristics to predict individual risk of kidney failure among 5-year survivors of childhood cancer.<br><br>METHODS: Five-year survivors from the Childhood Cancer Survivor Study (CCSS) without history of kidney failure (n = 25,483) were assessed for subsequent kidney failure (ie, dialysis, kidney transplantation, or kidney-related death) by age 40 years. Outcomes were identified by self-report and linkage with the Organ Procurement and Transplantation Network and the National Death Index. A sibling cohort (n = 5,045) served as a comparator. Piecewise exponential models accounting for race/ethnicity, age at diagnosis, nephrectomy, chemotherapy, radiotherapy, congenital genitourinary anomalies, and early-onset hypertension estimated the relationships between potential predictors and kidney failure, using area under the curve (AUC) and concordance (C) statistic to evaluate predictive power. Regression coefficient estimates were converted to integer risk scores. The St Jude Lifetime Cohort Study and the National Wilms Tumor Study served as validation cohorts.<br><br>RESULTS: Among CCSS survivors, 204 developed late kidney failure. Prediction models achieved an AUC of 0.65-0.67 and a C-statistic of 0.68-0.69 for kidney failure by age 40 years. Validation cohort AUC and C-statistics were 0.88/0.88 for the St Jude Lifetime Cohort Study (n = 8) and 0.67/0.64 for the National Wilms Tumor Study (n = 91). Risk scores were collapsed to form statistically distinct low- (n = 17,762), moderate- (n = 3,784), and high-risk (n = 716) groups, corresponding to cumulative incidences in CCSS of kidney failure by age 40 years of 0.6% (95% CI, 0.4 to 0.7), 2.1% (95% CI, 1.5 to 2.9), and 7.5% (95% CI, 4.3 to 11.6), respectively, compared with 0.2% (95% CI, 0.1 to 0.5) among siblings.<br><br>CONCLUSION: Prediction models accurately identify childhood cancer survivors at low, moderate, and high risk for late kidney failure and may inform screening and interventional strategies.},
}
@article {pmid36795962,
year = {2023},
author = {Kirk, PS and Lotan, Y and Zargar, H and Fairey, AS and Dinney, CP and Mir, MC and Krabbe, LM and Cookson, MS and Jacobson, NE and Montgomery, JS and Vasdev, N and Yu, EY and Xylinas, E and Kassouf, W and Dall'Era, MA and Sridhar, SS and McGrath, JS and Aning, J and Shariat, SF and Thorpe, AC and Morgan, TM and Holzbeierlein, JM and Bivalacqua, TJ and North, S and Barocas, DA and Grivas, P and Garcia, JA and Stephenson, AJ and Shah, JB and Daneshmand, S and Spiess, PE and van Rhijn, BWG and Mertens, L and Black, P and Wright, JL},
title = {Impact of Maximal Transurethral Resection on Pathological Outcomes at Cystectomy in a Large, Multi-institutional Cohort.},
journal = {The Journal of urology},
volume = {},
number = {},
pages = {101097JU0000000000003193},
doi = {10.1097/JU.0000000000003193},
pmid = {36795962},
issn = {1527-3792},
abstract = {PURPOSE: While the presence of residual disease at the time of radical cystectomy for bladder cancer is an established prognostic indicator, controversy remains regarding the importance of maximal transurethral resection prior to neoadjuvant chemotherapy. We characterized the influence of maximal transurethral resection on pathological and survival outcomes using a large, multi-institutional cohort.<br><br>MATERIALS AND METHODS: We identified 785 patients from a multi-institutional cohort undergoing radical cystectomy for muscle-invasive bladder cancer after neoadjuvant chemotherapy. We employed bivariate comparisons and stratified multivariable models to quantify the effect of maximal transurethral resection on pathological findings at cystectomy and survival.<br><br>RESULTS: Of 785 patients, 579 (74%) underwent maximal transurethral resection. Incomplete transurethral resection was more frequent in patients with more advanced clinical tumor (cT) and nodal (cN) stage (P < .001 and P < .01, respectively), with more advanced ypT stage at cystectomy and higher rates of positive surgical margins (P < .01 and P < .05, respectively). In multivariable models, maximal transurethral resection was associated with downstaging at cystectomy (adjusted odds ratio 1.6, 95% CI 1.1-2.5). In Cox proportional hazards analysis, maximal transurethral resection was not associated with overall survival (adjusted HR 0.8, 95% CI 0.6-1.1).<br><br>CONCLUSIONS: In patients undergoing transurethral resection for muscle-invasive bladder cancer prior to neoadjuvant chemotherapy, maximal resection may improve pathological response at cystectomy. However, the ultimate effects on long-term survival and oncologic outcomes warrant further investigation.},
}
@article {pmid36791762,
year = {2023},
author = {Saad, A and Loren, A and Bolaños-Meade, J and Chen, G and Couriel, D and Di Stasi, A and El-Jawahri, A and Elmariah, H and Farag, S and Gundabolu, K and Gutman, J and Ho, V and Hoeg, R and Horwitz, M and Hsu, J and Kassim, A and Kharfan Dabaja, M and Magenau, J and Martin, T and Mielcarek, M and Moreira, J and Nakamura, R and Nieto, Y and Ninos, C and Oliai, C and Patel, S and Randolph, B and Schroeder, M and Tzachanis, D and Varshavsky-Yanovsky, AN and Vusirikala, M and Algieri, F and Pluchino, LA},
title = {NCCN Guidelines® Insights: Hematopoietic Cell Transplantation, Version 3.2022.},
journal = {Journal of the National Comprehensive Cancer Network : JNCCN},
volume = {21},
number = {2},
pages = {108-115},
doi = {10.6004/jnccn.2023.0007},
pmid = {36791762},
issn = {1540-1413},
mesh = {Adult ; Humans ; Transplantation, Homologous ; Neoplasm Recurrence, Local ; *Hematopoietic Stem Cell Transplantation/adverse effects ; *Graft vs Host Disease/diagnosis/etiology/prevention &amp; control ; Transplantation Conditioning/adverse effects ; },
abstract = {The NCCN Guidelines for Hematopoietic Cell Transplantation (HCT) provide an evidence- and consensus-based approach for the use of autologous and allogeneic HCT in the management of malignant diseases in adult patients. HCT is a potentially curative treatment option for patients with certain types of malignancies; however, recurrent malignancy and transplant-related complications often limit the long-term survival of HCT recipients. The purpose of these guidelines is to provide guidance regarding aspects of HCT, including pretransplant recipient evaluation, hematopoietic cell mobilization, and treatment of graft-versus-host disease-a major complication of allogeneic HCT-to enable the patient and clinician to assess management options in the context of an individual patient's condition. These NCCN Guidelines Insights provide a summary of the important recent updates to the NCCN Guidelines for HCT, including the incorporation of a newly developed section on the Principles of Conditioning for HCT.},
}
@article {pmid36791750,
year = {2023},
author = {Abu-Rustum, N and Yashar, C and Arend, R and Barber, E and Bradley, K and Brooks, R and Campos, SM and Chino, J and Chon, HS and Chu, C and Crispens, MA and Damast, S and Fisher, CM and Frederick, P and Gaffney, DK and Giuntoli, R and Han, E and Holmes, J and Howitt, BE and Lea, J and Mariani, A and Mutch, D and Nagel, C and Nekhlyudov, L and Podoll, M and Salani, R and Schorge, J and Siedel, J and Sisodia, R and Soliman, P and Ueda, S and Urban, R and Wethington, SL and Wyse, E and Zanotti, K and McMillian, NR and Aggarwal, S},
title = {Uterine Neoplasms, Version 1.2023, NCCN Clinical Practice Guidelines in Oncology.},
journal = {Journal of the National Comprehensive Cancer Network : JNCCN},
volume = {21},
number = {2},
pages = {181-209},
doi = {10.6004/jnccn.2023.0006},
pmid = {36791750},
issn = {1540-1413},
mesh = {Female ; Humans ; *Uterine Neoplasms/diagnosis/therapy/pathology ; *Endometrial Neoplasms/diagnosis/therapy ; *Carcinoma, Endometrioid/pathology ; *Carcinosarcoma/diagnosis/therapy ; *Adenocarcinoma, Clear Cell ; },
abstract = {Adenocarcinoma of the endometrium (also known as endometrial cancer, or more broadly as uterine cancer or carcinoma of the uterine corpus) is the most common malignancy of the female genital tract in the United States. It is estimated that 65,950 new uterine cancer cases will have occurred in 2022, with 12,550 deaths resulting from the disease. Endometrial carcinoma includes pure endometrioid cancer and carcinomas with high-risk endometrial histology (including uterine serous carcinoma, clear cell carcinoma, carcinosarcoma [also known as malignant mixed Müllerian tumor], and undifferentiated/dedifferentiated carcinoma). Stromal or mesenchymal sarcomas are uncommon subtypes accounting for approximately 3% of all uterine cancers. This selection from the NCCN Guidelines for Uterine Neoplasms focuses on the diagnosis, staging, and management of pure endometrioid carcinoma. The complete version of the NCCN Guidelines for Uterine Neoplasms is available online at NCCN.org.},
}
@article {pmid36794719,
year = {2023},
author = {Shen, BW and Doyle, LA and Werther, R and Westburg, AA and Bies, DP and Walter, SI and Luyten, YA and Morgan, RD and Stoddard, BL and Kaiser, BK},
title = {Structure, substrate binding and activity of a unique AAA+ protein: the BrxL phage restriction factor.},
journal = {Nucleic acids research},
volume = {},
number = {},
pages = {},
doi = {10.1093/nar/gkad083},
pmid = {36794719},
issn = {1362-4962},
support = {R01 GM105691/GM/NIGMS NIH HHS/United States ; R15 GM140375/GM/NIGMS NIH HHS/United States ; /GM/NIGMS NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; },
abstract = {Bacteriophage exclusion ('BREX') systems are multi-protein complexes encoded by a variety of bacteria and archaea that restrict phage by an unknown mechanism. One BREX factor, termed BrxL, has been noted to display sequence similarity to various AAA+ protein factors including Lon protease. In this study we describe multiple CryoEM structures of BrxL that demonstrate it to be a chambered, ATP-dependent DNA binding protein. The largest BrxL assemblage corresponds to a dimer of heptamers in the absence of bound DNA, versus a dimer of hexamers when DNA is bound in its central pore. The protein displays DNA-dependent ATPase activity, and ATP binding promotes assembly of the complex on DNA. Point mutations within several regions of the protein-DNA complex alter one or more in vitro behaviors and activities, including ATPase activity and ATP-dependent association with DNA. However, only the disruption of the ATPase active site fully eliminates phage restriction, indicating that other mutations can still complement BrxL function within the context of an otherwise intact BREX system. BrxL displays significant structural homology to MCM subunits (the replicative helicase in archaea and eukaryotes), implying that it and other BREX factors may collaborate to disrupt initiation of phage DNA replication.},
}
@article {pmid36791419,
year = {2023},
author = {Westerman, KE and Walker, ME and Gaynor, SM and Wesse, J and DiCorpo, D and Ma, J and Alonso, A and Aslibekyan, S and Baldridge, AS and Bertoni, AG and Biggs, ML and Brody, JA and Chen, YI and Dupuis, J and Goodarzi, MO and Guo, X and Hasbani, NR and Heath, A and Hidalgo, B and Irvin, MR and Johnson, WC and Kalyani, RR and Lange, L and Lemaitre, RN and Liu, CT and Liu, S and Moon, JY and Nassir, R and Pankow, JS and Pettinger, M and Raffield, L and Rasmussen-Torvik, LJ and Selvin, E and Senn, MK and Shadyab, AH and Smith, AV and Smith, NL and Steffen, L and Talegakwar, S and Taylor, KD and Vries, PS and Wilson, JG and Wood, AC and Yanek, LR and Yao, J and Zheng, Y and Boerwinkle, E and Morrison, AC and Fornage, M and Russell, TP and Psaty, BM and Levy, D and Heard-Costa, NL and Ramachandran, VS and Mathias, RA and Arnett, DK and Kaplan, R and North, KE and Correa, A and Carson, A and Rotter, JI and Rich, SS and Manson, JE and Reiner, AP and Kooperberg, C and Florez, JC and Meigs, JB and Merino, J and Tobias, DK and Chen, H and Manning, AK},
title = {Investigating gene-diet interactions impacting the association between macronutrient intake and glycemic traits.},
journal = {Diabetes},
volume = {},
number = {},
pages = {},
doi = {10.2337/db22-0851},
pmid = {36791419},
issn = {1939-327X},
abstract = {Few studies have demonstrated reproducible gene-diet interactions (GDIs) impacting metabolic disease risk factors, likely due in part to measurement error in dietary intake estimation and insufficient capture of rare genetic variation. We aimed to identify GDIs across the genetic frequency spectrum impacting the macronutrient-glycemia relationship in genetically and culturally diverse cohorts. We analyzed N=33,187 diabetes-free participants from 10 NHLBI Trans-Omics for Precision Medicine (TOPMed) program cohorts with whole-genome sequencing, self-reported diet, and glycemic trait data. We fit cohort-specific, multivariable-adjusted linear mixed models for the effect of diet, modeled as an isocaloric substitution of carbohydrate for fat, and its interactions with common and rare variants genome-wide. In main effect meta-analyses, participants consuming more carbohydrate had modestly lower glycemic trait values (e.g. for hemoglobin A1c [HbA1c], -0.013 %HbA1c per 250 kcal substitution). In GDI meta-analyses, a common African ancestry-enriched variant (rs79762542) reached study-wide significance and replicated in the UK Biobank cohort, indicating a negative carbohydrate-HbA1c association among major allele homozygotes only. Simulations revealed that over 150,000 samples may be necessary to identify similar macronutrient GDIs under realistic assumptions about effect size and measurement error. These results generate hypotheses for further exploration of modifiable metabolic disease risk in additional cohorts with African ancestry.},
}
@article {pmid36790925,
year = {2023},
author = {Lindsay, J and Walti, CS and Halpern, AB and Xie, H and Chung, EL and Schonhoff, KG and Huebner, EM and Cheng, GS and Kimball, L and Leisenring, WM and Greenwood, M and Chen, SC and Kong, DC and Slavin, MA and Boeckh, M and Fredricks, D and Liu, C and Pergam, SA and Walter, RB and Hill, JA},
title = {Invasive Fungal Infections After CLAG-M/CLAG Chemotherapy for Acute Myeloid Leukemia and High-Grade Myeloid Neoplasms.},
journal = {Blood advances},
volume = {},
number = {},
pages = {},
doi = {10.1182/bloodadvances.2022009562},
pmid = {36790925},
issn = {2473-9537},
abstract = {CLAG-M (cladribine, high-dose cytarabine [HiDAC], G-CSF, mitoxantrone)/CLAG are contemporary intensive chemotherapy regimens associated with higher and deeper complete remission rates than 7+3 (cytarabine, anthracycline)/HiDAC, but with greater myelosuppression and potential infection risks. Here, we compared the cumulative incidence (CI) and patterns of invasive fungal disease (IFD) between these regimens by identifying proven/probable and possible cases of IFD following CLAG-M (n=332) and 7+3 (n=115) chemotherapy and subsequent treatment cycles in adults ≥18 years old with newly diagnosed (ND) or relapsed/refractory (R/R) AML or other high-grade myeloid neoplasms between 2006 and 2018. By 90 days (D90) after initiating treatment, the CI of proven/probable IFD was 20% with CLAG-M and 12% with 7+3 (p=0.17). There was no significant difference in the CI of IFD between ND CLAG-M and R/R CLAG-M. Without mold-active prophylaxis, the D90 CI of proven/probable IFD was significantly higher in the CLAG-M than the 7+3 cohort (28% versus 11%; p=0.007), but this difference was mitigated with mold-active prophylaxis (CLAG-M, 7.5%; 7+3, 0%; p=0.65). After each chemotherapy treatment cycle, the CI of newly diagnosed IFD was similar, ranging from 15-20%. Use of mold-active prophylaxis was the only factor associated with reduced IFD risk in adjusted models (HR, 0.32; 95% confidence interval, 0.18-0.56). Together, these data indicate that the IFD risk with CLAG-M is higher than with 7+3 in the absence of mold-active prophylaxis; use of mold-active prophylaxis mitigates this risk.},
}
@article {pmid36790617,
year = {2023},
author = {Matsuzaki, M and Annamalay, A and Garcia-Gonzalez, P and Radich, J},
title = {CML Outcomes and Care Delivery During the COVID-19 Pandemic in Low- and Middle-Income Countries.},
journal = {Current hematologic malignancy reports},
volume = {},
number = {},
pages = {1-7},
pmid = {36790617},
issn = {1558-822X},
abstract = {PURPOSE OF REVIEW: The study aims to evaluate the impact of COVID-19 on the delivery of health care and services to patients with chronic myeloid leukemia in low- and middle-income countries (LMICs) accessing treatment through The Max Foundation.<br><br>RECENT FINDINGS: An online survey was developed and sent via email to 527 partner physicians who had active patients under their care in July 2020, asking about the disruption of health services with multiple-choice answers or a five-point ordinal scale. Data from The Max Foundation's Patient Access Tracking System (PATS&#xae;) was analyzed to evaluate program performance in 2020 compared with 2019. PATS&#xae; is used to track key patient information and supply chain data to ensure robust reporting, quality assurance, and safety. Among the 111 physicians who responded (20% response rate), 48% reported that someone on their team had contracted COVID-19. A total of 95 (85%) physicians reported at least some disruption of services to patients due to COVID-19, with 29 (26%) reporting frequent or complete disruption. Almost all physicians in the South Asia and Asia Pacific regions reported disruption (96% and 95%, respectively), compared with three quarters of physicians in Latin America. Institutions overcame challenges using a variety of solutions including telemedicine (60%), electronic prescriptions (45%), home delivery via courier services (31%), government workers (9%), and dispensation coordination with regional hospitals (14%). The COVID-19 pandemic has disrupted services for CML physicians and patients worldwide. Overall, these disruptions did not appear to significantly affect The Max Foundation's ability to provide patients with access to treatment, as novel approaches in telemedicine, supply chain, and dispensing, as well as provision of guidance and support for physicians were utilized to overcame disruption of services.},
}
@article {pmid36789951,
year = {2023},
author = {Horr, B and Kurtz, R and Pandey, A and Hoffstrom, BG and Schock, E and LaBonne, C and Alfandari, D},
title = {Production and characterization of monoclonal antibodies to Xenopus proteins.},
journal = {Development (Cambridge, England)},
volume = {150},
number = {4},
pages = {},
doi = {10.1242/dev.201309},
pmid = {36789951},
issn = {1477-9129},
support = {R24OD021485/NH/NIH HHS/United States ; R01DE016289/DE/NIDCR NIH HHS/United States ; },
mesh = {Animals ; Mice ; *Antibodies, Monoclonal ; Hybridomas ; Xenopus laevis ; *Xenopus Proteins/genetics ; },
abstract = {Monoclonal antibodies are powerful and versatile tools that enable the study of proteins in diverse contexts. They are often utilized to assist with identification of subcellular localization and characterization of the function of target proteins of interest. However, because there can be considerable sequence diversity between orthologous proteins in Xenopus and mammals, antibodies produced against mouse or human proteins often do not recognize Xenopus counterparts. To address this issue, we refined existing mouse monoclonal antibody production protocols to generate antibodies against Xenopus proteins of interest. Here, we describe several approaches for the generation of useful mouse anti-Xenopus antibodies to multiple Xenopus proteins and their validation in various experimental approaches. These novel antibodies are now available to the research community through the Developmental Study Hybridoma Bank (DSHB).},
}
@article {pmid36789739,
year = {2023},
author = {Lowry, KP and Ichikawa, L and Hubbard, RA and Buist, DSM and Bowles, EJA and Henderson, LM and Kerlikowske, K and Specht, JM and Sprague, BL and Wernli, KJ and Lee, JM},
title = {Variation in second breast cancer risk after primary invasive cancer by time since primary cancer diagnosis and estrogen receptor status.},
journal = {Cancer},
volume = {},
number = {},
pages = {},
doi = {10.1002/cncr.34679},
pmid = {36789739},
issn = {1097-0142},
support = {PCS-1504-30370/PCORI/Patient-Centered Outcomes Research Institute/United States ; P01CA154292/CA/NCI NIH HHS/United States ; R50CA211115/CA/NCI NIH HHS/United States ; U54CA163303/CA/NCI NIH HHS/United States ; },
abstract = {BACKGROUND: In women with previously treated breast cancer, occurrence and timing of second breast cancers have implications for surveillance. The authors examined the timing of second breast cancers by primary cancer estrogen receptor (ER) status in the Breast Cancer Surveillance Consortium.<br><br>METHODS: Women who were diagnosed with American Joint Commission on Cancer stage I-III breast cancer were identified within six Breast Cancer Surveillance Consortium registries from 2000 to 2017. Characteristics collected at primary breast cancer diagnosis included demographics, ER status, and treatment. Second breast cancer events included subsequent ipsilateral or contralateral breast cancers diagnosed >6&#xa0;months after primary diagnosis. The authors examined cumulative incidence and second breast cancer rates by primary cancer ER status during 1-5 versus 6-10&#xa0;years after diagnosis.<br><br>RESULTS: At 10&#xa0;years, the cumulative second breast cancer incidence was 11.8% (95% confidence interval [CI], 10.7%-13.1%) for women with ER-negative disease and 7.5% (95% CI, 7.0%-8.0%) for those with ER-positive disease. Women with ER-negative cancer had higher second breast cancer rates than those with ER-positive cancer during the first 5 years of follow-up (16.0 per 1000 person-years [PY]; 95% CI, 14.2-17.9 per 1000 PY; vs. 7.8 per 1000 PY; 95% CI, 7.3-8.4 per 1000 PY, respectively). After 5 years, second breast cancer rates were similar for women with ER-negative versus ER-positive breast cancer (12.1 per 1000 PY; 95% CI, 9.9-14.7; vs. 9.3 per 1000 PY; 95% CI, 8.4-10.3 per 1000 PY, respectively).<br><br>CONCLUSIONS: ER-negative primary breast cancers are associated with a higher risk of second breast cancers than ER-positive cancers during the first 5 years after diagnosis. Further study is needed to examine the potential benefit of more intensive surveillance targeting these women in the early postdiagnosis period.},
}
@article {pmid36789545,
year = {2023},
author = {Chisholm, KM and Smith, J and Heerema-McKenney, AE and Choi, JK and Ries, RE and Hirsch, BA and Raimondi, SC and Wang, YC and Dang, A and Alonzo, TA and Sung, L and Aplenc, R and Gamis, AS and Meshinchi, S and Kahwash, SB},
title = {Pathologic, cytogenetic, and molecular features of acute myeloid leukemia with megakaryocytic differentiation: A report from the Children's Oncology Group.},
journal = {Pediatric blood &amp; cancer},
volume = {},
number = {},
pages = {e30251},
doi = {10.1002/pbc.30251},
pmid = {36789545},
issn = {1545-5017},
abstract = {BACKGROUND: Acute myeloid leukemia (AML) with megakaryocytic differentiation (AMkL) is a rare subtype of AML more common in children. Recent literature has identified multiple fusions associated with this type of leukemia.<br><br>METHODS: Morphology, cytogenetics, and genomic sequencing were assessed in patients from Children's Oncology Group trials AAML0531 and AAML1031 with central-pathology review confirmed non-Down syndrome AMkL. The 5-year event-free survival (EFS), overall survival (OS), and RR were evaluated in these AMkL subcategories.<br><br>RESULTS: A total of 107 cases of AMkL (5.5%) were included. Distinct fusions were identified in the majority: RBM15::MRTFA (20%), CBFA2T3::GLIS2 (16%), NUP98 (10%), KMT2A (7%), TEC::MLLT10 (2%), MECOM (1%), and FUS::ERG (1%); many of the remaining cases were classified as AMkL with (other) myelodysplasia-related changes (MRC). Very few cases had AML-associated somatic mutations. Cases with CBFA2T3::GLIS2 were enriched in trisomy 3 (p&#xa0;=&#xa0;.015) and the RAM phenotype, with associated high CD56 expression (p&#xa0;<&#xa0;.001). Cases with NUP98 fusions were enriched in trisomy 6 (p&#xa0;<&#xa0;.001), monosomy 13/del(13q) (p&#xa0;<&#xa0;.001), trisomy 21 (p&#xa0;=&#xa0;.026), and/or complex karyotypes (p&#xa0;=&#xa0;.026). While different 5-year EFS and OS were observed in AMkL in each trial, in general, those with CBFA2T3::GLIS2 or KMT2A rearrangements had worse outcomes compared to other AMkL, while those with RBM15::MRTFA or classified as AMkl-MRC fared better. AMkL with NUP98 fusions also had poor outcomes in the AAML1031 trial.<br><br>CONCLUSION: Given the differences in outcomes, AMkL classification by fusions, cytogenetics, and morphology may be warranted to help in risk stratification and therapeutic options.},
}
@article {pmid36788358,
year = {2023},
author = {Lee, Y and Buchanan, AL and Ogburn, EL and Friedman, SR and Halloran, ME and Katenka, NV and Wu, J and Nikolopoulos, G},
title = {Finding influential subjects in a network using a causal framework.},
journal = {Biometrics},
volume = {},
number = {},
pages = {},
doi = {10.1111/biom.13841},
pmid = {36788358},
issn = {1541-0420},
abstract = {Researchers across a wide array of disciplines are interested in finding the most influential subjects in a network. In a network setting, intervention effects and health outcomes can spill over from one node to another through network ties, and influential subjects are expected to have a greater impact than others. For this reason, network research in public health has attempted to maximize health and behavioral changes by intervening on a subset of influential subjects. Although influence is often defined only implicitly in most of the literature, the operative notion of influence is inherently causal in many cases: influential subjects are those we should intervene on to achieve the greatest overall effect across the entire network. In this work, we define a causal notion of influence using potential outcomes. We review existing influence measures, such as node centrality, that largely rely on the particular features of the network structure and/or on certain diffusion models that predict the pattern of information or diseases spreads through network ties. We provide simulation studies to demonstrate when popular centrality measures can agree with our causal measure of influence. As an illustrative example, we apply several popular centrality measures to the HIV risk network in the Transmission Reduction Intervention Project and demonstrate the assumptions under which each centrality can represent the causal influence of each participant in the study. This article is protected by copyright. All rights reserved.},
}
@article {pmid36787739,
year = {2023},
author = {Lee, OW and Rodrigues, C and Lin, SH and Luo, W and Jones, K and Brown, DW and Zhou, W and Karlins, E and Khan, SM and Baulande, S and Raynal, V and Surdez, D and Reynaud, S and Rubio, RA and Zaidi, S and Grossetête, S and Ballet, S and Lapouble, E and Laurence, V and Pierron, G and Gaspar, N and Corradini, N and Marec-Bérard, P and Rothman, N and Dagnall, CL and Burdett, L and Manning, M and Wyatt, K and Yeager, M and Chari, R and Leisenring, WM and Kulozik, AE and Kriebel, J and Meitinger, T and Strauch, K and Kirchner, T and Dirksen, U and Mirabello, L and Tucker, MA and Tirode, F and Armstrong, GT and Bhatia, S and Robison, LL and Yasui, Y and Romero-Pérez, L and Hartmann, W and Metzler, M and Diver, WR and Lori, A and Freedman, ND and Hoover, RN and Morton, LM and Chanock, SJ and Grünewald, TGP and Delattre, O and Machiela, MJ},
title = {Targeted long-read sequencing of the Ewing sarcoma 6p25.1 susceptibility locus identifies germline-somatic interactions with EWSR1-FLI1 binding.},
journal = {American journal of human genetics},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.ajhg.2023.01.017},
pmid = {36787739},
issn = {1537-6605},
abstract = {Ewing sarcoma (EwS) is a rare bone and soft tissue malignancy driven by chromosomal translocations encoding chimeric transcription factors, such as EWSR1-FLI1, that bind GGAA motifs forming novel enhancers that alter nearby expression. We propose that germline microsatellite variation at the 6p25.1 EwS susceptibility locus could impact downstream gene expression and EwS biology. We performed targeted long-read sequencing of EwS blood DNA to characterize variation and genomic features important for EWSR1-FLI1 binding. We identified 50 microsatellite alleles at 6p25.1 and observed that EwS-affected individuals had longer alleles (>135 bp) with more GGAA repeats. The 6p25.1 GGAA microsatellite showed chromatin features of an EWSR1-FLI1 enhancer and regulated expression of RREB1, a transcription factor associated with RAS/MAPK signaling. RREB1 knockdown reduced proliferation and clonogenic potential and reduced expression of cell cycle and DNA replication genes. Our integrative analysis at 6p25.1 details increased binding of longer GGAA microsatellite alleles with acquired EWSR-FLI1 to promote Ewing sarcomagenesis by RREB1-mediated proliferation.},
}
@article {pmid36787249,
year = {2023},
author = {Cohen, KW and Fiore-Gartland, A and Walsh, SR and Yusim, K and Frahm, N and Elizaga, ML and Maenza, J and Scott, H and Mayer, KH and Goepfert, PA and Edupuganti, S and Pantaleo, G and Hutter, J and Morris, DE and De Rosa, SC and Geraghty, DE and Robb, ML and Michael, NL and Fischer, W and Giorgi, EE and Malhi, H and Pensiero, MN and Ferrari, G and Tomaras, GD and Montefiori, DC and Gilbert, PB and McElrath, MJ and Haynes, BF and Korber, BT and Baden, LR and , },
title = {Trivalent mosaic or consensus HIV immunogens prime humoral and broader cellular immune responses in adults.},
journal = {The Journal of clinical investigation},
volume = {133},
number = {4},
pages = {},
doi = {10.1172/JCI163338},
pmid = {36787249},
issn = {1558-8238},
abstract = {BACKGROUNDMosaic and consensus HIV-1 immunogens provide two distinct approaches to elicit greater breadth of coverage against globally circulating HIV-1 and have shown improved immunologic breadth in nonhuman primate models.METHODSThis double-blind randomized trial enrolled 105 healthy HIV-uninfected adults who received 3 doses of either a trivalent global mosaic, a group M consensus (CON-S), or a natural clade B (Nat-B) gp160 env DNA vaccine followed by 2 doses of a heterologous modified vaccinia Ankara-vectored HIV-1 vaccine or placebo. We performed prespecified blinded immunogenicity analyses at day 70 and day 238 after the first immunization. T cell responses to vaccine antigens and 5 heterologous Env variants were fully mapped.RESULTSEnv-specific CD4+ T cell responses were induced in 71% of the mosaic vaccine recipients versus 48% of the CON-S recipients and 48% of the natural Env recipients. The mean number of T cell epitopes recognized was 2.5 (95% CI, 1.2-4.2) for mosaic recipients, 1.6 (95% CI, 0.82-2.6) for CON-S recipients, and 1.1 (95% CI, 0.62-1.71) for Nat-B recipients. Mean breadth was significantly greater in the mosaic group than in the Nat-B group using overall (P = 0.014), prime-matched (P = 0.002), heterologous (P = 0.046), and boost-matched (P = 0.009) measures. Overall T cell breadth was largely due to Env-specific CD4+ T cell responses.CONCLUSIONPriming with a mosaic antigen significantly increased the number of epitopes recognized by Env-specific T cells and enabled more, albeit still limited, cross-recognition of heterologous variants. Mosaic and consensus immunogens are promising approaches to address global diversity of HIV-1.TRIAL REGISTRATIONClinicalTrials.gov NCT02296541.FUNDINGUS NIH grants UM1 AI068614, UM1 AI068635, UM1 AI068618, UM1 AI069412, UL1 RR025758, P30 AI064518, UM1 AI100645, and UM1 AI144371, and Bill &amp; Melinda Gates Foundation grant OPP52282.},
}
@article {pmid36786906,
year = {2023},
author = {Wu, W and Collins, BF and Gardner, GC and Hippe, DS and Ho, LA and Raghu, G and Pipavath, SNJ},
title = {Antisynthetase syndrome-related interstitial lung disease (ASyS-ILD): longitudinal imaging findings.},
journal = {European radiology},
volume = {},
number = {},
pages = {},
pmid = {36786906},
issn = {1432-1084},
abstract = {OBJECTIVES: Interstitial lung disease (ILD) impacts mortality in antisynthetase syndrome (ASyS). Computed tomographic (CT) patterns and evolution in ASyS ILD are not well described. We report longitudinal CT patterns in ASyS-ILD and their impact on survival.<br><br>METHODS: This is a monocentric retrospective study of 47 patients with ASyS-ILD. Longitudinal CT patterns and fibrosis severity (severity of radiographic features indicating fibrosis) were analyzed by two radiologists in consensus. The association between imaging features and survival was examined using univariate Cox regression analysis.<br><br>RESULTS: In total, 211 CT scans were analyzed with an average of 4&#x2009;&#xb1;&#x2009;2 CT scans/patient with a median follow-up of 79&#xa0;months in 47 patients. Non-fibrotic patterns were present initially in 63.8% (n&#x2009;=&#x2009;30) of patients, while fibrotic patterns occurred in 36.2% (n&#x2009;=&#x2009;17). The initial non-fibrotic patterns/abnormalities resolved in 23.3% (n&#x2009;=&#x2009;7), evolved in 6.7% (n&#x2009;=&#x2009;2), persisted in 13.3% (n&#x2009;=&#x2009;4), and progressed in 56.7% (n&#x2009;=&#x2009;17), while initial fibrotic patterns persisted in 82.4% (n&#x2009;=&#x2009;14) and progressed in 17.6% (n&#x2009;=&#x2009;3). Radiographic progression of ILD (progression in CT pattern or increased fibrosis severity) occurred in 53.2% (n&#x2009;=&#x2009;25) of patients. Advanced age and radiographic progression were associated with decreased survival (all p&#x2009;<&#x2009;0.05). The presence of ground-glass opacities (GGO) and predominant lower lung distribution of abnormalities on initial CTs were associated with increased survival (all p&#x2009;<&#x2009;0.05).<br><br>CONCLUSION: Progression occurred in 56.7% of ASyS-ILD patients presenting with non-fibrotic patterns. Fibrotic patterns tended to persist. Age and radiographic progression were associated with reduced survival while the initial presence of GGO and predominant lower lobe distribution were associated with increased survival.<br><br>KEY POINTS: &#x2022; In ASyS-ILD, initial non-fibrotic patterns such as OP, cNSIP, or OP-cNSIP tended to progress to fNSIP. &#x2022; Fibrotic patterns such as fNSIP or UIP in ASyS-ILD tended to persist without pattern changes. &#x2022; GGO and lower lung predominance on initial CT were associated with better survival while advanced baseline age and radiographic ILD progression during follow-up were associated with decreased survival.},
}
@article {pmid36786311,
year = {2023},
author = {Horr, B and Kurtz, R and Pandey, A and Hoffstrom, BG and Schock, E and LaBonne, C and Alfandari, D},
title = {Production and characterization of monoclonal antibodies to xenopus proteins.},
journal = {Development (Cambridge, England)},
volume = {},
number = {},
pages = {},
doi = {10.1242/dev.201309},
pmid = {36786311},
issn = {1477-9129},
abstract = {Monoclonal antibodies are powerful and versatile tools that enable the study of proteins in diverse contexts. They are often utilized to assist with identifying subcellular localization and characterizing the function of target proteins of interest. However, because there can be considerable sequence diversity between orthologous proteins in Xenopus and mammals, antibodies produced against mouse or human proteins often do not recognize Xenopus counterparts. To address this issue, we refined existing protocols to produce mouse monoclonal antibodies directed against Xenopus proteins of interest. Here we describe several approaches for the generation of useful mouse anti-Xenopus antibodies to multiple Xenopus proteins and their validation in various experimental approaches. These novel antibodies are now available to the research community through the Developmental Study Hybridoma Bank (DSHB).},
}
@article {pmid36784121,
year = {2023},
author = {Savinov, A and Fernandez, A and Fields, S},
title = {Mapping functional regions of essential bacterial proteins with dominant-negative protein fragments.},
journal = {Biophysical journal},
volume = {122},
number = {3S1},
pages = {415a},
doi = {10.1016/j.bpj.2022.11.2255},
pmid = {36784121},
issn = {1542-0086},
}
@article {pmid36782065,
year = {2023},
author = {Fernandez-Rozadilla, C and Timofeeva, M and Chen, Z and Law, P and Thomas, M and Schmit, S and Díez-Obrero, V and Hsu, L and Fernandez-Tajes, J and Palles, C and Sherwood, K and Briggs, S and Svinti, V and Donnelly, K and Farrington, S and Blackmur, J and Vaughan-Shaw, P and Shu, XO and Long, J and Cai, Q and Guo, X and Lu, Y and Broderick, P and Studd, J and Huyghe, J and Harrison, T and Conti, D and Dampier, C and Devall, M and Schumacher, F and Melas, M and Rennert, G and Obón-Santacana, M and Martín-Sánchez, V and Moratalla-Navarro, F and Oh, JH and Kim, J and Jee, SH and Jung, KJ and Kweon, SS and Shin, MH and Shin, A and Ahn, YO and Kim, DH and Oze, I and Wen, W and Matsuo, K and Matsuda, K and Tanikawa, C and Ren, Z and Gao, YT and Jia, WH and Hopper, J and Jenkins, M and Win, AK and Pai, R and Figueiredo, J and Haile, R and Gallinger, S and Woods, M and Newcomb, P and Duggan, D and Cheadle, J and Kaplan, R and Maughan, T and Kerr, R and Kerr, D and Kirac, I and Böhm, J and Mecklin, LP and Jousilahti, P and Knekt, P and Aaltonen, L and Rissanen, H and Pukkala, E and Eriksson, J and Cajuso, T and Hänninen, U and Kondelin, J and Palin, K and Tanskanen, T and Renkonen-Sinisalo, L and Zanke, B and Männistö, S and Albanes, D and Weinstein, S and Ruiz-Narvaez, E and Palmer, J and Buchanan, D and Platz, E and Visvanathan, K and Ulrich, C and Siegel, E and Brezina, S and Gsur, A and Campbell, P and Chang-Claude, J and Hoffmeister, M and Brenner, H and Slattery, M and Potter, J and Tsilidis, K and Schulze, M and Gunter, M and Murphy, N and Castells, A and Castellví-Bel, S and Moreira, L and Arndt, V and Shcherbina, A and Stern, M and Pardamean, B and Bishop, T and Giles, G and Southey, M and Idos, G and McDonnell, K and Abu-Ful, Z and Greenson, J and Shulman, K and Lejbkowicz, F and Offit, K and Su, YR and Steinfelder, R and Keku, T and van Guelpen, B and Hudson, T and Hampel, H and Pearlman, R and Berndt, S and Hayes, R and Martinez, ME and Thomas, S and Corley, D and Pharoah, P and Larsson, S and Yen, Y and Lenz, HJ and White, E and Li, L and Doheny, K and Pugh, E and Shelford, T and Chan, A and Cruz-Correa, M and Lindblom, A and Hunter, D and Joshi, A and Schafmayer, C and Scacheri, P and Kundaje, A and Nickerson, D and Schoen, R and Hampe, J and Stadler, Z and Vodicka, P and Vodickova, L and Vymetalkova, V and Papadopoulos, N and Edlund, C and Gauderman, W and Thomas, D and Shibata, D and Toland, A and Markowitz, S and Kim, A and Chanock, S and van Duijnhoven, F and Feskens, E and Sakoda, L and Gago-Dominguez, M and Wolk, A and Naccarati, A and Pardini, B and FitzGerald, L and Lee, SC and Ogino, S and Bien, S and Kooperberg, C and Li, C and Lin, Y and Prentice, R and Qu, C and Bézieau, S and Tangen, C and Mardis, E and Yamaji, T and Sawada, N and Iwasaki, M and Haiman, C and Le Marchand, L and Wu, A and Qu, C and McNeil, C and Coetzee, G and Hayward, C and Deary, I and Harris, S and Theodoratou, E and Reid, S and Walker, M and Ooi, LY and Moreno, V and Casey, G and Gruber, S and Tomlinson, I and Zheng, W and Dunlop, M and Houlston, R and Peters, U},
title = {Author Correction: Deciphering colorectal cancer genetics through multi-omic analysis of 100,204 cases and 154,587 controls of European and east Asian ancestries.},
journal = {Nature genetics},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41588-023-01334-w},
pmid = {36782065},
issn = {1546-1718},
}
@article {pmid36781872,
year = {2023},
author = {Cabán, M and Rodarte, JV and Bibby, M and Gray, MD and Taylor, JJ and Pancera, M and Boonyaratanakornkit, J},
title = {Cross-protective antibodies against common endemic respiratory viruses.},
journal = {Nature communications},
volume = {14},
number = {1},
pages = {798},
pmid = {36781872},
issn = {2041-1723},
abstract = {Respiratory syncytial virus (RSV), human metapneumovirus (HMPV), and human parainfluenza virus types one (HPIV1) and three (HPIV3) can cause severe disease and death in immunocompromised patients, the elderly, and those with underlying lung disease. A protective monoclonal antibody exists for RSV, but clinical use is limited to high-risk infant populations. Hence, therapeutic options for these viruses in vulnerable patient populations are currently limited. Here, we present the discovery, in vitro characterization, and in vivo efficacy testing of two cross-neutralizing monoclonal antibodies, one targeting both HPIV3 and HPIV1 and the other targeting both RSV and HMPV. The 3 × 1 antibody is capable of targeting multiple parainfluenza viruses; the MxR antibody shares features with other previously reported monoclonal antibodies that are capable of neutralizing both RSV and HMPV. We obtained structures using cryo-electron microscopy of these antibodies in complex with their antigens at 3.62 Å resolution for 3 × 1 bound to HPIV3 and at 2.24 Å for MxR bound to RSV, providing a structural basis for in vitro binding and neutralization. Together, a cocktail of 3 × 1 and MxR could have clinical utility in providing broad protection against four of the respiratory viruses that cause significant morbidity and mortality in at-risk individuals.},
}
@article {pmid36779982,
year = {2023},
author = {Hall, AG and Syrjala, KL and Ketterl, TG and Ganz, PA and Jacobs, LA and Palmer, SC and Partridge, A and Rajotte, EJ and Mueller, BA and Baker, KS},
title = {Socioeconomic Factors and Adherence to Health Care Recommendations in Adolescent and Young Adult Cancer Survivors.},
journal = {Journal of adolescent and young adult oncology},
volume = {},
number = {},
pages = {},
doi = {10.1089/jayao.2022.0109},
pmid = {36779982},
issn = {2156-535X},
abstract = {Purpose: The majority of adolescent and young adult (AYA) cancer survivors do not receive recommended health care surveillance after therapy. We used cross-sectional survey data to evaluate the impact of income, education, marital status, and insurance on health care adherence among AYA survivors. Methods: Eligible survivors were 18-39 years at diagnosis with invasive malignancy, 1-5 years from therapy completion. Online surveys assessed sociodemographic factors and self-report of completion of recommended health care services. Diagnosis and treatment data were abstracted from medical records. Multivariable logistic regression calculated odds ratios (ORs) and 95% confidence intervals (CIs) for adherence in relation to socioeconomic status and support. Results: Of 344 participants, 36% were adherent to at least 80% of recommendations. Adherence varied by cancer type: 34% for breast cancer, 52% for leukemia/lymphoma, 23% for other tumors. Adherence rates were similar among White, Asian, and Hispanic/Latinx patients. Lower adherence was associated with lower education (OR: 0.43; 95% CI: 0.23-0.80 for <4-year college degree) and lower annual income (OR: 0.51; 95% CI: 0.28-0.95 for $41,000-$80,000; OR: 0.40; 95% CI: 0.19-0.86 for ≤$40,000). Adherence decreased with decreasing income levels among those who were 1 to less than 3 years after diagnosis (OR: 0.25; 95% CI: 0.07-0.93 for $81,000-$120,000; OR: 0.24; 95% CI: 0.07-0.84 for $41,000-$80,000; OR: 0.13; 95% CI: 0.03-0.60 for ≤$40,000). Conclusion: Risk of nonadherence to health care guidelines was associated with lower income and lower education among AYA cancer survivors. Identification of these risks and related barriers to adherence in AYA survivors will inform interventions designed to meet needs of these high-risk groups, particularly during the first years after diagnosis. Trial Registration: NCT02192333.},
}
@article {pmid36779595,
year = {2023},
author = {Murthy, GSG and Kim, S and Estrada-Merly, N and Abid, MB and Aljurf, M and Assal, A and Badar, T and Badawy, SM and Ballen, K and Beitinjaneh, A and Cerny, J and Chhabra, S and DeFilipp, Z and Dholaria, B and Perez, MAD and Farhan, S and Freytes, CO and Gale, RP and Ganguly, S and Gupta, V and Grunwald, MR and Hamad, N and Hildebrandt, GC and Inamoto, Y and Jain, T and Jamy, O and Juckett, M and Kalaycio, M and Krem, MM and Lazarus, HM and Litzow, M and Munker, R and Murthy, HS and Nathan, S and Nishihori, T and Ortí, G and Patel, SS and Van der Poel, M and Rizzieri, DA and Savani, BN and Seo, S and Solh, M and Verdonck, LF and Wirk, B and Yared, JA and Nakamura, R and Oran, B and Scott, B and Saber, W},
title = {Association between the choice of the conditioning regimen and outcomes of allogeneic hematopoietic cell transplantation for myelofibrosis.},
journal = {Haematologica},
volume = {},
number = {},
pages = {},
doi = {10.3324/haematol.2022.281958},
pmid = {36779595},
issn = {1592-8721},
abstract = {Allogeneic hematopoietic cell transplantation (allo-HCT) remains the only curative treatment for myelofibrosis. However, the optimal conditioning regimen either with reduced intensity conditioning (RIC) or myeloablative conditioning (MAC) is not well known. Using the Center for International Blood and Marrow Transplant Research database, we identified adults aged ≥18 years with myelofibrosis undergoing allo-HCT between 2008-2019 and analyzed the outcomes separately in the RIC and MAC cohorts based on the conditioning regimens used. Among 872 eligible patients, 493 underwent allo-HCT using RIC (Fludarabine/busulfan=166, Fludarabine/melphalan=327) and 379 using MAC (Fludarabine/busulfan=247, Busulfan/cyclophosphamide=132). In multivariable analysis with RIC, Fludarabine/melphalan was associated with inferior overall survival (HR 1.80, 95% CI 1.15-2.81, p=0.009), higher early non-relapse mortality (HR 1.81, 95% CI 1.12-2.91, p=0.01) and higher acute graft versus host disease (GVHD) (grade II-IV- HR 1.45, 95% CI 1.03-2.03, p=0.03; grade III-IV HR 2.21, 95%CI 1.28-3.83, p=0.004) compared to Fludarabine/busulfan. In the MAC setting, Busulfan/cyclophosphamide was associated with a higher acute GVHD (grade II-IV HR 2.33, 95% CI 1.67-3.25, p<0.001; grade III-IV HR 2.31, 95% CI 1.52-3.52, p<0.001) and inferior GVHD-free relapse-free survival (GRFS) (HR 1.94, 95% CI 1.49-2.53, p<0.001) as compared to Fludarabine/busulfan. Hence, our study suggests that Fludarabine/busulfan is associated with better outcomes in RIC (better overall survival, lower early non-relapse mortality, lower acute GVHD) and MAC (lower acute GVHD and better GRFS) in myelofibrosis.},
}
@article {pmid36779502,
year = {2023},
author = {Gabert, R and Lama, JR and Valdez, R and Dasgupta, S and Cabello, R and Sanchez, H and Leon, M and Huamani, JV and Rae, JM and Montalban, E and Pasalar, S and Ignacio, RB and Duerr, A and , },
title = {Acute retroviral syndrome is associated with lower CD4 nadir and delayed viral suppression, which are blunted by immediate ART initiation.},
journal = {AIDS (London, England)},
volume = {},
number = {},
pages = {},
doi = {10.1097/QAD.0000000000003511},
pmid = {36779502},
issn = {1473-5571},
abstract = {OBJECTIVES: :To describe the prevalence of acute retroviral syndrome (ARS) and associated findings during primary HIV, and explore the relationship of ARS to clinical, virological, and immunological outcomes within a longitudinal screen, retest and treat study that minimized ascertainment bias.<br><br>DESIGN: :We evaluated ARS symptoms among 216 persons with acute and early incident HIV within the Sabes study of timing of antiretroviral therapy (ART) initiation during primary HIV in Peru.<br><br>METHODS: :We evaluated patient reported symptoms and exam findings during primary HIV and used logistic regression and generalized linear models to evaluate associations with CD4+ and CD8+ T cell counts, HIV viral load, and a panel of 23 soluble markers of immune activation.<br><br>RESULTS: :61% of participants had at least one ARS finding and 35% had at least 3. More ARS findings were reported in those enrolled within a month of estimated date of detectable infection (EDDI). Having more ARS signs/symptoms was associated with increased risk of CD4 decrease below 350&#x200a;cells/mL within the first 24&#x200a;weeks, failure to suppress HIV viral load, and was most strongly associated with elevated IP-10. Immediate ART blunted effects on symptoms, CD4 and viral load, as associations were strongest in the arm that started ART after 24&#x200a;weeks. Detrimental associations of ARS with CD4 counts, and CD4/CD8 ratio were not maintained at 2 or 4&#x200a;years.<br><br>CONCLUSIONS: :ARS has marked associations with short-term immunologic function and virologic suppression, which were mitigated in participants randomized to initiate ART immediately during primary infection.},
}
@article {pmid36779490,
year = {2023},
author = {Svensson Akusjärvi, S and Krishnan, S and Ambikan, AT and Mikaeloff, F and Munusamy Ponnan, S and Vesterbacka, J and Lourda, M and Nowak, P and Sönnerborg, A and Neogi, U},
title = {Role of myeloid cells in system-level immunometabolic dysregulation during prolonged successful HIV-1 treatment.},
journal = {AIDS (London, England)},
volume = {},
number = {},
pages = {},
doi = {10.1097/QAD.0000000000003512},
pmid = {36779490},
issn = {1473-5571},
abstract = {OBJECTIVE: :Why people living with HIV-1 on ART (PLWHART) display convoluted metabolism and immune cell functions during prolonged suppressive therapy is not well evaluated. In this study, we aimed to address this question using multiomics methodologies to investigate immunological and metabolic differences between PLWHART and HIV-1 negative individuals (HC).<br><br>DESIGN: :Cross-sectional study.<br><br>METHODS: :Untargeted and targeted metabolomics was performed using gas and liquid chromatography/mass spectrometry, and targeted proteomics using OlinkTM inflammation panel on plasma samples. The cellular metabolic state was further investigated using flow cytometry and intracellular metabolic measurement in single-cell populations isolated by EasySep cell isolation. Finally, flow cytometry was performed for deep-immunophenotyping of mononuclear phagocytes.<br><br>RESULTS: :We detected increased levels of glutamate, lactate, and pyruvate by plasma metabolomics and increased inflammatory markers (e.g., CCL20 and CCL7) in PLWHART compared to HC. The metabolite transporter detection by flow cytometry in T-cells and monocytes indicated an increased expression of glucose transporter 1 (Glut1) and monocarboxylate transporter 1 (MCT-1) in PLWHART. Single cell-type metabolite measurement identified decreased glucose, glutamate, and lactate in monocytic cell populations in PLWHART. Deep-immunophenotyping of myeloid cell lineages subpopulations showed no difference in cell frequency, but expression levels of CCR5 were increased on classical monocytes and some dendritic cells.<br><br>CONCLUSIONS: :Our data thus suggest that the myeloid cell populations potentially contribute significantly to the modulated metabolic environment during suppressive HIV-1 Infection.},
}
@article {pmid36779357,
year = {2023},
author = {Graham, LS and Haffner, MC and Sayar, E and Gawne, A and Schweizer, MT and Pritchard, CC and Coleman, I and Nelson, PS and Yu, EY},
title = {Clinical, pathologic, and molecular features of amphicrine prostate cancer.},
journal = {The Prostate},
volume = {},
number = {},
pages = {},
doi = {10.1002/pros.24497},
pmid = {36779357},
issn = {1097-0045},
support = {2021184/DDCF/Doris Duke Charitable Foundation/United States ; Pacific Northwest Prostate Cancer SPORE P50 CA0971/NH/NIH HHS/United States ; P01 CA 163227/CA/NCI NIH HHS/United States ; R01 CA234715/CA/NCI NIH HHS/United States ; },
abstract = {BACKGROUND: Amphicrine prostate carcinoma (AMPC) is a poorly defined subset of prostate cancer in which cells co-express luminal prostate epithelial and neuroendocrine markers. The optimal treatment strategy is unknown. We sought to further characterize the clinical, histomorphologic, and molecular characteristics of AMPC and to identify areas of potential future treatment investigations.<br><br>METHODS: We retrospectively identified 17 cases of AMPC at a single institution, defined as synaptophysin expression in >70% of cells and co-expression of androgen receptor&#xa0;(AR) signaling markers (either AR, PSA, or NKX3.1) in >50% of cells. Clinical and histologic features of AMPC cases as well as response to treatment and clinical outcomes were described.<br><br>RESULTS: Five AMPC cases arose de novo in the absence of prior systemic treatment and behaved distinctly from cases that were treatment-emergent. In these de novo cases, despite expression of neuroendocrine markers, prognosis appeared more favorable than high-grade neuroendocrine carcinoma, with two (40%) patients with de novo metastatic disease, universal response to androgen deprivation therapy, and no deaths at a median follow-up of 12.3 months. Treatment-emergent AMPC arose a median of 41.1 months after androgen deprivation therapy initiation and was associated with poor response to therapy.<br><br>CONCLUSIONS: We show that amphicrine prostate cancer is a unique entity and differs in clinical and molecular features from high-grade neuroendocrine carcinomas of the prostate. Our study highlights the need to recognize AMPC as a unique molecularly defined subgroup of prostate cancer.},
}
@article {pmid36778937,
year = {2022},
author = {González-Arriagada, WA and Ottaviani, G and Dean, D and Ottaviani, G and Santos-Silva, AR and Treister, NS},
title = {Editorial: Oral complications in cancer patients.},
journal = {Frontiers in oral health},
volume = {3},
number = {},
pages = {1116885},
pmid = {36778937},
issn = {2673-4842},
}
@article {pmid36777968,
year = {2022},
author = {Zhang, B and Tchetgen Tchetgen, EJ},
title = {A Semiparametric Approach to Model-Based Sensitivity Analysis in Observational Studies.},
journal = {Journal of the Royal Statistical Society. Series A, (Statistics in Society)},
volume = {185},
number = {Suppl 2},
pages = {S668-S691},
pmid = {36777968},
issn = {0964-1998},
abstract = {When drawing causal inference from observational data, there is almost always concern about unmeasured confounding. One way to tackle this is to conduct a sensitivity analysis. One widely-used sensitivity analysis framework hypothesizes the existence of a scalar unmeasured confounder U and asks how the causal conclusion would change were U measured and included in the primary analysis. Work along this line often makes various parametric assumptions on U, for the sake of mathematical and computational convenience. In this article, we further this line of research by developing a valid sensitivity analysis that leaves the distribution of U unrestricted. Compared to many existing methods in the literature, our method allows for a larger and more flexible family of models, mitigates observable implications (Franks et al., 2019), and works seamlessly with any primary analysis that models the outcome regression parametrically. We construct both pointwise confidence intervals and confidence bands that are uniformly valid over a given sensitivity parameter space, thus formally accounting for unknown sensitivity parameters. We apply our proposed method on an influential yet controversial study of the causal relationship between war experiences and political activeness using observational data from Uganda.},
}
@article {pmid36776432,
year = {2022},
author = {Ulrich, AK and Adamson, BJ and Saldarriaga, EM and Grecca, R and Wood, D and Babigumira, JB and Sanchez, JL and Lama, JR and Dimitrov, D and Duerr, A},
title = {Finding and treating early-stage HIV infections: A cost-effectiveness analysis of the Sabes study in Lima, Peru.},
journal = {Lancet regional health. Americas},
volume = {12},
number = {},
pages = {100281},
pmid = {36776432},
issn = {2667-193X},
abstract = {BACKGROUND: Sabes, a treatment-as-prevention intervention among men who have sex with men and transgender women in Lima, Peru, was developed to identify HIV during early primary infection (<3 months from acquisition) through monthly serologic assays and HIV RNA tests. Newly diagnosed individuals were rapidly linked to care and offered to initiate ART. In this study we sought to study the cost-effectiveness of Sabes compared to the standard of care (SOC) for HIV testing and initiation of treatment.<br><br>METHODS: We adapted a compartmental model of HIV transmission to evaluate the cost-effectiveness of the Sabes approach compared to the SOC using a government health care perspective, 20-year time horizon, and 3% annual discounting. We estimated the proportion of cases of HIV detected during early primary infection, reduction in HIV incidence and prevalence, incremental cost-effectiveness ratio (ICER), and net monetary benefit. We analyzed costs using data from the Sabes study, the Peruvian Ministry of Health, published literature, and expert consultation.<br><br>FINDINGS: The Sabes intervention is projected to identify 9294 early primary HIV infections in Lima, Peru over 20 years. The intervention costs $6,896 per early primary infection diagnosed and by 2038 is expected to decrease the fraction of early infections among prevalent infections by 62%. Sabes is expected to improve health, resulting in greater total discounted QALYs per person than the SOC (16&#xb7;7 vs 16&#xb7;4, respectively). Sabes had an ICER of $1431 (22% per capita GDP in Peru) per QALY compared to SOC.<br><br>INTERPRETATION: Our analysis suggests that in Lima, Peru the Sabes intervention could be a cost-effective approach to reduce the burden of HIV even under stringent cost-effectiveness criteria. This finding suggests that programs that use frequent HIV testing, rapid linkage to care and initiation of ART should be considered as part of a comprehensive HIV prevention strategy.<br><br>FUNDING: National Institutes of Health.},
}
@article {pmid36776124,
year = {2023},
author = {Nyame, YA and Holt, SK and Etzioni, RD and Gore, JL},
title = {Racial inequities in the quality of surgical care among Medicare beneficiaries with localized prostate cancer.},
journal = {Cancer},
volume = {},
number = {},
pages = {},
doi = {10.1002/cncr.34681},
pmid = {36776124},
issn = {1097-0142},
abstract = {BACKGROUND: US Black men are twice as likely to die from prostate cancer as men of other races. Lower quality care may contribute to this higher death rate.<br><br>METHODS: Sociodemographic and clinical data were obtained for men in Surveillance, Epidemiology, and End Results-Medicare diagnosed with clinically localized prostate cancer (cT1-4N0/xM0/x) and managed primarily by radical prostatectomy (2005-2015). Surgical volume was determined for facility and surgeon. Relationships between race, surgeon and/or facility volume, and characteristics of treating facility with survival (all-cause and cancer-specific) were assessed using multivariable Cox regression and competing risk analysis.<br><br>RESULTS: Black men represented 6.7% (n&#xa0;=&#xa0;2123) of 31,478 cohort. They were younger at diagnosis, had longer time from diagnosis to surgery, lower socioeconomic status, higher prostate-specific antigen (PSA), and higher comorbid status compared with men of other races (p&#xa0;<&#xa0;.001). They were less likely to receive care from a surgeon or facility in the top volume percentile (p&#xa0;<&#xa0;.001); less likely to receive surgical care at a National Cancer Institute-designated cancer center and more likely seen at a minority-serving hospital; and less likely to travel &#x2265;50 miles for surgical care. On multivariable analysis stratified by surgical volume, Black men receiving care from a surgeon or facility with lower volumes demonstrated increased risk of prostate cancer mortality (hazard ratio, 1.61; 95% confidence interval, 1.01-2.69) adjusting for age, clinical stage, PSA, and comorbidity index.<br><br>CONCLUSIONS: Black Medicare beneficiaries with prostate cancer more commonly receive care from surgeons and facilities with lower volumes, likely affecting surgical quality and outcomes. Access to high-quality prostate cancer care may reduce racial inequities in disease outcomes, even among insured men.<br><br>PLAIN LANGUAGE SUMMARY: Black men are twice as likely to die of prostate cancer than other US men. Lower quality care may contribute to higher rates of prostate cancer death. We used surgical volume to evaluate the relationship between race and quality of care. Black Medicare beneficiaries with prostate cancer more commonly received care from surgeons and facilities with lower volumes, correlating&#xa0;with a higher risk of prostate cancer death and indicating scarce resources for care. Access to high-quality prostate cancer care eases disparities in disease outcomes. Patient-centered interventions that increase access to high-quality care for Black men with prostate cancer are needed.},
}
@article {pmid36775202,
year = {2023},
author = {Fraint, E and Abdel-Azim, H and Bhatt, NS and Broglie, L and Chattha, A and Kohorst, M and Ktena, YP and Lee, MA and Long, S and Qayed, M and Sharma, A and Stefanski, H and Vatsayan, A and Wray, L and Hamadani, M and Carpenter, PA},
title = {Evaluation of children with malignancies for blood and marrow transplantation: A report from the ASTCT Committee on Practice Guidelines.},
journal = {Transplantation and cellular therapy},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jtct.2023.02.003},
pmid = {36775202},
issn = {2666-6367},
abstract = {Evaluation of a candidate for hematopoietic cell transplant (HCT) is a complex process with substantial inter-center variability. Although literature providing guidance for evaluating the eligibility of adults is well established, similar guidance for children is lacking. To address gaps between adult recommendations and the specific needs of children, we convened a panel of pediatric HCT experts from a wide geographic range of American Society of Transplantation and Cellular Therapy (ASTCT) member institutions to offer pediatric-focused pre-HCT evaluation recommendations. In this report from the ASTCT Committee on Practice Guidelines, we present a practical framework for evaluating children with malignancies who are candidates for HCT. We also highlight key differences from adults and emphasize areas of unmet need that require additional research to delineate best practices.},
}
@article {pmid36774056,
year = {2022},
author = {Gibbons, SM and Gurry, T and Lampe, JW and Chakrabarti, A and Dam, V and Everard, A and Goas, A and Gross, G and Kleerebezem, M and Lane, J and Maukonen, J and Penna, ALB and Pot, B and Valdes, AM and Walton, G and Weiss, A and Zanzer, YC and Venlet, NV and Miani, M},
title = {Perspective: Leveraging the Gut Microbiota to Predict Personalized Responses to Dietary, Prebiotic, and Probiotic Interventions.},
journal = {Advances in nutrition (Bethesda, Md.)},
volume = {13},
number = {5},
pages = {1450-1461},
doi = {10.1093/advances/nmac075},
pmid = {36774056},
issn = {2156-5376},
abstract = {Humans often show variable responses to dietary, prebiotic, and probiotic interventions. Emerging evidence indicates that the gut microbiota is a key determinant for this population heterogeneity. Here, we provide an overview of some of the major computational and experimental tools being applied to critical questions of microbiota-mediated personalized nutrition and health. First, we discuss the latest advances in in silico modeling of the microbiota-nutrition-health axis, including the application of statistical, mechanistic, and hybrid artificial intelligence models. Second, we address high-throughput in vitro techniques for assessing interindividual heterogeneity, from ex vivo batch culturing of stool and continuous culturing in anaerobic bioreactors, to more sophisticated organ-on-a-chip models that integrate both host and microbial compartments. Third, we explore in vivo approaches for better understanding of personalized, microbiota-mediated responses to diet, prebiotics, and probiotics, from nonhuman animal models and human observational studies, to human feeding trials and crossover interventions. We highlight examples of existing, consumer-facing precision nutrition platforms that are currently leveraging the gut microbiota. Furthermore, we discuss how the integration of a broader set of the tools and techniques described in this piece can generate the data necessary to support a greater diversity of precision nutrition strategies. Finally, we present a vision of a precision nutrition and healthcare future, which leverages the gut microbiota to design effective, individual-specific interventions.},
}
@article {pmid36773962,
year = {2023},
author = {Glenn, BA and Crespi, CM and Herrmann, AK and Nonzee, NJ and Debra L Rosen, RN and Park, CL and Gina Johnson, MD and L Cindy Chang, MS and Singhal, R and Taylor, VM and Bastani, R},
title = {Effectiveness and feasibility of three types of parent reminders to increase adolescent human papillomavirus (HPV) vaccination.},
journal = {Preventive medicine},
volume = {},
number = {},
pages = {107448},
doi = {10.1016/j.ypmed.2023.107448},
pmid = {36773962},
issn = {1096-0260},
abstract = {Parent reminders have produced modest improvements in human papillomavirus (HPV) vaccination among adolescents. However, little prior research has compared the effectiveness and feasibility of different HPV reminder types in resource-limited settings. We conducted a quasi-experimental study (2016-2017) to evaluate the effectiveness of three parent reminder types (mailed letters, robocalls, text messages) on next-dose HPV vaccine receipt among 12-year-olds in a large Federally Qualified Health Center in Los Angeles County. Six clinics were matched into three pairs: randomly assigning one clinic within each pair to intervention and control. Intervention clinics were randomly assigned to deliver one of the three parent reminder types. We calculated rates of next-dose vaccine receipt and assessed intervention effects using logistic regression models. We calculated the proportion of each type of reminder successfully delivered as a feasibility measure. The study sample comprised 877 12-year-olds due for an HPV vaccine dose (47% female, >85% Latino). At 4-month follow-up, 23% of intervention patients received an HPV vaccine dose compared to only 12% of control patients. Overall, receipt of any reminder increased rates of the next-needed HPV vaccine compared to usual care (p = 0.046). Significant improvements were observed for text reminders (p = 0.036) and boys (p = 0.006). Robocalls were the least feasible reminder type. Text message reminders are feasible and effective for promoting HPV vaccination. Future research is needed to assess the effectiveness and feasibility of reminders compared to other vaccine promotion strategies.},
}
@article {pmid36773607,
year = {2023},
author = {Schuster, IS and Sng, XYX and Lau, CM and Powell, DR and Weizman, OE and Fleming, P and Neate, GEG and Voigt, V and Sheppard, S and Maraskovsky, AI and Daly, S and Koyama, M and Hill, GR and Turner, SJ and O'Sullivan, TE and Sun, JC and Andoniou, CE and Degli-Esposti, MA},
title = {Infection induces tissue-resident memory NK cells that safeguard tissue health.},
journal = {Immunity},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.immuni.2023.01.016},
pmid = {36773607},
issn = {1097-4180},
abstract = {Tissue health is dictated by the capacity to respond to perturbations and then return to homeostasis. Mechanisms that initiate, maintain, and regulate immune responses in tissues are therefore essential. Adaptive immunity plays a key role in these responses, with memory and tissue residency being cardinal features. A corresponding role for innate cells is unknown. Here, we have identified a population of innate lymphocytes that we term tissue-resident memory-like natural killer (NKRM) cells. In response to murine cytomegalovirus infection, we show that circulating NK cells were recruited in a CX3CR1-dependent manner to the salivary glands where they formed NKRM cells, a long-lived, tissue-resident population that prevented autoimmunity via TRAIL-dependent elimination of CD4[+] T cells. Thus, NK cells develop adaptive-like features, including long-term residency in non-lymphoid tissues, to modulate inflammation, restore immune equilibrium, and preserve tissue health. Modulating the functions of NKRM cells may provide additional strategies to treat inflammatory and autoimmune diseases.},
}
@article {pmid36773220,
year = {2023},
author = {Winn, A and Basu, A and Ramsey, SD},
title = {A Framework for a Health Economic Evaluation Model for Patients with Sickle Cell Disease to Estimate the Value of New Treatments in the United States of America.},
journal = {PharmacoEconomics - open},
volume = {},
number = {},
pages = {},
pmid = {36773220},
issn = {2509-4254},
abstract = {BACKGROUND: Sickle cell disease (SCD) is an inherited blood disorder associated with lifelong morbidity and increased risk of mortality that affects approximately 100,000 individuals in the United States (US), primarily of African-American descent. Due to these complications, individuals with SCD typically incur high healthcare costs. With a number of costly but potentially curative SCD therapies on the horizon, understanding the progression of SCD and economic burden to insurers and patients is vital.<br><br>OBJECTIVE: The aim is to develop a framework to understand the progression and costs of SCD that could be used to estimate how new treatments can impact the progression and costs of the disease.<br><br>METHODS: We detail how we will create a simulation model that represents the natural history of a population and allows for the characterization of the impact of novel therapies on the disease, associated costs, and outcomes in comparison to current management.<br><br>CONCLUSION: In this report, we describe a conceptual approach to modeling SCD to determine the relative clinical and economic impact of new gene therapies compared to conventional therapies with a goal of providing a flexible approach that could inform the clinical management of SCD for patients, payers, and policy makers.},
}
@article {pmid36765324,
year = {2023},
author = {Ausenhus, C and Gold, JM and Perry, CK and Kozak, A and Wang, ML and Jang, SH and Leong, J and Rodriguez, E and Duggan, C and Ko, LK},
title = {Factors impacting implementation of nutrition and physical activity policies in rural schools.},
journal = {BMC public health},
volume = {23},
number = {1},
pages = {308},
pmid = {36765324},
issn = {1471-2458},
abstract = {BACKGROUND: Rural Latino children have higher rates of obesity compared to non-Latino Whites. Schools are in a unique position to address rural childhood obesity through policies. While evidence exists on factors that promote or impede school-based physical activity (PA) and nutrition policies, only a fraction has been in rural communities. This study seeks to understand 1) the knowledge and perceptions of school nutrition and PA policies and 2) barriers and facilitators to their implementation among rural school stakeholders from Washington State.<br><br>METHODS: We conducted 20 semi-structured, in-depth interviews with school stakeholders (e.g., principals and school nutrition directors) from four K-12 school districts in the Lower Yakima Valley of Eastern Washington State. Thematic analysis was conducted using inductive, constant comparison approach to identify themes around knowledge and perceptions of policies and barriers and facilitators of policy implementation.<br><br>RESULTS: Three main themes were identified: perceptions and knowledge of school PA and nutrition policies, barriers to policy implementation, and facilitators of policy implementation. The majority of stakeholders were supportive of school-based policies promoting PA and a healthy diet, even when lacking a specific understanding of these policies. Four subthemes were identified as barriers to policy implementation: viewing PA as a low priority, misuse of recess time, funding constraints, and lack of strong leadership. Facilitators of implementation included strong leadership at the district level, creating healthy norms through school-community linkages and pooling community resources to improve nutrition and PA among children.<br><br>CONCLUSIONS: Schools provide a unique setting to promote healthy diet and PA behaviors among children and their families. Study findings show that while knowledge of specific nutrition and PA policies may vary, support for such policies were high among rural stakeholders. Study findings can inform policy development and support strategies for policy implementation in rural settings. Future studies may want to examine whether implementation of strategies addressing the barriers and enhancing facilitators lead to success in rural school settings.},
}
@article {pmid36764753,
year = {2023},
author = {Mehta, S and Buyanbat, A and Orkin, S and Nabet, B},
title = {High-efficiency knock-in of degradable tags (dTAG) at endogenous loci in cell lines.},
journal = {Methods in enzymology},
volume = {681},
number = {},
pages = {1-22},
doi = {10.1016/bs.mie.2022.08.045},
pmid = {36764753},
issn = {1557-7988},
abstract = {The dTAG system is a versatile strategy for tunable control of protein abundance and facilitates the time-resolved assessment of disease-associated protein function. A "co-opted" fusion-based degron peptide, the "dTAG" facilitates the study of endogenous protein function when knocked-in at the endogenous genetic loci of proteins of interest. We combine CRISPR/Cas9 mediated induction of double-strand breaks (DSB) with the delivery of a single-stranded DNA HDR-donor-template via crude preparations of recombinant adeno-associated virus (rAAV). Our approach to knock-in of large (1-2kb) DNA fragments via crude-rAAV mediated HDR donor delivery is rapid and inexpensive. It facilitates genetic modification of a variety of human as well as mouse cell lines at high efficiency and precision.},
}
@article {pmid36763922,
year = {2023},
author = {Frederick, NN and Klosky, JL and Meacham, L and Quinn, GP and Kelvin, JF and Cherven, B and Freyer, DR and Dvorak, CC and Brackett, J and Ahmed-Winston, S and Bryson, E and Su, HI and Chow, EJ and Levine, J},
title = {Fertility Preservation Practices at Pediatric Oncology Institutions in the United States: A Report From the Children's Oncology Group.},
journal = {JCO oncology practice},
volume = {},
number = {},
pages = {OP2200349},
doi = {10.1200/OP.22.00349},
pmid = {36763922},
issn = {2688-1535},
abstract = {PURPOSE: Fertility discussions are an integral part of comprehensive care for pediatric, adolescent, and young adult patients newly diagnosed with cancer and are supported by national guidelines. Current institutional practices are poorly understood.<br><br>METHODS: A cross-sectional survey was distributed to 220 Children's Oncology Group member institutions regarding fertility discussion practices. Descriptive statistics were calculated for all variables. The association between specific practices and selected outcomes on the basis of sex was examined via multivariable logistic regression.<br><br>RESULTS: One hundred forty-four programs (65.5%) returned surveys. Of these, 65 (45.1%) reported routine discussions of fertility with all female patients and 55 (38.5%) all male patients (P = .25). Ninety-two (63.8%) reported no specific criteria for offering females fertility preservation (FP), compared with 40 (27.7%) for males (P < .001). Program characteristics associated with fertility discussions included reproductive endocrinology and infertility on site (females odds ratio [OR], 2.1; 95% CI, 1.0 to 4.3), discussion documentation mandate (females OR, 2.3; 95% CI, 1.0 to 5.5; males OR, 3.5; 95% CI, 1.4 to 8.7), and cumulative institution-based FP infrastructure (which included [1] routine practice of documentation, [2] template for documentation, [3] mandate for documentation, and [4] availability of FP navigation; females OR, 1.6; 95% CI, 1.1 to 2.3; males OR, 2.3; 95% CI, 1.6 to 3.4). Utilization of practices unsupported by guidelines included offering sperm banking after treatment initiation (39/135 programs; 28.9%), gonadotropin-releasing hormone analogs for ovarian suppression/FP (75/144 programs; 52.1%), ovarian tissue cryopreservation at diagnosis for patients with leukemia (19/64 programs; 29.7%), and testicular tissue cryopreservation (23/138 programs; 16.7%) not part of a clinical trial.<br><br>CONCLUSION: Despite recommended guidelines, fertility discussions with patients/families before treatment initiation are not routine at Children's Oncology Group institutions. Standard criteria to determine which options should be offered to patients are more common for males than females.},
}
@article {pmid36763666,
year = {2023},
author = {Marcink, TC and Zipursky, G and Cheng, W and Stearns, K and Stenglein, S and Golub, K and Cohen, F and Bovier, F and Pfalmer, D and Greninger, AL and Porotto, M and des Georges, A and Moscona, A},
title = {Subnanometer structure of an enveloped virus fusion complex on viral surface reveals new entry mechanisms.},
journal = {Science advances},
volume = {9},
number = {6},
pages = {eade2727},
doi = {10.1126/sciadv.ade2727},
pmid = {36763666},
issn = {2375-2548},
abstract = {Paramyxoviruses-including important pathogens like parainfluenza, measles, and Nipah viruses-use a receptor binding protein [hemagglutinin-neuraminidase (HN) for parainfluenza] and a fusion protein (F), acting in a complex, to enter cells. We use cryo-electron tomography to visualize the fusion complex of human parainfluenza virus 3 (HN/F) on the surface of authentic clinical viruses at a subnanometer resolution sufficient to answer mechanistic questions. An HN loop inserts in a pocket on F, showing how the fusion complex remains in a ready but quiescent state until activation. The globular HN heads are rotated with respect to each other: one downward to contact F, and the other upward to grapple cellular receptors, demonstrating how HN/F performs distinct steps before F activation. This depiction of viral fusion illuminates potentially druggable targets for paramyxoviruses and sheds light on fusion processes that underpin wide-ranging biological processes but have not been visualized in situ or at the present resolution.},
}
@article {pmid36763635,
year = {2023},
author = {Gristick, HB and Hartweger, H and Loewe, M and van Schooten, J and Ramos, V and Oliveira, TY and Nishimura, Y and Koranda, NS and Wall, A and Yao, KH and Poston, D and Gazumyan, A and Wiatr, M and Horning, M and Keeffe, JR and Hoffmann, MAG and Yang, Z and Abernathy, ME and Dam, KA and Gao, H and Gnanapragasam, PNP and Kakutani, LM and Pavlovitch-Bedzyk, AJ and Seaman, MS and Howarth, M and McGuire, AT and Stamatatos, L and Martin, MA and West, AP and Nussenzweig, MC and Bjorkman, PJ},
title = {CD4 binding site immunogens elicit heterologous anti-HIV-1 neutralizing antibodies in transgenic and wild-type animals.},
journal = {Science immunology},
volume = {8},
number = {80},
pages = {eade6364},
doi = {10.1126/sciimmunol.ade6364},
pmid = {36763635},
issn = {2470-9468},
abstract = {Passive transfer of broadly neutralizing anti-HIV-1 antibodies (bNAbs) protects against infection, and therefore, eliciting bNAbs by vaccination is a major goal of HIV-1 vaccine efforts. bNAbs that target the CD4 binding site (CD4bs) on HIV-1 Env are among the most broadly active, but to date, responses elicited against this epitope in vaccinated animals have lacked potency and breadth. We hypothesized that CD4bs bNAbs resembling the antibody IOMA might be easier to elicit than other CD4bs antibodies that exhibit higher somatic mutation rates, a difficult-to-achieve mechanism to accommodate Env's N276gp120 N-glycan, and rare five-residue light chain complementarity-determining region 3. As an initial test of this idea, we developed IOMA germline-targeting Env immunogens and evaluated a sequential immunization regimen in transgenic mice expressing germline-reverted IOMA. These mice developed CD4bs epitope-specific responses with heterologous neutralization, and cloned antibodies overcame neutralization roadblocks, including accommodating the N276gp120 glycan, with some neutralizing selected HIV-1 strains more potently than IOMA. The immunization regimen also elicited CD4bs-specific responses in mice containing polyclonal antibody repertoires as well as rabbits and rhesus macaques. Thus, germline targeting of IOMA-class antibody precursors represents a potential vaccine strategy to induce CD4bs bNAbs.},
}
@article {pmid36763517,
year = {2023},
author = {Petersdorf, EW and McKallor, C and Malkki, M and He, M and Spellman, S and Hsu, KC and Strong, R and Gooley, TA and Stevenson, PA},
title = {Role of NKG2D Ligands and Receptor in Haploidentical Related Donor Hematopoietic Cell Transplantation.},
journal = {Blood advances},
volume = {},
number = {},
pages = {},
doi = {10.1182/bloodadvances.2022008922},
pmid = {36763517},
issn = {2473-9537},
abstract = {The recurrence of malignancy after hematopoietic cell transplantation (HCT) is the primary cause of transplant failure. The NKG2D axis is a powerful pathway for anti-tumor responses, but its role in the control of malignancy after HCT is not well-defined. We tested the hypothesis that gene variation of the NKG2D receptor and its ligands MICA and MICB affect relapse and survival in 1,629 patients who received a haploidentical HCT for the treatment of a malignant blood disorder. Patients and donors were characterized for MICA residue 129 and the exon 5 short tandem repeat (STR), and MICB residues 52, 57, 98, 189. Donors were additionally defined for NKG2D residue 72. Mortality was higher in patients with MICB-52Asn relative to 52Asp (HR 1.83 [95% CI 1.24-2.71; P = 0.002]) and lower with MICA STR-mismatching relative to STR-matching (HR 0.66 [95% CI 0.54-0.79; P = 0.00002]). Relapse was lower with NKG2D-72Thr donors relative to 72Ala (relapse HR 0.57 [95% CI 0.35-0.91; P = 0.02]). The protective effects of patient MICB-52Asp with donor MICA STR-mismatching and NKG2D-72Thr were enhanced when all three features were present. The NKG2D ligand/receptor pathway is a transplantation determinant. The immunobiology of relapse is defined by the concerted effects of MICA, MICB and NKG2D germline variation. Consideration of NKG2D ligand/receptor pairings may improve survival for future patients.},
}
@article {pmid36763410,
year = {2023},
author = {Chang, CH and Mejia Natividad, I and Malik, HS},
title = {Expansion and loss of sperm nuclear basic protein genes in Drosophila correspond with genetic conflicts between sex chromosomes.},
journal = {eLife},
volume = {12},
number = {},
pages = {},
doi = {10.7554/eLife.85249},
pmid = {36763410},
issn = {2050-084X},
support = {DRG 2438-21//Damon Runyon Cancer Research Foundation/United States ; },
abstract = {Many animal species employ sperm nuclear basic proteins (SNBPs) or protamines to package sperm genomes tightly. SNBPs vary across animal lineages and evolve rapidly in mammals. We used a phylogenomic approach to investigate SNBP diversification in Drosophila species. We found that most SNBP genes in Drosophila melanogaster evolve under positive selection except for genes essential for male fertility. Unexpectedly, evolutionarily young SNBP genes are more likely to be critical for fertility than ancient, conserved SNBP genes. For example, CG30056 is dispensable for male fertility despite being one of three SNBP genes universally retained in Drosophila species. We found 19 independent SNBP gene amplification events that occurred preferentially on sex chromosomes. Conversely, the montium group of Drosophila species lost otherwise-conserved SNBP genes, coincident with an X-Y chromosomal fusion. Furthermore, SNBP genes that became linked to sex chromosomes via chromosomal fusions were more likely to degenerate or relocate back to autosomes. We hypothesize that autosomal SNBP genes suppress meiotic drive, whereas sex-chromosomal SNBP expansions lead to meiotic drive. X-Y fusions in the montium group render autosomal SNBPs dispensable by making X-versus-Y meiotic drive obsolete or costly. Thus, genetic conflicts between sex chromosomes may drive SNBP rapid evolution during spermatogenesis in Drosophila species.},
}
@article {pmid36761837,
year = {2022},
author = {Tercan, B and Qin, G and Kim, TK and Aguilar, B and Phan, J and Longabaugh, W and Pot, D and Kemp, CJ and Chambwe, N and Shmulevich, I},
title = {SL-Cloud: A Cloud-based resource to support synthetic lethal interaction discovery.},
journal = {F1000Research},
volume = {11},
number = {},
pages = {493},
doi = {10.12688/f1000research.110903.1},
pmid = {36761837},
issn = {2046-1402},
abstract = {Synthetic lethal interactions (SLIs), genetic interactions in which the simultaneous inactivation of two genes leads to a lethal phenotype, are promising targets for therapeutic intervention in cancer, as exemplified by the recent success of PARP inhibitors in treating BRCA1/2-deficient tumors. We present SL-Cloud, a new component of the Institute for Systems Biology Cancer Gateway in the Cloud (ISB-CGC), that provides an integrated framework of cloud-hosted data resources and curated workflows to enable facile prediction of SLIs. This resource addresses two main challenges related to SLI inference: the need to wrangle and preprocess large multi-omic datasets and the availability of multiple comparable prediction approaches. SL-Cloud enables customizable computational inference of SLIs and testing of prediction approaches across multiple datasets. We anticipate that cancer researchers will find utility in this tool for discovery of SLIs to support further investigation into potential drug targets for anticancer therapies.},
}
@article {pmid36761036,
year = {2023},
author = {Lin, D and Wahid, KA and Nelms, BE and He, R and Naser, MA and Duke, S and Sherer, MV and Christodouleas, JP and Mohamed, ASR and Cislo, M and Murphy, JD and Fuller, CD and Gillespie, EF},
title = {E pluribus unum: prospective acceptability benchmarking from the Contouring Collaborative for Consensus in Radiation Oncology crowdsourced initiative for multiobserver segmentation.},
journal = {Journal of medical imaging (Bellingham, Wash.)},
volume = {10},
number = {Suppl 1},
pages = {S11903},
pmid = {36761036},
issn = {2329-4302},
abstract = {PURPOSE: Contouring Collaborative for Consensus in Radiation Oncology (C3RO) is a crowdsourced challenge engaging radiation oncologists across various expertise levels in segmentation. An obstacle to artificial intelligence (AI) development is the paucity of multiexpert datasets; consequently, we sought to characterize whether aggregate segmentations generated from multiple nonexperts could meet or exceed recognized expert agreement.<br><br>APPROACH: Participants who contoured &#x2265; 1 region of interest (ROI) for the breast, sarcoma, head and neck (H&amp;N), gynecologic (GYN), or gastrointestinal (GI) cases were identified as a nonexpert or recognized expert. Cohort-specific ROIs were combined into single simultaneous truth and performance level estimation (STAPLE) consensus segmentations. STAPLE nonexpert ROIs were evaluated against STAPLE expert contours using Dice similarity coefficient (DSC). The expert interobserver DSC (IODSC expert) was calculated as an acceptability threshold between STAPLE nonexpert and STAPLE expert . To determine the number of nonexperts required to match the IODSC expert for each ROI, a single consensus contour was generated using variable numbers of nonexperts and then compared to the IODSC expert .<br><br>RESULTS: For all cases, the DSC values for STAPLE nonexpert versus STAPLE expert were higher than comparator expert IODSC expert for most ROIs. The minimum number of nonexpert segmentations needed for a consensus ROI to achieve IODSC expert acceptability criteria ranged between 2 and 4 for breast, 3 and 5 for sarcoma, 3 and 5 for H&amp;N, 3 and 5 for GYN, and 3 for GI.<br><br>CONCLUSIONS: Multiple nonexpert-generated consensus ROIs met or exceeded expert-derived acceptability thresholds. Five nonexperts could potentially generate consensus segmentations for most ROIs with performance approximating experts, suggesting nonexpert segmentations as feasible cost-effective AI inputs.},
}
@article {pmid36760126,
year = {2023},
author = {Li, C and Anderson, AK and Wang, H and Gil, S and Kim, J and Huang, L and Germond, A and Baldessari, A and Nelson, V and Peterson, CW and Bui, J and Kiem, HP and Lieber, A},
title = {Stable expression of an HIV decoy receptor after in vivo HSC transduction in mice and NHPs: Safety and efficacy in protection from SHIV.},
journal = {Molecular therapy : the journal of the American Society of Gene Therapy},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.ymthe.2023.02.002},
pmid = {36760126},
issn = {1525-0024},
abstract = {We aim to develop an in vivo hematopoietic stem cells (HSC) gene therapy approach for persistent control/protection of HIV-1 infection based on the stable expression of a secreted decoy protein for HIV receptors CD4 and CCR5 (eCD4-Ig) from blood cells. HSCs in mice and a rhesus macaque were mobilized from the bone marrow and transduced by an intravenous injection of HSC-tropic, integrating HDAd5/35++ vectors expressing rhesus eCD4-Ig. In vivo HSC transduction/selection resulted in stable serum eCD4-Ig levels of ∼100 μg/ml (mice) and >20 μg/ml (rhesus) with IC50s of 1 μg/ml measured by an HIV neutralization assay. After SHIV.D challenge of rhesus macaques injected with HDAd-eCD4-Ig or a control HDAd5/35++ vector, peak plasma viral load levels were ∼50-fold lower in the eCD4-Ig expressing animal. Furthermore, the viral load was lower in tissues with the highest eCD4-Ig expression, specifically the spleen and lymph nodes. SHIV.D challenge triggered a selective expansion of transduced CD4[+]CCR5[+] cells, thereby increasing serum eCD4-Ig levels. The latter, however, broke immune tolerance and triggered anti-eCD4-Ig antibody responses, which could have contributed to the inability to eliminate SHIV.D. Our data will guide us in the improvement of the in vivo approach. Clearly, our conclusions need to be validated in larger animal cohorts.},
}
@article {pmid36759047,
year = {2023},
author = {Shadman, M},
title = {Allogenic Hematopoietic Cell Transplantation after CAR-T Failure: When Your Old Friend Comes to Rescue.},
journal = {Transplantation and cellular therapy},
volume = {29},
number = {2},
pages = {67-68},
doi = {10.1016/j.jtct.2023.01.002},
pmid = {36759047},
issn = {2666-6367},
}
@article {pmid36754839,
year = {2023},
author = {Sunga, CGG and Higgins, MS and Ricciotti, RW and Liu, YJ and Cranmer, LD},
title = {Inflammatory myofibroblastic tumor of the mesentery with a SQSTM1::ALK fusion responding to alectinib.},
journal = {Cancer reports (Hoboken, N.J.)},
volume = {},
number = {},
pages = {e1792},
doi = {10.1002/cnr2.1792},
pmid = {36754839},
issn = {2573-8348},
abstract = {BACKGROUND: Inflammatory myofibroblastic tumor (IMT) is an ultra-rare soft tissue neoplasm associated with fusion proteins encompassing the anaplastic lymphoma kinase (ALK) protein fused to a variety of partner proteins. Data regarding response to ALK-targeting agents based on fusion partner is limited.<br><br>CASE: A 30-year-old female sought emergency care after onset of abdominal and lower back pain in 2019. Computed tomography (CT) demonstrated a cystic, mesenteric mass within the pelvis measuring up to 8.9&#xa0;cm. Complete laparoscopic excision of the mass from the mesentery of the right colon and terminal ileum was performed. Pathologic assessment revealed IMT with a fusion between sequestosome 1 and ALK (SQSTM1::ALK), described in only two other cases of IMT. Four months after surgery, CT revealed multi-focal, unresectable disease recurrence. She was referred to the University of Washington/Fred&#xa0;Hutchinson&#xa0;Cancer&#xa0;Center and placed on therapy with alectinib, after which she experienced a partial response. Three years after IMT recurrence, disease remains under control.<br><br>CONCLUSION: This is the third reported case of IMT associated with the novel SQSTM1::ALK fusion protein, and the second treated with alectinib. Treatment with the ALK inhibitor alectinib appears to be active in this setting.},
}
@article {pmid36754086,
year = {2023},
author = {Li, YL and Langley, CA and Azumaya, CM and Echeverria, I and Chesarino, NM and Emerman, M and Cheng, Y and Gross, JD},
title = {The structural basis for HIV-1 Vif antagonism of human APOBEC3G.},
journal = {Nature},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41586-023-05779-1},
pmid = {36754086},
issn = {1476-4687},
abstract = {The APOBEC3 (A3) proteins are host antiviral cellular proteins that hypermutate the viral genome of diverse viral families. In retroviruses, this process requires A3 packaging into viral particles[1-4]. The lentiviruses encode a protein Vif that antagonizes A3 family members by targeting them for degradation. Diversification of A3 allows host escape from Vif whereas adaptations in Vif enable cross-species transmission of primate lentiviruses. How this molecular arms race plays out at the structural level is unknown. Here, we report the cryogenic electron microscopy structure of human APOBE3G (A3G) bound to HIV-1 Vif and hijacked cellular proteins that promote ubiquitin mediated proteolysis. A small surface explains the molecular arms race, including a cross-species transmission event that led to the birth of HIV-1. Unexpectedly, we find RNA is a molecular glue for the Vif-A3G interaction, enabling Vif to repress A3G by ubiquitin dependent and independent mechanisms. Our results suggest a model where Vif antagonizes A3G by intercepting it in its most dangerous form for the virus, when bound to RNA and on pathway to packaging, to prevent viral restriction. By engaging essential surfaces required for restriction, Vif exploits a vulnerability in A3G, suggesting a general mechanism where RNA binding helps position key residues necessary for viral antagonism of a host antiviral gene.},
}
@article {pmid36753746,
year = {2023},
author = {Leapman, MS and Wang, R and Loeb, S and Seibert, TM and Gaylis, FD and Lowentritt, B and Brown, GA and Chen, R and Lin, D and Witte, J and Cooperberg, MR and Catalona, WJ and Gross, CP and Ma, X},
title = {Use of Monitoring Tests Among Patients With Localized Prostate Cancer Managed With Observation.},
journal = {The Journal of urology},
volume = {},
number = {},
pages = {101097JU0000000000003159},
doi = {10.1097/JU.0000000000003159},
pmid = {36753746},
issn = {1527-3792},
abstract = {PURPOSE: It is unknown whether compliance with recommended monitoring tests during observation of localized prostate cancer has changed over time.<br><br>MATERIALS AND METHODS: We performed a retrospective cohort study of Medicare beneficiaries diagnosed with low- or intermediate-risk prostate cancer in 2004-2016 who were initially managed with observation for a minimum of 12 months. The primary objective was to examine rates of PSA testing, prostate biopsy, and prostate MRI. We used multivariable mixed effects Poisson regression to determine whether rates of PSA testing and prostate biopsy increased over time. In addition, we identified clinical, sociodemographic, and provider factors associated with the frequency of monitoring tests during observation.<br><br>RESULTS: We identified 10,639 patients diagnosed at a median age of 73 (IQR 69-77) years. The median follow-up time was 4.3 (IQR 2.7-6.6) years after diagnosis. Among patients managed without treatment for 5 years, 98% received at &#x2265;1 PSA test, 48.0% &#x2265;1 additional prostate biopsy, and 31.0% &#x2265;1 prostate MRI. Among patients managed with observation for &#x2265;12 months, mixed effects Poisson regression revealed that rates of PSA testing and biopsy increased over time (per calendar year: RR 1.02, 95% CI: 1.02-1.03 and RR 1.10, 95% CI: 1.08-1.11, respectively). Clinical and sociodemographic factors including age, clinical risk, race/ethnicity, census tract poverty, and region were associated with rates of biopsy and PSA testing.<br><br>CONCLUSIONS: Use of recommended monitoring tests including repeat prostate biopsy remains low among Medicare beneficiaries undergoing observation for low and intermediate-risk prostate cancer.},
}
@article {pmid36748802,
year = {2022},
author = {Hill, JA and Kiem, ES and Bhatti, A and Liu, W and Keane-Candib, J and Fitzpatrick, KS and Boonyaratanakornkit, J and Gardner, RA and Green, DJ and Maloney, DG and Turtle, CJ and Smith, JM and Gimferrer, I and Blosser, CD and Jackson, SW},
title = {Anti-HLA antibodies in recipients of CD19 versus BCMA-targeted CAR T-cell therapy.},
journal = {American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.ajt.2022.11.001},
pmid = {36748802},
issn = {1600-6143},
abstract = {Antibodies against foreign human leukocyte antigen (HLA) molecules are barriers to successful organ transplantation. B cell-depleting treatments are used to reduce anti-HLA antibodies but have limited efficacy. We hypothesized that the primary source for anti-HLA antibodies is long-lived plasma cells, which are ineffectively targeted by B cell depletion. To study this, we screened for anti-HLA antibodies in a prospectively enrolled cohort of 49 patients who received chimeric antigen receptor T-cell therapy (CARTx), targeting naïve and memory B cells (CD19-targeted, n = 21) or plasma cells (BCMA-targeted, n = 28) for hematologic malignancies. Longitudinal samples were collected before and up to 1 year after CARTx. All individuals were in sustained remission. We identified 4 participants with anti-HLA antibodies before CD19-CARTx. Despite B cell depletion, anti-HLA antibodies and calculated panel reactive antibody scores were stable for 1 year after CD19-CARTx. Only 1 BCMA-CARTx recipient had pre-CARTx low-level anti-HLA antibodies, with no follow-up samples available. These data implicate CD19[neg] long-lived plasma cells as an important source for anti-HLA antibodies, a model supported by infrequent HLA sensitization in BCMA-CARTx subjects receiving previous plasma cell-targeted therapies. Thus, plasma cell-targeted therapies may be more effective against HLA antibodies, thereby enabling improved access to organ transplantation and rejection management.},
}
@article {pmid36747283,
year = {2023},
author = {Xiao, H and Liu, F and Unger, JM},
title = {Automatic electronic reporting improved the completeness of AMI and stroke incident surveillance in Tianjin, China: a modeling study.},
journal = {Population health metrics},
volume = {21},
number = {1},
pages = {2},
pmid = {36747283},
issn = {1478-7954},
mesh = {Male ; Humans ; Female ; Adult ; Middle Aged ; Reproducibility of Results ; *Myocardial Infarction/epidemiology ; *Stroke/epidemiology ; Incidence ; China/epidemiology ; },
abstract = {BACKGROUND: AMI and stroke are the leading causes of premature mortality and hospitalizations in China. Incidence data at the population level for the two diseases is limited and the reliability and completeness of the existing incidence registry have not been investigated. We aim to assess if the completeness of case ascertainment of AMI and stroke incidence has improved since the implementation of electronic reporting and to estimate the incidence of AMI and stroke in Tianjin, China.<br><br>METHODS: We applied the DisMod II program to model the incidence of AMI and stroke from other epidemiological indicators. Inputs include mortality rates from Tianjin's mortality surveillance system, and the point prevalence, remission rates and relative risks taken from IHME's Global Burden of Disease studies. The completeness of AMI and stroke incidence reporting was assessed by comparing the sex and age-specific incidence rates derived from the incidence surveillance system with the modeled incidence rates.<br><br>RESULTS: The age and sex standardized modeled incidence per 100,000 person-year decreased (p&#x2009;<&#x2009;0.0001) from 138 in 2007 to 119 in 2015 for AMI and increased (p&#x2009;<&#x2009;0.0001) from 520 in 2007 to 534 in 2015 for stroke. The overall completeness of incidence report was 36% (95% CI 35-38%) for AMI and 54% (95% CI 53-55%) for stroke. The completeness was higher in men than in women for both AMI (42% vs 30%, p&#x2009;<&#x2009;0.0001) and stroke (55% vs 53%, p&#x2009;<&#x2009;0.0001) and was higher in residents aged 30-59 than those aged 60 or older for AMI (57% vs 38%, p&#x2009;<&#x2009;0.0001). The completeness of reporting increased by 7.2 (95% CI 4.6-9.7) and 15.7 (95% CI 14.4-16.9) percentage points for AMI and stroke, respectively, from 2007 to 2015 among those aged 30 or above. The increases were observed in both men and women (p&#x2009;<&#x2009;0.0001) and were more profound (p&#x2009;<&#x2009;0.0001) among those aged between 30 and 59 and occurred primarily during the 2010 and 2015 period.<br><br>CONCLUSIONS: Completeness of AMI and stroke incidence surveillance was low in Tianjin but has improved in recent years primarily owing to the incorporation of an automatic reporting component into the information systems of health facilities.},
}
@article {pmid36746374,
year = {2023},
author = {Ford, ES and Papanicolaou, GA and Dadwal, SS and Pergam, S and Spallone, A},
title = {Frequently Asked Questions on mpox (formerly monkeypox disease) for Hematopoietic Cell Transplantation and Chimeric Antigen Receptor T-Cell Recipients from the American Society for Transplantation and Cellular Therapy.},
journal = {Transplantation and cellular therapy},
volume = {},
number = {},
pages = {},
pmid = {36746374},
issn = {2666-6367},
}
@article {pmid36746170,
year = {2023},
author = {Donnell, D},
title = {Addressing the evidence gap for HIV prevention in pregnancy.},
journal = {The lancet. HIV},
volume = {},
number = {},
pages = {},
doi = {10.1016/S2352-3018(23)00025-5},
pmid = {36746170},
issn = {2352-3018},
}
@article {pmid36744886,
year = {2023},
author = {Montoya, VR and Ready, TM and Felton, A and Fine, SR and OhAinle, M and Emerman, M},
title = {A Virus-Packageable CRISPR System Identifies Host Dependency Factors Co-Opted by Multiple HIV-1 Strains.},
journal = {mBio},
volume = {},
number = {},
pages = {e0000923},
doi = {10.1128/mbio.00009-23},
pmid = {36744886},
issn = {2150-7511},
abstract = {At each stage of the HIV life cycle, host cellular proteins are hijacked by the virus to establish and enhance infection. We adapted the virus packageable HIV-CRISPR screening technology at a genome-wide scale to comprehensively identify host factors that affect HIV replication in a human T cell line. Using a smaller, targeted HIV Dependency Factor (HIVDEP) sublibrary, we then performed screens across HIV strains representing different clades and with different biological properties to define which T cell host factors are important across multiple HIV strains. Nearly 90% of the genes selected across various host pathways validated in subsequent assays as bona fide host dependency factors, including numerous proteins not previously reported to play roles in HIV biology, such as UBE2M, MBNL1, FBXW7, PELP1, SLC39A7, and others. Our ranked list of screen hits across diverse HIV-1 strains form a resource of HIV dependency factors for future investigation of host proteins involved in HIV biology. IMPORTANCE With a small genome of ~9.2 kb that encodes 14 major proteins, HIV must hijack host cellular machinery to successfully establish infection. These host proteins necessary for HIV replication are called "dependency factors." Whole-genome, and then targeted screens were done to try to comprehensively identify all dependency factors acting throughout the HIV replication cycle. Many host processes were identified and validated as critical for HIV replication across multiple HIV strains.},
}
@article {pmid36742268,
year = {2022},
author = {Ha, TV and Hoffman, IF and Miller, WC and Mollan, KR and Lancaster, KE and Richardson, P and Zeziulin, O and Djoerban, Z and Sripaipan, T and Chu, VA and Guo, X and Hanscom, B and Go, VF},
title = {Association between drug use and ART use among people living with HIV who inject drugs in Vietnam, Ukraine and Indonesia: results from HPTN 074.},
journal = {Journal of substance use},
volume = {27},
number = {6},
pages = {648-657},
pmid = {36742268},
issn = {1465-9891},
support = {UM1 AI068619/AI/NIAID NIH HHS/United States ; },
abstract = {BACKGROUND AND OBJECTIVE: Drug use type and frequency may affect Anti-Retroviral Therapy (ART) uptake for HIV-infected people who inject drugs (PWID). This paper assesses the association between self-reported baseline drug use and ART among HIV-infected PWID in Indonesia, Ukraine and Vietnam.<br><br>METHODS: Data on self-reported baseline drug use and ART among HIV-infected PWID at the 26- and 52-week follow-ups were extracted from the HIV Prevention Trials Network (HPTN) 074, a randomized, controlled vanguard study to facilitate HIV treatment for PWID in Indonesia, Ukraine, and Vietnam. Multivariable logistic regression models were fit by study site and the whole HPTN 074 sample, using a 0.5 type I error rate.<br><br>RESULTS: The response rate were 83.3% and 77.0% at 26[th] and 52[th] weeks. At 26-week, baseline use of over one non-opiate/non-stimulant drug was associated with lower odds of ART use among Indonesian participants (OR = 0.21, 95%CI: 0.05-0.82); and baseline injecting drugs for over 20 days in the previous month was associated with lower odds of ART use among all HPTN 074 sample (OR = 0.59, 95% CI: 0.36-0.97).<br><br>CONCLUSION: The association of a specific drug use pattern with later ART uptake implies the importance of medication-assisted treatment to enhance ART uptake and adherence among participants.},
}
@article {pmid36739603,
year = {2023},
author = {Velloza, J and Roche, SD and Owidi, EJ and Irungu, EM and Dollah, A and Kwach, B and Thuo, NB and Morton, JF and Mugo, N and Bukusi, EA and O'Malley, G and Ngure, K and Baeten, JM and Mugwanya, KK and , },
title = {Provider perspectives on service delivery modifications to maintain access to HIV pre-exposure prophylaxis during the COVID-19 pandemic: qualitative results from a PrEP implementation project in Kenya.},
journal = {Journal of the International AIDS Society},
volume = {26},
number = {2},
pages = {e26055},
doi = {10.1002/jia2.26055},
pmid = {36739603},
issn = {1758-2652},
support = {K99MH123369/MH/NIMH NIH HHS/United States ; R00MH118134/MH/NIMH NIH HHS/United States ; R01MH095507/MH/NIMH NIH HHS/United States ; },
abstract = {INTRODUCTION: HIV pre-exposure prophylaxis (PrEP) is an essential prevention strategy being scaled up for priority populations in Kenya, including for HIV serodiscordant couples. The COVID-19 pandemic posed challenges to PrEP rollout. We conducted a qualitative study of PrEP providers to understand how clinics adjusted PrEP delivery during the COVID-19 pandemic.<br><br>METHODS: Since 2017, the Partners Scale-Up Project has integrated PrEP into 25 HIV clinics in Central and Western Kenya. We conducted qualitative interviews with 40 purposively sampled clinic personnel. We interviewed personnel once during the first pandemic wave (May-Aug 2020) and again after some decline in COVID-19 rates (Nov-Jan 2021). We analysed data using inductive memo-writing and summarized data by themes along the PrEP delivery cascade, guided by the Framework for Reporting Adaptation and Modifications (FRAME).<br><br>RESULTS: We interviewed 27 clinical officers, five nurses, four health records and information officers, and four counsellors from Central (n&#xa0;=&#xa0;20) and Western (n&#xa0;=&#xa0;20) Kenya. About half (n&#xa0;=&#xa0;19) were female, with a median age of 32 (IQR: 29-34) and 2.3 years of experience delivering PrEP (IQR: 2-3). All participants reported clinic changes in PrEP demand creation and service delivery during the pandemic. Modifications occurred during PrEP implementation and sustainment phases, were partly reactive to the pandemic and also facilitated by interim Ministry of Health guidance on PrEP delivery during COVID, and were made by PrEP delivery teams, clients and clinic managers. Commonly reported modifications included dispensing multiple-month PrEP refills, intensifying phone-based client engagement and collaborating with other HIV clinics to ensure that clients with prolonged stays in other regions could continue to access PrEP. Some clinics also adopted practices to streamline visits, such as within clinical-room PrEP dispensing, pre-packing PrEP and task-shifting. Most providers liked these changes and hoped they would continue after the pandemic subsides.<br><br>CONCLUSIONS: COVID-19 served as a catalyst for PrEP delivery innovations in Kenya. HIV clinics successfully and rapidly adapted their PrEP demand creation, refill and retention strategies to promote PrEP uptake and effective use. These modified implementation strategies highlight opportunities to streamline the delivery of PrEP, as well as other HIV and chronic care services, and strengthen engagement with populations post-pandemic.},
}
@article {pmid36735485,
year = {2023},
author = {Miller, CP and Shokri, F and Akilesh, S and Xu, Y and Warren, EH and Tykodi, SS and Tretiakova, M},
title = {Immunohistochemical Detection of 5T4 in Renal Cell Carcinoma.},
journal = {Applied immunohistochemistry &amp; molecular morphology : AIMM},
volume = {},
number = {},
pages = {},
doi = {10.1097/PAI.0000000000001101},
pmid = {36735485},
issn = {1533-4058},
abstract = {5T4 (trophoblast glycoprotein encoded by TPBG) is a cancer/testis antigen highly expressed in renal cell carcinoma (RCC) and many other cancers but rarely in normal tissues. Interest in developing 5T4 as a prognostic biomarker and direct targeting of 5T4 by emerging receptor-engineered cellular immunotherapies has been hampered by the lack of validated 5T4-specific reagents for immunohistochemistry (IHC). We tested 4 commercially available monoclonal antibodies (mAbs) for the detection of 5T4 in formalin-fixed, paraffin-embedded RCC and normal tissues. Using parental and TPBG-edited A498 cells, 3 mAbs showed 5T4 specificity. Further analyses focused on 2 mAbs with the most robust staining (MBS1750093, Ab134162). IHC on tissue microarrays incorporating 263 renal tumors showed high staining concordance of these 2 mAbs ranging from 0.80 in chromophobe RCC to 0.89 in advanced clear cell RCC (ccRCC). MBS1750093, the most sensitive, exhibited 2+/3+ staining in papillary RCC (92.2%) > advanced ccRCC (60.0%) > chromophobe RCC (43.6%) > localized ccRCC (39.6%) > oncocytoma (22.7%). RNA in situ hybridization also revealed high levels of TPBG RNA were present most frequently in papillary and advanced ccRCC. In advanced ccRCC, there was a trend towards higher 5T4 expression and regional or distant metastases. Normal organ controls showed no or weak staining with the exception of focal moderate staining in kidney glomeruli and distal tubules by IHC. These data identify mAbs suitable for detecting 5T4 in formalin-fixed, paraffin-embedded tissues and demonstrate both interpatient and histologic subtype heterogeneity. Our validated 5T4 IHC protocol will facilitate biomarker studies and support the therapeutic targeting of 5T4.},
}
@article {pmid36735393,
year = {2023},
author = {Shouse, G and Kaempf, A and Gordon, MJ and Artz, AS and Yashar, D and Sigmund, AM and Smilnak, G and Bair, SM and Mian, A and Fitzgerald, LA and Bajwa, A and Jaglowski, SM and Bailey, N and Shadman, M and Patel, K and Stephens, DM and Kamdar, M and Hill, BT and Gauthier, J and Karmali, R and Nastoupil, LJ and Kittai, AS and Danilov, AV},
title = {A validated composite comorbidity index predicts outcomes of CAR T-cell therapy in patients with diffuse large B cell lymphoma.},
journal = {Blood advances},
volume = {},
number = {},
pages = {},
doi = {10.1182/bloodadvances.2022009309},
pmid = {36735393},
issn = {2473-9537},
abstract = {Chimeric antigen receptor T-cell therapy (CART) has extended survival of patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL). However, limited durability of response and prevalent toxicities remain problematic. Identifying patients at high risk of disease progression, toxicity, and death would inform treatment decisions. Although the cumulative illness rating scale (CIRS) has been shown to correlate with survival in B-cell malignancies, no prognostic score has been independently validated in CART recipients. We retrospectively identified 577 patients with relapsed/refractory DLBCL indicated for CART at 9 academic centers to form a learning cohort (LC). Random survival forest modeling of overall survival (OS) and progression-free survival (PFS) was performed to determine the most influential CIRS organ systems and severity grades. The presence of a severe comorbidity (CIRS score ≥3) in the respiratory, upper gastrointestinal, hepatic, or renal system - herein termed "Severe4" - had the greatest impact on post-CART survival. Controlling for other prognostic factors (number of prior therapies, Eastern Cooperative Oncology Group performance status, BCL6 translocation, molecular subtype), Severe4 was strongly associated with shorter PFS and OS in the LC (hazards ratio [HR]=2.15 and 1.94, respectively; p<0.001) and in an independent single-center validation cohort (VC) (n=218; HR=1.85, p=0.003; HR=1.70, p=0.019, respectively). Severe4 was also a significant predictor of grade ≥3 cytokine release syndrome in the LC (odds ratio [OR]=2.43, p=0.042), while maintaining this trend in the VC (OR=2.05, p=0.114). Thus, our results indicate that adverse outcomes for patients with DLBCL meant to receive CART can be predicted using a simplified CIRS-derived comorbidity index.},
}
@article {pmid36734636,
year = {2023},
author = {Kampouri, E and Manuel, O},
title = {Preemptive therapy versus universal prophylaxis: Time for reconciliation?.},
journal = {Transplant infectious disease : an official journal of the Transplantation Society},
volume = {},
number = {},
pages = {e14014},
doi = {10.1111/tid.14014},
pmid = {36734636},
issn = {1399-3062},
}
@article {pmid36734200,
year = {2023},
author = {Henpita, C and Vyas, R and Healy, CL and Kieu, TL and Gurkar, AU and Yousefzadeh, MJ and Cui, Y and Lu, A and Angelini, LA and O'Kelly, RD and McGowan, SJ and Chandrasekhar, S and Vanderpool, RR and Hennessy-Wack, D and Ross, MA and Bachman, TN and McTiernan, C and Pillai, SPS and Ladiges, W and Lavasani, M and Huard, J and Beer-Stolz, D and St Croix, CM and Watkins, SC and Robbins, PD and Mora, AL and Kelley, EE and Wang, Y and O'Connell, TD and Niedernhofer, LJ},
title = {Loss of DNA repair mechanisms in cardiac myocytes induce dilated cardiomyopathy.},
journal = {Aging cell},
volume = {},
number = {},
pages = {e13782},
doi = {10.1111/acel.13782},
pmid = {36734200},
issn = {1474-9726},
support = {R01 HL161106/HL/NHLBI NIH HHS/United States ; R00 AG049126/AG/NIA NIH HHS/United States ; },
abstract = {Cardiomyopathy is a progressive disease of the myocardium leading to impaired contractility. Genotoxic cancer therapies are known to be potent drivers of cardiomyopathy, whereas causes of spontaneous disease remain unclear. To test the hypothesis that endogenous genotoxic stress contributes to cardiomyopathy, we deleted the DNA repair gene Ercc1 specifically in striated muscle using a floxed allele of Ercc1 and mice expressing Cre under control of the muscle-specific creatinine kinase (Ckmm) promoter or depleted systemically (Ercc1[-/D] mice). Ckmm-Cre[+/-] ;Ercc1[-/fl] mice expired suddenly of heart disease by 7 months of age. As young adults, the hearts of Ckmm-Cre[+/-] ;Ercc1[-/fl] mice were structurally and functionally normal, but by 6-months-of-age, there was significant ventricular dilation, wall thinning, interstitial fibrosis, and systolic dysfunction indicative of dilated cardiomyopathy. Cardiac tissue from the tissue-specific or systemic model showed increased apoptosis and cardiac myocytes from Ckmm-Cre[+/-] ;Ercc1[-/fl] mice were hypersensitive to genotoxins, resulting in apoptosis. p53 levels and target gene expression, including several antioxidants, were increased in cardiac tissue from Ckmm-Cre[+/-] ;Ercc1[-/fl] and Ercc1[-/D] mice. Despite this, cardiac tissue from older mutant mice showed evidence of increased oxidative stress. Genetic or pharmacologic inhibition of p53 attenuated apoptosis and improved disease markers. Similarly, overexpression of mitochondrial-targeted catalase improved disease markers. Together, these data support the conclusion that DNA damage produced endogenously can drive cardiac disease and does so mechanistically via chronic activation of p53 and increased oxidative stress, driving cardiac myocyte apoptosis, dilated cardiomyopathy, and sudden death.},
}
@article {pmid36734029,
year = {2023},
author = {Marcoux, C and Marin, D and Ramdial, J and AlAtrash, G and Alousi, AM and Oran, B and Kebriaei, P and Popat, UR and Rezvani, K and Champlin, RE and Shpall, EJ and Mehta, RS},
title = {Younger Haploidentical Donor Versus Older Matched Unrelated Donor for Patients With AML/MDS.},
journal = {American journal of hematology},
volume = {},
number = {},
pages = {},
doi = {10.1002/ajh.26870},
pmid = {36734029},
issn = {1096-8652},
abstract = {Optimal donor selection is fundamental to successful allogeneic hematopoietic cell transplantation (HCT), and donor age influences survival after both matched unrelated donor (MUD) and haploidentical donor HCT. Though recent studies have shown similar outcomes between MUD and haploidentical HCT, it is unknown if outcomes differ following HCT with younger haploidentical donors compared to HCT with older MUDs. Therefore, we performed a retrospective analysis comparing outcomes of myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) patients who underwent HCT with younger (≤35 years) haploidentical donors (n = 494) or older (>35 years) MUDs (n = 1005). Patients in the haploidentical and MUD groups received post-transplant cyclophosphamide (PTCy) and conventional graft-versus-host-disease (GVHD) prophylaxis, respectively. In multivariate analysis, use of younger haploidentical donors was associated with improved overall survival (hazard ratio (HR) 0.81, 95% confidence interval (CI) 0.69-0.95, p = 0.01) and lower rates of grade II-IV acute GVHD (HR 0.64, 95%CI 0.53-0.77, p < 0.001), grade III-IV acute GVHD (HR 0.37, 95%CI 0.25-0.53, p < 0.001), and chronic GVHD (HR 0.49, 95%CI 0.40-0.60, p < 0.001). Relapse rates were similar among those who received myeloablative conditioning but were higher in patients of the younger haploidentical group who received reduced intensity conditioning (HR 1.49, 95%CI 1.18-1.88, p = 0.001). The younger haploidentical group had significantly lower non-relapse mortality ≥3 months post-HCT (HR 0.59, 95%CI 0.38-0.90, p = 0.02). Our data support the use of younger haploidentical donors with PTCy over older MUDs with conventional prophylaxis in patients with MDS or AML. Further studies on the importance of donor age in haploidentical and MUD HCT with PTCy prophylaxis are warranted. This article is protected by copyright. All rights reserved.},
}
@article {pmid36733187,
year = {2023},
author = {Li, W and Li, R and Yan, Q and Feng, Z and Ning, J},
title = {Conditional concordance-assisted learning under matched case-control design for combining biomarkers for population screening.},
journal = {Statistics in medicine},
volume = {},
number = {},
pages = {},
doi = {10.1002/sim.9677},
pmid = {36733187},
issn = {1097-0258},
abstract = {Incorporating promising biomarkers into cancer screening practices for early-detection is increasingly appealing because of the unsatisfactory performance of current cancer screening strategies. The matched case-control design is commonly adopted in biomarker development studies to evaluate the discriminative power of biomarker candidates, with an intention to eliminate confounding effects. Data from matched case-control studies have been routinely analyzed by the conditional logistic regression, although the assumed logit link between biomarker combinations and disease risk may not always hold. We propose a conditional concordance-assisted learning method, which is distribution-free, for identifying an optimal combination of biomarkers to discriminate cases and controls. We are particularly interested in combinations with a clinically and practically meaningful specificity to prevent disease-free subjects from unnecessary and possibly intrusive diagnostic procedures, which is a top priority for cancer population screening. We establish asymptotic properties for the derived combination and confirm its favorable finite sample performance in simulations. We apply the proposed method to the prostate cancer data from the carotene and retinol efficacy trial (CARET).},
}
@article {pmid36732631,
year = {2023},
author = {Hu, X and Wu, X and Berry, K and Zhao, C and Xin, D and Ogurek, S and Liu, X and Zhang, L and Luo, Z and Sakabe, M and Trubicka, J and Łastowska, M and Szulzewsky, F and Holland, EC and Lee, L and Hu, M and Xin, M and Lu, QR},
title = {Nuclear condensates of YAP fusion proteins alter transcription to drive ependymoma tumourigenesis.},
journal = {Nature cell biology},
volume = {},
number = {},
pages = {},
pmid = {36732631},
issn = {1476-4679},
abstract = {Nuclear localization of HIPPO-YAP fusion proteins has been implicated in supratentorial ependymoma development. Here, unexpectedly, we find that liquid-liquid phase separation, rather than nuclear localization, of recurrent patient-derived YAP fusions, YAP-MAMLD1 and C11ORF95-YAP, underlies ependymoma tumourigenesis from neural progenitor cells. Mutagenesis and chimaera assays demonstrate that an intrinsically disordered region promotes oligomerization of the YAP fusions into nuclear, puncta-like, membrane-less condensates. Oligomerization and nuclear condensates induced by YAP fusion with a coiled-coil domain of transcriptional activator GCN4 also promote ependymoma formation. YAP-MAMLD1 concentrates transcription factors and co-activators, including BRD4, MED1 and TEAD, in condensates while excluding transcriptional repressive PRC2, and induces long-range enhancer-promoter interactions that promote transcription and oncogenic programmes. Blocking condensate-mediated transcriptional co-activator activity inhibits tumourigenesis, indicating a critical role of liquid phase separation for YAP fusion oncogenic activity in ependymoma. YAP fusions containing the intrinsically disordered region features are common in human tumours, suggesting that nuclear condensates could be targeted to treat YAP-fusion-induced cancers.},
}
@article {pmid36732025,
year = {2023},
author = {Mitchell, K and Sprowls, SA and Arora, S and Shakya, S and Silver, DJ and Goins, CM and Wallace, L and Roversi, G and Schafer, R and Kay, K and Miller, TE and Lauko, A and Bassett, J and Kashyap, A and D'Amato Kass, J and Mulkearns-Hubert, EE and Johnson, S and Alvarado, J and Rich, JN and Holland, EC and Paddison, PJ and Patel, AP and Stauffer, SR and Hubert, CG and Lathia, JD},
title = {WDR5 represents a therapeutically exploitable target for cancer stem cells in glioblastoma.},
journal = {Genes &amp; development},
volume = {},
number = {},
pages = {},
doi = {10.1101/gad.349803.122},
pmid = {36732025},
issn = {1549-5477},
abstract = {Glioblastomas (GBMs) are heterogeneous, treatment-resistant tumors driven by populations of cancer stem cells (CSCs). However, few molecular mechanisms critical for CSC population maintenance have been exploited for therapeutic development. We developed a spatially resolved loss-of-function screen in GBM patient-derived organoids to identify essential epigenetic regulators in the SOX2-enriched, therapy-resistant niche and identified WDR5 as indispensable for this population. WDR5 is a component of the WRAD complex, which promotes SET1 family-mediated Lys4 methylation of histone H3 (H3K4me), associated with positive regulation of transcription. In GBM CSCs, WDR5 inhibitors blocked WRAD complex assembly and reduced H3K4 trimethylation and expression of genes involved in CSC-relevant oncogenic pathways. H3K4me3 peaks lost with WDR5 inhibitor treatment occurred disproportionally on POU transcription factor motifs, including the POU5F1(OCT4)::SOX2 motif. Use of a SOX2/OCT4 reporter demonstrated that WDR5 inhibitor treatment diminished cells with high reporter activity. Furthermore, WDR5 inhibitor treatment and WDR5 knockdown altered the stem cell state, disrupting CSC in vitro growth and self-renewal, as well as in vivo tumor growth. These findings highlight the role of WDR5 and the WRAD complex in maintaining the CSC state and provide a rationale for therapeutic development of WDR5 inhibitors for GBM and other advanced cancers.},
}
@article {pmid36728804,
year = {2023},
author = {Nip, Y and Bennett, SR and Smith, AA and Jones, TI and Jones, PL and Tapscott, SJ},
title = {Human DUX4 and porcine DUXC activate similar early embryonic programs in pig muscle cells: implications for preclinical models of FSHD.},
journal = {Human molecular genetics},
volume = {},
number = {},
pages = {},
doi = {10.1093/hmg/ddad021},
pmid = {36728804},
issn = {1460-2083},
abstract = {Human DUX4 and its mouse ortholog Dux are normally expressed in the early embryo-the 4-cell or 2-cell cleavage stage embryo, respectively-and activate a portion of the first wave of zygotic gene expression. DUX4 is epigenetically suppressed in nearly all somatic tissue, whereas FSHD-causing mutations result in its aberrant expression in skeletal muscle, transcriptional activation of the early embryonic program, and subsequent muscle pathology. Although DUX4 and Dux both activate an early totipotent transcriptional program, divergence of their DNA binding domains limits the use of DUX4 expressed in mice as a preclinical model for FSHD. In this study, we identify the porcine DUXC mRNA expressed in early development and show that both pig DUXC and human DUX4 robustly activate a highly similar early embryonic program in pig muscle cells. These results support further investigation of pig preclinical models for FSHD.},
}
@article {pmid36728351,
year = {2023},
author = {Jiao, B and Fredricks, DN and Srinivasan, S and Hansen, R},
title = {Economic Evaluation of a Point-of-Care Test for Bacterial Vaginosis among Women with Vaginal Symptoms.},
journal = {Sexually transmitted diseases},
volume = {},
number = {},
pages = {},
doi = {10.1097/OLQ.0000000000001766},
pmid = {36728351},
issn = {1537-4521},
abstract = {BACKGROUND: There is an unmet need for a clinical diagnostic technology to detect bacterial vaginosis (BV) rapidly and accurately. Novel point-of-care (POC) tests have the potential to fulfill this gap. Our objective was to determine the cost-effectiveness of a hypothetical clinician-administered POC test for diagnosing BV in the United States.<br><br>METHODS: We developed a state-transition microsimulation model to evaluate the cost-effectiveness of using the POC test versus usual care among women of reproductive age with vaginal symptoms. We adopted a healthcare sector perspective that included relevant healthcare costs and a societal perspective that further incorporated productivity costs. Model parameters were empirically estimated based on commercial insurance claims data or derived from published literature. The primary model outcome was incremental cost-effectiveness ratio (ICER). We started with analyzing a hypothetical POC test with a sensitivity and specificity of 0.9 and a cost of $40, followed by extensive sensitivity analyses.<br><br>RESULTS: Using the hypothetical POC test to diagnose BV increased costs by $16 and quality-adjusted life year (QALYs) by 0.0005 per person compared with the usual care, leading to an ICER of $31,108 per QALY gained. When also capturing the productivity costs, the POC test resulted in an average cost savings of $57. The sensitivity analyses showed that the POC test's sensitivity was more influential on its cost-effectiveness than specificity.<br><br>CONCLUSIONS: Using the POC test to diagnose BV is likely to be cost-effective relative to usual care, especially with a high sensitivity or a substantial positive effect on productivity.},
}
@article {pmid32995830,
year = {2020},
author = {Goldman, JD and Wang, K and Röltgen, K and Nielsen, SCA and Roach, JC and Naccache, SN and Yang, F and Wirz, OF and Yost, KE and Lee, JY and Chun, K and Wrin, T and Petropoulos, CJ and Lee, I and Fallen, S and Manner, PM and Wallick, JA and Algren, HA and Murray, KM and Su, Y and Hadlock, J and Jeharajah, J and Berrington, WR and Pappas, GP and Nyatsatsang, ST and Greninger, AL and Satpathy, AT and Pauk, JS and Boyd, SD and Heath, JR},
title = {Reinfection with SARS-CoV-2 and Failure of Humoral Immunity: a case report.},
journal = {medRxiv : the preprint server for health sciences},
volume = {},
number = {},
pages = {},
pmid = {32995830},
support = {R01 AI141953/AI/NIAID NIH HHS/United States ; },
abstract = {Recovery from COVID-19 is associated with production of anti-SARS-CoV-2 antibodies, but it is uncertain whether these confer immunity. We describe viral RNA shedding duration in hospitalized patients and identify patients with recurrent shedding. We sequenced viruses from two distinct episodes of symptomatic COVID-19 separated by 144 days in a single patient, to conclusively describe reinfection with a new strain harboring the spike variant D614G. With antibody and B cell analytics, we show correlates of adaptive immunity, including a differential response to D614G. Finally, we discuss implications for vaccine programs and begin to define benchmarks for protection against reinfection from SARS-CoV-2.},
}
@article {pmid36728078,
year = {2023},
author = {Del Vecchio, NJ and Beaber, EF and Garcia, MP and Wheeler, CM and Kamineni, A and Chao, C and Chubak, J and Corley, DA and Owens, CL and Winer, RL and Pruitt, SL and Raine-Bennett, T and Feldman, S and Silverberg, M},
title = {Provider- and Facility-Level Variation in Pre-Cancerous Cervical Biopsy Diagnoses.},
journal = {Journal of lower genital tract disease},
volume = {},
number = {},
pages = {},
doi = {10.1097/LGT.0000000000000721},
pmid = {36728078},
issn = {1526-0976},
abstract = {OBJECTIVES: Reproducibility of cervical biopsy diagnoses is low and may vary based on where the diagnostic test is performed and by whom. Our objective was to measure multilevel variation in diagnoses across colposcopists, pathologists, and laboratory facilities.<br><br>METHODS: We cross-sectionally examined variation in cervical biopsy diagnoses within the 5 sites of the Population-Based Research Optimizing Screening through Personalized Regimens (PROSPR I) consortium within levels defined by colposcopists, pathologists, and laboratory facilities. Patients aged 18 to 65 years with a colposcopy with biopsy performed were included, with diagnoses categorized as normal, cervical intraepithelial neoplasia grade 1 (CIN1), grade 2 (CIN2), and grade 3 (CIN3). Using Markov Chain Monte-Carlo methods, we fit mixed-effects logistic regression models for biopsy diagnoses and presented median odds ratios (MORs), which reflect the variability within each level. Median odds ratios can be interpreted as the average increased odds a patient would have for a given outcome (e.g., CIN2 or CIN3 vs normal or CIN1) when switching to a provider with higher odds of diagnosing that outcome. The MOR is always 1 or greater, and a value of 1 indicates no variation in outcome for that level, with higher values indicating greater variation.<br><br>RESULTS: A total of 130,110 patients were included who received care across 82 laboratory facilities, 2,620 colposcopists, and 489 pathologists. Substantial variation in biopsy diagnoses was found at each level, with the most occurring between laboratory facilities, followed by pathologists and colposcopists. Substantial variation in biopsy diagnoses of CIN2 or CIN3 (vs normal or CIN1) was present between laboratory facilities (MOR: 1.26; 95% credible interval = 1.19-1.36).<br><br>CONCLUSIONS: Improving consistency in cervical biopsy diagnoses is needed to reduce underdiagnosis, overdiagnosis, and unnecessary treatment resulting from variation in cervical biopsy diagnoses.},
}
@article {pmid36727752,
year = {2023},
author = {Chlebowski, RT and Aragaki, AK},
title = {The Women's Health Initiative randomized trials of menopausal hormone therapy and breast cancer: findings in context.},
journal = {Menopause (New York, N.Y.)},
volume = {},
number = {},
pages = {},
pmid = {36727752},
issn = {1530-0374},
abstract = {IMPORTANCE AND OBJECTIVE: The menopausal hormone therapy (MHT) association with breast cancer has been controversial for more than 40 years. Most recently, findings from cohort studies have been discordant compared with those from the Women's Health Initiative (WHI) randomized trials. In cohort studies, both estrogen therapy and estrogen plus progestin were associated with higher breast cancer incidence. In contrast, in the WHI randomized trials, findings for estrogen plus progestin are concordant with cohort study reports, whereas estrogen therapy significantly reduced breast cancer incidence. In addition, concerns have been raised regarding the WHI findings from both trials. In this report, we briefly summarize findings for MHT on breast cancer from cohort studies and the WHI randomized trials. The report focus is addressing, point-by-point, concerns raised regarding the WHI findings.<br><br>METHODS: For cohort studies, we relied on the latest findings from (1) the meta-analysis of the Collaborative Group on Hormonal Factors in Breast Cancer and (2) the Million Women's Study. To identify commentaries and editorials, "Menopause" and "Climacteric" were searched from 2002 to present; PubMed and Google Scholar were searched for commentaries, editorials, and breast cancer, MHT, estrogen, conjugated equine estrogen, estradiol, "hormone replacement therapy," and "HRT."<br><br>DISCUSSION AND CONCLUSIONS: Thirty commentaries challenging WHI findings were identified. All were reviewed, and issues needing response were identified. Findings from the meta-analysis from the Collaborative Group on Hormonal Factors in Breast Cancer and the Million Women Study were summarized and compared with finding in the two WHI randomized trials evaluating estrogen therapy and estrogen plus progestin. Based on the randomized clinical trials, estrogen therapy, for women with prior hysterectomy, decreases breast cancer incidence and mortality. In contrast, estrogen plus progestin increases breast cancer incidence, which persists through two decades. Women considering estrogen plus progestin use for vasomotor symptoms should understand the breast cancer risk.},
}
@article {pmid36727597,
year = {2023},
author = {Zewdie, K and Pickles, M and Floyd, S and Fidler, S and Ayles, H and Bock, P and Hoddinott, G and Mandla, N and Shanaube, K and Simwinga, M and Fraser, C and Seeley, J and Piwowar-Manning, E and Hayes, R and Donnell, D},
title = {Uptake of medical male circumcision with household-based testing, and the association of traditional male circumcision and HIV infection.},
journal = {AIDS (London, England)},
volume = {},
number = {},
pages = {},
doi = {10.1097/QAD.0000000000003463},
pmid = {36727597},
issn = {1473-5571},
abstract = {OBJECTIVES: Voluntary medical male circumcision (VMMC) is an important component of combination HIV prevention. Inclusion of traditionally circumcised HIV negative men in VMMC uptake campaigns may be important if traditional male circumcision is less protective against HIV acquisition than VMMC.<br><br>METHODS: We used data from the HPTN 071 (PopART) study. This cluster-randomized trial assessed the impact of a combination prevention package on population-level HIV incidence in 21 study communities in Zambia and South Africa.We evaluated uptake of VMMC, using a two-stage analysis approach and used discrete-time survival analysis to evaluate the association between the types of male circumcision and HIV incidence.<br><br>RESULTS: 10,803 HIV-negative men with self-reported circumcision status were included in this study. At baseline, 56% reported being uncircumcised, 26% traditionally circumcised and 18% were medically circumcised. During the PopART intervention, 11% of uncircumcised men reported uptake of medical male circumcision. We found no significant difference in the uptake of VMMC in communities receiving the PopART intervention package and standard of care (adj rate ratio=1&#xb7;10 (95% CI 0&#xb7;82, 1&#xb7;50, P&#x200a;=&#x200a;0&#xb7;48)). The rate of HIV acquisition for medically circumcised men was 70% lower than for those who were uncircumcised adjHR=0&#xb7;30 (95% CI 0&#xb7;16 to 0&#xb7;55; p&#x200a;<&#x200a;0&#xb7;0001). There was no difference in rate of HIV acquisition for traditionally circumcised men compared to those uncircumcised adjHR= 0&#xb7;84 (95% CI 0&#xb7;54, 1&#xb7;31; P&#x200a;=&#x200a;0&#xb7;45).<br><br>CONCLUSIONS: Household-based delivery of HIV testing followed by referral for medical male circumcision did not result in substantial VMMC uptake. Traditional circumcision is not associated with lower risk of HIV acquisition.},
}
@article {pmid36727397,
year = {2023},
author = {Radich, JP and Wall, M and Branford, S and Campbell, CD and Chaturvedi, S and DeAngelo, DJ and Deininger, M and Guinney, J and Hochhaus, A and Hughes, TP and Kantarjian, HM and Larson, RA and Li, S and Maegawa, R and Mishra, K and Obourn, V and Pinilla-Ibarz, J and Purkayastha, D and Sadek, I and Saglio, G and Shrestha, A and White, BS and Druker, BJ},
title = {Molecular response in newly diagnosed chronic-phase chronic myeloid leukemia: prediction modeling and pathway analysis.},
journal = {Haematologica},
volume = {},
number = {},
pages = {},
doi = {10.3324/haematol.2022.281878},
pmid = {36727397},
issn = {1592-8721},
abstract = {Tyrosine kinase inhibitor therapy revolutionized chronic myeloid leukemia treatment and showed how targeted therapy and molecular monitoring could be used to substantially improve survival outcomes. We used chronic myeloid leukemia as a model to understand a critical question: Why do some patients have an excellent response to therapy, while others have a poor response? We studied gene expression in whole blood samples from 112 patients from a large phase 3 randomized trial, dichotomizing cases into good responders (BCR::ABL1 ≤10% International Scale by 3 and 6 months and ≤0.1% by 12 months) and poor responders (failure to meet these criteria). Predictive models based on gene expression demonstrated the best performance (area under the curve [SD], 0.76 [0.07]). All of the top 20 pathways overexpressed in good responders involved immune regulation, a finding validated in an independent data set. This study emphasizes the importance of pretreatment adaptive immune response in treatment efficacy and suggests biological pathways that can be targeted to improve response.},
}
@article {pmid36723512,
year = {2023},
author = {Neary, J and Fish, CS and Cassidy, NA and Wamalwa, D and Langat, A and Ngugi, E and Benki-Nugent, S and Moraa, H and Richardson, BA and Njuguna, I and Slyker, JA and Lehman, DA and John-Stewart, G},
title = {Predictors of intact HIV DNA levels among children in Kenya.},
journal = {AIDS (London, England)},
volume = {},
number = {},
pages = {},
doi = {10.1097/QAD.0000000000003499},
pmid = {36723512},
issn = {1473-5571},
abstract = {OBJECTIVE: We determined predictors of both intact (estimate of replication-competent) and total (intact and defective) HIV DNA in the reservoir among children with HIV.<br><br>DESIGN: HIV DNA in the reservoir was quantified longitudinally in children who initiated antiretroviral therapy (ART) at <1&#x200a;year of age using a novel cross-subtype intact proviral DNA assay that measures both intact and total proviruses. Quantitative PCR was used to measure pre-ART cytomegalovirus (CMV) viral load. Linear mixed effects models were used to determine predictors of intact and total HIV DNA levels (log10copies/million).<br><br>RESULTS: Among 65 children, median age at ART initiation was 5&#x200a;months and median follow-up was 5.2&#x200a;years; 86% of children had CMV viremia pre-ART. Lower pre-ART CD4 percent (adjusted relative risk [aRR]: 0.87, 95% confidence intervals [95%CI]: 0.79-0.97; p&#x200a;=&#x200a;0.009) and higher HIV RNA (aRR: 1.21, 95%CI: 1.06-1.39; p&#x200a;=&#x200a;0.004) predicted higher levels of total HIV DNA during ART. Pre-ART CD4 percent (aRR: 0.76, 95%CI: 0.65-0.89; p<0.001), CMV viral load (aRR: 1.16, 95%CI: 1.01-1.34; p&#x200a;=&#x200a;0,041), and first line protease inhibitor-based regimens compared to non-nucleoside reverse transcriptase-based regimens (aRR: 1.36, 95%CI: 1.04-1.77; p&#x200a;=&#x200a;0,025) predicted higher levels of intact HIV DNA.<br><br>CONCLUSION: Pre-ART immunosuppression, first-line ART regimen, and CMV viral load may influence establishment and sustainment of intact HIV DNA in the reservoir.},
}
@article {pmid36722810,
year = {2023},
author = {Wen, T and Liao, D and Wellenius, GA and Whitsel, EA and Margolis, HG and Tinker, LF and Stewart, JD and Kong, L and Yanosky, JD},
title = {Short-term Air Pollution Levels and Blood Pressure in Older Women.},
journal = {Epidemiology (Cambridge, Mass.)},
volume = {34},
number = {2},
pages = {271-281},
doi = {10.1097/EDE.0000000000001577},
pmid = {36722810},
issn = {1531-5487},
mesh = {Female ; Humans ; Aged ; Blood Pressure ; Nitrogen Dioxide ; *Air Pollution/adverse effects ; *Environmental Pollutants ; Particulate Matter ; },
abstract = {BACKGROUND: Evidence of associations between daily variation in air pollution and blood pressure (BP) is varied and few prior longitudinal studies adjusted for calendar time.<br><br>METHODS: We studied 143,658 postmenopausal women 50 to 79 years of age from the Women's Health Initiative (1993-2005). We estimated daily atmospheric particulate matter (PM) (in three size fractions: PM2.5, PM2.5-10, and PM10) and nitrogen dioxide (NO2) concentrations at participants' residential addresses using validated lognormal kriging models. We used linear mixed-effects models to estimate the association between air pollution concentrations and repeated measures of systolic and diastolic BP (SBP, DBP) adjusting for confounders and calendar time.<br><br>RESULTS: Short-term PM2.5 and NO2 were each positively associated with DBP {0.10 mmHg [95% confidence interval (CI): 0.04, 0.15]; 0.13 mmHg (95% CI: 0.09, 0.18), respectively}
for interquartile range changes in lag 3-5 day PM2.5 and NO2. Short-term NO2 was negatively associated with SBP [-0.21 mmHg (95%CI: -0.30, -0.13)]. In two-pollutant models, the NO2-DBP association was slightly stronger, but for PM2.5 was attenuated to null, compared with single-pollutant models. Associations between short-term NO2 and DBP were more pronounced among those with higher body mass index, lower neighborhood socioeconomic position, and diabetes. When long-term (annual) and lag 3-5 day PM2.5 were in the same model, associations with long-term PM2.5 were stronger than for lag 3-5 day.<br><br>CONCLUSIONS: We observed that short-term PM2.5 and NO2 levels were associated with increased DBP, although two-pollutant model results suggest NO2 was more likely responsible for observed associations. Long-term PM2.5 effects were larger than short-term.},
}
@article {pmid36517247,
year = {2022},
author = {Reynolds, KM and Lin, BM and Armstrong, ND and Ottosson, F and Zhang, Y and Williams, AS and Yu, B and Boerwinkle, E and Thygarajan, B and Daviglus, ML and Muoio, D and Qi, Q and Kaplan, R and Melander, O and Lash, JP and Cai, J and Irvin, MR and Newgard, CB and Sofer, T and Franceschini, N},
title = {Circulating Metabolites Associated with Albuminuria in a Hispanic/Latino Population.},
journal = {Clinical journal of the American Society of Nephrology : CJASN},
volume = {},
number = {},
pages = {},
pmid = {36517247},
issn = {1555-905X},
support = {R01 DK117445/DK/NIDDK NIH HHS/United States ; R01 MD012765/MD/NIMHD NIH HHS/United States ; },
abstract = {BACKGROUND: Albuminuria is associated with metabolic abnormalities, but these relationships are not well understood. We studied the association of metabolites with albuminuria in Hispanic/Latino people, a population with high risk for metabolic disease.<br><br>METHODS: We used data from 3736 participants from the Hispanic Community Health Study/Study of Latinos, of which 16% had diabetes and 9% had an increased urine albumin-to-creatinine ratio (UACR). Metabolites were quantified in fasting serum through nontargeted mass spectrometry (MS) analysis using ultra-performance liquid chromatography-MS/MS. Spot UACR was inverse normally transformed and tested for the association with each metabolite or combined, correlated metabolites, in covariate-adjusted models that accounted for the study design. In total, 132 metabolites were available for replication in the Hypertension Genetic Epidemiology Network study (n =300), and 29 metabolites were available for replication in the Malm&#xf6; Offspring Study (n =999).<br><br>RESULTS: Among 640 named metabolites, we identified 148 metabolites significantly associated with UACR, including 18 novel associations that replicated in independent samples. These metabolites showed enrichment for D-glutamine and D-glutamate metabolism and arginine biosynthesis, pathways previously reported for diabetes and insulin resistance. In correlated metabolite analyses, we identified two modules significantly associated with UACR, including a module composed of lipid metabolites related to the biosynthesis of unsaturated fatty acids and alpha linolenic acid and linoleic acid metabolism.<br><br>CONCLUSIONS: Our study identified associations of albuminuria with metabolites involved in glucose dysregulation, and essential fatty acids and precursors of arachidonic acid in Hispanic/Latino population.},
}
@article {pmid36722323,
year = {2023},
author = {Totiger, TM and Chaudhry, S and Musi, E and Afaghani, J and Montoya, S and Owusu-Ansah, F and Lee, S and Schwartz, G and Klimek, V and Taylor, J},
title = {Protein biomarkers for response to XPO1 inhibition in haematologic malignancies.},
journal = {Journal of cellular and molecular medicine},
volume = {},
number = {},
pages = {},
doi = {10.1111/jcmm.17667},
pmid = {36722323},
issn = {1582-4934},
support = {K08CA230319/CA/NCI NIH HHS/United States ; /DDCF/Doris Duke Charitable Foundation/United States ; },
abstract = {XPO1 (Exportin-1) is the nuclear export protein responsible for the normal shuttling of several proteins and RNA species between the nucleocytoplasmic compartment of eukaryotic cells. XPO1 recognizes the nuclear export signal (NES) of its cargo proteins to facilitate its export. Alterations of nuclear export have been shown to play a role in oncogenesis in several types of solid tumour and haematologic cancers. Over more than a decade, there has been substantial progress in targeting nuclear export in cancer using selective XPO1 inhibitors. This has resulted in recent approval for the first-in-class drug selinexor for use in relapsed, refractory multiple myeloma and diffuse large B-cell lymphoma (DLBCL). Despite these successes, not all patients respond effectively to XPO1 inhibition and there has been lack of biomarkers for response to XPO1 inhibitors in the clinic. Using haematologic malignancy cell lines and samples from patients with myelodysplastic neoplasms treated with selinexor, we have identified XPO1, NF-κB(p65), MCL-1 and p53 protein levels as protein markers of response to XPO1 inhibitor therapy. These markers could lead to the identification of response upon XPO1 inhibition for more accurate decision-making in the personalized treatment of cancer patients undergoing treatment with selinexor.},
}
@article {pmid36721977,
year = {2023},
author = {McQuoid, J and Durazo, A and Mooney, E and Heffner, J and Tan, ASL and Kong, AY and Clifton, S and Horn, E},
title = {Tobacco cessation and prevention interventions for sexual and/or gender minority-identified people and the theories that underpin them: A scoping review.},
journal = {Nicotine &amp; tobacco research : official journal of the Society for Research on Nicotine and Tobacco},
volume = {},
number = {},
pages = {},
doi = {10.1093/ntr/ntad018},
pmid = {36721977},
issn = {1469-994X},
abstract = {INTRODUCTION: This scoping review takes stock of the social and behavior change theories that have underpinned tobacco interventions tailored to sexual and/or gender minority (SGM) people and reflects on the need to target contextually-based drivers of SGM tobacco use inequities.<br><br>METHODS: Data sources were Medline (Ovid), Scopus, PubMed, Google Scholar (01/01/1946 - 10/27/2022). Peer-reviewed publications in English from anywhere in the world describing SGM-tailored tobacco cessation and/or prevention interventions were independently identified by a librarian and screened by the first and third authors. 367 articles were extracted; an additional 2 were found by hand searching. 369 articles were assessed for eligibility. Exclusion criteria were: not an intervention, review article, not SGM-tailored or tobacco-focused. We documented intervention name, intervention components, theoretical frameworks cited in reference to intervention design and/or implementation, and evaluation outcomes. All authors provided input on theoretical framework categorization.<br><br>RESULTS: We identified 22 publications corresponding to 15 unique interventions. Individual-level behavior change theories (i.e., those focusing on within-person behavior change processes) were the most prominent. Among these, the Transtheoretical Model was the most frequently utilized, while Social Inoculation Theory, Theory of Reasoned Action, and Theory of Psychological Reactance were also employed. A minority of interventions referenced frameworks that more explicitly engaged with SGM people's social contexts, namely, Theory of Diffusion of Innovations and Minority Stress Model.<br><br>CONCLUSIONS: Future SGM-tailored tobacco interventions should leverage both the strengths of individual-level behavior change theories and those of frameworks that understand tobacco use inequities as indivisible from place, context, and policy.<br><br>IMPLICATIONS: This scoping review describes the theoretical underpinnings of sexual and/or gender minority (SGM)-tailored tobacco interventions published in the peer-review literature in English. It reflects on the need for greater utilization of social and behavior change theoretical frameworks that can engage with unique drivers of SGM tobacco use and barriers to cessation.},
}
@article {pmid36721044,
year = {2023},
author = {Kurniansyah, N and Wallace, DA and Zhang, Y and Yu, B and Cade, B and Wang, H and Ochs-Balcom, HM and Reiner, AP and Ramos, AR and Smith, JD and Cai, J and Daviglus, M and Zee, PC and Kaplan, R and Kooperberg, C and Rich, SS and Rotter, JI and Gharib, SA and Redline, S and Sofer, T},
title = {An integrated multi-omics analysis of sleep-disordered breathing traits implicates P2XR4 purinergic signaling.},
journal = {Communications biology},
volume = {6},
number = {1},
pages = {125},
doi = {10.1038/s42003-023-04520-y},
pmid = {36721044},
issn = {2399-3642},
abstract = {Sleep Disordered Breathing (SDB) is a common disease associated with increased risk for cardiometabolic, cardiovascular, and cognitive diseases. How SDB affects the molecular environment is still poorly understood. We study the association of three SDB measures with gene expression measured using RNA-seq in multiple blood tissues from the Multi-Ethnic Study of Atherosclerosis. We develop genetic instrumental variables for the associated transcripts as polygenic risk scores (tPRS), then generalize and validate the tPRS in the Women's Health Initiative. We measure the associations of the validated tPRS with SDB and serum metabolites in Hispanic Community Health Study/Study of Latinos. Here we find differential gene expression by blood cell type in relation to SDB traits and link P2XR4 expression to average oxyhemoglobin saturation during sleep and butyrylcarnitine (C4) levels. These findings can be used to develop interventions to alleviate the effect of SDB on the human molecular environment.},
}
@article {pmid36720973,
year = {2023},
author = {Boila, LD and Ghosh, S and Bandyopadhyay, SK and Jin, L and Murison, A and Zeng, AGX and Shaikh, W and Bhowmik, S and Muddineni, SSNA and Biswas, M and Sinha, S and Chatterjee, SS and Mbong, N and Gan, OI and Bose, A and Chakraborty, S and Arruda, A and Kennedy, JA and Mitchell, A and Lechman, ER and Banerjee, D and Milyavsky, M and Minden, MD and Dick, JE and Sengupta, A},
title = {KDM6 demethylases integrate DNA repair gene regulation and loss of KDM6A sensitizes human acute myeloid leukemia to PARP and BCL2 inhibition.},
journal = {Leukemia},
volume = {},
number = {},
pages = {},
pmid = {36720973},
issn = {1476-5551},
abstract = {Acute myeloid leukemia (AML) is a heterogeneous, aggressive malignancy with dismal prognosis and with limited availability of targeted therapies. Epigenetic deregulation contributes to AML pathogenesis. KDM6 proteins are histone-3-lysine-27-demethylases that play context-dependent roles in AML. We inform that KDM6-demethylase function critically regulates DNA-damage-repair-(DDR) gene expression in AML. Mechanistically, KDM6 expression is regulated by genotoxic stress, with deficiency of KDM6A-(UTX) and KDM6B-(JMJD3) impairing DDR transcriptional activation and compromising repair potential. Acquired KDM6A loss-of-function mutations are implicated in chemoresistance, although a significant percentage of relapsed-AML has upregulated KDM6A. Olaparib treatment reduced engraftment of KDM6A-mutant-AML-patient-derived xenografts, highlighting synthetic lethality using Poly-(ADP-ribose)-polymerase-(PARP)-inhibition. Crucially, a higher KDM6A expression is correlated with venetoclax tolerance. Loss of KDM6A increased mitochondrial activity, BCL2 expression, and sensitized AML cells to venetoclax. Additionally, BCL2A1 associates with venetoclax resistance, and KDM6A loss was accompanied with a downregulated BCL2A1. Corroborating these results, dual targeting of PARP and BCL2 was superior to PARP or BCL2 inhibitor monotherapy in inducing AML apoptosis, and primary AML cells carrying KDM6A-domain mutations were even more sensitive to the combination. Together, our study illustrates a mechanistic rationale in support of a novel combination therapy for AML based on subtype-heterogeneity, and establishes KDM6A as a molecular regulator for determining therapeutic efficacy.},
}
@article {pmid36720638,
year = {2023},
author = {Manselle, MK and Ries, RE and Hylkema, T and Leonti, A and Kirkey, DC and Furlan, SN and Meshinchi, S},
title = {Functional consequence and therapeutic targeting of cryptic ALK fusions in monosomy 7 acute myeloid leukemia.},
journal = {Pediatric blood &amp; cancer},
volume = {},
number = {},
pages = {e30180},
doi = {10.1002/pbc.30180},
pmid = {36720638},
issn = {1545-5017},
abstract = {Acute myeloid leukemia (AML) patients have a wide array of cytogenetic and molecular aberrations, which can influence response to therapy. Monosomy 7 is a rare subset within pediatric AML (prevalence of <2%) that is highly associated with poor outcomes. Fusions involving the anaplastic tyrosine kinase (ALK) gene were exclusively identified in 14.3% of this high-risk cohort, while absent across all other AML. Given the dismal outcomes of monosomy 7, we evaluated the use of crizotinib, an FDA-approved tyrosine kinase inhibitor, used to treat patients with ALK fusions. Our findings suggest that crizotinib may serve as a novel therapy for these patients.},
}
@article {pmid36720468,
year = {2023},
author = {Yagishita, Y and Joshi, T and Kensler, TW and Wakabayashi, N},
title = {Transcriptional Regulation of Math1 by Aryl Hydrocarbon Receptor: Effect on Math1[+] Progenitor Cells in Mouse Small Intestine.},
journal = {Molecular and cellular biology},
volume = {43},
number = {1},
pages = {43-63},
doi = {10.1080/10985549.2022.2160610},
pmid = {36720468},
issn = {1098-5549},
abstract = {The physiological roles of aryl hydrocarbon receptor (AhR) in the small intestine have been revealed as immunomodulatory and barrier functions. However, its contributions to cell fate regulation are incompletely understood. The Notch-activated signaling cascade is a central component of intestinal cell fate determinations. The lateral inhibitory mechanism governed by Notch directs cell fates toward distinct cell lineages (i.e., absorptive and secretory cell lineages) through its downstream effector, mouse atonal homolog 1 (MATH1). An investigation employing cell lines and intestinal crypt cells revealed that AhR regulates Math1 expression in a xenobiotic response element (XRE)-dependent manner. The AhR-Math1 axis was further addressed using intestinal organoids, where AhR-Math1 and HES1-Math1 axes appeared to coexist within the underlying Math1 transcriptional machinery. When the HES1-Math1 axis was pharmacologically suppressed, β-naphthoflavone-mediated AhR activation increased the number of goblet and Math1[+] progenitor cells in the organoids. The same pharmacological dissection of the AhR-Math1 axis was applied in vivo, demonstrating an enhanced number of Math1[+] progenitor cells in the small intestine following AhR activation. We report here that AhR-Math1 is a direct transcriptional axis with effects on Math1[+] progenitor cells in the small intestine, highlighting a novel molecular basis for fine-tuning Notch-mediated cell fate regulation.},
}
@article {pmid36720089,
year = {2023},
author = {Tagliamento, M and Gennari, A and Lambertini, M and Salazar, R and Harbeck, N and Del Mastro, L and Aguilar-Company, J and Bower, M and Sharkey, R and Dalla Pria, A and Plaja, A and Jackson, A and Handford, J and Sita-Lumsden, A and Martinez-Vila, C and Matas, M and Miguel Rodriguez, A and Vincenzi, B and Tonini, G and Bertuzzi, A and Brunet, J and Pedrazzoli, P and D'Avanzo, F and Biello, F and Sinclair, A and Lee, AJX and Rossi, S and Rizzo, G and Mirallas, O and Pimentel, I and Iglesias, M and Sanchez de Torre, A and Guida, A and Berardi, R and Zambelli, A and Tondini, C and Filetti, M and Mazzoni, F and Mukherjee, U and Diamantis, N and Parisi, A and Aujayeb, A and Prat, A and Libertini, M and Grisanti, S and Rossi, M and Zoratto, F and Generali, D and Saura, C and Lyman, GH and Kuderer, NM and Pinato, DJ and Cortellini, A and , },
title = {Pandemic Phase-Adjusted Analysis of COVID-19 Outcomes Reveals Reduced Intrinsic Vulnerability and Substantial Vaccine Protection From Severe Acute Respiratory Syndrome Coronavirus 2 in Patients With Breast Cancer.},
journal = {Journal of clinical oncology : official journal of the American Society of Clinical Oncology},
volume = {},
number = {},
pages = {JCO2201667},
doi = {10.1200/JCO.22.01667},
pmid = {36720089},
issn = {1527-7755},
abstract = {PURPOSE: Although representing the majority of newly diagnosed cancers, patients with breast cancer appear less vulnerable to COVID-19 mortality compared with other malignancies. In the absence of patients on active cancer therapy included in vaccination trials, a contemporary real-world evaluation of outcomes during the various pandemic phases, as well as of the impact of vaccination, is needed to better inform clinical practice.<br><br>METHODS: We compared COVID-19 morbidity and mortality among patients with breast cancer across prevaccination (February 27, 2020-November 30, 2020), Alpha-Delta (December 1, 2020-December 14, 2021), and Omicron (December 15, 2021-January 31, 2022) phases using OnCovid registry participants (ClinicalTrials.gov identifier: NCT04393974). Twenty-eight-day case fatality rate (CFR28) and COVID-19 severity were compared in unvaccinated versus double-dosed/boosted patients (vaccinated) with inverse probability of treatment weighting models adjusted for country of origin, age, number of comorbidities, tumor stage, and receipt of systemic anticancer therapy within 1 month of COVID-19 diagnosis.<br><br>RESULTS: By the data lock of February 4, 2022, the registry counted 613 eligible patients with breast cancer: 60.1% (n = 312) hormone receptor-positive, 25.2% (n = 131) human epidermal growth factor receptor 2-positive, and 14.6% (n = 76) triple-negative. The majority (61%; n = 374) had localized/locally advanced disease. Median age was 62 years (interquartile range, 51-74 years). A total of 193 patients (31.5%) presented &#x2265; 2 comorbidities and 69% (n = 330) were never smokers. In total, 392 (63.9%), 164 (26.8%), and 57 (9.3%) were diagnosed during the prevaccination, Alpha-Delta, and Omicron phases, respectively. Analysis of CFR28 demonstrates comparable estimates of mortality across the three pandemic phases (13.9%, 12.2%, 5.3%, respectively; P = .182). Nevertheless, a significant improvement in outcome measures of COVID-19 severity across the three pandemic time periods was observed. Importantly, when reported separately, unvaccinated patients from the Alpha-Delta and Omicron phases achieved comparable outcomes to those from the prevaccination phase. Of 566 patients eligible for the vaccination analysis, 72 (12.7%) were fully vaccinated and 494 (87.3%) were unvaccinated. We confirmed with inverse probability of treatment weighting multivariable analysis and following a clustered robust correction for participating center that vaccinated patients achieved improved CFR28 (odds ratio [OR], 0.19; 95% CI, 0.09 to 0.40), hospitalization (OR, 0.28; 95% CI, 0.11 to 0.69), COVID-19 complications (OR, 0.16; 95% CI, 0.06 to 0.45), and reduced requirement of COVID-19-specific therapy (OR, 0.24; 95% CI, 0.09 to 0.63) and oxygen therapy (OR, 0.24; 95% CI, 0.09 to 0.67) compared with unvaccinated controls.<br><br>CONCLUSION: Our findings highlight a consistent reduction of COVID-19 severity in patients with breast cancer during the Omicron outbreak in Europe. We also demonstrate that even in this population, a complete severe acute respiratory syndrome coronavirus 2 vaccination course is a strong determinant of improved morbidity and mortality from COVID-19.},
}
@article {pmid36718537,
year = {2023},
author = {Cable, J and Balachandran, S and Daley-Bauer, LP and Rustagi, A and Antony, F and Frere, JJ and Strampe, J and Kedzierska, K and Cannon, JL and McGargill, MA and Weiskopf, D and Mettelman, RC and Niessl, J and Thomas, PG and Briney, B and Valkenburg, SA and Bloom, JD and Bjorkman, PJ and Iketani, S and Rappazzo, CG and Crooks, CM and Crofts, KF and Pöhlmann, S and Krammer, F and Sant, AJ and Nabel, GJ and Schultz-Cherry, S},
title = {Viral immunity: Basic mechanisms and therapeutic applications-a Keystone Symposia report.},
journal = {Annals of the New York Academy of Sciences},
volume = {},
number = {},
pages = {},
doi = {10.1111/nyas.14960},
pmid = {36718537},
issn = {1749-6632},
support = {/NH/NIH HHS/United States ; },
abstract = {Viruses infect millions of people each year. Both endemic viruses circulating throughout the population as well as novel epidemic and pandemic viruses pose ongoing threats to global public health. Developing more effective tools to address viruses requires not only in-depth knowledge of the virus itself but also of our immune system's response to infection. On June 29 to July 2, 2022, researchers met for the Keystone symposium "Viral Immunity: Basic Mechanisms and Therapeutic Applications." This report presents concise summaries from several of the symposium presenters.},
}
@article {pmid36716812,
year = {2023},
author = {Joachim, GE and Bohnert, KM and As-Sanie, S and Harris, HR and Upson, K},
title = {Cannabis smoking, tobacco cigarette smoking, and adenomyosis risk.},
journal = {Fertility and sterility},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.fertnstert.2023.01.035},
pmid = {36716812},
issn = {1556-5653},
abstract = {OBJECTIVE: To investigate cannabis smoking and tobacco cigarette smoking in relation to adenomyosis risk.<br><br>DESIGN: We used data from a case-control study of adenomyosis conducted among enrollees ages 18-59 years of an integrated healthcare system in Washington State. The case-control study employed two control groups given the challenge of selecting non-cases when cases are diagnosed by hysterectomy.<br><br>SUBJECTS: Cases (n=386) were enrollees with incident, pathology-confirmed adenomyosis diagnosed between April 1, 2001, and March 31, 2006. The two control groups comprised hysterectomy controls (n=233) with pathology-confirmed absence of adenomyosis and population controls (n=323) with an intact uterus randomly selected from the healthcare system population and frequency-matched to cases on age.<br><br>EXPOSURE: Detailed data on cannabis and tobacco cigarette smoking history were ascertained through in-person structured interviews, allowing estimation of joint-years of cannabis smoking and pack-years of tobacco cigarette smoking.<br><br>MAIN OUTCOME MEASURES: Odds ratios (ORs) and 95% confidence intervals (CIs) for the associations between cannabis smoking, tobacco cigarette smoking, and adenomyosis were estimated using multivariable unconditional logistic regression. Analyses were adjusted for age, reference year, menarche age, education, and pack-years of cigarette smoking (or joint-years of cannabis smoking).<br><br>RESULTS: No association was observed between cannabis smoking history and adenomyosis risk. However, we did observe the suggestion of an association between ever tobacco cigarette smoking and adenomyosis risk, comparing cases to hysterectomy controls (OR 1.3, 95% CI: 0.9-1.9) and population controls (OR 1.2 95% CI: 0.8-1.8). Our data suggested a 50% increased odds of adenomyosis with >15 pack-years of smoking (vs. never smoking), comparing cases to hysterectomy controls (OR 1.5, 95% CI: 0.9-2.6, Ptrend=0.135). The suggestion of a 40% increased adenomyosis odds was observed with smoking >5-15 pack-years (vs. never smoking), comparing cases to population controls (OR 1.4, 95% CI: 0.8-2.4, Ptrend=0.136).<br><br>CONCLUSION: In the first study of cannabis smoking and adenomyosis risk, no association was observed. However, our data suggested an increased odds of adenomyosis with history of tobacco cigarette smoking. Further research is warranted to replicate our results given the substantial morbidity with adenomyosis and frequency of cigarette smoking and recreational and medical cannabis use.},
}
@article {pmid36716445,
year = {2023},
author = {Rubenstein, JH and Burns, JA and Arasim, ME and Firsht, EM and Harbrecht, M and Widerquist, M and Evans, RR and Inadomi, JM and Chang, JW and Hazelton, WD and Hur, C and Kurlander, JE and Lim, F and Luebeck, G and Macdonald, PW and Reddy, CA and Saini, SD and Tan, SX and Waljee, AK and Lansdorp-Vogelaar, I},
title = {Yield of Repeat Endoscopy for Barrett's Esophagus after Normal Index Endoscopy.},
journal = {The American journal of gastroenterology},
volume = {},
number = {},
pages = {},
doi = {10.14309/ajg.0000000000002204},
pmid = {36716445},
issn = {1572-0241},
abstract = {OBJECTIVE: Guidelines suggest one time screening with esophagogastroduodenoscopy (EGD) for Barrett's esophagus (BE) in individuals at increased risk for esophageal adenocarcinoma (EAC). We aimed to estimate the yield of repeat EGD performed at prolonged intervals following a normal index EGD.<br><br>DESIGN: We conducted a national retrospective analysis within the United States Veterans Health Administration, identifying patients with a normal index EGD between 2003 and 2009 who subsequently had a repeat EGD. We tabulated the proportion with a new diagnosis of BE, EAC or esophagogastric junction adenocarcinoma (EGJAC), and conducted manual chart review of a sample. We fitted logistic regression models for the odds of a new diagnosis of BE/EAC/EGJAC.<br><br>RESULTS: We identified 71,216 individuals who had a repeat EGD between 1 and 16 years following an index EGD without billing or cancer registry codes for BE/EAC/EGJAC. Of those, 4,088 had a new billing or cancer registry code for BE/EAC/EGJAC following the repeat EGD. On manual review of a stratified sample, most did not truly have new BE/EAC/EGJAC. Longer duration between EGDs was associated with greater odds of a new diagnosis (adjusted odds ratio [aOR] for each 5 years = 1.31; 95% confidence interval [CI] = 1.19, 1.44), particularly among those who were younger at the time of the index EGD (ages 19-29: aOR = 3.92; 95% CI = 1.24, 12.4; ages 60-69: aOR = 1.19; 95% CI = 1.01, 1.40).<br><br>CONCLUSION: The yield of repeat EGD for BE/EAC/EGJAC appears to increase with time following a normal index EGD, particularly for younger individuals. Prospective studies are warranted to confirm these findings.},
}
@article {pmid36716178,
year = {2023},
author = {Devasia, TP and Mariotto, AB and Nyame, YA and Etzioni, R},
title = {Estimating the Number of Men Living with Metastatic Prostate Cancer in the United States.},
journal = {Cancer epidemiology, biomarkers &amp; prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology},
volume = {},
number = {},
pages = {},
doi = {10.1158/1055-9965.EPI-22-1038},
pmid = {36716178},
issn = {1538-7755},
abstract = {BACKGROUND: Metastatic prostate cancer (MPC) includes metastases detected at diagnosis (de novo) and those occurring after diagnosis with early-stage disease (recurrent). Cancer registries collect data only on de novo MPC, providing a partial picture of the burden of MPC. We use cancer registry data to estimate the number of men living with MPC in the US including both de novo and recurrent cases.<br><br>METHODS: We apply a back-calculation method to estimate MPC incidence and prevalence from US prostate cancer (PC) mortality and de novo MPC relative survival for cases diagnosed between 2000-2017 in 18 Surveillance, Epidemiology, and End Results registries. We hold overall PC mortality and MPC survival constant for future prevalence projections.<br><br>RESULTS: On January 1, 2018, we estimated 120,400 US men living with MPC (45% de novo, 55% recurrent). The age-adjusted prevalence in 2018 for Black men was over double that of White men (137.1 vs. 62.2 per 100,000 men). By 2030, 192,500 men are expected to be living with MPC, with the increase being driven by population growth projections.<br><br>CONCLUSIONS: The number of men living with MPC in the US exceeds 100,000 and represents a small fraction of the >3 million men living with a prior diagnosis of PC.<br><br>IMPACT: Relatively similar fractions of de novo and recurrent MPC among prevalent cases highlight opportunities for early detection and management of localized disease in reducing the MPC burden. Changes in diagnostic technologies could lead to greater growth in MPC cases in the US than projected.},
}
@article {pmid36712924,
year = {2023},
author = {Lee, S and Lee, C and Won Nam, J and Vernez Moudon, A and Mendoza, J},
title = {Street environments and crime around low-income and minority schools: Adopting an environmental audit tool to assess crime prevention through environmental design (CPTED).},
journal = {Landscape and urban planning},
volume = {232},
number = {},
pages = {},
pmid = {36712924},
issn = {0169-2046},
abstract = {Crime prevention through environmental design (CPTED) suggests an association between micro-scale environmental conditions and crime, but little empirical research exists on the detailed street-level environmental features associated with crime near low-income and minority schools. This study focuses on the neighborhoods around 14 elementary schools serving lower income populations in Seattle, WA to assess if the distribution of crime incidences (2013-2017) is linked with the street-level environmental features that reflect CPTED principles. We used a total of 40 audit variables that were included in the four domains derived from the broken windows theory and CPTED principles: natural surveillance (e.g., number of windows, balconies, and a sense of surveillance), territoriality (e.g., crime watch signs, trees), image/maintenance (e.g., graffiti and a sense of maintenance/cleanness), and geographical juxtaposition (e.g., bus stops, presence of arterial). We found that multiple crime types had significant associations with CPTED components at the street level. Among the CPTED domains, two image/maintenance features (i.e., maintenance of streets and visual quality of buildings) and two geographical juxtaposition features (i.e., being adjacent to multi-family housing and bus stops) were consistently associated with both violent and property crime. The findings suggest that local efforts to improve maintenance of streets and visual quality of buildings and broader planning efforts to control specific land uses near schools are important to improve safety in marginalized neighborhoods near schools that tend to be more vulnerable to crime. Our research on micro-scale environmental determinants of crime can also serve as promising targets for CPTED research and initiatives.},
}
@article {pmid36710203,
year = {2023},
author = {Montgomery, B and Mostaghel, EA},
title = {Neoadjuvant Therapy Prior to Prostatectomy: Is the Glass Half Full?.},
journal = {European urology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.eururo.2023.01.021},
pmid = {36710203},
issn = {1873-7560},
}
@article {pmid36710146,
year = {2022},
author = {Makrakis, D and Wright, JL and Roudier, MP and Garcia, J and Vakar-Lopez, F and Porter, MP and Wang, Y and Dash, A and Lin, D and Schade, G and Winters, B and Zhang, X and Nelson, P and Mostaghel, E and Cheng, HH and Schweizer, M and Holt, SK and Gore, JL and Yu, EY and Lam, HM and Montgomery, B},
title = {A Phase 1/2 Study of Rapamycin and Cisplatin/Gemcitabine for Treatment of Patients With Muscle-Invasive Bladder Cancer.},
journal = {Clinical genitourinary cancer},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.clgc.2022.12.003},
pmid = {36710146},
issn = {1938-0682},
abstract = {INTRODUCTION: Cisplatin-based neoadjuvant chemotherapy (NAC) followed by cystectomy is the standard for muscle-invasive bladder cancer (MIBC), however, NAC confers only a small survival benefit and new strategies are needed to increase its efficacy. Pre-clinical data suggest that in response to DNA damage the tumor microenvironment (TME) adopts a paracrine secretory phenotype dependent on mTOR signaling which may provide an escape mechanism for tumor resistance, thus offering an opportunity to increase NAC effectiveness with mTOR blockade.<br><br>PATIENTS &amp; METHODS: We conducted a phase I/II clinical trial to assess the safety and efficacy of gemcitabine-cisplatin-rapamycin combination. Grapefruit juice was administered to enhance rapamycin pharmacokinetics by inhibiting intestinal enzymatic degradation. Phase I was a dose determination/safety study followed by a single arm Phase II study of NAC prior to radical cystectomy evaluating pathologic response with a 26% pCR rate target.<br><br>RESULTS: In phase I, 6 patients enrolled, and the phase 2 dose of 35 mg rapamycin established. Fifteen patients enrolled in phase II; 13 were evaluable. Rapamycin was tolerated without serious adverse events. At the preplanned analysis, the complete response rate (23%) did not meet the prespecified level for continuing and the study was stopped due to futility. With immunohistochemistry, successful suppression of the mTOR signaling pathway in the tumor was achieved while limited mTOR activity was seen in the TME.<br><br>CONCLUSION: Adding rapamycin to gemcitabine-cisplatin therapy for patients with MIBC was well tolerated but failed to improve therapeutic efficacy despite evidence of mTOR blockade in tumor cells. Further efforts to understand the role of the tumor microenvironment in chemotherapy resistance is needed.},
}
@article {pmid36709831,
year = {2023},
author = {Bossarte, RM and Ross, EL and Liu, H and Turner, B and Bryant, C and Zainal, NH and Puac-Polanco, V and Ziobrowski, HN and Cui, R and Cipriani, A and Furukawa, TA and Leung, LB and JoormannN, J and Nierenberg, AA and Oslin, DW and Pigeon, WR and Post, EP and Zaslavsky, AM and Zubizarreta, JR and Luedtke, A and Kennedy, CJ and Kessler, RC},
title = {Development of a model to predict combined antidepressant medication and psychotherapy treatment response for depression among veterans.},
journal = {Journal of affective disorders},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jad.2023.01.082},
pmid = {36709831},
issn = {1573-2517},
abstract = {BACKGROUND: Although research shows that more depressed patients respond to combined antidepressants (ADM) and psychotherapy than either alone, many patients do not respond even to combined treatment. A reliable prediction model for this could help treatment decision-making. We attempted to create such a model using machine learning methods among patients in the US Veterans Health Administration (VHA).<br><br>METHODS: A 2018-2020 national sample of VHA patients beginning combined depression treatment completed self-report assessments at baseline and 3&#x202f;months (n&#x202f;=&#x202f;658). A learning model was developed using baseline self-report, administrative, and geospatial data to predict 3-month treatment response defined by reductions in the Quick Inventory of Depression Symptomatology Self-Report and/or in the Sheehan Disability Scale. The model was developed in a 70&#x202f;% training sample and tested in the remaining 30&#x202f;% test sample.<br><br>RESULTS: 30.0&#x202f;% of patients responded to treatment. The prediction model had a test sample AUC-ROC of 0.657. A strong gradient was found in probability of treatment response from 52.7&#x202f;% in the highest predicted quintile to 14.4&#x202f;% in the lowest predicted quintile. The most important predictors were episode characteristics (symptoms, comorbidities, history), personality/psychological resilience, recent stressors, and treatment characteristics.<br><br>LIMITATIONS: Restrictions in sample definition, a low recruitment rate, and reliance on patient self-report rather than clinician assessments to determine treatment response limited the generalizability of results.<br><br>CONCLUSIONS: A machine learning model could help depressed patients and providers predict likely response to combined ADM-psychotherapy. Parallel information about potential harms and costs of alternative treatments would be needed, though, to inform optimal treatment selection.},
}
@article {pmid36709040,
year = {2023},
author = {Luen, SJ and Viale, G and Nik-Zainal, S and Savas, P and Kammler, R and Dell'Orto, P and Biasi, O and Degasperi, A and Brown, LC and Láng, I and MacGrogan, G and Tondini, C and Bellet, M and Villa, F and Bernardo, A and Ciruelos, E and Karlsson, P and Neven, P and Climent, M and Müller, B and Joshum, W and Bonnefoi, H and Martino, S and Davidson, NE and Geyer, C and Chia, SK and Ingle, JN and Coleman, R and Solbach, C and Thürlimann, B and Colleoni, M and Coates, AS and Goldhirsch, A and Fleming, GF and Francis, PA and Speed, TP and Regan, MM and Loi, S},
title = {Genomic characterisation of hormone receptor-positive breast cancer arising in very young women.},
journal = {Annals of oncology : official journal of the European Society for Medical Oncology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.annonc.2023.01.009},
pmid = {36709040},
issn = {1569-8041},
abstract = {BACKGROUND: Very young premenopausal women diagnosed with hormone receptor-positive, HER2-negative (HR+HER2-) early breast cancer (EBC) have higher rates of recurrence and death for reasons that remain largely unexplained.<br><br>PATIENTS AND METHODS: Genomic sequencing was applied to HR+HER2- tumours from patients enrolled in the SOFT clinical trial to determine genomic drivers that are enriched in young premenopausal women. Genomic alterations were characterised using next-generation sequencing from a subset of 1,276 patients (deep targeted sequencing, N=1258; whole-exome sequencing in a young-age, case-control subsample, N=82). We defined copy number (CN) subgroups and assessed for features suggestive of homologous recombination deficiency (HRD). Genomic alteration frequencies were compared between young premenopausal women (<40 years) and older premenopausal women (&#x2265;40 years), and assessed for associations with distant recurrence-free interval (DRFI), and overall survival (OS).<br><br>RESULTS: Younger women (<40 years, N=359) compared with older women (&#x2265;40 years, N=917) had significantly higher frequencies of mutations in GATA3 (19%vs16%) and CN-amplifications (47%vs26%), but significantly lower frequencies of mutations in PIK3CA (32%vs47%), CDH1 (3%vs9%), and MAP3K1 (7%vs12%). Additionally, significantly higher frequencies of features suggestive of HRD (27%vs21%), and a higher proportion of PIK3CA mutations with concurrent CN-amplifications (23%vs11%).Genomic features suggestive of HRD, PIK3CA mutations with CN-amplifications, and CN-amplifications associated with significantly worse DRFI and OS compared with those without these features. These poor prognostic features were enriched in younger patients: present in 72% of patients aged <35 years, 54% aged 35-39 years, and 40% &#x2265;40 years. Poor prognostic features (N=584[46%]) vs none (N=692[54%]) had an 8-year DRFI of 84%vs94% and OS of 88%vs96%. Younger women (<40) had the poorest outcomes: 8-year DRFI 74%vs85% and OS of 80%vs93% respectively.<br><br>CONCLUSION: These results provide insights into genomic alterations that are enriched in young women with HR+HER2-EBC, provide rationale for genomic subgrouping, and highlight priority molecular targets for future clinical trials.},
}
@article {pmid36708497,
year = {2023},
author = {Peters, BA and Burk, RD and Kaplan, RC and Qi, Q},
title = {The Gut Microbiome, Microbial Metabolites, and Cardiovascular Disease in People Living with HIV.},
journal = {Current HIV/AIDS reports},
volume = {},
number = {},
pages = {},
pmid = {36708497},
issn = {1548-3576},
support = {K01HL160146/HL/NHLBI NIH HHS/United States ; R01HL140976/HL/NHLBI NIH HHS/United States ; },
abstract = {PURPOSE OF REVIEW: To synthesize recent evidence relating the gut microbiome and microbial metabolites to cardiovascular disease (CVD) in people living with HIV (PLWH).<br><br>RECENT FINDINGS: A few cross-sectional studies have reported on the gut microbiome and cardiovascular outcomes in the context of HIV, with no consistent patterns emerging. The largest such study found that gut Fusobacterium was associated with carotid artery plaque. More studies have evaluated microbial metabolite trimethylamine N-oxide with CVD risk in PLWH, but results were inconsistent, with recent prospective analyses showing null effects. Studies of other microbial metabolites are scarce. Microbial translocation biomarkers (e.g., lipopolysaccharide binding protein) have been related to incident CVD in PLWH. Microbial translocation may increase CVD risk in PLWH, but there is insufficient and/or inconsistent evidence regarding specific microbial species and microbial metabolites associated with cardiovascular outcomes in PLWH. Further research is needed in large prospective studies integrating the gut microbiome, microbial translocation, and microbial metabolites with cardiovascular outcomes in PLWH.},
}
@article {pmid36442770,
year = {2022},
author = {Schoettler, ML and Carreras, E and Cho, B and Dandoy, CE and Ho, VT and Jodele, S and Moissev, I and Sanchez-Ortega, I and Srivastava, A and Atsuta, Y and Carpenter, P and Koreth, J and Kroger, N and Ljungman, P and Page, K and Popat, U and Shaw, BE and Sureda, A and Soiffer, R and Vasu, S},
title = {Harmonizing Definitions for Diagnostic Criteria and Prognostic Assessment of Transplantation-Associated Thrombotic Microangiopathy: A Report on Behalf of the European Society for Blood and Marrow Transplantation, American Society for Transplantation and Cellular Therapy, Asia-Pacific Blood and Marrow Transplantation Group, and Center for International Blood and Marrow Transplant Research.},
journal = {Transplantation and cellular therapy},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jtct.2022.11.015},
pmid = {36442770},
issn = {2666-6367},
abstract = {Transplantation-associated thrombotic microangiopathy (TA-TMA) is an increasingly recognized complication of hematopoietic cell transplantation (HCT) associated with significant morbidity and mortality. However, TA-TMA is a clinical diagnosis, and multiple criteria have been proposed without universal application. Although some patients have a self-resolving disease, others progress to multiorgan failure and/or death. Poor prognostic features also are not uniformly accepted. The lack of harmonization of diagnostic and prognostic markers has precluded multi-institutional studies to better understand incidence and outcomes. Even current interventional trials use different criteria, making it challenging to interpret the data. To address this urgent need, the American Society for Transplantation and Cellular Therapy, Center for International Bone Marrow Transplant Research, Asia-Pacific Blood and Marrow Transplantation, and European Society for Blood and Marrow Transplantation nominated representatives for an expert panel tasked with reaching consensus on diagnostic and prognostic criteria. The panel reviewed literature, generated consensus statements regarding diagnostic and prognostic features of TA-TMA using the Delphi method, and identified future directions of investigation. Consensus was reached on 4 key concepts: (1) TA-TMA can be diagnosed using clinical and laboratory criteria or tissue biopsy of kidney or gastrointestinal tissue; however, biopsy is not required; (2) consensus diagnostic criteria are proposed using the modified Jodele criteria with additional definitions of anemia and thrombocytopenia. TA-TMA is diagnosed when ≥4 of the following 7 features occur twice within 14 days: anemia, defined as failure to achieve transfusion independence despite neutrophil engraftment; hemoglobin decline by ≥1 g/dL or new-onset transfusion dependence; thrombocytopenia, defined as failure to achieve platelet engraftment, higher-than-expected transfusion needs, refractory to platelet transfusions, or ≥50% reduction in baseline platelet count after full platelet engraftment; lactate dehydrogenase (LDH) exceeding the upper limit of normal (ULN); schistocytes; hypertension; soluble C5b-9 (sC5b-9) exceeding the ULN; and proteinuria (≥1 mg/mg random urine protein-to-creatinine ratio [rUPCR]); (3) patients with any of the following features are at increased risk of nonrelapse mortality and should be stratified as high-risk TA-TMA: elevated sC5b-9, LDH ≥2 times the ULN, rUPCR ≥1 mg/mg, multiorgan dysfunction, concurrent grade II-IV acute graft-versus-host disease (GVHD), or infection (bacterial or viral); and (4) all allogeneic and pediatric autologous HCT recipients with neuroblastoma should be screened weekly for TA-TMA during the first 100 days post-HCT. Patients diagnosed with TA-TMA should be risk-stratified, and those with high-risk disease should be offered participation in a clinical trial for TA-TMA-directed therapy if available. We propose that these criteria and risk stratification features be used in data registries, prospective studies, and clinical practice across international settings. This harmonization will facilitate the investigation of TA-TMA across populations diverse in race, ethnicity, age, disease indications, and transplantation characteristics. As these criteria are widely used, we expect continued refinement as necessary. Efforts to identify more specific diagnostic and prognostic biomarkers are a top priority of the field. Finally, an investigation of the impact of TA-TMA-directed treatment, particularly in the setting of concurrent highly morbid complications, such as steroid-refractory GVHD and infection, is critically needed.},
}
@article {pmid36708363,
year = {2023},
author = {Azizoğlu, A and Loureiro, C and Venetz, J and Brent, R},
title = {Autorepression-Based Conditional Gene Expression System in Yeast for Variation-Suppressed Control of Protein Dosage.},
journal = {Current protocols},
volume = {3},
number = {1},
pages = {e647},
doi = {10.1002/cpz1.647},
pmid = {36708363},
issn = {2691-1299},
support = {/CA/NCI NIH HHS/United States ; /NH/NIH HHS/United States ; },
abstract = {Conditional control of gene expression allows an experimenter to investigate many aspects of a gene's function. In the model organism Saccharomyces cerevisiae, a number of methods to control gene expression are widely practiced, including induction by metabolites, small molecules, and even light. However, all current methods suffer from at least one of a set of drawbacks, including need for specialized growth conditions, leaky expression, or requirement of specialized equipment. Here we describe protocols using two transformations to construct strains that carry a new controller in which all these drawbacks are overcome. In these strains, the expression of a controlled gene of interest is repressed by the bacterial repressor TetR and induced by anhydrotetracycline. TetR also regulates its own expression, creating an autorepression loop. This autorepression allows tight control of gene expression and protein dosage with low cell-to-cell variation in expression. A second repressor, TetR-Tup1, prevents any leaky expression. We also present a protocol showing a particular workhorse application of such strains to generate synchronized cell populations. We turn off expression of the cell cycle regulator CDC20 completely, arresting the cell population, and then we turn it back on so that the synchronized cells resume cell cycle progression. This control system can be applied to any endogenous or exogenous gene for precise expression. © 2023 Wiley Periodicals LLC. Basic Protocol 1: Generating a parent WTC846 strain Basic Protocol 2: Generating a WTC846 strain with controlled expression of the targeted gene Alternate Protocol: CRISPR-mediated promoter replacement Basic Protocol 3: Cell cycle synchronization/arrest and release using the WTC846- K3 ::CDC20 strain.},
}
@article {pmid36707929,
year = {2023},
author = {Ugai, T and Haruki, K and Harrison, TA and Cao, Y and Qu, C and Chan, AT and Campbell, PT and Akimoto, N and Berndt, S and Brenner, H and Buchanan, DD and Chang-Claude, J and Fujiyoshi, K and Gallinger, SJ and Gunter, MJ and Hidaka, A and Hoffmeister, M and Hsu, L and Jenkins, MA and Milne, RL and Moreno, V and Newcomb, PA and Nishihara, R and Pai, RK and Sakoda, LC and Slattery, ML and Sun, W and Amitay, EL and Alwers, E and Thibodeau, SN and Toland, AE and Van Guelpen, B and Woods, MO and Zaidi, SH and Potter, JD and Giannakis, M and Song, M and Nowak, JA and Phipps, AI and Peters, U and Ogino, S},
title = {Molecular Characteristics of Early-Onset Colorectal Cancer According to Detailed Anatomical Locations: Comparison With Later-Onset Cases.},
journal = {The American journal of gastroenterology},
volume = {},
number = {},
pages = {},
doi = {10.14309/ajg.0000000000002171},
pmid = {36707929},
issn = {1572-0241},
abstract = {INTRODUCTION: Early-onset colorectal cancer diagnosed before the age of 50 years has been increasing. Likely reflecting the pathogenic role of the intestinal microbiome, which gradually changes across the entire colorectal length, the prevalence of certain tumor molecular characteristics gradually changes along colorectal subsites. Understanding how colorectal tumor molecular features differ by age and tumor location is important in personalized patient management.<br><br>METHODS: Using 14,004 cases with colorectal cancer including 3,089 early-onset cases, we examined microsatellite instability (MSI), CpG island methylator phenotype (CIMP), and KRAS and BRAF mutations in carcinomas of the cecum, ascending colon, transverse colon, descending colon, sigmoid colon, and rectum and compared early-onset cases with later-onset cases.<br><br>RESULTS: The proportions of MSI-high, CIMP-high, and BRAF-mutated early-onset tumors were lowest in the rectum (8.8%, 3.4%, and 3.5%, respectively) and highest in the ascending colon (46% MSI-high; 15% CIMP-high) or transverse colon (8.6% BRAF-mutated) (all Ptrend <0.001 across the rectum to ascending colon). Compared with later-onset tumors, early-onset tumors showed a higher prevalence of MSI-high status and a lower prevalence of CIMP-high status and BRAF mutations in most subsites. KRAS mutation prevalence was higher in the cecum compared with that in the other subsites in both early-onset and later-onset tumors (P < 0.001). Notably, later-onset MSI-high tumors showed a continuous decrease in KRAS mutation prevalence from the rectum (36%) to ascending colon (9%; Ptrend <0.001), followed by an increase in the cecum (14%), while early-onset MSI-high cancers showed no such trend.<br><br>DISCUSSION: Our findings support biogeographical and pathogenic heterogeneity of colorectal carcinomas in different colorectal subsites and age groups.},
}
@article {pmid36706896,
year = {2023},
author = {Vieyra, G and Hankinson, SE and Oulhote, Y and Vandenberg, LN and Tinker, L and Manson, JE and Shadyab, AH and Thomson, CA and Bao, W and Allison, M and Odegaard, AO and Reeves, KW},
title = {Association between urinary phthalate biomarker concentrations and adiposity among postmenopausal women.},
journal = {Environmental research},
volume = {},
number = {},
pages = {115356},
doi = {10.1016/j.envres.2023.115356},
pmid = {36706896},
issn = {1096-0953},
abstract = {BACKGROUND: Obesity is a leading risk factor for chronic diseases, potentially related to excess abdominal adiposity. Phthalates are environmental chemicals that have been suggested to act as obesogens, driving obesity risk. For the associations between phthalates and adiposity, prior studies have focused primarily on body mass index. We hypothesize that more refined measures of adiposity and fat distribution may provide greater insights into these associations given the role of central adiposity in chronic disease risk.<br><br>OBJECTIVES: To evaluate associations between urinary phthalate biomarkers and both visceral and subcutaneous adipose tissue (VAT and SAT) among postmenopausal women enrolled in the Women's Health Initiative (WHI).<br><br>METHODS: We included 1125 WHI participants with available, coincident measurements of urinary phthalate biomarkers (baseline, year 3) and VAT and SAT (baseline, year 3, year 6). VAT and SAT measurements were estimated from DXA scans. Multilevel mixed-effects models estimated the prospective associations between urinary phthalate biomarkers at baseline and VAT and SAT three years later.<br><br>RESULTS: In multivariable adjusted models, we observed positive associations between some phthalate biomarkers, including the sum of di-isobutyl phthalate (&#x3a3;DiBP) biomarkers, MCNP, and DEHP, with VAT three years later. For example, we observed positive associations between concentrations of &#x3a3;DiBP and VAT (Q4 vs Q1 &#x3b2;&#x202f;=&#x202f;7.15, 95% CI -1.76-16.06; Q3 vs Q1 &#x3b2;&#x202f;=&#x202f;10.94, 95% CI 3.55-18.33). Associations were generally attenuated but remained significant after additional adjustment for SAT. MBzP was positively associated with SAT. Other phthalate biomarkers investigated (MEP, MCOP, MCPP, &#x3a3;DBP) were not significantly associated with VAT or SAT.<br><br>DISCUSSION: Based on robust measures of adiposity, this study provides supportive evidence that higher urinary concentrations of select phthalate compounds were associated with higher VAT levels over time in postmenopausal women. Efforts to replicate these findings are needed.},
}
@article {pmid36706161,
year = {2023},
author = {Hsieh, E and Janssens, DH and Paddison, PJ and Browne, EP and Henikoff, S and OhAinle, M and Emerman, M},
title = {A modular CRISPR screen identifies individual and combination pathways contributing to HIV-1 latency.},
journal = {PLoS pathogens},
volume = {19},
number = {1},
pages = {e1011101},
doi = {10.1371/journal.ppat.1011101},
pmid = {36706161},
issn = {1553-7374},
abstract = {Transcriptional silencing of latent HIV-1 proviruses entails complex and overlapping mechanisms that pose a major barrier to in vivo elimination of HIV-1. We developed a new latency CRISPR screening strategy, called Latency HIV-CRISPR which uses the packaging of guideRNA-encoding lentiviral vector genomes into the supernatant of budding virions as a direct readout of factors involved in the maintenance of HIV-1 latency. We developed a custom guideRNA library targeting epigenetic regulatory genes and paired the screen with and without a latency reversal agent-AZD5582, an activator of the non-canonical NFκB pathway-to examine a combination of mechanisms controlling HIV-1 latency. A component of the Nucleosome Acetyltransferase of H4 histone acetylation (NuA4 HAT) complex, ING3, acts in concert with AZD5582 to activate proviruses in J-Lat cell lines and in a primary CD4+ T cell model of HIV-1 latency. We found that the knockout of ING3 reduces acetylation of the H4 histone tail and BRD4 occupancy on the HIV-1 LTR. However, the combination of ING3 knockout accompanied with the activation of the non-canonical NFκB pathway via AZD5582 resulted in a dramatic increase in initiation and elongation of RNA Polymerase II on the HIV-1 provirus in a manner that is nearly unique among all cellular promoters.},
}
@article {pmid36705281,
year = {2023},
author = {Aslam, S and Li, E and Bell, E and Lal, L and Anderson, AJ and Peterson-Brandt, J and Lyman, G},
title = {Risk of chemotherapy-induced febrile neutropenia in intermediate-risk regimens: Clinical and economic outcomes of granulocyte colony-stimulating factor prophylaxis.},
journal = {Journal of managed care &amp; specialty pharmacy},
volume = {29},
number = {2},
pages = {128-138},
doi = {10.18553/jmcp.2023.29.2.128},
pmid = {36705281},
issn = {2376-1032},
abstract = {BACKGROUND: Chemotherapy-induced neutropenia increases the risk of febrile neutropenia (FN) and infection with resultant hospitalizations, with substantial health care resource utilization (HCRU) and costs. Granulocyte-colony stimulating factor (GCSF) is recommended as primary prophylaxis for chemotherapy regimens having more than a 20% risk of FN. Yet, for intermediate-risk (10%-20%) regimens, it should be considered only for patients with 1 or more clinical risk factors (RFs) for FN. It is unclear whether FN prophylaxis for intermediate-risk patients is being optimally implemented. OBJECTIVE: To examine RFs, prophylaxis use, HCRU, and costs associated with incident FN during chemotherapy. METHODS: This retrospective study used administrative claims data for commercial and Medicare Advantage enrollees with nonmyeloid cancer treated with intermediate-risk chemotherapy regimens during January 1, 2009, to March 31, 2020. Clinical RFs, GCSF prophylaxis, incident FN, HCRU, and costs were analyzed descriptively by receipt of primary GCSF, secondary GCSF, or no GCSF prophylaxis. Multivariable Cox regression analysis was used to examine the association between number of RFs and cumulative FN risk. RESULTS: The sample comprised 13,937 patients (mean age 67 years, 55% female). Patients had a mean of 2.3 RFs, the most common being recent surgery, were aged 65 years or greater, and had baseline liver or renal dysfunction; 98% had 1 or more RFs. However, only 35% of patients received primary prophylaxis; 12% received secondary prophylaxis. The hazard ratio of incident FN was higher with increasing number of RFs during the first line of therapy, yet more than 54% of patients received no prophylaxis, regardless of RFs. Use of GCSF prophylaxis varied more by chemotherapeutic regimen than by number of RFs. Among patients treated with rituximab, cyclophosphamide, hydroxydaunorubicin hydrochloride (doxorubicin hydrochloride), vincristine, and prednisone, 76% received primary prophylaxis, whereas only 22% of patients treated with carboplatin/paclitaxel received primary prophylaxis. Among patients with a first line of therapy FN event, 78% had an inpatient stay and 42% had an emergency visit. During cycle 1, mean FN-related coordination of benefits-adjusted medical costs per patient per month ($13,886 for patients with primary prophylaxis and $18,233 for those with none) were driven by inpatient hospitalizations, at 91% and 97%, respectively. CONCLUSIONS: Incident FN occurred more often with increasing numbers of RFs, but GCSF prophylaxis use did not rise correspondingly. Variation in prophylaxis use was greater based on regimen than RF number. Lower health care costs were observed among patients with primary prophylaxis use. Improved individual risk identification for intermediate-risk regimens and appropriate prophylaxis may decrease FN events toward the goal of better clinical and health care cost outcomes. DISCLOSURES: This work was funded by Sandoz Inc., which participated in the design of the study, interpretation of the data, writing and revision of the manuscript, and the decision to submit the manuscript for publication. The study was performed by Optum under contract with Sandoz Inc. The author(s) meet criteria for authorship as recommended by the International Committee of Medical Journal Editors. The authors received no direct compensation related to the development of the manuscript. Dr Li is an employee of Sandoz Inc. Drs Bell and Lal and Mr Peterson-Brandt were employees of Optum at the time of the study. Ms Anderson and Dr Aslam are employees of Optum. Dr Lyman has been primary investigator on a research grant from Amgen to their institution and has consulted for Sandoz, G1 Therapeutics, Partners Healthcare, BeyondSpring, ER Squibb, Merck, Jazz Pharm, Kallyope, Teva; Fresenius Kabi, Seattle Genetics, and Samsung.},
}
@article {pmid36705262,
year = {2023},
author = {Schiffer, JT},
title = {The continuing puzzle of defining duration of SARS-CoV-2 infectivity.},
journal = {The Journal of infectious diseases},
volume = {},
number = {},
pages = {},
doi = {10.1093/infdis/jiad019},
pmid = {36705262},
issn = {1537-6613},
}
@article {pmid36702996,
year = {2023},
author = {Chen, F and Wang, X and Jang, SK and Quach, BC and Weissenkampen, JD and Khunsriraksakul, C and Yang, L and Sauteraud, R and Albert, CM and Allred, NDD and Arnett, DK and Ashley-Koch, AE and Barnes, KC and Barr, RG and Becker, DM and Bielak, LF and Bis, JC and Blangero, J and Boorgula, MP and Chasman, DI and Chavan, S and Chen, YI and Chuang, LM and Correa, A and Curran, JE and David, SP and Fuentes, LL and Deka, R and Duggirala, R and Faul, JD and Garrett, ME and Gharib, SA and Guo, X and Hall, ME and Hawley, NL and He, J and Hobbs, BD and Hokanson, JE and Hsiung, CA and Hwang, SJ and Hyde, TM and Irvin, MR and Jaffe, AE and Johnson, EO and Kaplan, R and Kardia, SLR and Kaufman, JD and Kelly, TN and Kleinman, JE and Kooperberg, C and Lee, IT and Levy, D and Lutz, SM and Manichaikul, AW and Martin, LW and Marx, O and McGarvey, ST and Minster, RL and Moll, M and Moussa, KA and Naseri, T and North, KE and Oelsner, EC and Peralta, JM and Peyser, PA and Psaty, BM and Rafaels, N and Raffield, LM and Reupena, MS and Rich, SS and Rotter, JI and Schwartz, DA and Shadyab, AH and Sheu, WH and Sims, M and Smith, JA and Sun, X and Taylor, KD and Telen, MJ and Watson, H and Weeks, DE and Weir, DR and Yanek, LR and Young, KA and Young, KL and Zhao, W and Hancock, DB and Jiang, B and Vrieze, S and Liu, DJ},
title = {Multi-ancestry transcriptome-wide association analyses yield insights into tobacco use biology and drug repurposing.},
journal = {Nature genetics},
volume = {},
number = {},
pages = {},
pmid = {36702996},
issn = {1546-1718},
abstract = {Most transcriptome-wide association studies (TWASs) so far focus on European ancestry and lack diversity. To overcome this limitation, we aggregated genome-wide association study (GWAS) summary statistics, whole-genome sequences and expression quantitative trait locus (eQTL) data from diverse ancestries. We developed a new approach, TESLA (multi-ancestry integrative study using an optimal linear combination of association statistics), to integrate an eQTL dataset with a multi-ancestry GWAS. By exploiting shared phenotypic effects between ancestries and accommodating potential effect heterogeneities, TESLA improves power over other TWAS methods. When applied to tobacco use phenotypes, TESLA identified 273 new genes, up to 55% more compared with alternative TWAS methods. These hits and subsequent fine mapping using TESLA point to target genes with biological relevance. In silico drug-repurposing analyses highlight several drugs with known efficacy, including dextromethorphan and galantamine, and new drugs such as muscle relaxants that may be repurposed for treating nicotine addiction.},
}
@article {pmid36701146,
year = {2023},
author = {Cheng, E and Shi, Q and Shields, AF and Nixon, AB and Shergill, AP and Ma, C and Guthrie, KA and Couture, F and Kuebler, P and Kumar, P and Tan, B and Krishnamurthi, SS and Ng, K and O'Reilly, EM and Brown, JC and Philip, PA and Caan, BJ and Cespedes Feliciano, EM and Meyerhardt, JA},
title = {Association of Inflammatory Biomarkers With Survival Among Patients With Stage III Colon Cancer.},
journal = {JAMA oncology},
volume = {},
number = {},
pages = {},
doi = {10.1001/jamaoncol.2022.6911},
pmid = {36701146},
issn = {2374-2445},
abstract = {IMPORTANCE: The association of chronic inflammation with colorectal cancer recurrence and death is not well understood, and data from large well-designed prospective cohorts are limited.<br><br>OBJECTIVE: To assess the associations of inflammatory biomarkers with survival among patients with stage III colon cancer.<br><br>This cohort study was derived from a National Cancer Institute-sponsored adjuvant chemotherapy trial Cancer and Leukemia Group B/Southwest Oncology Group 80702 (CALGB/SWOG 80702) conducted between June 22, 2010, and November 20, 2015, with follow-up ending on August 10, 2020. A total of 1494 patients with plasma samples available for inflammatory biomarker assays were included. Data were analyzed from July 29, 2021, to February 27, 2022.<br><br>EXPOSURES: Plasma inflammatory biomarkers (interleukin 6 [IL-6], soluble tumor necrosis factor &#x3b1; receptor 2 [sTNF-&#x3b1;R2], and high-sensitivity C-reactive protein [hsCRP]; quintiles) that were assayed 3 to 8 weeks after surgery but before chemotherapy randomization.<br><br>MAIN OUTCOMES AND MEASURES: The primary outcome was disease-free survival, defined as time from randomization to colon cancer recurrence or death from any cause. Secondary outcomes were recurrence-free survival and overall survival. Hazard ratios for the associations of inflammatory biomarkers and survival were estimated via Cox proportional hazards regression.<br><br>RESULTS: Of 1494 patients (median follow-up, 5.9 years [IQR, 4.7-6.1 years]), the median age was 61.3 years (IQR, 54.0-68.8 years), 828 (55.4%) were male, and 327 recurrences, 244 deaths, and 387 events for disease-free survival were observed. Plasma samples were collected at a median of 6.9 weeks (IQR, 5.6-8.1 weeks) after surgery. The median plasma concentration was 3.8 pg/mL (IQR, 2.3-6.2 pg/mL) for IL-6, 2.9&#x2009;&#xd7;&#x2009;103 pg/mL (IQR, 2.3-3.6&#x2009;&#xd7;&#x2009;103 pg/mL) for sTNF-&#x3b1;R2, and 2.6 mg/L (IQR, 1.2-5.6 mg/L) for hsCRP. Compared with patients in the lowest quintile of inflammation, patients in the highest quintile of inflammation had a significantly increased risk of recurrence or death (adjusted hazard ratios for IL-6: 1.52 [95% CI, 1.07-2.14]; P&#x2009;=&#x2009;.01 for trend; for sTNF-&#x3b1;R2: 1.77 [95% CI, 1.23-2.55]; P&#x2009;<&#x2009;.001 for trend; and for hsCRP: 1.65 [95% CI, 1.17-2.34]; P&#x2009;=&#x2009;.006 for trend). Additionally, a significant interaction was not observed between inflammatory biomarkers and celecoxib intervention for disease-free survival. Similar results were observed for recurrence-free survival and overall survival.<br><br>CONCLUSIONS AND RELEVANCE: This cohort study found that higher inflammation after diagnosis was significantly associated with worse survival outcomes among patients with stage III colon cancer. This finding warrants further investigation to evaluate whether anti-inflammatory interventions may improve colon cancer outcomes.<br><br>TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01150045.},
}
@article {pmid36652935,
year = {2023},
author = {Kumar, SK and Callander, NS and Adekola, K and Anderson, LD and Baljevic, M and Campagnaro, E and Castillo, JJ and Costello, C and D'Angelo, C and Devarakonda, S and Elsedawy, N and Garfall, A and Godby, K and Hillengass, J and Holmberg, L and Htut, M and Huff, CA and Hultcrantz, M and Kang, Y and Larson, S and Lee, HC and Liedtke, M and Martin, T and Omel, J and Rosenberg, A and Sborov, D and Valent, J and Berardi, R and Kumar, R},
title = {Systemic Light Chain Amyloidosis, Version 2.2023, NCCN Clinical Practice Guidelines in Oncology.},
journal = {Journal of the National Comprehensive Cancer Network : JNCCN},
volume = {21},
number = {1},
pages = {67-81},
doi = {10.6004/jnccn.2023.0001},
pmid = {36652935},
issn = {1540-1413},
mesh = {Humans ; *Amyloid ; *Amyloidosis/diagnosis/therapy/etiology ; Plasma Cells ; },
abstract = {Primary systemic light chain amyloidosis (SLCA) is characterized by production of light chains that get converted to amyloid fibrils with an affinity for visceral organs and causing organ dysfunction. The therapy for SLCA is directed to recovering the function of the affected organs by targeting the abnormal plasma cell clone and slowing deposition of amyloid fibrils. The NCCN Guidelines for SLCA provide recommendations for workup, diagnosis, and treatment of primary as well as previously treated SLCA.},
}
@article {pmid36704639,
year = {2021},
author = {Ling, W and Qi, Y and Hua, X and Wu, MC},
title = {Deep ensemble learning over the microbial phylogenetic tree (DeepEn-Phy).},
journal = {Proceedings. IEEE International Conference on Bioinformatics and Biomedicine},
volume = {2021},
number = {},
pages = {470-477},
pmid = {36704639},
issn = {2156-1125},
abstract = {Successful prediction of clinical outcomes facilitates tailored diagnosis and treatment. The microbiome has been shown to be an important biomarker to predict host clinical outcomes. Further, the incorporation of microbial phylogeny, the evolutionary relationship among microbes, has been demonstrated to improve prediction accuracy. We propose a phylogeny-driven deep neural network (PhyNN) and develop an ensemble method, DeepEn-Phy, for host clinical outcome prediction. The method is designed to optimally extract features from phylogeny, thereby take full advantage of the information in phylogeny while harnessing the core principles of phylogeny (in contrast to taxonomy). We apply DeepEn-Phy to a real large microbiome data set to predict both categorical and continuous clinical outcomes. DeepEn-Phy demonstrates superior prediction performance to existing machine learning and deep learning approaches. Overall, DeepEn-Phy provides a new strategy for designing deep neural network architectures within the context of phylogeny-constrained microbiome data.},
}
@article {pmid36700653,
year = {2023},
author = {Goodrum, F and Lowen, A and Lakdawala, S and Alwine, J and Casadevall, A and Imperiale, M and Atwood, W and Avgousti, D and Baines, J and Banfield, B and Banks, L and Bhaduri-McIntosh, S and Bhattacharya, D and Blanco-Melo, D and Bloom, D and Boon, A and Boulant, S and Brandt, C and Broadbent, A and Brooke, C and Cameron, C and Campos, S and Caposio, P and Chan, G and Cliffe, A and Coffin, J and Collins, K and Damania, B and Daugherty, M and Debbink, K and DeCaprio, J and Dermody, T and Dikeakos, J and DiMaio, D and Dinglasan, R and Duprex, WP and Dutch, R and Elde, N and Emerman, M and Enquist, L and Fane, B and Fernandez-Sesma, A and Flenniken, M and Frappier, L and Frieman, M and Frueh, K and Gack, M and Gaglia, M and Gallagher, T and Galloway, D and García-Sastre, A and Geballe, A and Glaunsinger, B and Goff, S and Greninger, A and Hancock, M and Harris, E and Heaton, N and Heise, M and Heldwein, E and Hogue, B and Horner, S and Hutchinson, E and Hyser, J and Jackson, W and Kalejta, R and Kamil, J and Karst, S and Kirchhoff, F and Knipe, D and Kowalik, T and Lagunoff, M and Laimins, L and Langlois, R and Lauring, A and Lee, B and Leib, D and Liu, SL and Longnecker, R and Lopez, C and Luftig, M and Lund, J and Manicassamy, B and McFadden, G and McIntosh, M and Mehle, A and Miller, WA and Mohr, I and Moody, C and Moorman, N and Moscona, A and Mounce, B and Munger, J and Münger, K and Murphy, E and Naghavi, M and Nelson, J and Neufeldt, C and Nikolich, J and O'Connor, C and Ono, A and Orenstein, W and Ornelles, D and Ou, JH and Parker, J and Parrish, C and Pekosz, A and Pellett, P and Pfeiffer, J and Plemper, R and Polyak, S and Purdy, J and Pyeon, D and Quinones-Mateu, M and Renne, R and Rice, C and Schoggins, J and Roller, R and Russell, C and Sandri-Goldin, R and Sapp, M and Schang, L and Schmid, S and Schultz-Cherry, S and Semler, B and Shenk, T and Silvestri, G and Simon, V and Smith, G and Smith, J and Spindler, K and Stanifer, M and Subbarao, K and Sundquist, W and Suthar, M and Sutton, T and Tai, A and Tarakanova, V and tenOever, B and Tibbetts, S and Tompkins, S and Toth, Z and van Doorslaer, K and Vignuzzi, M and Wallace, N and Walsh, D and Weekes, M and Weinberg, J and Weitzman, M and Weller, S and Whelan, S and White, E and Williams, B and Wobus, C and Wong, S and Yurochko, A},
title = {Virology under the Microscope-a Call for Rational Discourse.},
journal = {mSphere},
volume = {},
number = {},
pages = {e0003423},
doi = {10.1128/msphere.00034-23},
pmid = {36700653},
issn = {2379-5042},
abstract = {Viruses have brought humanity many challenges: respiratory infection, cancer, neurological impairment and immunosuppression to name a few. Virology research over the last 60+ years has responded to reduce this disease burden with vaccines and antivirals. Despite this long history, the COVID-19 pandemic has brought unprecedented attention to the field of virology. Some of this attention is focused on concern about the safe conduct of research with human pathogens. A small but vocal group of individuals has seized upon these concerns - conflating legitimate questions about safely conducting virus-related research with uncertainties over the origins of SARS-CoV-2. The result has fueled public confusion and, in many instances, ill-informed condemnation of virology. With this article, we seek to promote a return to rational discourse. We explain the use of gain-of-function approaches in science, discuss the possible origins of SARS-CoV-2 and outline current regulatory structures that provide oversight for virological research in the United States. By offering our expertise, we - a broad group of working virologists - seek to aid policy makers in navigating these controversial issues. Balanced, evidence-based discourse is essential to addressing public concern while maintaining and expanding much-needed research in virology.},
}
@article {pmid36700642,
year = {2023},
author = {Goodrum, F and Lowen, A and Lakdawala, S and Alwine, J and Casadevall, A and Imperiale, M and Atwood, W and Avgousti, D and Baines, J and Banfield, B and Banks, L and Bhaduri-McIntosh, S and Bhattacharya, D and Blanco-Melo, D and Bloom, D and Boon, A and Boulant, S and Brandt, C and Broadbent, A and Brooke, C and Cameron, C and Campos, S and Caposio, P and Chan, G and Cliffe, A and Coffin, J and Collins, K and Damania, B and Daugherty, M and Debbink, K and DeCaprio, J and Dermody, T and Dikeakos, J and DiMaio, D and Dinglasan, R and Duprex, WP and Dutch, R and Elde, N and Emerman, M and Enquist, L and Fane, B and Fernandez-Sesma, A and Flenniken, M and Frappier, L and Frieman, M and Frueh, K and Gack, M and Gaglia, M and Gallagher, T and Galloway, D and García-Sastre, A and Geballe, A and Glaunsinger, B and Goff, S and Greninger, A and Hancock, M and Harris, E and Heaton, N and Heise, M and Heldwein, E and Hogue, B and Horner, S and Hutchinson, E and Hyser, J and Jackson, W and Kalejta, R and Kamil, J and Karst, S and Kirchhoff, F and Knipe, D and Kowalik, T and Lagunoff, M and Laimins, L and Langlois, R and Lauring, A and Lee, B and Leib, D and Liu, SL and Longnecker, R and Lopez, C and Luftig, M and Lund, J and Manicassamy, B and McFadden, G and McIntosh, M and Mehle, A and Miller, WA and Mohr, I and Moody, C and Moorman, N and Moscona, A and Mounce, B and Munger, J and Münger, K and Murphy, E and Naghavi, M and Nelson, J and Neufeldt, C and Nikolich, J and O'Connor, C and Ono, A and Orenstein, W and Ornelles, D and Ou, JH and Parker, J and Parrish, C and Pekosz, A and Pellett, P and Pfeiffer, J and Plemper, R and Polyak, S and Purdy, J and Pyeon, D and Quinones-Mateu, M and Renne, R and Rice, C and Schoggins, J and Roller, R and Russell, C and Sandri-Goldin, R and Sapp, M and Schang, L and Schmid, S and Schultz-Cherry, S and Semler, B and Shenk, T and Silvestri, G and Simon, V and Smith, G and Smith, J and Spindler, K and Stanifer, M and Subbarao, K and Sundquist, W and Suthar, M and Sutton, T and Tai, A and Tarakanova, V and tenOever, B and Tibbetts, S and Tompkins, S and Toth, Z and van Doorslaer, K and Vignuzzi, M and Wallace, N and Walsh, D and Weekes, M and Weinberg, J and Weitzman, M and Weller, S and Whelan, S and White, E and Williams, B and Wobus, C and Wong, S and Yurochko, A},
title = {Virology under the Microscope-a Call for Rational Discourse.},
journal = {mBio},
volume = {},
number = {},
pages = {e0018823},
doi = {10.1128/mbio.00188-23},
pmid = {36700642},
issn = {2150-7511},
abstract = {Viruses have brought humanity many challenges: respiratory infection, cancer, neurological impairment and immunosuppression to name a few. Virology research over the last 60+ years has responded to reduce this disease burden with vaccines and antivirals. Despite this long history, the COVID-19 pandemic has brought unprecedented attention to the field of virology. Some of this attention is focused on concern about the safe conduct of research with human pathogens. A small but vocal group of individuals has seized upon these concerns - conflating legitimate questions about safely conducting virus-related research with uncertainties over the origins of SARS-CoV-2. The result has fueled public confusion and, in many instances, ill-informed condemnation of virology. With this article, we seek to promote a return to rational discourse. We explain the use of gain-of-function approaches in science, discuss the possible origins of SARS-CoV-2 and outline current regulatory structures that provide oversight for virological research in the United States. By offering our expertise, we - a broad group of working virologists - seek to aid policy makers in navigating these controversial issues. Balanced, evidence-based discourse is essential to addressing public concern while maintaining and expanding much-needed research in virology.},
}
@article {pmid36700640,
year = {2023},
author = {Goodrum, F and Lowen, A and Lakdawala, S and Alwine, J and Casadevall, A and Imperiale, M and Atwood, W and Avgousti, D and Baines, J and Banfield, B and Banks, L and Bhaduri-McIntosh, S and Bhattacharya, D and Blanco-Melo, D and Bloom, D and Boon, A and Boulant, S and Brandt, C and Broadbent, A and Brooke, C and Cameron, C and Campos, S and Caposio, P and Chan, G and Cliffe, A and Coffin, J and Collins, K and Damania, B and Daugherty, M and Debbink, K and DeCaprio, J and Dermody, T and Dikeakos, J and DiMaio, D and Dinglasan, R and Duprex, WP and Dutch, R and Elde, N and Emerman, M and Enquist, L and Fane, B and Fernandez-Sesma, A and Flenniken, M and Frappier, L and Frieman, M and Frueh, K and Gack, M and Gaglia, M and Gallagher, T and Galloway, D and García-Sastre, A and Geballe, A and Glaunsinger, B and Goff, S and Greninger, A and Hancock, M and Harris, E and Heaton, N and Heise, M and Heldwein, E and Hogue, B and Horner, S and Hutchinson, E and Hyser, J and Jackson, W and Kalejta, R and Kamil, J and Karst, S and Kirchhoff, F and Knipe, D and Kowalik, T and Lagunoff, M and Laimins, L and Langlois, R and Lauring, A and Lee, B and Leib, D and Liu, SL and Longnecker, R and Lopez, C and Luftig, M and Lund, J and Manicassamy, B and McFadden, G and McIntosh, M and Mehle, A and Miller, WA and Mohr, I and Moody, C and Moorman, N and Moscona, A and Mounce, B and Munger, J and Münger, K and Murphy, E and Naghavi, M and Nelson, J and Neufeldt, C and Nikolich, J and O'Connor, C and Ono, A and Orenstein, W and Ornelles, D and Ou, JH and Parker, J and Parrish, C and Pekosz, A and Pellett, P and Pfeiffer, J and Plemper, R and Polyak, S and Purdy, J and Pyeon, D and Quinones-Mateu, M and Renne, R and Rice, C and Schoggins, J and Roller, R and Russell, C and Sandri-Goldin, R and Sapp, M and Schang, L and Schmid, S and Schultz-Cherry, S and Semler, B and Shenk, T and Silvestri, G and Simon, V and Smith, G and Smith, J and Spindler, K and Stanifer, M and Subbarao, K and Sundquist, W and Suthar, M and Sutton, T and Tai, A and Tarakanova, V and tenOever, B and Tibbetts, S and Tompkins, S and Toth, Z and van Doorslaer, K and Vignuzzi, M and Wallace, N and Walsh, D and Weekes, M and Weinberg, J and Weitzman, M and Weller, S and Whelan, S and White, E and Williams, B and Wobus, C and Wong, S and Yurochko, A},
title = {Virology under the Microscope-a Call for Rational Discourse.},
journal = {Journal of virology},
volume = {},
number = {},
pages = {e0008923},
doi = {10.1128/jvi.00089-23},
pmid = {36700640},
issn = {1098-5514},
abstract = {Viruses have brought humanity many challenges: respiratory infection, cancer, neurological impairment and immunosuppression to name a few. Virology research over the last 60+ years has responded to reduce this disease burden with vaccines and antivirals. Despite this long history, the COVID-19 pandemic has brought unprecedented attention to the field of virology. Some of this attention is focused on concern about the safe conduct of research with human pathogens. A small but vocal group of individuals has seized upon these concerns - conflating legitimate questions about safely conducting virus-related research with uncertainties over the origins of SARS-CoV-2. The result has fueled public confusion and, in many instances, ill-informed condemnation of virology. With this article, we seek to promote a return to rational discourse. We explain the use of gain-of-function approaches in science, discuss the possible origins of SARS-CoV-2 and outline current regulatory structures that provide oversight for virological research in the United States. By offering our expertise, we - a broad group of working virologists - seek to aid policy makers in navigating these controversial issues. Balanced, evidence-based discourse is essential to addressing public concern while maintaining and expanding much-needed research in virology.},
}
@article {pmid36697405,
year = {2023},
author = {Doebley, AL and Ko, M and Liao, H and Cruikshank, AE and Santos, K and Kikawa, C and Hiatt, JB and Patton, RD and De Sarkar, N and Collier, KA and Hoge, ACH and Chen, K and Zimmer, A and Weber, ZT and Adil, M and Reichel, JB and Polak, P and Adalsteinsson, VA and Nelson, PS and MacPherson, D and Parsons, HA and Stover, DG and Ha, G},
title = {Author Correction: A framework for clinical cancer subtyping from nucleosome profiling of cell-free DNA.},
journal = {Nature communications},
volume = {14},
number = {1},
pages = {403},
doi = {10.1038/s41467-023-36187-8},
pmid = {36697405},
issn = {2041-1723},
}
@article {pmid36696954,
year = {2023},
author = {Sheikh, MT and Chen, MH and Gelfond, JA and Sun, W and Ibrahim, JG},
title = {New C-indices for assessing importance of longitudinal biomarkers in fitting competing risks survival data in the presence of partially masked causes.},
journal = {Statistics in medicine},
volume = {},
number = {},
pages = {},
doi = {10.1002/sim.9671},
pmid = {36696954},
issn = {1097-0258},
support = {#GM 70335/GF/NIH HHS/United States ; },
abstract = {Competing risks survival data in the presence of partially masked causes are frequently encountered in medical research or clinical trials. When longitudinal biomarkers are also available, it is of great clinical importance to examine associations between the longitudinal biomarkers and the cause-specific survival outcomes. In this article, we propose a cause-specific C-index for joint models of longitudinal and competing risks survival data accounting for masked causes. We also develop a posterior predictive algorithm for computing the out-of-sample cause-specific C-index using Markov chain Monte Carlo samples from the joint posterior of the in-sample longitudinal and competing risks survival data. We further construct the Δ $$ \Delta $$ C-index to quantify the strength of association between the longitudinal and cause-specific survival data, or between the out-of-sample longitudinal and survival data. Empirical performance of the proposed assessment criteria is examined through an extensive simulation study. An in-depth analysis of the real data from large cancer prevention trials is carried out to demonstrate the usefulness of the proposed methodology.},
}
@article {pmid36695426,
year = {2023},
author = {Nguyen, S and LaCroix, AZ and Hayden, KM and Di, C and Palta, P and Stefanick, ML and Manson, JE and Rapp, SR and LaMonte, MJ and Bellettiere, J},
title = {Accelerometer-measured physical activity and sitting with incident mild cognitive impairment or probable dementia among older women.},
journal = {Alzheimer's &amp; dementia : the journal of the Alzheimer's Association},
volume = {},
number = {},
pages = {},
doi = {10.1002/alz.12908},
pmid = {36695426},
issn = {1552-5279},
support = {P01 AG052352/AG/NIA NIH HHS/United States ; 5T32AG058529-04/AG/NIA NIH HHS/United States ; R01 HL105065/HL/NHLBI NIH HHS/United States ; 75N92021D00001/HL/NHLBI NIH HHS/United States ; 75N92021D00002/HL/NHLBI NIH HHS/United States ; 75N92021D00003/HL/NHLBI NIH HHS/United States ; 75N92021D00004/HL/NHLBI NIH HHS/United States ; 75N92021D00005/HL/NHLBI NIH HHS/United States ; },
abstract = {INTRODUCTION: Physical activity (PA) is prospectively inversely associated with dementia risk, but few studies examined accelerometer measures of PA and sitting with rigorously-adjudicated mild cognitive impairment (MCI) and dementia risk.<br><br>METHODS: We examined the associations of accelerometer measures (PA and sitting) with incident MCI/probable dementia in the Women's Health Initiative (n&#xa0;=&#xa0;1277; mean age&#xa0;=&#xa0;82&#xa0;&#xb1;&#xa0;6 years) RESULTS: Over a median follow-up of 4.2 years, 267 MCI/probable dementia cases were identified. Adjusted Cox regression HRs (95% CI) across moderate-to-vigorous PA (MVPA) min/d quartiles were 1.00 (reference), 1.28 (0.90 to 1.81), 0.79 (0.53 to 1.17), and 0.69 (0.45 to 1.06); P-trend&#xa0;=&#xa0;0.01. Adjusted HRs (95% CI) across steps/d quartiles were 1.00 (reference), 0.73 (0.51 to 1.03), 0.64 (0.43 to 0.94), and 0.38 (0.23 to 0.61); P-trend&#xa0;<&#xa0;0.001. The HR (95% CI) for each 1-SD increment in MVPA (31 min/d) and steps/d (1865) were 0.79 (0.67 to 0.94) and 0.67 (0.54 to 0.82), respectively. Sitting was not associated with MCI/probable dementia.<br><br>DISCUSSION: Findings suggest &#x2265; moderate intensity PA, particularly stepping, associates with lower MCI and dementia risk.<br><br>HIGHLIGHTS: Few studies have examined accelerometer-measured physical activity, including steps, and sitting with incident ADRD. Moderate-to-vigorous physical activity and steps, but not light physical activity or sitting, were inversely associated with lower ADRD risk. Among older women, at least moderate intensity physical activity may be needed to reduce ADRD risk.},
}
@article {pmid36695358,
year = {2023},
author = {Siegel, DA and Thanh, C and Wan, E and Hoh, R and Hobbs, K and Pan, T and Gibson, EA and Kroetz, DL and Martin, J and Hecht, F and Pilcher, C and Martin, M and Carrington, M and Pillai, S and Busch, MP and Stone, M and Levy, CN and Huang, ML and Roychoudhury, P and Hladik, F and Jerome, KR and Kiem, HP and Henrich, TJ and Deeks, SG and Lee, SA},
title = {Host variation in type I interferon signaling genes (MX1), C-C chemokine receptor type 5 gene, and major histocompatibility complex class I alleles in treated HIV+ noncontrollers predict viral reservoir size.},
journal = {AIDS (London, England)},
volume = {37},
number = {3},
pages = {477-488},
pmid = {36695358},
issn = {1473-5571},
abstract = {OBJECTIVE: Prior genomewide association studies have identified variation in major histocompatibility complex (MHC) class I alleles and C-C chemokine receptor type 5 gene (CCR5Δ32) as genetic predictors of viral control, especially in 'elite' controllers, individuals who remain virally suppressed in the absence of therapy.<br><br>DESIGN: Cross-sectional genomewide association study.<br><br>METHODS: We analyzed custom whole exome sequencing and direct human leukocyte antigen (HLA) typing from 202 antiretroviral therapy (ART)-suppressed HIV+ noncontrollers in relation to four measures of the peripheral CD4+ T-cell reservoir: HIV intact DNA, total (t)DNA, unspliced (us)RNA, and RNA/DNA. Linear mixed models were adjusted for potential covariates including age, sex, nadir CD4+ T-cell count, pre-ART HIV RNA, timing of ART initiation, and duration of ART suppression.<br><br>RESULTS: Previously reported 'protective' host genetic mutations related to viral setpoint (e.g. among elite controllers) were found to predict smaller HIV reservoir size. The HLA 'protective' B&#x2217;57:01 was associated with significantly lower HIV usRNA (q&#x200a;=&#x200a;3.3 &#xd7; 10-3), and among the largest subgroup, European ancestry individuals, the CCR5&#x394;32 deletion was associated with smaller HIV tDNA (P&#x200a;=&#x200a;4.3 &#xd7; 10-3) and usRNA (P&#x200a;=&#x200a;8.7 &#xd7; 10-3). In addition, genomewide analysis identified several single nucleotide polymorphisms in MX1 (an interferon stimulated gene) that were significantly associated with HIV tDNA (q&#x200a;=&#x200a;0.02), and the direction of these associations paralleled MX1 gene eQTL expression.<br><br>CONCLUSIONS: We observed a significant association between previously reported 'protective' MHC class I alleles and CCR5&#x394;32 with the HIV reservoir size in noncontrollers. We also found a novel association between MX1 and HIV total DNA (in addition to other interferon signaling relevant genes, PPP1CB, DDX3X). These findings warrant further investigation in future validation studies.},
}
@article {pmid36693927,
year = {2023},
author = {Perchetti, GA and Biernacki, MA and Xie, H and Castor, J and Joncas-Schronce, L and Ueda Oshima, M and Kim, Y and Jerome, KR and Sandmaier, BM and Martin, PJ and Boeckh, M and Greninger, AL and Zamora, D},
title = {Cytomegalovirus breakthrough and resistance during letermovir prophylaxis.},
journal = {Bone marrow transplantation},
volume = {},
number = {},
pages = {},
pmid = {36693927},
issn = {1476-5365},
abstract = {Letermovir is a relatively new antiviral for prophylaxis against cytomegalovirus (CMV) after allogeneic hematopoietic cell transplantation (HCT). CMV-seropositive HCT recipients who received letermovir prophylaxis from 2018 to 2020 at our center were evaluated for letermovir resistance and breakthrough CMV reactivation. Two-hundred twenty-six letermovir recipients were identified and 7/15 (47%) with CMV DNAemia ≥200 IU/mL were successfully genotyped for UL56 resistance. A single C325Y resistance mutation was identified in an umbilical cord blood recipient. Ninety-five (42%), 43 (19%), and 15 (7%) patients had breakthrough CMV at any level, ≥150 IU/mL, and ≥500 IU/mL, respectively. Risk factors for breakthrough CMV reactivation at each viral threshold were examined. Cumulative steroid exposure was the strongest risk factor for CMV at all evaluated viral thresholds. Graft-versus-host disease prophylaxis with post-transplantation cyclophosphamide (aHR 2.34, 95% CI 1.28-4.28, p = 0.001) or calcineurin inhibitors plus mycophenolate (aHR 2.24, 95% CI 1.30-3.86, p = 0.004) were also associated with an increased risk of CMV reactivation at any level. De novo letermovir resistance is rare and can be successfully treated using other antivirals. Letermovir effectively prevents clinically significant CMV, however, subclinical CMV reactivation occurs frequently at our center.},
}
@article {pmid36693221,
year = {2023},
author = {Weil, BR and Murphy, AJ and Liu, Q and Howell, RM and Smith, SA and Weldon, CB and Mullen, EA and Madenci, AL and Leisenring, WM and Neglia, JP and Turcotte, LM and Oeffinger, KC and Termuhlen, AM and Mostoufi-Moab, S and Levine, JM and Krull, KR and Yasui, Y and Robison, LL and Armstrong, GT and Chow, EJ and Armenian, SH},
title = {Late Health Outcomes Among Survivors of Wilms Tumor Diagnosed Over Three Decades: A Report From the Childhood Cancer Survivor Study.},
journal = {Journal of clinical oncology : official journal of the American Society of Clinical Oncology},
volume = {},
number = {},
pages = {JCO2202111},
doi = {10.1200/JCO.22.02111},
pmid = {36693221},
issn = {1527-7755},
abstract = {PURPOSE: To evaluate long-term morbidity and mortality among unilateral, nonsyndromic Wilms tumor (WT) survivors according to conventional treatment regimens.<br><br>METHODS: Cumulative incidence of late mortality (&#x2265; 5 years from diagnosis) and chronic health conditions (CHCs) were evaluated in WT survivors from the Childhood Cancer Survivor Study. Outcomes were evaluated by treatment, including nephrectomy combined with vincristine and actinomycin D (VA), VA + doxorubicin + abdominal radiotherapy (VAD + ART), VAD + ART + whole lung radiotherapy, or receipt of &#x2265; 4 chemotherapy agents.<br><br>RESULTS: Among 2,008 unilateral WT survivors, 142 deaths occurred (standardized mortality ratio, 2.9, 95% CI, 2.5 to 3.5; 35-year cumulative incidence of death, 7.8%, 95% CI, 6.3 to 9.2). The 35-year cumulative incidence of any grade 3-5 CHC was 34.1% (95% CI, 30.7 to 37.5; rate ratio [RR] compared with siblings 3.0, 95% CI, 2.6 to 3.5). Survivors treated with VA alone had comparable risk for all-cause late mortality relative to the general population (standardized mortality ratio, 1.0; 95% CI, 0.5 to 1.7) and modestly increased risk for grade 3-5 CHCs compared with siblings (RR, 1.5; 95% CI, 1.1 to 2.0), but remained at increased risk for intestinal obstruction (RR, 9.4; 95% CI, 3.9 to 22.2) and kidney failure (RR, 11.9; 95% CI, 4.2 to 33.6). Magnitudes of risk for grade 3-5 CHCs, including intestinal obstruction, kidney failure, premature ovarian insufficiency, and heart failure, increased by treatment group intensity.<br><br>CONCLUSION: With approximately 40% of patients with newly diagnosed WT currently treated with VA alone, the burden of late mortality/morbidity in future decades is projected to be lower than that for survivors from earlier eras. Nevertheless, the risk of late effects such as intestinal obstruction and kidney failure was elevated across all treatment groups, and there was a dose-dependent increase in risk for all grade 3-5 CHCs by treatment group intensity.},
}
@article {pmid36692401,
year = {2023},
author = {Yokoo, T and Masaki, N and Parikh, ND and Lane, BF and Feng, Z and Mendiratta-Lala, M and Lee, CH and Khatri, G and Marsh, TL and Shetty, K and Dunn, CT and Al-Jarrah, T and Aslam, A and Davenport, MS and Gopal, P and Rich, NE and Lok, AS and Singal, AG},
title = {Multicenter Validation of Abbreviated MRI for Detecting Early-Stage Hepatocellular Carcinoma.},
journal = {Radiology},
volume = {},
number = {},
pages = {220917},
doi = {10.1148/radiol.220917},
pmid = {36692401},
issn = {1527-1315},
abstract = {Background Abbreviated MRI is a proposed paradigm shift for hepatocellular carcinoma (HCC) surveillance, but data on its performance are lacking for histopathologically confirmed early-stage HCC. Purpose To evaluate the sensitivity and specificity of dynamic contrast-enhanced abbreviated MRI for early-stage HCC detection, using surgical pathologic findings as the reference standard. Materials and Methods This retrospective study was conducted at three U.S. liver transplant centers in patients with cirrhosis who underwent liver resection or transplant between January 2009 and December 2019 and standard "full" liver MRI with and without contrast enhancement within 3 months before surgery. Patients who had HCC-directed treatment before surgery were excluded. Dynamic abbreviated MRI examinations were simulated from the presurgical full MRI by selecting the coronal T2-weighted and axial three-dimensional fat-suppressed T1-weighted dynamic contrast-enhanced sequences at precontrast, late arterial, portal venous, and delayed phases. Two abdominal radiologists at each center independently interpreted the simulated abbreviated examinations with use of the Liver Imaging Reporting and Data System version 2018. Patients with any high-risk liver observations (>LR-3) were classified as positive; otherwise, they were classified as negative. With liver pathologic findings as the reference standard for the presence versus absence of early-stage HCC, the sensitivity, specificity, and their 95% CIs were calculated. Logistic regression was used to identify factors associated with correct classification. Results A total of 161 patients with early-stage HCC (median age, 62 years [IQR, 58-67 years]; 123 men) and 138 patients without HCC (median age, 55 years [IQR, 47-63 years]; 85 men) were confirmed with surgical pathologic findings. The sensitivity and specificity of abbreviated MRI were 88.2% (142 of 161 patients) (95% CI: 83.5, 92.5) and 89.1% (123 of 138 patients) (95% CI: 84.4, 93.8), respectively. Sensitivity was lower for Child-Pugh class B or C versus Child-Pugh class A cirrhosis (64.1% vs 94.2%; P < .001). Conclusion With surgical pathologic findings as the reference standard, dynamic abbreviated MRI had high sensitivity and specificity for early-stage hepatocellular carcinoma detection in patients with compensated cirrhosis but lower sensitivity in those with decompensated cirrhosis. © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Kim in this issue.},
}
@article {pmid36692284,
year = {2023},
author = {Hu, C and Bugbee, T and Palinski, R and Akinyemi, IA and McIntosh, MT and MacCarthy, T and Bhaduri-McIntosh, S and Wallace, N},
title = {Beta human papillomavirus 8E6 promotes alternative end-joining.},
journal = {eLife},
volume = {12},
number = {},
pages = {},
doi = {10.7554/eLife.81923},
pmid = {36692284},
issn = {2050-084X},
support = {P20GM130448/GM/NIGMS NIH HHS/United States ; },
abstract = {Double strand breaks (DSBs) are one of the most lethal DNA lesions in cells. The E6 protein of beta-human papillomavirus (HPV8 E6) impairs two critical DSB repair pathways; homologous recombination (HR) and non-homologous end-joining (NHEJ). However, HPV8 E6 only delays DSB repair. How DSBs are repaired in cells with HPV8 E6 remains to be studied. We hypothesize that HPV8 E6 promotes a less commonly used DSB repair pathway, alternative end-joining (Alt-EJ). Using CAS9 based Alt-EJ reporters, we show that HPV8 E6 promotes Alt-EJ. Further, using small molecule inhibitors, CRISPR/CAS9 gene knockout, and HPV8 E6 mutant, we find that HPV8 E6 promotes Alt-EJ by binding p300, an acetyltransferase that facilitates DSB repair by HR and NHEJ. At least some of this repair occurs through a subset of Alt-EJ known as polymerase theta dependent end joining. Finally, whole genome sequencing analysis showed HPV8 E6 caused an increased frequency of deletions bearing the microhomology signatures of Alt-EJ. This study fills the knowledge gap of how DSB is repaired in cells with HPV8 E6 and the mutagenic consequences of HPV8 E6 mediated p300 destabilization. Broadly, this study supports the hypothesis that beta-HPV promotes cancer formation by increasing genomic instability.},
}
@article {pmid36691979,
year = {2023},
author = {Guest, DD and Cox, T and Voss, AC and Kelley, K and Ma, X and Nguyen, A and McMillen, K and Williams, V and Lee, JA and Petersen, J and Lenning, K and Yakes Jimenez, E},
title = {Assessing Impact of Nutrition Care by Registered Dietitian Nutritionists on Patient Medical and Treatment Outcomes in Outpatient Cancer Clinics: A Cohort Feasibility Study.},
journal = {Nutrition and cancer},
volume = {},
number = {},
pages = {1-14},
doi = {10.1080/01635581.2023.2170431},
pmid = {36691979},
issn = {1532-7914},
abstract = {More information is needed about the impact of outpatient nutrition care from a registered dietitian nutritionist (RDN) on patient outcomes. This study aimed to assess the feasibility of a cohort study design to evaluate impact of RDN nutrition care on patient outcomes, describe clinic malnutrition screening practices, and estimate statistical parameters for a larger study. Seventy-seven patients with lung, esophageal, colon, rectal, or pancreatic cancer from six facilities were included (41 received RDN care and 36 did not). RDN nutrition care was prospectively documented for six months and documented emergency room visits, unplanned hospitalizations and treatment changes were retrospectively abstracted from medical records. Most facilities used the Malnutrition Screening Tool (MST) to determine malnutrition risk. Patients receiving RDN care had, on average, five, half hour visits and had more severe disease and higher initial malnutrition risk, although this varied across sites. Documented medical and treatment outcomes were relatively rare and similar between groups. Estimated sample size requirements varied from 113 to 5856, depending on tumor type and outcome, and intracluster correlation coefficients (ICCs) ranged from 0 to 0.47. Overall, the methods used in this study are feasible but an interventional or implementation design might be advantageous for a larger study.},
}
@article {pmid36689724,
year = {2023},
author = {Marrero, RJ and Cao, X and Wu, H and Elsayed, AH and Klco, JM and Ribeiro, RC and Rubnitz, JE and Ma, X and Meshinchi, S and Aplenc, R and Kolb, EA and Ries, RE and Alonzo, T and Pounds, SB and Lamba, JK},
title = {SAMHD1 Single Nucleotide Polymorphisms Impact Outcome in Children with Newly Diagnosed Acute Myeloid Leukemia.},
journal = {Blood advances},
volume = {},
number = {},
pages = {},
doi = {10.1182/bloodadvances.2022009088},
pmid = {36689724},
issn = {2473-9537},
abstract = {Cytarabine arabinoside (Ara-C) has been the cornerstone of AML chemotherapy for decades. Following cellular uptake, it is phosphorylated into its active triphosphate form (Ara-CTP), which primarily exerts its cytotoxic effects by inhibiting DNA synthesis in proliferating cells. Interpatient variation in the enzymes involved in the Ara-C metabolic pathway have been shown to impact intracellular abundance of Ara-CTP and thus its therapeutic benefit. Recently, SAMHD1 (SAM and HD domain containing deoxynucleoside triphosphate triphosphohydrolase 1) has emerged to play a role in Ara-CTP inactivation, development of drug resistance and consequently, clinical response in AML. Despite this the impact of genetic variations in SAMHD1 on outcome in AML has not been investigated in depth. In this study, we evaluated 25 single nucleotide polymorphisms (SNPs) within SAMHD1 gene for association with clinical outcome in 400 newly diagnosed pediatric AML patients from two clinical trials- AML02 and AML08. Three SNPs, rs1291128, rs1291141, and rs7265241 located in the 3' region of SAMHD1 were significantly associated with at least one clinical outcome endpoint: minimal residual disease (MRD) after induction I, event free survival (EFS), or overall survival (OS) in the two cohorts. In an independent cohort of patients from COG-AAML1031 trial (n=854), rs7265241 A>G remained significantly associated with EFS and OS. In multivariable analysis, adjusting for other prognostic factors such as race, age, risk group, and white blood cell count, all the SNPs remained independent predictors of clinical outcome endpoints. These results highlight the relevance of the SAMHD1 pharmacogenomics in context of response to Ara-C in AML and warrants the need for further validation in expanded patient cohorts.},
}
@article {pmid36689221,
year = {2023},
author = {Mena Lora, AJ and Long, JE and Huang, Y and Baden, LR and El Sahly, HM and Follmann, D and Goepfert, P and Gray, G and Grinsztejn, B and Kotloff, K and Rouphael, N and Sobieszczyk, M and Walsh, SR and Andriesen, J and Shah, KA and Zhang, Y and Gilbert, P and Janes, H and Gay, CL and Falsey, AR and Tripp, RL and Gorman, RL and Tong, T and Marovich, M and Neuzil, K and Corey, L and Kublin, JG and , },
title = {Rapid Development of an Integrated Network Infrastructure to Conduct Phase 3 COVID-19 Vaccine Trials.},
journal = {JAMA network open},
volume = {6},
number = {1},
pages = {e2251974},
doi = {10.1001/jamanetworkopen.2022.51974},
pmid = {36689221},
issn = {2574-3805},
abstract = {IMPORTANCE: The COVID-19 pandemic has caused millions of infections and deaths and resulted in unprecedented international public health social and economic crises. As SARS-CoV-2 spread across the globe and its impact became evident, the development of safe and effective vaccines became a priority. Outlining the processes used to establish and support the conduct of the phase 3 randomized clinical trials that led to the rapid emergency use authorization and approval of several COVID-19 vaccines is of major significance for current and future pandemic response efforts.<br><br>OBSERVATIONS: To support the rapid development of vaccines for the US population and the rest of the world, the National Institute of Allergy and Infectious Diseases established the COVID-19 Prevention Network (CoVPN) to assist in the coordination and implementation of phase 3 efficacy trials for COVID-19 vaccine candidates and monoclonal antibodies. By bringing together multiple networks, CoVPN was able to draw on existing clinical and laboratory infrastructure, community partnerships, and research expertise to quickly pivot clinical trial sites to conduct COVID-19 vaccine trials as soon as the investigational products were ready for phase 3 testing. The mission of CoVPN was to operationalize phase 3 vaccine trials using harmonized protocols, laboratory assays, and a single data and safety monitoring board to oversee the various studies. These trials, while staggered in time of initiation, overlapped in time and course of conduct and ultimately led to the successful completion of multiple studies and US Food and Drug Administration-licensed or -authorized vaccines, the first of which was available to the public less than 1 year from the discovery of the virus.<br><br>CONCLUSIONS AND RELEVANCE: This Special Communication describes the design, geographic distribution, and underlying principles of conduct of these efficacy trials and summarizes data from 136&#x202f;382 prospectively followed-up participants, including more than 2500 with documented COVID-19. These successful efforts can be replicated for other important research initiatives and point to the importance of investments in clinical trial infrastructure integral to pandemic preparedness.},
}
@article {pmid36688725,
year = {2023},
author = {Shi, J and Kraft, P and Rosner, B and Benavente, Y and Black, A and Brinton, LA and Chen, C and Clarke, MA and Cook, LS and Costas, L and Dal Maso, L and Freudenheim, JL and Frias-Gomez, J and Friedenreich, CM and Garcia-Closas, M and Goodman, MT and Johnson, L and La Vecchia, C and Levi, F and Lissowska, J and Lu, L and McCann, SE and Moysich, KB and Negri, E and O'Connell, K and Parazzini, F and Petruzella, S and Polesel, J and Ponte, J and Rebbeck, TR and Reynolds, P and Ricceri, F and Risch, H and Sacerdote, C and Setiawan, VW and Shu, XO and Spurdle, AB and Trabert, B and Webb, PM and Wentzensen, N and Wilkens, LR and Xu, WH and Yang, HP and Yu, H and Du, M and De Vivo, I},
title = {Risk prediction models for endometrial cancer: development and validation in an international consortium.},
journal = {Journal of the National Cancer Institute},
volume = {},
number = {},
pages = {},
doi = {10.1093/jnci/djad014},
pmid = {36688725},
issn = {1460-2105},
abstract = {BACKGROUND: Endometrial cancer risk stratification may help target interventions, screening, or prophylactic hysterectomy to mitigate the rising burden of this cancer. However, existing prediction models have been developed in select cohorts and have not considered genetic factors.<br><br>METHODS: We developed endometrial cancer risk prediction models using data on postmenopausal white women aged 45-85&#x2009;years from 19 case-control studies in the Epidemiology of Endometrial Cancer Consortium. Relative risk estimates for predictors were combined with age-specific endometrial cancer incidence rates and estimates for the underlying risk factor distribution. We externally validated the models in three cohorts: Nurses' Health Study (NHS), Nurses' Health Study II (NHS II) and the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial.<br><br>RESULTS: Area under the receiver operating characteristic curves for the epidemiologic model ranged from 0.64 (95% CI: 0.62, 0.67) to 0.69 (95% CI: 0.66, 0.72). Improvements in discrimination from the addition of genetic factors were modest (no change in AUC in NHS,; PLCO: 0.64 to 0.66). The epidemiologic model was well calibrated in NHS II (overall E/O&#x2009;=&#x2009;1.09; 95% CI: 0.98, 1.22) and PLCO (overall E/O&#x2009;=&#x2009;1.04; 95% CI: 0.95, 1.13) but poorly calibrated in NHS (overall E/O&#x2009;=&#x2009;0.55; 95% CI: 0.51, 0.59).<br><br>CONCLUSION: Using data from the largest, most heterogeneous study population to date, prediction models based on epidemiologic factors alone successfully identified women at high risk of endometrial cancer. Genetic factors offered limited improvements in discrimination. Further work is needed to refine this tool for clinical or public health practice and expand these models to multiethnic populations.},
}
@article {pmid36688720,
year = {2023},
author = {Fu, Z and Brooks, MM and Irvin, S and Jordan, S and Aben, KKH and Anton-Culver, H and Bandera, EV and Beckmann, MW and Berchuck, A and Brooks-Wilson, A and Chang-Claude, J and Cook, LS and Cramer, DW and Cushing-Haugen, KL and Doherty, JA and Ekici, AB and Fasching, PA and Fortner, RT and Gayther, SA and Gentry-Maharaj, A and Giles, GG and Goode, EL and Goodman, MT and , and Harris, HR and Hein, A and Kaaks, R and Kiemeney, LA and Köbel, M and Kotsopoulos, J and Kotsopoulos, J and Le, ND and Lee, AW and Matsuo, K and McGuire, V and McLaughlin, JR and Menon, U and Milne, RL and Moysich, KB and Pearce, CL and Pike, MC and Qin, B and Ramus, SJ and Riggan, MJ and Rothstein, JH and Schildkraut, JM and Sieh, W and Sutphen, R and Terry, KL and Thompson, PJ and Titus, L and van Altena, AM and White, E and Whittemore, AS and Wu, AH and Zheng, W and Ziogas, A and Taylor, SE and Tang, L and Songer, T and Wentzensen, N and Webb, PM and Risch, HA and Modugno, F and , },
title = {Lifetime ovulatory years and risk of epithelial ovarian cancer: a multinational pooled analysis.},
journal = {Journal of the National Cancer Institute},
volume = {},
number = {},
pages = {},
doi = {10.1093/jnci/djad011},
pmid = {36688720},
issn = {1460-2105},
abstract = {BACKGROUND: The role of ovulation in epithelial ovarian cancer (EOC) is supported by the consistent protective effects of parity and oral contraceptive (OC) use. Whether these factors protect through anovulation alone remains unclear. We explored the association between lifetime ovulatory years (LOY) and EOC.<br><br>METHODS: LOY was calculated using 12 algorithms. Odds ratios (ORs) and 95% confidence intervals (CIs) estimated the association between LOY or LOY components and EOC among 26,204 controls and 21,267 cases from 25 studies. To assess whether LOY components act through ovulation suppression alone, we compared beta coefficients obtained from regression models to expected estimates assuming one year of ovulation suppression has the same effect regardless of source.<br><br>RESULTS: LOY was associated with increased EOC risk (ORs per year increase: 1.014 (95%CI 1.009-1.020) to 1.044 (95%CI 1.041-1.048)). Individual LOY components, except age at menarche, also associated with EOC. The estimated model coefficient for OC use and pregnancies were 4.45 times and 12-15 fold greater than expected, respectively. LOY was associated with high-grade serous (HGSOC), low-grade serous (LGSOC), endometrioid, and clear cell histotypes (ORs per year increase: 1.054, 1.040, 1.065, and 1.098, respectively), but not mucinous tumors. Estimated coefficients of LOY components were close to expected estimates for HGSOC but larger than expected for LGSOC, endometrioid, and clear cell histotypes.<br><br>CONCLUSIONS: LOY is positively associated with non-mucinous EOC. Differences between estimated and expected model coefficients for LOY components suggest factors beyond ovulation underlie the associations between LOY components and EOC in general and for non-HGSOC.},
}
@article {pmid36687294,
year = {2022},
author = {Zheng, J and Zheng, Y and Hsu, L},
title = {Risk Projection for Time-to-event Outcome Leveraging Summary Statistics With Source Individual-level Data.},
journal = {Journal of the American Statistical Association},
volume = {117},
number = {540},
pages = {2043-2055},
pmid = {36687294},
issn = {0162-1459},
abstract = {Predicting risks of chronic diseases has become increasingly important in clinical practice. When a prediction model is developed in a cohort, there is a great interest to apply the model to other cohorts. Due to potential discrepancy in baseline disease incidences between different cohorts and shifts in patient composition, the risk predicted by the model built in the source cohort often under- or over-estimates the risk in a new cohort. In this article, we assume the relative risks of predictors are the same between the two cohorts, and propose a novel weighted estimating equation approach to re-calibrating the projected risk for the targeted population through updating the baseline risk. The recalibration leverages the knowledge about survival probabilities for the disease of interest and competing events, and summary information of risk factors from the target population. We establish the consistency and asymptotic normality of the proposed estimators. Extensive simulation demonstrate that the proposed estimators are robust, even if the risk factor distributions differ between the source and target populations, and gain efficiency if they are the same, as long as the information from the target is precise. The method is illustrated with a recalibration of colorectal cancer prediction model.},
}
@article {pmid36684526,
year = {2022},
author = {Zhang, L and Gilbert, PB and Capparelli, E and Huang, Y},
title = {Simulation-Based Pharmacokinetics Sampling Design for Evaluating Correlates of Prevention Efficacy of Passive HIV Monoclonal Antibody Prophylaxis.},
journal = {Statistics in biopharmaceutical research},
volume = {14},
number = {4},
pages = {611-625},
pmid = {36684526},
issn = {1946-6315},
abstract = {We address sampling design of population pharmacokinetics (popPK) experiments in the context of two ongoing phase 2b efficacy trials that evaluate the efficacy of VRC01 (vs. placebo) in reducing the rate of HIV infection among 4625 participants. Blood samples are collected at up to 22 study visits from all participants for immediate HIV diagnosis as the primary trial outcome, and stored for future outcome-dependent marker measurements. A key secondary objective of the trials is to evaluate correlates of prevention efficacy among a sub-cohort of VRC01 recipients in terms of whether the current value of VRC01 serum concentration is associated with the instantaneous rate of HIV infection. To accomplish this, concentrations on a daily grid are estimated via non-linear mixed effects popPK modeling of observed 4-weekly concentrations. Given the impracticality of measuring concentrations in all stored blood samples, we devised a simulation-based sampling design framework to evaluate the impact of sub-cohort sample sizes (m) and sampling schemes of time-points on the accuracy and precision of the popPK model parameters. We accounted for specific study schedules and heterogeneity in participants' characteristics and study adherence patterns. We found that with m = 120, reasonably unbiased and consistent estimates of most fixed and random effect terms could be obtained without complete sampling of all 22 time-points, even under low study adherence (about half of the 4-weekly visits missing per participant). The described simulation framework is not only novel in its application to popPK sampling design for studying correlates of prevention efficacy in a subcohort of the parent trial, but also flexible in accommodating real-life study setup options, and can be generalized to other single- or multiple-dose PK sampling design settings.},
}
@article {pmid36683573,
year = {2023},
author = {Santiago-Torres, M and Mull, KE and Sullivan, BM and Rigotti, NA and Bricker, JB},
title = {Acceptance and Commitment Therapy-Based Smartphone Applications for Cessation of Tobacco Use among Adults with High Nicotine Dependence: Results from the iCanQuit Randomized Trial.},
journal = {Substance use &amp; misuse},
volume = {},
number = {},
pages = {1-11},
doi = {10.1080/10826084.2022.2161317},
pmid = {36683573},
issn = {1532-2491},
abstract = {Background: With 1 in 2 adult tobacco users being highly dependent on nicotine, population-based interventions specifically designed for this group are urgently needed. This study used data from a randomized trial to evaluate whether (1) Acceptance and Commitment Therapy (ACT) delivered via a smartphone application (iCanQuit) would be more efficacious for cessation of nicotine-containing tobacco products than the US Clinical Practice Guidelines (USCPG)-based application (QuitGuide) among highly nicotine-dependent adults, (2) the effect of treatment on cessation was mediated by increases in acceptance of cravings to smoke, and (3) treatment utilization and satisfaction differed by arm. Methods: A total of 1452 highly nicotine-dependent adults received the iCanQuit or QuitGuide application for 12-months. Cessation outcomes were self-reported complete-case 30-day abstinence of nicotine-containing tobacco products (e.g., combustible cigarettes, e-cigarettes, chewing tobacco, snus, hookahs, cigars, cigarillos, tobacco pipes, and kreteks) at 3, 6, and 12-month post-randomization timepoints, missing-as-smoking, and multiple imputation analyses. Acceptance of cues to smoke and satisfaction with the applications was also reported. Results: Participants who received iCanQuit were significantly more likely to report 30-day abstinence of nicotine-containing tobacco products than those who received QuitGuide at 12-months (24% vs. 17%; OR = 1.47 95% CI: 1.11, 1.95). iCanQuit participants utilized their application more frequently and reported greater satisfaction than those who received QuitGuide. Increases in participants' acceptance of cues to smoke mediated the intervention effect on cessation of nicotine-containing tobacco products. Conclusions: Among nicotine-dependent adults, an application-delivered ACT-based intervention was more engaging and efficacious than a USCPG-based intervention for cessation of nicotine-containing tobacco products.},
}
@article {pmid36682490,
year = {2023},
author = {Bricker, JB and Mull, KE and Sullivan, BM and Forman, EM and Lillis, J and McTiernan, A and Santiago-Torres, M},
title = {Telehealth acceptance and commitment therapy for weight loss: Protocol of the WeLNES full scale randomized controlled trial.},
journal = {Contemporary clinical trials},
volume = {},
number = {},
pages = {107091},
doi = {10.1016/j.cct.2023.107091},
pmid = {36682490},
issn = {1559-2030},
abstract = {Behavioral interventions delivered via one-on-one telephone coaching (hereafter referred to as telehealth) for weight loss have had great population-level reach but to date limited efficacy. Acceptance and Commitment Therapy (ACT) has promise to improve behavioral weight loss treatment efficacy by addressing the fundamental challenges of weight loss and maintenance: overeating in response to internal (stress) and external (high calorie foods) cues. Here we describe the Weight Loss, Nutrition, and Exercise Study (WeLNES) randomized controlled trial that is testing the efficacy of an ACT-based telehealth coaching intervention for weight loss in comparison to a Standard Behavioral Therapy (SBT)-based telehealth coaching intervention. A total of 398 adults with overweight or obesity are being recruited and randomized to either ACT or SBT telehealth coaching. Participants in both arms are offered twenty-five telehealth coaching sessions in year one and nine booster sessions in year two. All participants receive a Bluetooth-enabled scale to self-monitor weight and a Fitbit Inspire + Fitbit app for tracking diet and physical activity. The primary aim is to determine whether a greater proportion of ACT participants will achieve a clinically significant weight loss of ≥10% compared with SBT participants at 12-months. Secondary outcomes include change in weight from baseline to 6, 12, and 24-months. Whether the effect of ACT on weight loss is mediated by ACT processes and is moderated by baseline factors will also be examined. If ACT proves efficacious, ACT telehealth coaching will offer an effective, broadly scalable weight loss treatment-thereby making a high public health impact.},
}
@article {pmid36681479,
year = {2023},
author = {Morgan, C and Nayak, A and Hosoya, N and Smith, GR and Lambing, C},
title = {Meiotic chromosome organization and its role in recombination and cancer.},
journal = {Current topics in developmental biology},
volume = {151},
number = {},
pages = {91-126},
doi = {10.1016/bs.ctdb.2022.04.008},
pmid = {36681479},
issn = {1557-8933},
abstract = {Chromosomes adopt specific conformations to regulate various cellular processes. A well-documented chromosome configuration is the highly compacted chromosome structure during metaphase. More regional chromatin conformations have also been reported, including topologically associated domains encompassing mega-bases of DNA and local chromatin loops formed by kilo-bases of DNA. In this review, we discuss the changes in chromatin conformation taking place between somatic and meiotic cells, with a special focus on the establishment of a proteinaceous structure, called the chromosome axis, at the beginning of meiosis. The chromosome axis is essential to support key meiotic processes such as chromosome pairing, homologous recombination, and balanced chromosome segregation to transition from a diploid to a haploid stage. We review the role of the chromosome axis in meiotic chromatin organization and provide a detailed description of its protein composition. We also review the conserved and distinct roles between species of axis proteins in meiotic recombination, which is a major factor contributing to the creation of genetic diversity and genome evolution. Finally, we discuss situations where the chromosome axis is deregulated and evaluate the effects on genome integrity and the consequences from protein deregulation in meiocytes exposed to heat stress, and aberrant expression of genes encoding axis proteins in mammalian somatic cells associated with certain types of cancers.},
}
@article {pmid36681471,
year = {2023},
author = {Chuang, YC and Smith, GR},
title = {Meiotic crossover interference: Methods of analysis and mechanisms of action.},
journal = {Current topics in developmental biology},
volume = {151},
number = {},
pages = {217-244},
doi = {10.1016/bs.ctdb.2022.04.006},
pmid = {36681471},
issn = {1557-8933},
abstract = {Segregation of chromosomes during meiosis, to form haploid gametes from diploid precursor cells, requires in most species formation of crossovers physically connecting homologous chromosomes. Along with sister chromatid cohesion, crossovers allow tension to be generated when chromosomes begin to segregate; tension signals that chromosome movement is proceeding properly. But crossovers too close to each other might result in less sister chromatid cohesion and tension and thus failed meiosis. Interference describes the non-random distribution of crossovers, which occur farther apart than expected from independence. We discuss both genetic and cytological methods of assaying crossover interference and models for interference, whose molecular mechanism remains to be elucidated. We note marked differences among species.},
}
@article {pmid36681151,
year = {2023},
author = {Kourelis, T and Bansal, R and Berdeja, J and Siegel, D and Patel, K and Mailankody, S and Htut, M and Shah, N and Wong, SW and Sidana, S and Cowan, AJ and Alsina, M and Cohen, A and Holstein, SA and Bergsagel, L and Ailawadhi, S and Raje, N and Dhakal, B and Rossi, A and Lin, Y},
title = {Ethical challenges with multiple myeloma BCMA CAR-T slot allocation: a multi-institution experience.},
journal = {Transplantation and cellular therapy},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jtct.2023.01.012},
pmid = {36681151},
issn = {2666-6367},
abstract = {CAR T cell therapies are FDA approved for patients with triple refractory multiple myeloma (MM). Real-world access to CAR T remains challenging due to supply chain limitations impacting manufacturing. The goal of this study was to evaluate the extent of this issue and how major centers are handling the challenges of CART manufacturing slot allocation. MM CAR T physician leaders at each CART treatment center across the US were surveyed. We received response from 17/20 centers. A median of one slot is allocated per month per center and the median number of patients per center on the waitlist since ide-cel approval was 20 (range 5-100). As a result, patients remained on the waitlist for a median of 6 months prior to leukapheresis (range 2-8). For patient selection, all centers reported using a committee of experienced CART physicians to ensure consistency. To ensure transparency, 15 centers make selection criteria, selection timeline and priority score readily available for CAR-T providers. Centers also reported using ethical values for selection: a) equal treatment: time spent on waiting list (n=12); b) priority to the worst-off: limited therapeutic options (n=14), MM burden (n=11), high comorbidity index (n=5); c) maximize benefit: most likely to complete apheresis (n=13) or infusion (n=13) or achieve response (n=8) and d) social value: younger pts (n=3). Maximizing benefit was considered the most important criterion by 10 centers. Our study is the first attempt to evaluate existing issues with MM CAR T access and the variability and challenges in patient selection. Integrating ethical resource allocation strategies, similar to the ones described here, into formal institutional policies would help streamline CAR-T access and protect the needs of both current and future patients and physicians.},
}
@article {pmid36681010,
year = {2023},
author = {Johnson, AM and Teoh, D and Jewett, P and Darst, BF and Mattson, J and Hoffmann, C and Brown, K and Makaram, A and Keller, C and Blaes, AH and Everson-Rose, SA and Vogel, RI},
title = {Genetic variants associated with post-traumatic stress symptoms in patients with gynecologic cancer.},
journal = {Gynecologic oncology},
volume = {170},
number = {},
pages = {102-107},
doi = {10.1016/j.ygyno.2023.01.006},
pmid = {36681010},
issn = {1095-6859},
abstract = {OBJECTIVE: Patients with cancer experience symptoms of post-traumatic stress disorder (PTSD) more commonly than the general population. The objective of this study was to identify single nucleotide polymorphisms (SNPs) associated with increased risk of post-traumatic stress disorder (PTSD) in patients with gynecologic cancer.<br><br>METHODS: A prospective cohort study recruited 181 gynecologic cancer survivors receiving care at the University of Minnesota between 2017 and 2020 who completed PTSD DSM-V surveys to self-report their symptoms of PTSD and provided saliva samples. DNA samples were genotyped for 11 SNPs in 9 genes involved in dopaminergic, serotonergic, and opioidergic systems previously associated with risk of PTSD in populations without cancer.<br><br>RESULTS: Most participants had either ovarian (42.5%) or endometrial (46.4%) cancer; fewer had cervical (7.7%) or vaginal/vulvar (3.3%) cancer. Two SNPS were identified as statistically significantly associated with higher PTSD scores: rs622337 in HTR2A and rs510769 in OPRM1.<br><br>CONCLUSIONS: Genetic variation likely plays a role in development of PTSD. HTR2A is involved in the serotonin pathway, and OPRM1 is involved in the opioid receptor pathway. This information can be used by oncologic providers to identify patients at greater risk of developing PTSD and may facilitate referral to appropriate consultants and resources early in their treatment.},
}
@article {pmid36681001,
year = {2023},
author = {Abraham, A and Barcenas, CH and Bleicher, RJ and Cohen, AL and Javid, SH and Levine, EG and Lin, NU and Moy, B and Niland, JC and Wolff, AC and Hassett, MJ and Asad, S and Stover, DG},
title = {Clinicopathologic and sociodemographic factors associated with late relapse triple negative breast cancer in a multivariable logistic model: A multi-institution cohort study.},
journal = {Breast (Edinburgh, Scotland)},
volume = {67},
number = {},
pages = {89-93},
doi = {10.1016/j.breast.2023.01.004},
pmid = {36681001},
issn = {1532-3080},
abstract = {BACKGROUND: Most metastatic recurrences of triple negative breast cancer (TNBC) occur within five years of diagnosis, yet late relapses of TNBC (lrTNBC) do occur. Our objective was to develop a risk prediction model of lrTNBC using readily available clinicopathologic and sociodemographic features.<br><br>METHODS: We included patients diagnosed with stage I-III TNBC between 1998 and 2012&#xa0;at ten academic cancer centers. lrTNBC was defined as relapse or mortality greater than 5 years from diagnosis. Features associated with lrTNBC were included in a multivariable logistic model using backward elimination with a p&#xa0;<&#xa0;0.10 criterion, with a final multivariable model applied to training (70%) and independent validation (30%) cohorts.<br><br>RESULTS: A total 2210&#xa0;TNBC patients with at least five years follow-up and no relapse before 5 years were included. In final multivariable model, lrTNBC was significantly associated with higher stage at diagnosis (adjusted Odds Ratio [aOR] for stage III vs I, 10.9; 95% Confidence Interval [CI], 7.5-15.9; p&#xa0;<&#xa0;0.0001) and BMI (aOR for obese vs normal weight, 1.4; 95% CI, 1.0-1.8; p&#xa0;=&#xa0;0.03). Final model performance was consistent between training (70%) and validation (30%) cohorts.<br><br>CONCLUSIONS: A risk prediction model incorporating stage, BMI, and age at diagnosis offers potential utility for identification of patients at risk of development of lrTNBC and warrants further investigation.},
}
@article {pmid36679852,
year = {2022},
author = {Goldman, JD and Wang, K and Röltgen, K and Nielsen, SCA and Roach, JC and Naccache, SN and Yang, F and Wirz, OF and Yost, KE and Lee, JY and Chun, K and Wrin, T and Petropoulos, CJ and Lee, I and Fallen, S and Manner, PM and Wallick, JA and Algren, HA and Murray, KM and Hadlock, J and Chen, D and Dai, CL and Yuan, D and Su, Y and Jeharajah, J and Berrington, WR and Pappas, GP and Nyatsatsang, ST and Greninger, AL and Satpathy, AT and Pauk, JS and Boyd, SD and Heath, JR},
title = {Reinfection with SARS-CoV-2 and Waning Humoral Immunity: A Case Report.},
journal = {Vaccines},
volume = {11},
number = {1},
pages = {},
doi = {10.3390/vaccines11010005},
pmid = {36679852},
issn = {2076-393X},
abstract = {Recovery from COVID-19 is associated with production of anti-SARS-CoV-2 antibodies, but it is uncertain whether these confer immunity. We describe viral RNA shedding duration in hospitalized patients and identify patients with recurrent shedding. We sequenced viruses from two distinct episodes of symptomatic COVID-19 separated by 144 days in a single patient, to conclusively describe reinfection with a different strain harboring the spike variant D614G. This case of reinfection was one of the first cases of reinfection reported in 2020. With antibody, B cell and T cell analytics, we show correlates of adaptive immunity at reinfection, including a differential response in neutralizing antibodies to a D614G pseudovirus. Finally, we discuss implications for vaccine programs and begin to define benchmarks for protection against reinfection from SARS-CoV-2.},
}
@article {pmid36672803,
year = {2022},
author = {Xu, H and Nguyen, K and Gaynor, BJ and Ling, H and Zhao, W and McArdle, PF and O'Connor, TD and Stine, OC and Ryan, KA and Lynch, M and Smith, JA and Faul, JD and Hu, Y and Haessler, JW and Fornage, M and Kooperberg, C and On Behalf Of The Trans-Omics For Precision Medicine TOPMed Stroke Working Group, and Perry, JA and Hong, CC and Cole, JW and Pugh, E and Doheny, K and Kardia, SLR and Weir, DR and Kittner, SJ and Mitchell, BD and , },
title = {Exome Array Analysis of 9721 Ischemic Stroke Cases from the SiGN Consortium.},
journal = {Genes},
volume = {14},
number = {1},
pages = {},
doi = {10.3390/genes14010061},
pmid = {36672803},
issn = {2073-4425},
support = {R01 NS105150, R01 NS100178, R01NS114045/NH/NIH HHS/United States ; },
abstract = {Recent genome wide association studies have identified 89 common genetic variants robustly associated with ischemic stroke and primarily located in non-coding regions. To evaluate the contribution of coding variants, which are mostly rare, we performed an exome array analysis on 106,101 SNPs for 9721 ischemic stroke cases from the SiGN Consortium, and 12,345 subjects with no history of stroke from the Health Retirement Study and SiGN consortium. We identified 15 coding variants significantly associated with all ischemic stroke at array-wide threshold (i.e., p < 4.7 × 10[-7]), including two common SNPs in ABO that have previously been associated with stroke. Twelve of the remaining 13 variants were extremely rare in European Caucasians (MAF < 0.1%) and the associations were driven by African American samples. There was no evidence for replication of these associations in either TOPMed Stroke samples (n = 5613 cases) or UK Biobank (n = 5874 stroke cases), although power to replicate was very low given the low allele frequencies of the associated variants and a shortage of samples from diverse ancestries. Our study highlights the need for acquiring large, well-powered diverse cohorts to study rare variants, and the technical challenges using array-based genotyping technologies for rare variant genotyping.},
}
@article {pmid36672303,
year = {2023},
author = {Orvain, C and Rodríguez-Arbolí, E and Othus, M and Sandmaier, BM and Deeg, HJ and Appelbaum, FR and Walter, RB},
title = {Association between Prior Cytotoxic Therapy, Antecedent Hematologic Disorder, and Outcome after Allogeneic Hematopoietic Cell Transplantation in Adult Acute Myeloid Leukemia.},
journal = {Cancers},
volume = {15},
number = {2},
pages = {},
doi = {10.3390/cancers15020352},
pmid = {36672303},
issn = {2072-6694},
abstract = {(1) Background: Secondary acute myeloid leukemia (AML), i.e., AML arising from prior therapy (therapy-related) and/or an antecedent hematologic disorder (AHD) is generally associated with worse outcomes compared to de novo AML. However, recognizing the prognostic importance of genetic characteristics rather than clinical history, secondary AML is now considered a diagnostic qualifier rather than a separate disease entity. (2) Methods: To assess the association between clinical history and AML outcomes in the context of allogeneic hematopoietic cell transplantation (HCT), we retrospectively analyzed 759 patients with de novo AML, 115 with AHD AML, and 105 with therapy-related AML who received first allografts while in first or second remission. (3) Results: At the time of HCT, these three cohorts differed significantly regarding many patient and disease-specific characteristics, including age (p < 0.001), gender (p < 0.001), disease risk (p = 0.005), HCT-CI score (p < 0.001), blood count recovery (p = 0.003), first vs. second remission (p < 0.001), remission duration (p < 0.001), measurable residual disease (MRD; p < 0.001), and conditioning intensity (p < 0.001). Relative to patients with de novo AML, relapse rates were similar for patients with AHD (hazard ratio [HR] = 1.07, p = 0.7) and therapy-related AML (HR = 0.86, p = 0.4) after multivariable adjustment, as were relapse-free survival (HR = 1.20, p = 0.2, and HR = 0.89, p = 0.5) and overall survival (HR = 1.19, p = 0.2, and HR = 0.93, p = 0.6). Non-relapse mortality was higher for AHD AML (HR = 1.59, p = 0.047). (4) Conclusions: These data suggest that the clinical history by itself contains limited prognostic value for adults with AML undergoing allografting, supporting the most recent approach to use this information as a diagnostic qualifier rather than a disease entity.},
}
@article {pmid36669148,
year = {2023},
author = {Chow, EJ and Aggarwal, S and Doody, DR and Aplenc, R and Armenian, SH and Baker, KS and Bhatia, S and Blythe, N and Colan, SD and Constine, LS and Freyer, DR and Kopp, LM and Laverdière, C and Leisenring, WM and Sasaki, N and Vrooman, LM and Asselin, BL and Schwartz, CL and Lipshultz, SE},
title = {Dexrazoxane and Long-Term Heart Function in Survivors of Childhood Cancer.},
journal = {Journal of clinical oncology : official journal of the American Society of Clinical Oncology},
volume = {},
number = {},
pages = {JCO2202423},
doi = {10.1200/JCO.22.02423},
pmid = {36669148},
issn = {1527-7755},
abstract = {PURPOSE: For survivors of childhood cancer treated with doxorubicin, dexrazoxane is cardioprotective for at least 5 years. However, longer-term data are lacking.<br><br>METHODS: Within the Children's Oncology Group and the Dana Farber Cancer Institute's Childhood Acute Lymphoblastic Leukemia Consortium, we evaluated four randomized trials of children with acute lymphoblastic leukemia or Hodgkin lymphoma, who received doxorubicin with or without dexrazoxane, and a nonrandomized trial of patients with osteosarcoma who all received doxorubicin with dexrazoxane. Cumulative doxorubicin doses ranged from 100 to 600 mg/m[2] across these five trials, and dexrazoxane was administered uniformly (10:1 mg/m[2] ratio) as an intravenous bolus before doxorubicin. Cardiac function was prospectively assessed in survivors from these trials, plus a matched group of survivors of osteosarcoma treated with doxorubicin without dexrazoxane. Two-dimensional echocardiograms and blood biomarkers were analyzed centrally in blinded fashion. Multivariate analyses adjusted for demographic characteristics, cumulative doxorubicin dose, and chest radiotherapy determined the differences and associations by dexrazoxane status.<br><br>RESULTS: From 49 participating institutions, 195 participants were assessed at 18.1 &#xb1; 2.7 years since cancer diagnosis (51% dexrazoxane-exposed; cumulative doxorubicin dose 297 &#xb1; 91 mg/m[2]). Dexrazoxane administration was associated with superior left ventricular fractional shortening (absolute difference, +1.4% [95% CI, 0.3 to 2.5]) and ejection fraction (absolute difference, +1.6% [95% CI, 0.0 to 3.2]), and lower myocardial stress per B-type natriuretic peptide (-6.7 pg/mL [95% CI, -10.6 to -2.8]). Dexrazoxane was associated with a reduced risk of having lower left ventricular function (fractional shortening < 30% or ejection fraction < 50%; odds ratio, 0.24 [95% CI, 0.07 to 0.81]). This protective association was primarily seen in those treated with cumulative doxorubicin doses &#x2265; 250 mg/m[2].<br><br>CONCLUSION: Among young adult-aged survivors of childhood cancer, dexrazoxane was associated with a cardioprotective effect nearly 20 years after initial anthracycline exposure.},
}
@article {pmid36669145,
year = {2023},
author = {Crivello, P and Arrieta-Bolaños, E and He, M and Wang, T and Fingerson, S and Gadalla, SM and Paczesny, S and Marsh, SGE and Lee, SJ and Spellman, SR and Bolon, YT and Fleischhauer, K},
title = {Impact of the HLA Immunopeptidome on Survival of Leukemia Patients After Unrelated Donor Transplantation.},
journal = {Journal of clinical oncology : official journal of the American Society of Clinical Oncology},
volume = {},
number = {},
pages = {JCO2201229},
doi = {10.1200/JCO.22.01229},
pmid = {36669145},
issn = {1527-7755},
abstract = {PURPOSE: Immunopeptidome divergence between mismatched HLA-DP is a determinant of T-cell alloreactivity and clinical tolerability after fully HLA-A, -B, -C, -DRB1, -DQB1 matched unrelated donor hematopoietic cell transplantation (UD-HCT). Here, we tested this concept in HLA-A, -B, and -C disparities after single class I HLA-mismatched UD-HCT.<br><br>PATIENTS AND METHODS: We studied 2,391 single class I HLA-mismatched and 14,426 fully HLA-matched UD-HCT performed between 2008 and 2018 for acute leukemia or myelodysplastic syndromes. Hierarchical clustering of experimentally determined peptide-binding motifs (PBM) was used as a proxy for immunopeptidome divergence of HLA-A, -B, or -C disparities, allowing us to classify 1,629/2,391 (68.1%) of the HLA-mismatched UD-HCT as PBM-matched or PBM-mismatched. Risks associated with PBM-matching status were assessed by Cox proportional hazards models, with overall survival (OS) as the primary end point.<br><br>RESULTS: Relative to full matches, bidirectional or unidirectional PBM mismatches in graft-versus-host (GVH) direction (PBM-GVH mismatches, 60.7%) were associated with significantly lower OS (hazard ratio [HR], 1.48; P < .0001), while unidirectional PBM mismatches in host-versus-graft direction or PBM matches (PBM-GVH matches, 39.3%) were not (HR, 1.13; P = .1017). PBM-GVH mismatches also had significantly lower OS than PBM-GVH matches in direct comparison (HR, 1.32; P = .0036). The hazards for transplant-related mortality and acute and chronic graft-versus-host disease but not relapse increased stepwise from full HLA matches to single PBM-GVH matches, and single PBM-GVH mismatches. A webtool for PBM-matching of single class I HLA-mismatched donor-recipient pairs was developed.<br><br>CONCLUSION: PBM-GVH mismatches inform mortality risks after single class I HLA-mismatched UD-HCT, suggesting that prospective consideration of directional PBM-matching status might improve outcome. These findings highlight immunopeptidome divergence between mismatched HLA as a driver of clinical tolerability in UD-HCT.},
}
@article {pmid36410561,
year = {2022},
author = {Mehta, R and Ray, RM and Tussing-Humphreys, LM and Pasquale, LR and Maki, P and Haan, MN and Jackson, R and Vajaranant, TS},
title = {Effect of Low-Fat Dietary Modification on Incident Open-Angle Glaucoma.},
journal = {Ophthalmology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.ophtha.2022.11.014},
pmid = {36410561},
issn = {1549-4713},
abstract = {PURPOSE: We tested whether dietary modification (DM) altered the risk for incident primary open-angle glaucoma (POAG).<br><br>DESIGN: Secondary analysis of a randomized intervention trial.<br><br>PARTICIPANTS: We linked Medicare claims data to 45 203 women in the Women's Health Initiative Dietary Modification Trial, of which 23 776 participants were enrolled in fee-for-service Medicare Part B and had physician claims.<br><br>METHODS: Women were randomized to follow either DM (a low-fat diet, with increased vegetable, fruit, and grain intake) or their usual diet without modification. Nine thousand three hundred forty women were randomized to the DM intervention, whereas 13 877 women were randomized to the control group. Our analyses were based on an intention-to-treat design, with a follow-up to the end of continuous Medicare coverage, death, or the last clams date (12/31/2018), whichever occurred first. Primary open-angle glaucoma was defined as the first claim with the International Classification of Diseases, Ninth or Tenth Revision, codes. Dietary data were assessed using a food frequency questionnaire.<br><br>MAIN OUTCOME MEASURES: We used Cox proportional hazards models to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for risk of POAG. Subgroup analyses were performed with P values for interaction.<br><br>RESULTS: After exclusion of women with Medicare-derived glaucoma before randomization, the final analysis included 23 217 women (mean age, 64.4 &#xb1; 5.8 years). Baseline characteristics were balanced between the intervention and control groups. Primary open-angle glaucoma incidence was 11.1 per 1000 woman-years (mean follow-up, 11.6 &#xb1; 7.4 years; mean DM duration, 5.2 &#xb1; 3.2 years). We found no overall benefit of DM in reducing incident POAG (HR, 1.04; 95% CI, 0.96-1.12). Race and participant age did not modify this relation (P = 0.08 and P = 0.24 for interaction, respectively). In further analysis of baseline nutrient and food intake stratified by quartile groups, risk of open-angle glaucoma (OAG) in DM participants in the lowest quartile group for percentage calories (kilocalories) from total fat (33.8 or lower) was increased (HR, 1.22; 95% CI, 1.05-1.41; P = 0.007 for interaction).<br><br>CONCLUSIONS: Analysis suggests that DM in participants in the lowest quartile group for percentage calories from total fat at baseline increased the risk of incident OAG among women regardless of age or race.<br><br>FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.},
}
@article {pmid36662819,
year = {2023},
author = {Meric-Bernstam, F and Ford, JM and O'Dwyer, PJ and Shapiro, GI and McShane, LM and Freidlin, B and O'Cearbhaill, RE and George, S and Glade Bender, J and Lyman, GH and Tricoli, JV and Patton, D and Hamilton, SR and Gray, RJ and Hawkins, DS and Ramineni, B and Flaherty, KT and Grivas, P and Yap, TA and Berlin, J and Doroshow, JH and Harris, LN and Moscow, JA},
title = {National Cancer Institute Combination Therapy Platform Trial with Molecular Analysis for Therapy Choice (ComboMATCH).},
journal = {Clinical cancer research : an official journal of the American Association for Cancer Research},
volume = {},
number = {},
pages = {},
doi = {10.1158/1078-0432.CCR-22-3334},
pmid = {36662819},
issn = {1557-3265},
abstract = {Over the past decade, multiple trials, including the precision medicine trial NCI-MATCH (National Cancer Institute-Molecular Analysis for Therapy Choice, EAY131, NCT02465060) have sought to determine if treating cancer based on specific genomic alterations is effective, irrespective of the cancer histology. Although many therapies are now approved for the treatment of cancers harboring specific genomic alterations, most patients do not respond to therapies targeting a single alteration. Further, when antitumor responses do occur, they are often not durable due to the development of drug resistance. Therefore, there is a great need to identify rational combination therapies that may be more effective. To address this need, the National Cancer Institute (NCI) and National Clinical Trials Network have developed NCI-ComboMATCH, the successor to NCI-MATCH. Like the original trial, NCI-ComboMATCH is a signal-seeking study. The goal of ComboMATCH is to overcome drug resistance to single-agent therapy and/or utilize novel synergies to increase efficacy by developing genomically-directed combination therapies, supported by strong preclinical in vivo evidence. While NCI-MATCH was mainly comprised of multiple single-arm studies, NCI-ComboMATCH tests combination therapy, evaluating both combination of targeted agents as well as combinations of targeted therapy with chemotherapy. While NCI-MATCH was histology agnostic with selected tumor exclusions, ComboMATCH has histology-specific and histology-agnostic arms. While NCI-MATCH consisted of single arm studies, ComboMATCH utilizes single-arm as well as randomized designs. NCI-MATCH had a separate, parallel Pediatric MATCH trial, whereas ComboMATCH will include children within the same trial. We present rationale, scientific principles, study design and logistics supporting the ComboMATCH study.},
}
@article {pmid36662550,
year = {2023},
author = {Bricker, J and Miao, Z and Mull, K and Santiago-Torres, M and Vock, DM},
title = {Can a Single Variable Predict Early Dropout From Digital Health Interventions? Comparison of Predictive Models From Two Large Randomized Trials.},
journal = {Journal of medical Internet research},
volume = {25},
number = {},
pages = {e43629},
doi = {10.2196/43629},
pmid = {36662550},
issn = {1438-8871},
abstract = {BACKGROUND: A single generalizable metric that accurately predicts early dropout from digital health interventions has the potential to readily inform intervention targets and treatment augmentations that could boost retention and intervention outcomes. We recently identified a type of early dropout from digital health interventions for smoking cessation, specifically, users who logged in during the first week of the intervention and had little to no activity thereafter. These users also had a substantially lower smoking cessation rate with our iCanQuit smoking cessation app compared with users who used the app for longer periods.<br><br>OBJECTIVE: This study aimed to explore whether log-in count data, using standard statistical methods, can precisely predict whether an individual will become an iCanQuit early dropout while validating the approach using other statistical methods and randomized trial data from 3 other digital interventions for smoking cessation (combined randomized N=4529).<br><br>METHODS: Standard logistic regression models were used to predict early dropouts for individuals receiving the iCanQuit smoking cessation intervention app, the National Cancer Institute QuitGuide smoking cessation intervention app, the WebQuit.org smoking cessation intervention website, and the Smokefree.gov smoking cessation intervention website. The main predictors were the number of times a participant logged in per day during the first 7 days following randomization. The area under the curve (AUC) assessed the performance of the logistic regression models, which were compared with decision trees, support vector machine, and neural network models. We also examined whether 13 baseline variables that included a variety of demographics (eg, race and ethnicity, gender, and age) and smoking characteristics (eg, use of e-cigarettes and confidence in being smoke free) might improve this prediction.<br><br>RESULTS: The AUC for each logistic regression model using only the first 7 days of log-in count variables was 0.94 (95% CI 0.90-0.97) for iCanQuit, 0.88 (95% CI 0.83-0.93) for QuitGuide, 0.85 (95% CI 0.80-0.88) for WebQuit.org, and 0.60 (95% CI 0.54-0.66) for Smokefree.gov. Replacing logistic regression models with more complex decision trees, support vector machines, or neural network models did not significantly increase the AUC, nor did including additional baseline variables as predictors. The sensitivity and specificity were generally good, and they were excellent for iCanQuit (ie, 0.91 and 0.85, respectively, at the 0.5 classification threshold).<br><br>CONCLUSIONS: Logistic regression models using only the first 7 days of log-in count data were generally good at predicting early dropouts. These models performed well when using simple, automated, and readily available log-in count data, whereas including self-reported baseline variables did not improve the prediction. The results will inform the early identification of people at risk of early dropout from digital health interventions with the goal of intervening further by providing them with augmented treatments to increase their retention and, ultimately, their intervention outcomes.},
}
@article {pmid36661395,
year = {2023},
author = {Bradley, P},
title = {Structure-based prediction of T cell receptor:peptide-MHC interactions.},
journal = {eLife},
volume = {12},
number = {},
pages = {},
doi = {10.7554/eLife.82813},
pmid = {36661395},
issn = {2050-084X},
support = {R35 GM141457/NH/NIH HHS/United States ; R01 AI136514/NH/NIH HHS/United States ; },
abstract = {The regulatory and effector functions of T cells are initiated by the binding of their cell-surface T cell receptor (TCR) to peptides presented by major histocompatibility complex (MHC) proteins on other cells. The specificity of TCR:peptide-MHC interactions, thus, underlies nearly all adaptive immune responses. Despite intense interest, generalizable predictive models of TCR:peptide-MHC specificity remain out of reach; two key barriers are the diversity of TCR recognition modes and the paucity of training data. Inspired by recent breakthroughs in protein structure prediction achieved by deep neural networks, we evaluated structural modeling as a potential avenue for prediction of TCR epitope specificity. We show that a specialized version of the neural network predictor AlphaFold can generate models of TCR:peptide-MHC interactions that can be used to discriminate correct from incorrect peptide epitopes with substantial accuracy. Although much work remains to be done for these predictions to have widespread practical utility, we are optimistic that deep learning-based structural modeling represents a path to generalizable prediction of TCR:peptide-MHC interaction specificity.},
}
@article {pmid36661332,
year = {2023},
author = {Gornalusse, G and Spengler, RM and Sandford, E and Kim, Y and Levy, C and Tewari, M and Hladik, F and Vojtech, L},
title = {Men who inject opioids exhibit altered tRNA-Gly-GCC isoforms in semen.},
journal = {Molecular human reproduction},
volume = {},
number = {},
pages = {},
doi = {10.1093/molehr/gaad003},
pmid = {36661332},
issn = {1460-2407},
abstract = {In addition to their role in protein translation, tRNAs can be cleaved into shorter, biologically active fragments called tRFs. Specific tRFs from spermatocytes can propagate metabolic disorders in second generations of mice. Thus, tRFs in germline cells are a mechanism of epigenetic inheritance. It has also been shown that stress and toxins can cause alterations in tRF patterns. We were therefore interested in whether injecting illicit drugs, a major stressor, impacts tRFs in germline cells. We sequenced RNA from spermatocytes and from semen-derived exosomes from people who inject illicit drugs (PWID) and from non-drug using controls, both groups of unknown fertility status. All PWID injected opioids daily, but most also used other illicit drugs. The tRF cleavage products from Gly-GCC tRNA were markedly different between spermatocytes from PWID compared to controls. Over 90% of reads in controls mapped to shorter Gly-GCC tRFs, while in PWID only 45% did. In contrast, only 4.1% of reads in controls mapped to a longer tRFs versus 45.6% in PWID. The long/short tRF ratio was significantly higher in PWID than controls (0.23 versus 0.16, p = 0.0128). We also report differential expression of a group of small nucleolar RNAs in semen-derived exosomes, including, among others, ACA14a, U19 and U3-3. Thus, PWID exhibited an altered cleavage pattern of tRNA-Gly-GCC in spermatocytes and an altered cargo of snoRNAs in semen-derived exosomes. Participants were not exclusively using opioids and were not matched with controls in terms of diet, chronic disease, or other stressors, so our finding are not conclusively linked to opioid use. However, all individuals in the PWID group did inject heroin daily. Our study indicates a potential for opioid injection and/or its associated multi-drug use habits and lifestyle changes to influence epigenetic inheritance.},
}
@article {pmid36658484,
year = {2023},
author = {Song, H and Ling, W and Zhao, N and Plantinga, AM and Broedlow, CA and Klatt, NR and Hensley-McBain, T and Wu, MC},
title = {Accommodating multiple potential normalizations in microbiome associations studies.},
journal = {BMC bioinformatics},
volume = {24},
number = {1},
pages = {22},
pmid = {36658484},
issn = {1471-2105},
support = {R01 GM129512, R01 HL155417/NH/NIH HHS/United States ; },
abstract = {Microbial communities are known to be closely related to many diseases, such as obesity and HIV, and it is of interest to identify differentially abundant microbial species between two or more environments. Since the abundances or counts of microbial species usually have different scales and suffer from zero-inflation or over-dispersion, normalization is a critical step before conducting differential abundance analysis. Several normalization approaches have been proposed, but it is difficult to optimize the characterization of the true relationship between taxa and interesting outcomes. RESULTS: To avoid the challenge of picking an optimal normalization and accommodate the advantages of several normalization strategies, we propose an omnibus approach. Our approach is based on a Cauchy combination test, which is flexible and powerful by aggregating individual p values. We also consider a truncated test statistic to prevent substantial power loss. We experiment with a basic linear regression model as well as recently proposed powerful association tests for microbiome data and compare the performance of the omnibus approach with individual normalization approaches. Experimental results show that, regardless of simulation settings, the new approach exhibits power that is close to the best normalization strategy, while controling the type I error well. CONCLUSIONS: The proposed omnibus test releases researchers from choosing among various normalization methods and it is an aggregated method that provides the powerful result to the underlying optimal normalization, which requires tedious trial and error. While the power may not exceed the best normalization, it is always much better than using a poor choice of normalization.},
}
@article {pmid36658109,
year = {2023},
author = {Fong, Y and Huang, Y and Benkeser, D and Carpp, LN and Áñez, G and Woo, W and McGarry, A and Dunkle, LM and Cho, I and Houchens, CR and Martins, K and Jayashankar, L and Castellino, F and Petropoulos, CJ and Leith, A and Haugaard, D and Webb, B and Lu, Y and Yu, C and Borate, B and van der Laan, LWP and Hejazi, NS and Randhawa, AK and Andrasik, MP and Kublin, JG and Hutter, J and Keshtkar-Jahromi, M and Beresnev, TH and Corey, L and Neuzil, KM and Follmann, D and Ake, JA and Gay, CL and Kotloff, KL and Koup, RA and Donis, RO and Gilbert, PB and , and , and , },
title = {Immune correlates analysis of the PREVENT-19 COVID-19 vaccine efficacy clinical trial.},
journal = {Nature communications},
volume = {14},
number = {1},
pages = {331},
pmid = {36658109},
issn = {2041-1723},
abstract = {In the PREVENT-19 phase 3 trial of the NVX-CoV2373 vaccine (NCT04611802), anti-spike binding IgG concentration (spike IgG), anti-RBD binding IgG concentration (RBD IgG), and pseudovirus 50% neutralizing antibody titer (nAb ID50) measured two weeks post-dose two are assessed as correlates of risk and as correlates of protection against COVID-19. Analyses are conducted in the U.S. cohort of baseline SARS-CoV-2 negative per-protocol participants using a case-cohort design that measures the markers from all 12 vaccine recipient breakthrough COVID-19 cases starting 7 days post antibody measurement and from 639 vaccine recipient non-cases. All markers are inversely associated with COVID-19 risk and directly associated with vaccine efficacy. In vaccine recipients with nAb ID50 titers of 50, 100, and 7230 international units (IU50)/ml, vaccine efficacy estimates are 75.7% (49.8%, 93.2%), 81.7% (66.3%, 93.2%), and 96.8% (88.3%, 99.3%). The results support potential cross-vaccine platform applications of these markers for guiding decisions about vaccine approval and use.},
}
@article {pmid36658009,
year = {2023},
author = {Wang, M and Tapia, K and Oluoch, LM and Micheni, M and Selke, S and Kiptinness, C and Chohan, B and Wald, A and Ngure, K and Mugo, NR and Roxby, AC},
title = {Adolescent Girls and Young Women in Kenya Demonstrate Rapid STI Incidence Following First Sex: Data From a Longitudinal Cohort.},
journal = {The Journal of adolescent health : official publication of the Society for Adolescent Medicine},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jadohealth.2022.10.026},
pmid = {36658009},
issn = {1879-1972},
abstract = {PURPOSE: Adolescent girls and young women (AGYW) are disproportionately affected by STIs. Observation of life course events can describe behavioral and biological factors associated with STI risk.<br><br>METHODS: Sexually inexperienced AGYW aged 16-20 years in Kenya were followed for five years. Quarterly visits assessed for C.&#xa0;trachomatis (CT), N.&#xa0;gonorrhea (GC), and T.&#xa0;vaginalis (TV), bacterial vaginosis (BV), HSV-2, and HIV. Sexual activity was self-reported but amended if incongruent with results from STI, pregnancy, or any other testing. Cox regression and Generalized Estimating Equation models were used to determine hazard ratios (HRs) and relative risks (RRs) of STI.<br><br>RESULTS: During follow-up, 293 of 400 participants reported sex, 163 AGYW experienced an STI, and 72 participants had multiple STIs. Among 163 participants that experienced an STI, there were a total of 259 visits where STIs were detected, 78% (n&#xa0;= 201) of which included CT. Cox regression found participants with BV had over two-fold higher risk of first STI acquisition (adjusted hazard ratio (aHR): 2.35; 95% confidence interval (CI) 1.43-3.88; p&#xa0;= .001). Increased risk for first STI episode was associated with a new partner (aHR: 3.16; 95% CI 1.59-6.28; p&#xa0;= .001). AGYW who did not disclose sexual activity had the highest risk (aHR: 3.60; 95% CI 1.93-6.70; p < .001). Condom use was low, with 21% reporting condom use with sex. GEE analysis of all STIs including incident, prevalent, and recurrent, confirmed these risk factors.<br><br>DISCUSSION: During the critical years after first sex, AGYW with BV, new sexual partners, and those who did not disclose sexual activity were at highest risk for STI events, especially CT.},
}
@article {pmid36656572,
year = {2023},
author = {Cespedes Feliciano, EM and Vasan, S and Luo, J and Binder, AM and Chlebowski, RT and Quesenberry, C and Banack, HR and Caan, BJ and Paskett, ED and Williams, GR and Barac, A and LaCroix, AZ and Peters, U and Reding, KW and Pan, K and Shadyab, AH and Qi, L and Anderson, GL},
title = {Long-term Trajectories of Physical Function Decline in Women With and Without Cancer.},
journal = {JAMA oncology},
volume = {},
number = {},
pages = {},
doi = {10.1001/jamaoncol.2022.6881},
pmid = {36656572},
issn = {2374-2445},
abstract = {IMPORTANCE: Patients with cancer experience acute declines in physical function, hypothesized to reflect accelerated aging driven by cancer-related symptoms and effects of cancer therapies. No study has examined long-term trajectories of physical function by cancer site, stage, or treatment compared with cancer-free controls.<br><br>OBJECTIVE: Examine trajectories of physical function a decade before and after cancer diagnosis among older survivors and cancer-free controls.<br><br>This prospective cohort study enrolled patients from 1993 to 1998 and followed up until December 2020. The Women's Health Initiative, a diverse cohort of postmenopausal women, included 9203 incident cancers (5989 breast, 1352 colorectal, 960 endometrial, and 902 lung) matched to up to 5 controls (n&#x2009;=&#x2009;45&#x202f;358) on age/year of enrollment and study arm.<br><br>EXPOSURES: Cancer diagnosis (site, stage, and treatment) via Medicare and medical records.<br><br>MAIN OUTCOMES AND MEASURES: Trajectories of self-reported physical function (RAND Short Form 36 [RAND-36] scale; range: 0-100, higher scores indicate superior physical function) estimated from linear mixed effects models with slope changes at diagnosis and 1-year after diagnosis.<br><br>RESULTS: This study included 9203 women with cancer and 45&#x202f;358 matched controls. For the women with cancer, the mean (SD) age at diagnosis was 73.0 (7.6) years. Prediagnosis, physical function declines of survivors with local cancers were similar to controls; after diagnosis, survivors experienced accelerated declines relative to controls, whose scores declined 1 to 2 points per year. Short-term declines in the year following diagnosis were most severe in women with regional disease (eg, -5.3 [95% CI, -6.4 to -4.3] points per year in regional vs -2.8 [95% CI, -3.4 to -2.3] for local breast cancer) or who received systemic therapy (eg, for local endometrial cancer, -7.9 [95% CI, -12.2 to -3.6] points per year with any chemotherapy; -3.1 [95% CI, -6.0 to -0.3] with radiation therapy alone; and -2.6 [95% CI, -4.2 to -1.0] with neither, respectively). While rates of physical function decline slowed in the later postdiagnosis period (eg, women with regional colorectal cancer declined -4.3 [95% CI, -5.9 to -2.6] points per year in the year following diagnosis vs -1.4 [95% CI, -1.7 to -1.0] points per year in the decade thereafter), survivors had estimated physical function significantly below that of age-matched controls 5 years after diagnosis.<br><br>CONCLUSIONS AND RELEVANCE: In this prospective cohort study, survivors of cancer experienced accelerated declines in physical function after diagnosis, and physical function remained below that of age-matched controls even years later. Patients with cancer may benefit from supportive interventions to preserve physical functioning.},
}
@article {pmid36655191,
year = {2023},
author = {Fong, Y and Huang, Y and Borate, B and van der Laan, LWP and Zhang, W and Carpp, LN and Cho, I and Glenn, G and Fries, L and Gottardo, R and Gilbert, PB},
title = {Antibody Correlates of Protection From Severe Respiratory Syncytial Virus Disease in a Vaccine Efficacy Trial.},
journal = {Open forum infectious diseases},
volume = {10},
number = {1},
pages = {ofac693},
pmid = {36655191},
issn = {2328-8957},
abstract = {BACKGROUND: Respiratory syncytial virus (RSV) can cause serious lung infections in young children and there is currently no available vaccine.<br><br>METHODS: We used complementary statistical frameworks to analyze 4 RSV serology measurements in mothers and their infants in South Africa who participated in a phase 3 maternal immunization trial of an RSV F protein nanoparticle vaccine as correlates of risk and of protection against different RSV disease endpoints.<br><br>RESULTS: We found evidence to support each antibody measurement-encompassing RSV-neutralizing antibodies and F surface glycoprotein-binding antibodies-as an inverse correlate of risk of RSV-associated acute lower respiratory tract infection with severe hypoxia in at least 1 framework, with vaccine-induced fold-rise from the maternal enrollment to day 14 samples of anti-F immunoglobulin G (IgG) binding antibodies having the most consistent evidence. This evidence includes a significant association of fold-rise anti-F IgG with vaccine efficacy (VE); achieving a baseline covariate-adjusted VE of 75% requires a vaccine-induced maternal anti-F IgG fold-rise of around 16. Neither multivariable logistic regression nor superlearning analyses showed benefit to including multiple time points or assays in the same model, suggesting a parsimonious correlate. Post hoc exploratory analyses supported adherence of vaccine-induced maternal anti-F IgG fold-rise to the Prentice criteria for a valid surrogate endpoint.<br><br>CONCLUSIONS: Our results suggest that the vaccine induced protective anti-F antibody responses. If this finding is confirmed, VE could potentially be augmented by increasing these responses.},
}
@article {pmid36653422,
year = {2023},
author = {Midttun, &#xd8; and Ulvik, A and Meyer, K and Zahed, H and Giles, GG and Manjer, J and Sandsveden, M and Langhammer, A and Sørgjerd, EP and Behndig, AF and Johansson, M and Freedman, ND and Huang, WY and Chen, C and Prentice, R and Stevens, VL and Wang, Y and Le Marchand, L and Weinstein, SJ and Cai, Q and Arslan, AA and Chen, Y and Shu, XO and Zheng, W and Yuan, JM and Koh, WP and Visvanathan, K and Sesso, HD and Zhang, X and Gaziano, JM and Fanidi, A and Robbins, HA and Brennan, P and Johansson, M and Ueland, PM},
title = {A cross-sectional study of inflammatory markers as determinants of circulating kynurenines in the Lung Cancer Cohort Consortium.},
journal = {Scientific reports},
volume = {13},
number = {1},
pages = {1011},
pmid = {36653422},
issn = {2045-2322},
support = {209057/WT_/Wellcome Trust/United Kingdom ; HHSN268201600018C/NH/NIH HHS/United States ; HHSN268201600001C/NH/NIH HHS/United States ; HHSN268201600002C/NH/NIH HHS/United States ; HHSN268201600003C/NH/NIH HHS/United States ; HHSN268201600004C/NH/NIH HHS/United States ; U01 CA164973/NH/NIH HHS/United States ; Intramural Research Program of the U.S. National Cancer Institute/NH/NIH HHS/United States ; R01CA144034/NH/NIH HHS/United States ; UM1CA182876/NH/NIH HHS/United States ; CA097193/NH/NIH HHS/United States ; CA34944/NH/NIH HHS/United States ; CA40360/NH/NIH HHS/United States ; HL26490/NH/NIH HHS/United States ; HL34595/NH/NIH HHS/United States ; 1U1CA155340/NH/NIH HHS/United States ; U01CA202979/CA/NCI NIH HHS/United States ; U01 CA182934/CA/NCI NIH HHS/United States ; P30 CA16087/CA/NCI NIH HHS/United States ; UM1 CA182910/CA/NCI NIH HHS/United States ; UM1 CA173640/CA/NCI NIH HHS/United States ; U01 CA202979/CA/NCI NIH HHS/United States ; UM1 CA186107/CA/NCI NIH HHS/United States ; P50 CA127003/CA/NCI NIH HHS/United States ; P01 CA87969/CA/NCI NIH HHS/United States ; U01 CA167552/CA/NCI NIH HHS/United States ; U19 CA203654/CA/NCI NIH HHS/United States ; P30 ES000260/ES/NIEHS NIH HHS/United States ; NU58DP006333/CC/CDC HHS/United States ; },
abstract = {Circulating concentrations of metabolites (collectively called kynurenines) in the kynurenine pathway of tryptophan metabolism increase during inflammation, particularly in response to interferon-gamma (IFN-γ). Neopterin and the kynurenine/tryptophan ratio (KTR) are IFN-γ induced inflammatory markers, and together with C-reactive protein (CRP) and kynurenines they are associated with various diseases, but comprehensive data on the strength of associations of inflammatory markers with circulating concentrations of kynurenines are lacking. We measured circulating concentrations of neopterin, CRP, tryptophan and seven kynurenines in 5314 controls from 20 cohorts in the Lung Cancer Cohort Consortium (LC3). The associations of neopterin, KTR and CRP with kynurenines were investigated using regression models. In mixed models, one standard deviation (SD) higher KTR was associated with a 0.46 SD higher quinolinic acid (QA), and 0.31 SD higher 3-hydroxykynurenine (HK). One SD higher neopterin was associated with 0.48, 0.44, 0.36 and 0.28 SD higher KTR, QA, kynurenine and HK, respectively. KTR and neopterin respectively explained 24.1% and 16.7% of the variation in QA, and 11.4% and 7.5% of HK. CRP was only weakly associated with kynurenines in regression models. In summary, QA was the metabolite that was most strongly associated with the inflammatory markers. In general, the inflammatory markers were most strongly related to metabolites located along the tryptophan-NAD axis, which may support suggestions of increased production of NAD from tryptophan during inflammation.},
}
@article {pmid36653342,
year = {2023},
author = {Pintye, J and Odoyo, J and Nyerere, B and Achieng, P and Araka, E and Omondi, C and Ortblad, KF and Mugambi, ML and Baeten, JM and Bukusi, E},
title = {Nurse-facilitated PrEP delivery for adolescent girls and young women seeking contraception at retail pharmacies in Kisumu, Kenya.},
journal = {AIDS (London, England)},
volume = {},
number = {},
pages = {},
doi = {10.1097/QAD.0000000000003447},
pmid = {36653342},
issn = {1473-5571},
abstract = {OBJECTIVE: We evaluated PrEP uptake, initiation, and continuation within a nurse-facilitated pharmacy-based delivery model for Kenyan adolescent girls and young women (AGYW) seeking contraception at retail pharmacies.<br><br>METHODS: From October 2020 to March 2021, PrEP-trained nurses were stationed at three retail pharmacies in Kisumu, Kenya. AGYW (aged 15-24&#x200a;years) purchasing contraception (emergency contraception [EC], oral contraceptive pills, injectables, implants, condoms) were counseled on PrEP, completed HIV testing, and offered a free one-month supply of PrEP pills per national guidelines by nurses under supervision of a remote physician. We evaluated uptake among all AGYW offered PrEP. At 30&#x200a;days after uptake, we evaluated PrEP use initiation and plans for continuation.<br><br>RESULTS: We enrolled 235 AGYW clients who were HIV-negative and purchasing contraception at pharmacies. EC was the most frequently purchased contraceptive (35%). Median age was 22&#x200a;years (IQR 19-23), 44% were currently in school, and 33% currently had multiple sexual partners. One-fourth (24%) exchanged sex for money or favors and 14% had sex while intoxicated in the prior 6&#x200a;months. Overall, PrEP uptake was 85%; at one month, 82% had initiated PrEP use and 68% planned to continue use. Among those initiating PrEP, 69% were willing to pay for PrEP at retail pharmacies (median KES 150, IQR 100-200) even if available for free at public sector facilities.<br><br>CONCLUSIONS: In this evaluation of nurse-facilitated PrEP delivery at pharmacies in Kenya, a substantial proportion of AGYW who purchased contraception subsequently initiated PrEP, planned to continue use, and were willing to pay for PrEP.},
}
@article {pmid36652499,
year = {2023},
author = {Davis, K and Mitchell, C and Weissenfels, O and Bai, J and Raizen, DM and Ailion, M and Topalidou, I},
title = {G protein-coupled receptor kinase-2 (GRK-2) controls exploration through neuropeptide signaling in Caenorhabditis elegans.},
journal = {PLoS genetics},
volume = {19},
number = {1},
pages = {e1010613},
doi = {10.1371/journal.pgen.1010613},
pmid = {36652499},
issn = {1553-7404},
abstract = {Animals alter their behavior in manners that depend on environmental conditions as well as their developmental and metabolic states. For example, C. elegans is quiescent during larval molts or during conditions of satiety. By contrast, worms enter an exploration state when removed from food. Sensory perception influences movement quiescence (defined as a lack of body movement), as well as the expression of additional locomotor states in C. elegans that are associated with increased or reduced locomotion activity, such as roaming (exploration behavior) and dwelling (local search). Here we find that movement quiescence is enhanced, and exploration behavior is reduced in G protein-coupled receptor kinase grk-2 mutant animals. grk-2 was previously shown to act in chemosensation, locomotion, and egg-laying behaviors. Using neuron-specific rescuing experiments, we show that GRK-2 acts in multiple ciliated chemosensory neurons to control exploration behavior. grk-2 acts in opposite ways from the cGMP-dependent protein kinase gene egl-4 to control movement quiescence and exploration behavior. Analysis of mutants with defects in ciliated sensory neurons indicates that grk-2 and the cilium-structure mutants act in the same pathway to control exploration behavior. We find that GRK-2 controls exploration behavior in an opposite manner from the neuropeptide receptor NPR-1 and the neuropeptides FLP-1 and FLP-18. Finally, we show that secretion of the FLP-1 neuropeptide is negatively regulated by GRK-2 and that overexpression of FLP-1 reduces exploration behavior. These results define neurons and molecular pathways that modulate movement quiescence and exploration behavior.},
}
@article {pmid36652267,
year = {2023},
author = {Kessler, RC and Bauer, MS and Bishop, TM and Bossarte, RM and Castro, VM and Demler, OV and Gildea, SM and Goulet, JL and King, AJ and Kennedy, CJ and Landes, SJ and Liu, H and Luedtke, A and Mair, P and Marx, BP and Nock, MK and Petukhova, MV and Pigeon, WR and Sampson, NA and Smoller, JW and Miller, A and Haas, G and Benware, J and Bradley, J and Owen, RR and House, S and Urosevic, S and Weinstock, LM},
title = {Evaluation of a Model to Target High-risk Psychiatric Inpatients for an Intensive Postdischarge Suicide Prevention Intervention.},
journal = {JAMA psychiatry},
volume = {},
number = {},
pages = {},
doi = {10.1001/jamapsychiatry.2022.4634},
pmid = {36652267},
issn = {2168-6238},
abstract = {IMPORTANCE: The months after psychiatric hospital discharge are a time of high risk for suicide. Intensive postdischarge case management, although potentially effective in suicide prevention, is likely to be cost-effective only if targeted at high-risk patients. A previously developed machine learning (ML) model showed that postdischarge suicides can be predicted from electronic health records and geospatial data, but it is unknown if prediction could be improved by adding additional information.<br><br>OBJECTIVE: To determine whether model prediction could be improved by adding information extracted from clinical notes and public records.<br><br>Models were trained to predict suicides in the 12 months after Veterans Health Administration (VHA) short-term (less than 365 days) psychiatric hospitalizations between the beginning of 2010 and September 1, 2012 (299&#x202f;050 hospitalizations, with 916 hospitalizations followed within 12 months by suicides) and tested in the hospitalizations from September 2, 2012, to December 31, 2013 (149&#x202f;738 hospitalizations, with 393 hospitalizations followed within 12 months by suicides). Validation focused on net benefit across a range of plausible decision thresholds. Predictor importance was assessed with Shapley additive explanations (SHAP) values. Data were analyzed from January to August 2022.<br><br>MAIN OUTCOMES AND MEASURES: Suicides were defined by the National Death Index. Base model predictors included VHA electronic health records and patient residential data. The expanded predictors came from natural language processing (NLP) of clinical notes and a social determinants of health (SDOH) public records database.<br><br>RESULTS: The model included 448&#x202f;788 unique hospitalizations. Net benefit over risk horizons between 3 and 12 months was generally highest for the model that included both NLP and SDOH predictors (area under the receiver operating characteristic curve range, 0.747-0.780; area under the precision recall curve relative to the suicide rate range, 3.87-5.75). NLP and SDOH predictors also had the highest predictor class-level SHAP values (proportional SHAP&#x2009;=&#x2009;64.0% and 49.3%, respectively), although the single highest positive variable-level SHAP value was for a count of medications classified by the US Food and Drug Administration as increasing suicide risk prescribed the year before hospitalization (proportional SHAP&#x2009;=&#x2009;15.0%).<br><br>CONCLUSIONS AND RELEVANCE: In this study, clinical notes and public records were found to improve ML model prediction of suicide after psychiatric hospitalization. The model had positive net benefit over 3-month to 12-month risk horizons for plausible decision thresholds. Although caution is needed in inferring causality based on predictor importance, several key predictors have potential intervention implications that should be investigated in future studies.},
}
@article {pmid36203549,
year = {2022},
author = {Armistead, B and Jiang, Y and Carlson, M and Ford, ES and Jani, S and Houck, J and Wu, X and Jing, L and Pecor, T and Kachikis, A and Yeung, W and Nguyen, T and Minkah, N and Larsen, SE and Coler, RN and Koelle, DM and Harrington, WE},
title = {Spike-specific T cells are enriched in breastmilk following SARS-CoV-2 mRNA vaccination.},
journal = {medRxiv : the preprint server for health sciences},
volume = {},
number = {},
pages = {},
pmid = {36203549},
abstract = {UNLABELLED: Human breastmilk is rich in T cells; however, their specificity and function are largely unknown. We compared the phenotype, diversity, and antigen specificity of T cells in the breastmilk and peripheral blood of lactating individuals who received SARS-CoV-2 mRNA vaccination. Relative to blood, breastmilk contained higher frequencies of T effector and central memory populations that expressed mucosal-homing markers. T cell receptor (TCR) sequence overlap was limited between blood and breastmilk. Overabundan t breastmilk clones were observed in all individuals, were diverse, and contained CDR3 sequences with known epitope specificity including to SARS-CoV-2 Spike. Spike-specific TCRs were more frequent in breastmilk compared to blood and expanded in breastmilk following a third mRNA vaccine dose. Our observations indicate that the lactating breast contains a distinct T cell population that can be modulated by maternal vaccination with potential implications for infant passive protection.<br><br>ONE-SENTENCE SUMMARY: The breastmilk T cell repertoire is distinct and enriched for SARS-CoV-2 Spike-specificity after maternal mRNA vaccination.},
}
@article {pmid36651636,
year = {2023},
author = {Klebanoff, MA and Schuit, E and Lamont, RF and Larsson, PG and Odendaal, HJ and Ugwumadu, A and Kiss, H and Petricevic, L and Andrews, WW and Hoffman, MK and Shennan, A and Seed, PT and Goldenberg, RL and Emel, LM and Bhandaru, V and Weiner, S and Larsen, MD},
title = {Antibiotic treatment of bacterial vaginosis to prevent preterm delivery: Systematic review and individual participant data meta-analysis.},
journal = {Paediatric and perinatal epidemiology},
volume = {},
number = {},
pages = {},
doi = {10.1111/ppe.12947},
pmid = {36651636},
issn = {1365-3016},
abstract = {BACKGROUND: Bacterial vaginosis (BV) increases preterm delivery (PTD) risk, but treatment trials showed mixed results in preventing PTD.<br><br>OBJECTIVES: Determine, using individual participant data (IPD), whether BV treatment during pregnancy reduced PTD or prolonged time-to-delivery.<br><br>DATA SOURCES: Cochrane Systematic Review (2013), MEDLINE, EMBASE, journal searches, and searches (January 2013-September 2022) ("bacterial vaginosis AND pregnancy") of (i) clinicaltrials.gov; (ii) Cochrane Central Register of Controlled Trials; (iii) World Health Organization International Clinical Trials Registry Platform Portal; and (iv) Web of Science ("bacterial vaginosis").<br><br>Studies randomising asymptomatic pregnant individuals with BV to antibiotics or control, measuring delivery gestation. Extraction was from original data files. Bias risk was assessed using the Cochrane tool. Analysis used "one-step" logistic and Cox random effect models, adjusting gestation at randomisation and PTD history; heterogeneity by I[2] . Subgroup analysis tested interactions with treatment. In sensitivity analyses, studies not providing IPD were incorporated by "multiple random-donor hot-deck" imputation, using IPD studies as donors.<br><br>RESULTS: There were 121 references (96 studies) with 23 eligible trials (11,979 participants); 13 studies (6915 participants) provided IPD; 12 (6115) were incorporated. Results from 9 (4887 participants) not providing IPD were imputed. Odds ratios for PTD for metronidazole and clindamycin versus placebo were 1.00 (95% CI 0.84, 1.17), I[2] &#xa0;=&#x2009;62%, and 0.59 (95% CI 0.42, 0.82), I[2] &#xa0;=&#x2009;0 before; and 0.95 (95% CI 0.81, 1.11), I[2] &#xa0;=&#x2009;59%, and 0.90 (95% CI: 0.72, 1.12), I[2] &#xa0;=&#x2009;0, after imputation. Time-to-delivery did not differ from null with either treatment. Including imputed IPD, there was no evidence that either drug was more effective when administered earlier, or among those with a PTD history.<br><br>CONCLUSIONS: Clindamycin, but not metronidazole, was beneficial in studies providing IPD, but after imputing data from missing IPD studies, treatment of BV during pregnancy did not reduce PTD, nor prolong pregnancy, in any subgroup or when started earlier in gestation.},
}
@article {pmid36650676,
year = {2023},
author = {Kato, I and Sun, J and Hastert, TA and Abrams, J and Larson, JC and Bao, W and Shadyab, AH and Mouton, C and Qi, L and Warsinger Martin, L and Manson, JE},
title = {Association of calcium and vitamin D supplementation with cancer incidence and cause-specific mortality in Black women: extended follow-up of the Women's Health Initiative calcium-vitamin D trial.},
journal = {International journal of cancer},
volume = {},
number = {},
pages = {},
doi = {10.1002/ijc.34436},
pmid = {36650676},
issn = {1097-0215},
abstract = {Low circulating vitamin D levels are more prevalent in Black than White individuals. We analyzed the Women's Health Initiative (WHI) calcium plus vitamin D (CaD) randomized clinical trial extended follow-up data to evaluate associations between calcium plus vitamin D supplementation and incident cancer, cardiovascular disease (CVD), and cause-specific mortality endpoints among Black women. Intent-to-treat analysis was performed. Among 3325 Black women in the CaD trial who were randomized into either daily calcium (1000 mg of calcium carbonate) plus vitamin D (400 IU D3) or placebos for an average of 7 years, there were 813 deaths, 588 incident cancers, and 837 CVD events during an average of 15.7 years of follow up (52,230 total person-years). Using Cox's proportional hazards models, we calculated hazard ratios and their confidence intervals for outcomes ascertained during the trial period, post-trial follow-up period and overall periods combined. We found that total mortality, cause-specific mortality, and total cancer incidence were almost identical between CaD and placebo groups. These results suggest that calcium plus vitamin D supplementation does not reduce risks of cancer, CVD, or other major causes of death in Black women overall and, thus, other medical, behavioral or social interventions should be considered to narrow health disparities related to these outcomes. However, other finer endpoints, such as colorectal cancer, warrants further investigation. This article is protected by copyright. All rights reserved.},
}
@article {pmid36650259,
year = {2023},
author = {Lawrence, MG and Taylor, RA and Cuffe, GB and Ang, LS and Clark, AK and Goode, DL and Porter, LH and Le Magnen, C and Navone, NM and Schalken, JA and Wang, Y and van Weerden, WM and Corey, E and Isaacs, JT and Nelson, PS and Risbridger, GP},
title = {The future of patient-derived xenografts in prostate cancer research.},
journal = {Nature reviews. Urology},
volume = {},
number = {},
pages = {},
pmid = {36650259},
issn = {1759-4820},
abstract = {Patient-derived xenografts (PDXs) are generated by engrafting human tumours into mice. Serially transplantable PDXs are used to study tumour biology and test therapeutics, linking the laboratory to the clinic. Although few prostate cancer PDXs are available in large repositories, over 330 prostate cancer PDXs have been established, spanning broad clinical stages, genotypes and phenotypes. Nevertheless, more PDXs are needed to reflect patient diversity, and to study new treatments and emerging mechanisms of resistance. We can maximize the use of PDXs by exchanging models and datasets, and by depositing PDXs into biorepositories, but we must address the impediments to accessing PDXs, such as institutional, ethical and legal agreements. Through collaboration, researchers will gain greater access to PDXs representing diverse features of prostate cancer.},
}
@article {pmid36650052,
year = {2023},
author = {Islam, Z and Saravanan, B and Walavalkar, K and Farooq, U and Singh, AK and Sabarinathan, R and Thakur, J and Pandit, A and Henikoff, S and Notani, D},
title = {Active enhancers strengthen insulation by RNA-mediated CTCF binding at chromatin domain boundaries.},
journal = {Genome research},
volume = {},
number = {},
pages = {},
doi = {10.1101/gr.276643.122},
pmid = {36650052},
issn = {1549-5469},
abstract = {Vertebrate genomes are partitioned into chromatin domains or topologically associating domains (TADs), which are typically bound by head-to-head pairs of CTCF binding sites. Transcription at domain boundaries correlates with better insulation; however, it is not known whether the boundary transcripts themselves contribute to boundary function. Here we characterize boundary-associated RNAs genome-wide, focusing on the disease-relevant INK4a/ARF and MYC TAD. Using CTCF site deletions and boundary-associated RNA knockdowns, we observe that boundary-associated RNAs facilitate recruitment and clustering of CTCF at TAD borders. The resulting CTCF enrichment enhances TAD insulation, enhancer-promoter interactions, and TAD gene expression. Importantly, knockdown of boundary-associated RNAs results in loss of boundary insulation function. Using enhancer deletions and CRISPRi of promoters, we show that active TAD enhancers, but not promoters, induce boundary-associated RNA transcription, thus defining a novel class of regulatory enhancer RNAs.},
}
@article {pmid36649748,
year = {2023},
author = {Neofytos, D and Steinbach, WJ and Hanson, K and Carpenter, PA and Papanicolaou, GA and Slavin, MA},
title = {American Society for Transplantation and Cellular Therapy Series: #6 - Management of Invasive Candidiasis in Hematopoietic Cell Transplant Recipients.},
journal = {Transplantation and cellular therapy},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jtct.2023.01.011},
pmid = {36649748},
issn = {2666-6367},
abstract = {The Practice Guidelines Committee of the American Society of Transplantation and Cellular Therapy (ASTCT) partnered with its Transplant Infectious Disease Special Interest Group (TID-SIG) to update its 2009 compendium-style infectious disease guidelines for hematopoietic cell transplantation (HCT). A completely new approach was taken with the goal of better serving clinical providers by publishing each standalone topic in the infectious disease series as a concise format of frequently asked questions (FAQ), tables and figures.[1] Adult and pediatric infectious disease and HCT content experts developed, then answered FAQs, and finalized topics with harmonized recommendations that were made by assigning an A through E strength of recommendation paired with a level of supporting evidence graded I through III. This sixth guideline in the series focuses on invasive candidiasis (IC) with FAQs to address epidemiology, clinical diagnosis, prophylaxis and treatment of IC, plus special considerations for pediatric, cord blood, haploidentical and T-cell depleted HCT recipients, CAR-T cell recipients, as well as future research directions.},
}
@article {pmid36649247,
year = {2023},
author = {Begnel, ER and Chohan, BH and Ojee, E and Adhiambo, J and Owiti, P and Ogweno, V and Holland, LA and Fish, CS and Richardson, BA and Khan, AK and Maqsood, R and Lim, ES and Sadarangani, M and Lehman, DA and Slyker, J and Kinuthia, J and Wamalwa, D and Gantt, S},
title = {HIV and SARS-CoV-2 infection in postpartum Kenyan women and their infants.},
journal = {PloS one},
volume = {18},
number = {1},
pages = {e0278675},
doi = {10.1371/journal.pone.0278675},
pmid = {36649247},
issn = {1932-6203},
abstract = {BACKGROUND: HIV may increase SARS-CoV-2 infection risk and COVID-19 severity generally, but data are limited about its impact on postpartum women and their infants. As such, we characterized SARS-CoV-2 infection among mother-infant pairs in Nairobi, Kenya.<br><br>METHODS: We conducted a nested study of 62 HIV-uninfected and 64 healthy women living with HIV, as well as their HIV-exposed uninfected (N = 61) and HIV-unexposed (N = 64) infants, participating in a prospective cohort. SARS-CoV-2 serology was performed on plasma collected between May 1, 2020-February 1, 2022 to determine the incidence, risk factors, and symptoms of infection. SARS-CoV-2 RNA PCR and sequencing was also performed on available stool samples from seropositive participants.<br><br>RESULTS: SARS-CoV-2 seropositivity was found in 66% of the 126 mothers and in 44% of the 125 infants. There was no significant association between SARS-CoV-2 infection and maternal HIV (Hazard Ratio [HR] = 0.810, 95% CI: 0.517-1.27) or infant HIV exposure (HR = 1.47, 95% CI: 0.859-2.53). Maternal SARS-CoV-2 was associated with a two-fold increased risk of infant infection (HR = 2.31, 95% CI: 1.08-4.94). Few participants (13% mothers, 33% infants) had symptoms; no participant experienced severe COVID-19 or death. Seroreversion occurred in about half of mothers and infants. SARS-CoV-2 sequences obtained from stool were related to contemporaneously circulating variants.<br><br>CONCLUSIONS: These data indicate that postpartum Kenyan women and their infants were at high risk for SARS-CoV-2 infection and that antibody responses waned over an average of 8-10 months. However, most cases were asymptomatic and healthy women living with HIV did not have a substantially increased risk of infection or severe COVID-19.},
}
@article {pmid36648535,
year = {2023},
author = {Ugai, T and Akimoto, N and Haruki, K and Harrison, TA and Cao, Y and Qu, C and Chan, AT and Campbell, PT and Berndt, SI and Buchanan, DD and Cross, AJ and Diergaarde, B and Gallinger, SJ and Gunter, MJ and Harlid, S and Hidaka, A and Hoffmeister, M and Brenner, H and Chang-Claude, J and Hsu, L and Jenkins, MA and Lin, Y and Milne, RL and Moreno, V and Newcomb, PA and Nishihara, R and Obon-Santacana, M and Pai, RK and Sakoda, LC and Schoen, RE and Slattery, ML and Sun, W and Amitay, EL and Alwers, E and Thibodeau, SN and Toland, AE and Van Guelpen, B and Zaidi, SH and Potter, JD and Meyerhardt, JA and Giannakis, M and Song, M and Nowak, JA and Peters, U and Phipps, AI and Ogino, S},
title = {Prognostic role of detailed colorectal location and tumor molecular features: analyses of 13,101 colorectal cancer patients including 2994 early-onset cases.},
journal = {Journal of gastroenterology},
volume = {},
number = {},
pages = {},
pmid = {36648535},
issn = {1435-5922},
support = {U01 CA137088/NH/NIH HHS/United States ; R01 CA248857/NH/NIH HHS/United States ; P01 CA055075/NH/NIH HHS/United States ; UM1 CA167552/NH/NIH HHS/United States ; U01 CA167552/NH/NIH HHS/United States ; R01 CA137178/NH/NIH HHS/United States ; R01 CA151993/NH/NIH HHS/United States ; R00 CA215314/NH/NIH HHS/United States ; R35 CA197735/NH/NIH HHS/United States ; R01 CA137178/NH/NIH HHS/United States ; P01 CA087969/NH/NIH HHS/United States ; UM1 CA186107/NH/NIH HHS/United States ; R01 CA151993/NH/NIH HHS/United States ; R35 CA197735/NH/NIH HHS/United States ; U01 CA167551/NH/NIH HHS/United States ; U01/U24 CA074783/NH/NIH HHS/United States ; CA16058/NH/NIH HHS/United States ; CA67941/NH/NIH HHS/United States ; R01 CA48998/NH/NIH HHS/United States ; R01 CA076366/NH/NIH HHS/United States ; U01 CA167551/NH/NIH HHS/United States ; U01 CA074794/NH/NIH HHS/United States ; U24 CA074794/NH/NIH HHS/United States ; R01 CA076366/NH/NIH HHS/United States ; U01 CA167551/NH/NIH HHS/United States ; 14136 to EPIC-Norfolk/CRUK_/Cancer Research UK/United Kingdom ; C570/A16491/CRUK_/Cancer Research UK/United Kingdom ; C8221/A19170 to EPIC-Oxford/CRUK_/Cancer Research UK/United Kingdom ; 1000143 to EPIC-Norfolk/MRC_/Medical Research Council/United Kingdom ; MR/M012190/1 to EPICOxford/MRC_/Medical Research Council/United Kingdom ; UK C10674/A27140/CRUK_/Cancer Research UK/United Kingdom ; 209057/WT_/Wellcome Trust/United Kingdom ; 112746/CAPMC/CIHR/Canada ; },
abstract = {BACKGROUND: The pathogenic effect of colorectal tumor molecular features may be influenced by several factors, including those related to microbiota, inflammation, metabolism, and epigenetics, which may change along colorectal segments. We hypothesized that the prognostic association of colon cancer location might differ by tumor molecular characteristics.<br><br>METHODS: Utilizing a consortium dataset of 13,101 colorectal cancer cases, including 2994 early-onset cases, we conducted survival analyses of detailed tumor location stratified by statuses of microsatellite instability (MSI), CpG island methylator phenotype (CIMP), and KRAS and BRAF oncogenic mutation.<br><br>RESULTS: There was a statistically significant trend for better colon cancer-specific survival in relation to tumor location from the cecum to sigmoid colon (Ptrend&#x2009;=&#x2009;0.002), excluding the rectum. The prognostic association of colon location differed by MSI status (Pinteraction&#x2009;=&#x2009;0.001). Non-MSI-high tumors exhibited the cecum-to-sigmoid trend for better colon cancer-specific survival [Ptrend&#x2009;<&#x2009;0.001; multivariable hazard ratio (HR) for the sigmoid colon (vs. cecum), 0.80; 95% confidence interval (CI) 0.70-0.92], whereas MSI-high tumors demonstrated a suggestive cecum-to-sigmoid trend for worse survival (Ptrend&#x2009;=&#x2009;0.020; the corresponding HR, 2.13; 95% CI 1.15-3.92). The prognostic association of colon tumor location also differed by CIMP status (Pinteraction&#x2009;=&#x2009;0.003) but not significantly by age, stage, or other features. Furthermore, MSI-high status was a favorable prognostic indicator in all stages.<br><br>CONCLUSIONS: Both detailed colonic location and tumor molecular features need to be accounted for colon cancer prognostication to advance precision medicine. Our study indicates the important role of large-scale studies to robustly examine detailed colonic subsites in molecular oncology research.},
}
@article {pmid36647963,
year = {2022},
author = {Zhang, X and Liang, J and Du, Z and Xie, Q and Li, T and Tang, F},
title = {Comparison of nomogram with random survival forest for prediction of survival in patients with spindle cell carcinoma.},
journal = {Journal of cancer research and therapeutics},
volume = {18},
number = {7},
pages = {2006-2012},
doi = {10.4103/jcrt.jcrt_2375_21},
pmid = {36647963},
issn = {1998-4138},
abstract = {PURPOSE: Spindle cell carcinoma (SpCC) is a relatively rare tumor with an unfavorable prognosis. This study aimed to develop and validate a prediction model for the individual survival of patients with SpCC using Cox regression and the random survival forest (RSF) model.<br><br>METHODS: Patients diagnosed with SpCC between 2004 and 2016 were selected from the Surveillance, Epidemiology, and End Results (SEER) database, and randomly divided into training and validating cohorts. Cox regression and RSF were used to identify prognostic predictors and build prediction models. A nomogram based on Cox regression was constructed to predict the 1-, 3-, and 5-year survival of patients with SpCC. Internal validation was conducted using the bootstrapping method. We evaluated the discrimination accuracy and calibration of the model using Harrell's C-index and calibration plot, respectively.<br><br>RESULTS: Two hundred and fifty patients diagnosed with SpCC with required information were enrolled in this study. Multivariate Cox regression and RSF identified age, primary site, grade, SEER stage, tumor size, and treatment as significant prognostic predictors of SpCC. The bootstrapped and validated C-indices were 0.812 and 0.783 for nomogram, and 0.790 and 0.768 for RSF, respectively. Calibration plot of the nomogram showed an agreement between the prediction and actual observation.<br><br>CONCLUSIONS: The nomogram developed in this study is a promising tool with a simplified presentation that can easily be used and interpreted by clinicians for evaluating the survival of each patient with SpCC; its performance was comparable to that of RSF. Application of such models are needed to help oncologists identify the high-risk patients and improve clinical decision making of SpCC treatment.},
}
@article {pmid36646321,
year = {2023},
author = {Vigorito, AC and Miranda, ECM and Colturato, VAR and Funke, VAM and Fatobene, G and Mariano, L and Macedo, MCMA and Ribeiro, LB and Daudt, LE and Moreira, MCR and Bonfim, C and Colella, MP and Seber, A and Rodrigues, M and Duarte, FB and Martin, PJ and Flowers, MED and , },
title = {Chronic graft-versus-host-disease treatment in Brazil: analyses of failure-free survival.},
journal = {Transplantation and cellular therapy},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jtct.2023.01.007},
pmid = {36646321},
issn = {2666-6367},
abstract = {Failure-free survival (FFS), defined as the absence of new systemic treatment, recurrence of original malignancy and mortality not associated with recurrence after allogeneic hematopoietic stem cell transplantation (HCT), is a robust clinical measure to interpret results of initial systemic treatment of chronic graft-versus-host disease (cGVHD). We evaluate FFS after initial treatment of cGVHD in a mixed-race cohort from a resource-constrained country. This retrospective study included 354 consecutive patients after their first HCT between January 2014 and August 2020, who received initial systemic treatment for moderate or severe cGVHD at 13 Brazilian centers. Cox regression models were used to identify risk factors for treatment failure. The overall median follow-up among survivors was 28 months (range 1-71) after initial treatment. FFS was 89% at 6 months, 71% at 1 year and 52% at 2 years. New systemic treatment was the major cause of failure. In multivariable models, prior grades II-IV acute GVHD, a National Institutes of Health severity score of 3 in liver, gastrointestinal tract or lung involvement, and onset of initial treatment of cGVHD within 12 months after transplantation were all associated with an increased risk of treatment failure. Our results could serve as a benchmark for the design of future clinical trials evaluating initial treatment of cGVHD in resource-constrained locations.},
}
@article {pmid36646198,
year = {2023},
author = {Gomez, SE and Parizo, J and Ermakov, S and Larson, J and Wallace, R and Assimes, T and Hlatky, M and Stefanick, M and Perez, MV},
title = {Evaluation of the Association Between Circulating IL-1β and Other Inflammatory Cytokines and Incident Atrial Fibrillation in a Cohort of Postmenopausal Women.},
journal = {American heart journal},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.ahj.2023.01.010},
pmid = {36646198},
issn = {1097-6744},
abstract = {BACKGROUND: Inflammatory cytokines play a role in atrial fibrillation (AF). Interleukin (IL)-1β, which is targeted in the treatment of ischemic heart disease, has not been well-studied in relation to AF.<br><br>METHODS: Postmenopausal women from the Women's Health Initiative were included. Cox proportional hazards regression models were used to evaluate the association between log-transformed baseline cytokine levels and future AF incidence. Models were adjusted for body mass index, age, race, education, hypertension, diabetes, hyperlipidemia, current smoking, and history of coronary heart disease, congestive heart failure, or peripheral artery disease.<br><br>RESULTS: Of 16,729 women, 3,943 developed AF over an average of 8.5 years. Racial and ethnic groups included White (77.4%), Black/African-American (16.1%), Asian (2.7%), American Indian/Alaska Native (1.0%), and Hispanic (5.5%). Baseline IL-1&#x3b2; log continuous levels were not significantly associated with incident AF (HR 0.86 per 1 log (pg/mL) increase, p=0.24), similar to those of other inflammatory cytokines, IL-7, IL-8, IL-10, IGF-1, and TNF-&#x3b1;. There were significant associations between C-reactive protein (CRP) and IL-6 with incident AF.<br><br>CONCLUSIONS: In this large cohort of postmenopausal women, there was no significant association between IL-1&#x3b2; and incident AF, although downstream effectors, CRP and IL-6, were associated with incident AF.},
}
@article {pmid36346688,
year = {2023},
author = {Milewski, D and Jung, H and Brown, GT and Liu, Y and Somerville, B and Lisle, C and Ladanyi, M and Rudzinski, ER and Choo-Wosoba, H and Barkauskas, DA and Lo, T and Hall, D and Linardic, CM and Wei, JS and Chou, HC and Skapek, SX and Venkatramani, R and Bode, PK and Steinberg, SM and Zaki, G and Kuznetsov, IB and Hawkins, DS and Shern, JF and Collins, J and Khan, J},
title = {Predicting Molecular Subtype and Survival of Rhabdomyosarcoma Patients Using Deep Learning of H&amp;E Images: A Report from the Children's Oncology Group.},
journal = {Clinical cancer research : an official journal of the American Association for Cancer Research},
volume = {29},
number = {2},
pages = {364-378},
doi = {10.1158/1078-0432.CCR-22-1663},
pmid = {36346688},
issn = {1557-3265},
support = {U10 CA180899/CA/NCI NIH HHS/United States ; },
abstract = {PURPOSE: Rhabdomyosarcoma (RMS) is an aggressive soft-tissue sarcoma, which primarily occurs in children and young adults. We previously reported specific genomic alterations in RMS, which strongly correlated with survival; however, predicting these mutations or high-risk disease at diagnosis remains a significant challenge. In this study, we utilized convolutional neural networks (CNN) to learn histologic features associated with driver mutations and outcome using hematoxylin and eosin (H&amp;E) images of RMS.<br><br>EXPERIMENTAL DESIGN: Digital whole slide H&amp;E images were collected from clinically annotated diagnostic tumor samples from 321 patients with RMS enrolled in Children's Oncology Group (COG) trials (1998-2017). Patches were extracted and fed into deep learning CNNs to learn features associated with mutations and relative event-free survival risk. The performance of the trained models was evaluated against independent test sample data (n = 136) or holdout test data.<br><br>RESULTS: The trained CNN could accurately classify alveolar RMS, a high-risk subtype associated with PAX3/7-FOXO1 fusion genes, with an ROC of 0.85 on an independent test dataset. CNN models trained on mutationally-annotated samples identified tumors with RAS pathway with a ROC of 0.67, and high-risk mutations in MYOD1 or TP53 with a ROC of 0.97 and 0.63, respectively. Remarkably, CNN models were superior in predicting event-free and overall survival compared with current molecular-clinical risk stratification.<br><br>CONCLUSIONS: This study demonstrates that high-risk features, including those associated with certain mutations, can be readily identified at diagnosis using deep learning. CNNs are a powerful tool for diagnostic and prognostic prediction of rhabdomyosarcoma, which will be tested in prospective COG clinical trials.},
}
@article {pmid36646114,
year = {2023},
author = {Schiepers, A and van 't Wout, MFL and Greaney, AJ and Zang, T and Muramatsu, H and Lin, PJC and Tam, YK and Mesin, L and Starr, TN and Bieniasz, PD and Pardi, N and Bloom, JD and Victora, GD},
title = {Molecular fate-mapping of serum antibody responses to repeat immunization.},
journal = {Nature},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41586-023-05715-3},
pmid = {36646114},
issn = {1476-4687},
abstract = {The protective efficacy of serum antibody results from the interplay of antigen-specific B cell clones of different affinities and specificities. These cellular dynamics underlie serum-level phenomena such as "Original Antigenic Sin" (OAS), a proposed propensity of the immune system to rely repeatedly on the first cohort of B cells engaged by an antigenic stimulus when encountering related antigens, in detriment of inducing de novo responses[1-5]. OAS-type suppression of new, variant-specific antibodies may pose a barrier to vaccination against rapidly evolving viruses such as influenza and SARS-CoV-2[6,7]. Precise measurement of OAS-type suppression is challenging because cellular and temporal origins cannot readily be ascribed to antibodies in circulation; thus, its impact on subsequent antibody responses remains unclear[5,8]. Here, we introduce a molecular fate-mapping approach in which serum antibodies derived from specific cohorts of B cells can be differentially detected. We show that serum responses to sequential homologous boosting derive overwhelmingly from primary cohort B cells, while later induction of new antibody responses from naïve B cells is strongly suppressed. Such "primary addiction" decreases sharply as a function of antigenic distance, allowing reimmunization with divergent viral glycoproteins to produce de novo antibody responses targeting epitopes absent from the priming variant. Our findings have implications for the understanding of OAS and for the design and testing of vaccines against evolving pathogens.},
}
@article {pmid36645710,
year = {2023},
author = {Papini, C and Fayad, AA and Wang, M and Schulte, FSM and Huang, IC and Chang, YP and Howell, RM and Srivastava, D and Leisenring, WM and Armstrong, GT and Gibson, TM and Robison, LL and Oeffinger, KC and Krull, KR and Brinkman, TM},
title = {Emotional, behavioral, and physical health consequences of loneliness in young adult survivors of childhood cancer: Results from the Childhood Cancer Survivor Study.},
journal = {Cancer},
volume = {},
number = {},
pages = {},
doi = {10.1002/cncr.34633},
pmid = {36645710},
issn = {1097-0142},
support = {U24 CA055727/CA/NCI NIH HHS/United States ; },
abstract = {BACKGROUND: Young adults in the general population are at risk of experiencing loneliness, which has been associated with physical and mental health morbidities. The prevalence and consequences of loneliness in young adult survivors of childhood cancer remain unknown.<br><br>METHODS: A total of 9664 young adult survivors of childhood cancer (median age at diagnosis 10.5&#xa0;years [interquartile range (IQR), 5-15], 27.1&#xa0;years at baseline [IQR, 23-32]) and 2221 siblings enrolled in the Childhood Cancer Survivor Study completed a self-reported survey question assessing loneliness on the Brief Symptom Inventory-18 at baseline and follow-up (median follow-up, 6.6&#xa0;years). Multivariable models evaluated the prevalence of loneliness at baseline only, follow-up only, and baseline&#xa0;+&#xa0;follow-up, and its associations with emotional distress, health behaviors, and chronic conditions at follow-up.<br><br>RESULTS: Survivors were more likely than siblings to report loneliness at baseline&#xa0;+&#xa0;follow-up (prevalence ratio [PR] 2.2; 95% confidence interval [CI], 1.7-3.0) and at follow-up only (PR, 1.4; 95% CI, 1.1-1.7). Loneliness at baseline&#xa0;+&#xa0;follow-up was associated with elevated risk of anxiety (relative risk [RR], 9.8; 95% CI, 7.5-12.7), depression (RR, 17.9; 95% CI, 14.1-22.7), and current smoking (odds ratio [OR], 1.7; 95% CI, 1.3-2.3) at follow-up. Loneliness at follow-up only was associated with suicidal ideation (RR, 1.5; 95% CI, 1.1-2.1), heavy/risky alcohol consumption (RR, 1.3; 95% CI, 1.1-1.5), and new-onset grade 2-4 chronic conditions (RR, 1.3; 95% CI, 1.0-1.7).<br><br>CONCLUSIONS: Young adult survivors of childhood cancer have elevated risk of experiencing loneliness, which is associated with future emotional distress, risky health behaviors, and new-onset chronic conditions.},
}
@article {pmid36644296,
year = {2022},
author = {Ahmad, K and Henikoff, S},
title = {The Drosophila embryo as a tabula rasa for the epigenome.},
journal = {Faculty reviews},
volume = {11},
number = {},
pages = {40},
pmid = {36644296},
issn = {2732-432X},
abstract = {The control of gene expression in eukaryotes relies on how transcription factors and RNA polymerases manipulate the structure of chromatin. These interactions are especially important in development as gene expression programs change. Chromatin generally limits the accessibility of DNA, and thus exposing sequences at regulatory elements is critical for gene expression. However, it is challenging to understand how transcription factors manipulate chromatin structure and the sequence of regulatory events. The Drosophila embryo has provided a powerful setting to directly observe the establishment and elaboration of chromatin features and experimentally test the causality of transcriptional events that are shared among many metazoans. The large embryo is tractable by live imaging, and a variety of well-developed tools allow the manipulation of factors during early development. The early embryo develops as a syncytium with rapid nuclear divisions and no zygotic transcription, with largely featureless chromatin. Thus, studies in this system have revealed the progression of genome activation triggered by pioneer factors that initiate DNA exposure at regulatory elements and the establishment of chromatin domains, including heterochromatin, the nucleolus, and nuclear bodies. The de novo emergence of nuclear structures in the early embryo reveals features of chromatin dynamics that are likely to be central to transcriptional regulation in all cells.},
}
@article {pmid36642379,
year = {2023},
author = {Armistead, B and Jiang, Y and Carlson, M and Ford, ES and Jani, S and Houck, J and Wu, X and Jing, L and Pecor, T and Kachikis, A and Yeung, W and Nguyen, T and Coig, R and Minkah, N and Larsen, SE and Coler, RN and Koelle, DM and Harrington, WE},
title = {Spike-specific T cells are enriched in breastmilk following SARS-CoV-2 mRNA vaccination.},
journal = {Mucosal immunology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.mucimm.2023.01.003},
pmid = {36642379},
issn = {1935-3456},
abstract = {Human breastmilk is rich in T cells; however, their specificity and function are largely unknown. We compared the phenotype, diversity, and antigen specificity of T cells in the breastmilk and peripheral blood of lactating individuals who received SARS-CoV-2 mRNA vaccination. Relative to blood, breastmilk contained higher frequencies of T effector and central memory populations that expressed mucosal-homing markers. T cell receptor (TCR) sequence overlap was limited between blood and breastmilk. Overabundant breastmilk clones were observed in all individuals, were diverse, and contained CDR3 sequences with known epitope specificity including to SARS-CoV-2 Spike. SARS-CoV-2 Spike-specific TCRs were more frequent in breastmilk compared to blood and expanded in breastmilk following a third mRNA vaccine dose. Our observations indicate that the lactating breast contains a distinct T cell population that can be modulated by maternal vaccination with potential implications for infant passive protection.},
}
@article {pmid36642087,
year = {2023},
author = {Smith, J and Bansi-Matharu, L and Cambiano, V and Dimitrov, D and Bershteyn, A and van de Vijver, D and Kripke, K and Revill, P and Boily, MC and Meyer-Rath, G and Taramusi, I and Lundgren, JD and van Oosterhout, JJ and Kuritzkes, D and Schaefer, R and Siedner, MJ and Schapiro, J and Delany-Moretlwe, S and Landovitz, RJ and Flexner, C and Jordan, M and Venter, F and Radebe, M and Ripin, D and Jenkins, S and Resar, D and Amole, C and Shahmanesh, M and Gupta, RK and Raizes, E and Johnson, C and Inzaule, S and Shafer, R and Warren, M and Stansfield, S and Paredes, R and Phillips, AN and , },
title = {Predicted effects of the introduction of long-acting injectable cabotegravir pre-exposure prophylaxis in sub-Saharan Africa: a modelling study.},
journal = {The lancet. HIV},
volume = {},
number = {},
pages = {},
doi = {10.1016/S2352-3018(22)00365-4},
pmid = {36642087},
issn = {2352-3018},
abstract = {BACKGROUND: Long-acting injectable cabotegravir pre-exposure prophylaxis (PrEP) is recommended by WHO as an additional option for HIV prevention in sub-Saharan Africa, but there is concern that its introduction could lead to an increase in integrase-inhibitor resistance undermining treatment programmes that rely on dolutegravir. We aimed to project the health benefits and risks of cabotegravir-PrEP introduction in settings in sub-Saharan Africa.<br><br>METHODS: With HIV Synthesis, an individual-based HIV model, we simulated 1000 setting-scenarios reflecting both variability and uncertainty about HIV epidemics in sub-Saharan Africa and compared outcomes for each with and without cabotegravir-PrEP introduction. PrEP use is assumed to be risk-informed and to be used only in 3-month periods (the time step for the model) when having condomless sex. We consider three groups at risk of integrase-inhibitor resistance emergence: people who start cabotegravir-PrEP after (unknowingly) being infected with HIV, those who seroconvert while on PrEP, and those with HIV who have residual cabotegravir drugs concentrations during the early tail period after recently stopping PrEP. We projected the outcomes of policies of cabotegravir-PrEP introduction and of no introduction in 2022 across 50 years. In 50% of setting-scenarios we considered that more sensitive nucleic-acid-based HIV diagnostic testing (NAT), rather than regular antibody-based HIV rapid testing, might be used to reduce resistance risk. For cost-effectiveness analysis we assumed in our base case a cost of cabotegravir-PrEP drug to be similar to oral PrEP, resulting in a total annual cost of USD$144 per year ($114 per year and $264 per year considered in sensitivity analyses), a cost-effectiveness threshold of $500 per disability-adjusted life years averted, and a discount rate of 3% per year.<br><br>FINDINGS: Reflecting our assumptions on the appeal of cabotegravir-PrEP, its introduction is predicted to lead to a substantial increase in PrEP use with approximately 2&#xb7;6% of the adult population (and 46% of those with a current indication for PrEP) receiving PrEP compared with 1&#xb7;5% (28%) without cabotegravir-PrEP introduction across 20 years. As a result, HIV incidence is expected to be lower by 29% (90% range across setting-scenarios 6-52%) across the same period compared with no introduction of cabotegravir-PrEP. In people initiating antiretroviral therapy, the proportion with integrase-inhibitor resistance after 20 years is projected to be 1&#xb7;7% (0-6&#xb7;4%) without cabotegravir-PrEP introduction but 13&#xb7;1% (4&#xb7;1-30&#xb7;9%) with. Cabotegravir-PrEP introduction is predicted to lower the proportion of all people on antiretroviral therapy with viral loads less than 1000 copies per mL by 0&#xb7;9% (-2&#xb7;5% to 0&#xb7;3%) at 20 years. For an adult population of 10 million an overall decrease in number of AIDS deaths of about 4540 per year (-13&#x2009;000 to -300) across 50 years is predicted, with little discernible benefit with NAT when compared with standard antibody-based rapid testing. AIDS deaths are predicted to be averted with cabotegravir-PrEP introduction in 99% of setting-scenarios. Across the 50-year time horizon, overall HIV programme costs are predicted to be similar regardless of whether cabotegravir-PrEP is introduced (total mean discounted annual HIV programme costs per year across 50 years is $151&#xb7;3 million vs $150&#xb7;7 million), assuming the use of standard antibody testing. With antibody-based rapid HIV testing, the introduction of cabotegravir-PrEP is predicted to be cost-effective under an assumed threshold of $500 per disability-adjusted life year averted in 82% of setting-scenarios at the cost of $144 per year, in 52% at $264, and in 87% at $114.<br><br>INTERPRETATION: Despite leading to increases in integrase-inhibitor drug resistance, cabotegravir-PrEP introduction is likely to reduce AIDS deaths in addition to HIV incidence. Long-acting cabotegravir-PrEP is predicted to be cost-effective if delivered at similar cost to oral PrEP with antibody-based rapid HIV testing.<br><br>FUNDING: Bill &amp; Melinda Gates Foundation, National Institute of Allergy and Infectious Diseases of the National Institutes of Health.},
}
@article {pmid36640911,
year = {2023},
author = {MacKay, EJ and Zhang, B and Shah, RM and Augoustides, JG and Groeneveld, PW and Desai, ND},
title = {Predictors of Intraoperative Echocardiography: Analysis of The Society of Thoracic Surgeons Database.},
journal = {The Annals of thoracic surgery},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.athoracsur.2023.01.005},
pmid = {36640911},
issn = {1552-6259},
abstract = {BACKGROUND: Intraoperative transesophageal echocardiography (TEE) is associated with improved outcomes after cardiac surgery but unexplained practice pattern variation exists. This study aimed to identify and quantify the predictors of intraoperative TEE use among patients undergoing isolated coronary artery bypass graft (CABG) or cardiac valve surgery.<br><br>METHODS: This observational cohort study used Society of Thoracic Surgeon (STS), Adult Cardiac Surgery Database (ACSD) data to identify and quantify the predictors of intraoperative TEE use among adult patients aged &#x2265;18 years undergoing either isolated CABG surgery or open cardiac valve repair or replacement surgery between 01/01/2011 - 12/31/2019. Generalized linear mixed models (GLMMs) were used to measure the relationship between intraoperative TEE and patient characteristics, surgical volume, and geographic location, while accounting for clustering within hospitals (primary analysis) or surgeons (secondary analysis).<br><br>RESULTS: Of 1,973,655 patients, 1,365,708 underwent isolated CABG and 607,947 underwent cardiac valve surgery. Overall, intraoperative TEE was used in 62% of surgeries. The primary, hospital-level, GLMM analysis demonstrated that the strongest predictor of intraoperative TEE use was the hospital where the surgery occurred - with a median odds ratio (MOR) for TEE of 10.13 in isolated CABG surgery and 5.30 in cardiac valve surgery. The secondary, surgeon-level, GLMM analysis demonstrated similar findings.<br><br>CONCLUSIONS: Intraoperative TEE use (vs lack of use) during surgery was more strongly associated with hospital and surgeon practice patterns than any patient-level factor, surgical volume, or geographic location.},
}
@article {pmid36638200,
year = {2023},
author = {Richardson, A and Darst, B and Wojcik, G and Wagle, N and Haricharan, S},
title = {Research silos in cancer disparities: obstacles to improving clinical outcomes for under-served patient populations.},
journal = {Clinical cancer research : an official journal of the American Association for Cancer Research},
volume = {},
number = {},
pages = {},
doi = {10.1158/1078-0432.CCR-22-3182},
pmid = {36638200},
issn = {1557-3265},
abstract = {Despite much-vaunted progress in cancer therapeutics and diagnostics, outcomes for many groups of non-White cancer patients remain worse than those for their White compatriots. One reason for this is the lack of inclusion and representation of non-White patients in clinical trials, preclinical datasets, and amongst researchers, a shortfall that is gaining wide recognition within the cancer research community and the lay public. Several reviews and editorials have commented on the negative impacts of the status quo on progress in cancer research towards medical breakthroughs that help all communities and not just White cancer patients. In this perspective, we describe the existence of research silos focused either on the impact of socio-economic factors proceeding from systemic racism on cancer outcomes, or on genetic ancestry as it affects the molecular biology of cancer developing in specific patient populations. While both these research areas are critical for progress towards precision medicine equity, breaking down these silos will help us gain an integrated understanding of how race and racism impact cancer development, progression, and patient outcomes. Bringing this comprehensive approach to cancer disparities research will undoubtedly improve our overall understanding of how stress and environmental factors affect the molecular biology of cancer, which will lead to the development of new diagnostics and therapeutics that are applicable across cancer patient demographics.},
}
@article {pmid36637515,
year = {2023},
author = {Grzelak, CA and Ghajar, CM},
title = {Elimination of 4T1 Mammary Tumor Cells by BALB/cBy UBC-GFP Transgenics following Stable Inheritance of the H-2b MHC Allele.},
journal = {ImmunoHorizons},
volume = {7},
number = {1},
pages = {64-70},
doi = {10.4049/immunohorizons.2200101},
pmid = {36637515},
issn = {2573-7732},
abstract = {The human ubiquitin C promoter (UBC)-driven GFP-transgenic mouse (UBC-GFP) transgene integration site was mapped recently to chromosome 17, linked closely to the MHC locus. In this study, we demonstrate a functional consequence of this insertion site in the backcrossed UBC-GFP BALB/c congenic strain [CByJ.B6-Tg(UBC-GFP) 30Scha/J]: rejection of transplanted "syngeneic" 4T1 mammary tumor cells. Rejection of BALB/c-derived 4T1 cells is in all likelihood a consequence of MHC mismatch due to stable inheritance of C57BL/6-derived H-2b (rather than prototypical H-2d) by the BALB/c UBC-GFP strain. These data are a valuable resource to researchers who have previously employed the UBC-GFP congenic strain for attempted syngeneic MHC-matched and allogenic MHC-mismatched studies, as their data likely require reinterpretation. Further, this study reemphasizes the impact of mapping transgene integration sites of commonly used mouse strains as a way of increasing scientific rigor and reproducibility.},
}
@article {pmid36634606,
year = {2023},
author = {Horbinski, C and Nabors, LB and Portnow, J and Baehring, J and Bhatia, A and Bloch, O and Brem, S and Butowski, N and Cannon, DM and Chao, S and Chheda, MG and Fabiano, AJ and Forsyth, P and Gigilio, P and Hattangadi-Gluth, J and Holdhoff, M and Junck, L and Kaley, T and Merrell, R and Mrugala, MM and Nagpal, S and Nedzi, LA and Nevel, K and Nghiemphu, PL and Parney, I and Patel, TR and Peters, K and Puduvalli, VK and Rockhill, J and Rusthoven, C and Shonka, N and Swinnen, LJ and Weiss, S and Wen, PY and Willmarth, NE and Bergman, MA and Darlow, S},
title = {NCCN Guidelines® Insights: Central Nervous System Cancers, Version 2.2022.},
journal = {Journal of the National Comprehensive Cancer Network : JNCCN},
volume = {21},
number = {1},
pages = {12-20},
doi = {10.6004/jnccn.2023.0002},
pmid = {36634606},
issn = {1540-1413},
abstract = {The NCCN Guidelines for Central Nervous System (CNS) Cancers focus on management of the following adult CNS cancers: glioma (WHO grade 1, WHO grade 2-3 oligodendroglioma [1p19q codeleted, IDH-mutant], WHO grade 2-4 IDH-mutant astrocytoma, WHO grade 4 glioblastoma), intracranial and spinal ependymomas, medulloblastoma, limited and extensive brain metastases, leptomeningeal metastases, non-AIDS-related primary CNS lymphomas, metastatic spine tumors, meningiomas, and primary spinal cord tumors. The information contained in the algorithms and principles of management sections in the NCCN Guidelines for CNS Cancers are designed to help clinicians navigate through the complex management of patients with CNS tumors. Several important principles guide surgical management and treatment with radiotherapy and systemic therapy for adults with brain tumors. The NCCN CNS Cancers Panel meets at least annually to review comments from reviewers within their institutions, examine relevant new data from publications and abstracts, and reevaluate and update their recommendations. These NCCN Guidelines Insights summarize the panel's most recent recommendations regarding molecular profiling of gliomas.},
}
@article {pmid36634304,
year = {2023},
author = {Lamble, AJ and Hagiwara, K and Gerbing, RB and Smith, JL and Kolekar, P and Ries, RE and Kolb, EA and Alonzo, T and Ma, X and Meshinchi, S},
title = {CREBBP Alterations are Associated with A Poor Prognosis in de novo AML.},
journal = {Blood},
volume = {},
number = {},
pages = {},
doi = {10.1182/blood.2022017545},
pmid = {36634304},
issn = {1528-0020},
}
@article {pmid36634296,
year = {2023},
author = {Nanou, A and Miao, J and Coumans, FAW and Dolce, EM and Darga, E and Barlow, W and Smerage, JB and Paoletti, C and Godwin, AK and Pusztai, L and Sharma, P and Thompson, A and Hortobagyi, GN and Terstappen, LWMM and Hayes, DF},
title = {Tumor-Derived Extracellular Vesicles as Complementary Prognostic Factors to Circulating Tumor Cells in Metastatic Breast Cancer.},
journal = {JCO precision oncology},
volume = {7},
number = {},
pages = {e2200372},
doi = {10.1200/PO.22.00372},
pmid = {36634296},
issn = {2473-4284},
abstract = {PURPOSE: Circulating tumor cells (CTCs) are strongly prognostic for overall survival (OS) in metastatic breast cancer although additional prognostic biomarkers are needed. We evaluated the complementary prognostic value of tumor-derived extracellular vesicles (tdEVs) next to CTCs.<br><br>METHODS: We applied the open-source ACCEPT software to archived CellSearch images from the prospective clinical trial SWOG0500 to enumerate CTCs and tumor-derived extracellular vesicles (tdEVs) before and after one cycle of chemotherapy.<br><br>RESULTS: CTCs enumerated by ACCEPT were strongly correlated with classical ocular enumeration (correlation r = 0.98). OS was worse with elevated tdEVs (median OS for high/medium/low groups: 17.1 v 29.0 v 43.3 months; P < .0001). In patients with longer OS by CTC counts (< 5 CTC/7.5 mL blood), elevated tdEV levels were independently associated with poorer OS (multivariable analysis P < .001). OS was also longer for patients with low tdEVs after one cycle of chemotherapy (median OS for high/medium/low group: 10.8 v 17.8 v 26.7; P < .0001).<br><br>CONCLUSION: This study highlights the complementary prognostic significance of tdEVs in metastatic breast cancer before and after one cycle of chemotherapy.},
}
@article {pmid36633580,
year = {2023},
author = {Persky, V and Abasilim, C and Tsintsifas, K and Day, T and Sargis, RM and Daviglus, ML and Cai, J and Freels, S and Unterman, T and Chavez, N and Kaplan, R and Isasi, CR and Pirzada, A and Meyer, ML and Talavera, GA and Thyagarajan, B and Peters, BA and Madrigal, JM and Grieco, A and Turyk, ME},
title = {Sex Hormones and Diabetes in 45-74-Year- Old Men and Postmenopausal Women: the Hispanic Community Health Study.},
journal = {The Journal of clinical endocrinology and metabolism},
volume = {},
number = {},
pages = {},
doi = {10.1210/clinem/dgad018},
pmid = {36633580},
issn = {1945-7197},
abstract = {Previous studies demonstrated associations of endogenous sex hormones with diabetes. Less is known about their dynamic relationship with diabetes progression through different stages of the disease, independence of associations, and role of the hypothalamic-pituitary gonadal axis. The purpose of this analysis was to examine relationships of endogenous sex hormones with incident diabetes, prediabetes and diabetes traits in 693 postmenopausal women and 1,015 men aged 45-74 without diabetes at baseline participating in the Hispanic Community Health Study/Study of Latinos and followed six years. Baseline hormones included estradiol, luteinizing hormone (LH), follicle stimulating hormone (FSH), sex hormone-binding globulin (SHBG), dehydroepiandrosterone sulfate (DHEAS), and in men, testosterone and bioavailable testosterone. Associations were analyzed using multivariable Poison and linear regressions. In men, testosterone was inversely associated with conversion from prediabetes to diabetes (incidence rate ratio (IRR) for 1 SD increase in testosterone: 0.821; 95% CI 0.676, 0.997; p = 0.046), but not conversion from normoglycemia to prediabetes. Estradiol was positively associated with increase in fasting insulin and homeostatic model assessment of insulin resistance (HOMA-IR). In women, SHBG was inversely associated with change in glycosylated hemoglobin (HbA1c), post load glucose and conversion from prediabetes to diabetes (IRR = 0.62; 95% CI 0.44, 0.86, p = 0.005) but not from normoglycemia to prediabetes. Relationships with other hormones varied across glycemic measures. Stronger associations of testosterone and SHBG with transition from prediabetes to diabetes than from normoglycemic to prediabetes suggest they are operative at later stages of diabetes development. Biologic pathways by which sex hormones affect glucose homeostasis await future studies.},
}
@article {pmid36631866,
year = {2023},
author = {Zuercher, MD and Harvey, DJ and Santiago-Torres, M and Au, LE and Shivappa, N and Shadyab, AH and Allison, M and Snetselaar, L and Liu, B and Robbins, JA and Hébert, JR and Garcia, L},
title = {Dietary inflammatory index and cardiovascular disease risk in Hispanic women from the Women's Health Initiative.},
journal = {Nutrition journal},
volume = {22},
number = {1},
pages = {5},
pmid = {36631866},
issn = {1475-2891},
abstract = {BACKGROUND: To evaluate the association between the dietary inflammatory index (DII[®]) and incident cardiovascular disease (CVD) in Hispanic women from the Women's Health Initiative (WHI), and to determine if body mass index (BMI) interacted with the DII scores.<br><br>METHODS: Secondary analysis of baseline dietary data and long-term CVD outcomes among 3,469 postmenopausal women who self-identified as Hispanic enrolled in WHI. DII scores were calculated from self-administered food frequency questionnaires. The CVD outcomes included coronary heart disease (CHD) and stroke. Stratified Cox regression models were used to assess the relationship between DII scores and CVD in women with and without obesity. Models were adjusted for age, lifestyle risk factors, known risk factors, and neighborhood socioeconomic status.<br><br>RESULTS: The incidence of CHD was 3.4 and 2.8% for stroke after a median follow-up of 12.9&#xa0;years. None of the DIIs were associated with CVD risk in this sample of Hispanic women. BMI interacted with the DII (p&#x2009;<&#x2009;0.20) and stratified models showed that the associations between the DII and CVD were only significant in women with overweight (p&#x2009;<&#x2009;0.05). In this group, higher DII scores were associated with a higher risk of CHD (HR 1.27; 95% CI: 1.08, 1.51) and a higher risk of stroke (HR 1.32; 95% CI: 1.07, 1.64).<br><br>CONCLUSION: Among postmenopausal Hispanic women with overweight, greater adherence to pro-inflammatory diets was associated with higher risk of CVD. Additional research is needed to understand how to promote long-term heart-healthy dietary habits to reduce inflammation and prevent CVD in at-risk Hispanic women.},
}
@article {pmid36631794,
year = {2023},
author = {Tollefson, D and Ntombela, N and Reeves, S and Charalambous, S and O'Malley, G and Setswe, G and Duerr, A},
title = {"They are gaining experience; we are gaining extra hands": a mixed methods study to assess healthcare worker perceptions of a novel strategy to strengthen human resources for HIV in South Africa.},
journal = {BMC health services research},
volume = {23},
number = {1},
pages = {27},
pmid = {36631794},
issn = {1472-6963},
abstract = {BACKGROUND: Lay health workers (LHWs) can support the HIV response by bridging gaps in human resources for health. Innovative strategies are needed to expand LHW programs in many low- and middle-income countries. Youth Health Africa (YHA) is a novel LHW approach implemented in South Africa that places young adults needing work experience in one-year non-clinical internships at health facilities to support HIV programs (e.g., as HIV testers, data clerks). While research suggests YHA can increase HIV service delivery, we need to understand healthcare worker perceptions to know if this is an acceptable and appropriate approach to strengthen human resources for health and healthcare delivery.<br><br>METHODS: We conducted a convergent mixed methods study to assess healthcare worker acceptance and perceived appropriateness of YHA as implemented in Gauteng and North West provinces, South Africa and identify issues promoting or hindering high acceptability and perceived appropriateness. To do this, we adapted the Johns Hopkins Measure of Acceptability and Appropriateness to survey healthcare workers who supervised interns, which we analyzed descriptively. In parallel, we interviewed frontline healthcare workers who worked alongside YHA interns and conducted an inductive, thematic analysis. We merged quantitative and qualitative results using the Theoretical Framework of Acceptability to understand what promotes or hinders high acceptance and appropriateness of YHA.<br><br>RESULTS: Sixty intern supervisors responded to the survey (91% response rate), reporting an average score of 3.5 for acceptability and 3.6 for appropriateness, on a four-point scale. Almost all 33 frontline healthcare workers interviewed reported the program to be highly acceptable and appropriate. Perceptions that YHA was mutually beneficial, easy to integrate into facilities, and helped facilities be more successful promoted a strong sense of acceptability/appropriateness amongst healthcare workers, but this was tempered by the burden of training interns and limited program communication. Overall, healthcare workers were drawn to the altruistic nature of YHA.<br><br>CONCLUSION: Healthcare workers in South Africa believed YHA was an acceptable and appropriate LHW program to support HIV service delivery because its benefits outweighed its costs. This may be an effective, innovative approach to strengthen human resources for HIV services and the broader health sector.},
}
@article {pmid34991070,
year = {2022},
author = {Kumar, SK and Callander, NS and Adekola, K and Anderson, LD and Baljevic, M and Campagnaro, E and Castillo, JJ and Costello, C and D'Angelo, C and Devarakonda, S and Elsedawy, N and Garfall, A and Godby, K and Hillengass, J and Holmberg, L and Htut, M and Huff, CA and Hultcrantz, M and Kang, Y and Larson, S and Lee, HC and Liedtke, M and Martin, T and Omel, J and Rosenberg, A and Sborov, D and Valent, J and Berardi, R and Kumar, R},
title = {Kidney Cancer, Version 3.2022, NCCN Clinical Practice Guidelines in Oncology.},
journal = {Journal of the National Comprehensive Cancer Network : JNCCN},
volume = {20},
number = {1},
pages = {67-81},
doi = {10.6004/jnccn.2022.0001},
pmid = {34991070},
issn = {1540-1413},
mesh = {*Carcinoma, Renal Cell/diagnosis/therapy ; Humans ; *Kidney Neoplasms/diagnosis/therapy ; Medical Oncology ; },
abstract = {The NCCN Guidelines for Kidney Cancer focus on the screening, diagnosis, staging, treatment, and management of renal cell carcinoma (RCC). Patients with relapsed or stage IV RCC typically undergo surgery and/or receive systemic therapy. Tumor histology and risk stratification of patients is important in therapy selection. The NCCN Guidelines for Kidney Cancer stratify treatment recommendations by histology; recommendations for first-line treatment of ccRCC are also stratified by risk group. To further guide management of advanced RCC, the NCCN Kidney Cancer Panel has categorized all systemic kidney cancer therapy regimens as "Preferred," "Other Recommended Regimens," or "Useful in Certain Circumstances." This categorization provides guidance on treatment selection by considering the efficacy, safety, evidence, and other factors that play a role in treatment selection. These factors include pre-existing comorbidities, nature of the disease, and in some cases consideration of access to agents. This article summarizes surgical and systemic therapy recommendations for patients with relapsed or stage IV RCC.},
}
@article {pmid36631445,
year = {2023},
author = {Yun, J and Hansen, S and Morris, O and Madden, DT and Libeu, CP and Kumar, AJ and Wehrfritz, C and Nile, AH and Zhang, Y and Zhou, L and Liang, Y and Modrusan, Z and Chen, MB and Overall, CC and Garfield, D and Campisi, J and Schilling, B and Hannoush, RN and Jasper, H},
title = {Senescent cells perturb intestinal stem cell differentiation through Ptk7 induced noncanonical Wnt and YAP signaling.},
journal = {Nature communications},
volume = {14},
number = {1},
pages = {156},
pmid = {36631445},
issn = {2041-1723},
abstract = {Cellular senescence and the senescence-associated secretory phenotype (SASP) are implicated in aging and age-related disease, and SASP-related inflammation is thought to contribute to tissue dysfunction in aging and diseased animals. However, whether and how SASP factors influence the regenerative capacity of tissues remains unclear. Here, using intestinal organoids as a model of tissue regeneration, we show that SASP factors released by senescent fibroblasts deregulate stem cell activity and differentiation and ultimately impair crypt formation. We identify the secreted N-terminal domain of Ptk7 as a key component of the SASP that activates non-canonical Wnt / Ca[2+] signaling through FZD7 in intestinal stem cells (ISCs). Changes in cytosolic [Ca[2+]] elicited by Ptk7 promote nuclear translocation of YAP and induce expression of YAP/TEAD target genes, impairing symmetry breaking and stem cell differentiation. Our study discovers secreted Ptk7 as a factor released by senescent cells and provides insight into the mechanism by which cellular senescence contributes to tissue dysfunction in aging and disease.},
}
@article {pmid36630482,
year = {2023},
author = {Lastwika, KJ and Kunihiro, A and Solan, JL and Zhang, Y and Taverne, LR and Shelley, D and Rho, JH and Randolph, TW and Li, CI and Grogan, EL and Massion, PP and Fitzpatrick, AL and MacPherson, D and Houghton, AM and Lampe, PD},
title = {Posttranslational modifications induce autoantibodies with risk prediction capability in patients with small cell lung cancer.},
journal = {Science translational medicine},
volume = {15},
number = {678},
pages = {eadd8469},
doi = {10.1126/scitranslmed.add8469},
pmid = {36630482},
issn = {1946-6242},
abstract = {Small cell lung cancer (SCLC) elicits the generation of autoantibodies that result in unique paraneoplastic neurological syndromes. The mechanistic basis for the formation of such autoantibodies is largely unknown but is key to understanding their etiology. We developed a high-dimensional technique that enables detection of autoantibodies in complex with native antigens directly from patient plasma. Here, we used our platform to screen 1009 human plasma samples for 3600 autoantibody-antigen complexes, finding that plasma from patients with SCLC harbors, on average, fourfold higher disease-specific autoantibody signals compared with plasma from patients with other cancers. Across three independent SCLC cohorts, we identified a set of common but previously unknown autoantibodies that are produced in response to both intracellular and extracellular tumor antigens. We further characterized several disease-specific posttranslational modifications within extracellular proteins targeted by these autoantibodies, including citrullination, isoaspartylation, and cancer-specific glycosylation. Because most patients with SCLC have metastatic disease at diagnosis, we queried whether these autoantibodies could be used for SCLC early detection. We created a risk prediction model using five autoantibodies with an average area under the curve of 0.84 for the three cohorts that improved to 0.96 by incorporating cigarette smoke consumption in pack years. Together, our findings provide an innovative approach to identify circulating autoantibodies in SCLC with mechanistic insight into disease-specific immunogenicity and clinical utility.},
}
@article {pmid36629998,
year = {2023},
author = {Cheng, MM and Reyes, C and Satram, S and Birch, H and Gibbons, DC and Drysdale, M and Bell, CF and Suyundikov, A and Ding, X and Maher, MC and Yeh, W and Telenti, A and Corey, L},
title = {Real-World Effectiveness of Sotrovimab for the Early Treatment of COVID-19 During SARS-CoV-2 Delta and Omicron Waves in the USA.},
journal = {Infectious diseases and therapy},
volume = {},
number = {},
pages = {},
pmid = {36629998},
issn = {2193-8229},
abstract = {INTRODUCTION: Sotrovimab, a recombinant human monoclonal antibody (mAb) against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) had US Food and Drug Administration Emergency Use Authorization for the treatment of high-risk outpatients with mild-to-moderate coronavirus disease 2019 (COVID-19) from 26 May 2021 to 5 April 2022. Real-world clinical effectiveness of sotrovimab in reducing the risk of 30-day all-cause hospitalization and/or mortality was evaluated for the period when the prevalence of circulating SARS-CoV-2 variants changed between Delta and Omicron in the USA.<br><br>METHODS: A retrospective analysis was conducted of de-identified patients diagnosed with COVID-19 between 1 September 2021 to 30 April 2022 in the FAIR Health National Private Insurance Claims database. Patients meeting high-risk criteria were divided into two cohorts: sotrovimab and not treated with a mAb ("no mAb"). All-cause hospitalizations and facility-reported mortality&#x2009;&#x2264;&#x2009;30&#xa0;days of diagnosis ("30-day hospitalization or mortality") were identified. Multivariable and propensity score-matched Poisson and logistic regressions were conducted to estimate the adjusted relative risk (RR) and odds of 30-day hospitalization or mortality in each cohort.<br><br>RESULTS: Compared with the no mAb cohort (n&#x2009;=&#x2009;1,514,868), the sotrovimab cohort (n&#x2009;=&#x2009;15,633) was older and had a higher proportion of patients with high-risk conditions. In the no mAb cohort, 84,307 (5.57%) patients were hospitalized and 8167 (0.54%) deaths were identified, while in the sotrovimab cohort, 418 (2.67%) patients were hospitalized and 13 (0.08%) deaths were identified. After adjusting for potential confounders, the sotrovimab cohort had a 55% lower risk of 30-day hospitalization or mortality (RR 0.45, 95% CI 0.41-0.49) and an 85% lower risk of 30-day mortality (RR 0.15, 95% CI 0.08-0.29). Monthly, from September 2021 to April 2022, the RR reduction for 30-day hospitalization or mortality in the sotrovimab cohort was maintained, ranging from 46% to 71% compared with the no mAb cohort; the RR estimate in April 2022 was uncertain, with wide confidence intervals due to the small sample size.<br><br>CONCLUSION: Sotrovimab was associated with reduced risk of 30-day all-cause hospitalization and mortality versus no mAb treatment. Clinical effectiveness persisted during Delta and early Omicron variant waves and among all high-risk subgroups assessed.},
}
@article {pmid36629487,
year = {2023},
author = {Haiman, CA and Kote-Jarai, Z and Darst, BF and Conti, DV},
title = {RE: Polygenic risk of any, metastatic, and fatal prostate cancer in the Million Veteran Program.},
journal = {Journal of the National Cancer Institute},
volume = {},
number = {},
pages = {},
doi = {10.1093/jnci/djad005},
pmid = {36629487},
issn = {1460-2105},
}
@article {pmid36627630,
year = {2023},
author = {Garside, GB and Sandoval, M and Beronja, S and Rudolph, KL},
title = {Lentiviral in situ targeting of stem cells in unperturbed intestinal epithelium.},
journal = {BMC biology},
volume = {21},
number = {1},
pages = {6},
pmid = {36627630},
issn = {1741-7007},
support = {323136//European Research Council/International ; },
abstract = {BACKGROUND: Methods for the long-term in situ transduction of the unperturbed murine intestinal epithelium have not been developed in past research. Such a method could speed up functional studies and screens to identify genetic factors influencing intestinal epithelium biology. Here, we developed an efficient method achieving this long-sought goal.<br><br>RESULTS: We used ultrasound-guided microinjections to transduce the embryonic endoderm at day 8 (E8.0) in utero. The injection procedure can be completed in 20 min and had a 100% survival rate. By injecting a small volume (0.1-0.2 &#x3bc;l) of concentrated virus, single shRNA constructs as well as lentiviral libraries can successfully be transduced. The new method stably and reproducibly targets adult intestinal epithelium, as well as other endoderm-derived organs such as the lungs, pancreas, liver, stomach, and bladder. Postnatal analysis of young adult mice indicates that single transduced cells at E8.0 gave rise to crypt fields that were comprised of 20-30 neighbouring crypts per crypt-field at 90 days after birth. Lentiviral targeting of Apc[Min/+] mutant and wildtype mice revealed that heterozygous loss of Apc function suppresses the developmental normal growth pattern of intestinal crypt fields. This suppression of crypt field sizes did not involve a reduction of the crypt number per field, indicating that heterozygous Apc loss impaired the growth of individual crypts within the fields. Lentiviral-mediated shRNA knockdown of p53 led to an approximately 20% increase of individual crypts per field in both Apc[+/+] and Apc[Min/+] mice, associating with an increase in crypt size in Apc[Min/+] mice but a slight reduction in crypt size in Apc[+/+] mice. Overall, p53 knockdown rescued the reduction in crypt field size in Apc-mutant mice but had no effect on crypt field size in wildtype mice.<br><br>CONCLUSIONS: This study develops a novel technique enabling robust and reproducible in vivo targeting of intestinal stem cells in situ in the unperturbed intestinal epithelium across different regions of the intestine. In vivo somatic gene editing and genetic screening of lentiviral libraries has the potential to speed up discoveries and mechanistic understanding of genetic pathways controlling the biology of the intestinal epithelium during development and postnatal life.&#xa0;The here developed method enables such approaches.},
}
@article {pmid36627512,
year = {2023},
author = {Tihaya, MS and Mul, K and Balog, J and de Greef, JC and Tapscott, SJ and Tawil, R and Statland, JM and van der Maarel, SM},
title = {Facioscapulohumeral muscular dystrophy: the road to targeted therapies.},
journal = {Nature reviews. Neurology},
volume = {},
number = {},
pages = {},
pmid = {36627512},
issn = {1759-4766},
abstract = {Advances in the molecular understanding of facioscapulohumeral muscular dystrophy (FSHD) have revealed that FSHD results from epigenetic de-repression of the DUX4 gene in skeletal muscle, which encodes a transcription factor that is active in early embryonic development but is normally silenced in almost all somatic tissues. These advances also led to the identification of targets for disease-altering therapies for FSHD, as well as an improved understanding of the molecular mechanism of the disease and factors that influence its progression. Together, these developments led the FSHD research community to shift its focus towards the development of disease-modifying treatments for FSHD. This Review presents advances in the molecular and clinical understanding of FSHD, discusses the potential targeted therapies that are currently being explored, some of which are already in clinical trials, and describes progress in the development of FSHD-specific outcome measures and assessment tools for use in future clinical trials.},
}
@article {pmid36627445,
year = {2023},
author = {Bradley, RK and Anczuków, O},
title = {RNA splicing dysregulation and the hallmarks of cancer.},
journal = {Nature reviews. Cancer},
volume = {},
number = {},
pages = {},
pmid = {36627445},
issn = {1474-1768},
abstract = {Dysregulated RNA splicing is a molecular feature that characterizes almost all tumour types. Cancer-associated splicing alterations arise from both recurrent mutations and altered expression of trans-acting factors governing splicing catalysis and regulation. Cancer-associated splicing dysregulation can promote tumorigenesis via diverse mechanisms, contributing to increased cell proliferation, decreased apoptosis, enhanced migration and metastatic potential, resistance to chemotherapy and evasion of immune surveillance. Recent studies have identified specific cancer-associated isoforms that play critical roles in cancer cell transformation and growth and demonstrated the therapeutic benefits of correcting or otherwise antagonizing such cancer-associated mRNA isoforms. Clinical-grade small molecules that modulate or inhibit RNA splicing have similarly been developed as promising anticancer therapeutics. Here, we review splicing alterations characteristic of cancer cell transcriptomes, dysregulated splicing's contributions to tumour initiation and progression, and existing and emerging approaches for targeting splicing for cancer therapy. Finally, we discuss the outstanding questions and challenges that must be addressed to translate these findings into the clinic.},
}
@article {pmid36626154,
year = {2023},
author = {Boyd, DT and Nelson, LE and Hill, MJ and Whitfield, D and Ramos, SR and Akyirem, S and Emel, L and Wilton, L and Hightow-Weidman, L and Shoptaw, S and Magnus, M and Mayer, KH and Piwowar-Manning, E and Wallace, SE and Fields, SD and Wheeler, DP},
title = {Examining the Role of Autonomy Support, Goal Setting, and Care Coordination Quality on HIV PrEP Adherence in Black Men Who Have Sex with Men: HPTN 073.},
journal = {AIDS patient care and STDs},
volume = {37},
number = {1},
pages = {22-30},
doi = {10.1089/apc.2022.0139},
pmid = {36626154},
issn = {1557-7449},
abstract = {Autonomy support is a concept that is derived from self-determination theory. Autonomy refers to the freedom to act as one chooses. The current study aimed to examine if autonomy support was associated with dried blood spot validated pre-exposure prophylaxis (PrEP) adherence, and whether the association was mediated by PrEP adherence goal setting and progress toward PrEP adherence goals. Our sample was drawn from Black men who have sex with men (MSM) from across three cities (Chapel Hill, NC; Los Angeles, CA; and Washington, DC) in the United States between February 2013 and September 2014. We used logistic regression to evaluate associations between study variables and path analysis to test mediation effects. Participants were, on average, 28 [standard deviation (SD) = 1.12] years old and 25% were unemployed. We found that MSM who experienced high autonomy support were more likely to adhere to PrEP [odds ratio (OR) = 1.17; 95% confidence interval: 1.00-1.38]. MSM who set PrEP adherence goals were more likely to adhere to PrEP. Moreover, MSM who reported making progress toward their goals were also more likely to adhere to PrEP. Finally, client perception of coordination quality enhanced the magnitude of the association between goal setting and goal progress and the effect size of goal progress on PrEP adherence. Autonomy support, goal setting, goal monitoring/evaluation, and care coordination quality influenced PrEP adherence among Black MSM. Our findings indicate that while it is important to set goals for PrEP adherence, goal setting may need to be accompanied by progress monitoring to achieve the maximal effect.},
}
@article {pmid36625863,
year = {2023},
author = {Rock, MC and Vaidya, R and Till, C and Unger, JM and Hershman, D and Ramsey, S and Nehemiah, A and Maeng, D and Krouse, R},
title = {Racial and Ethnic Disparity in Preference-Weighted Quality of Life: Findings from the Selenium and Vitamin E Cancer Prevention Trial.},
journal = {Population health management},
volume = {},
number = {},
pages = {},
doi = {10.1089/pop.2022.0143},
pmid = {36625863},
issn = {1942-7905},
abstract = {Differences in preference-weighted health-related quality of life (HRQOL) scores by race/ethnicity may be due to social factors. Here, Short-Form Six-Dimension (SF-6D) scores are analyzed among men in a prostate cancer prevention trial to explore such differences. Selenium and vitamin E cancer prevention trial participants who completed the SF-6D at baseline, and in at least 1 of follow-up years 1, 3, and 5 were included. This study compared mean SF-6D scores across race/ethnicity at each point using a linear mixed model controlling for demographic and clinical characteristics. At baseline, 9691 men were eligible for analysis, of whom 7556 (78%) were non-Hispanic White, 1592 (16.4%) were non-Hispanic Black, and 543 (5.6%) were Hispanic. Hispanic and White participants had higher unadjusted mean SF-6D scores than Black participants at every time point (P < 0.05), while white participants had lower mean scores than Hispanic participants at every time point after baseline (P < 0.05). After adjusting for covariates, statistically significant differences in HRQOL among the 3 groups persisted. Hispanic participants had higher preference scores than White participants by 0.073 (P < 0.001), 0.075 (P < 0.001), and 0.040 (P < 0.001) in follow-up years 1, 3, and 5, respectively. Black participants had lower scores than White participants by 0.009 (P = 0.004) and 0.008 (P = 0.02) in follow-up years 1 and 3, respectively. The results suggest there is a preference-weighted HRQOL difference by race/ethnicity that cannot be explained by social and clinical variables alone. Understanding how individuals belonging to different racial/ethnic categories view their own HRQOL is necessary for culturally competent care and cost-effectiveness analyses.},
}
@article {pmid36625752,
year = {2023},
author = {Rahbar, H and Dontchos, BN},
title = {Disparities in Imaging Surveillance after a DCIS Diagnosis Elucidate Persistent Inequities in the Breast Cancer Care Continuum.},
journal = {Radiology},
volume = {},
number = {},
pages = {222900},
doi = {10.1148/radiol.222900},
pmid = {36625752},
issn = {1527-1315},
}
@article {pmid36625510,
year = {2023},
author = {Unger, JM and Qian, L and Redman, MW and Tavernier, SS and Minasian, L and Sigal, EV and Papadimitrakopoulou, VA and LeBlanc, M and Cleeland, CS and Dzingle, SA and Summers, TJ and Chao, H and Madhusudhana, S and Villaruz, L and Crawford, J and Gray, JE and Kelly, KL and Gandara, DR and Bazhenova, L and Herbst, RS and Gettinger, SN and Moinpour, CM},
title = {Quality-of-life outcomes and risk prediction for patients randomized to Nivolumab/Ipilimumab vs Nivolumab on LungMAP-S1400I.},
journal = {Journal of the National Cancer Institute},
volume = {},
number = {},
pages = {},
doi = {10.1093/jnci/djad003},
pmid = {36625510},
issn = {1460-2105},
abstract = {BACKGROUND: An important issue for patients with cancer treated with novel therapeutics is how they weigh the effects of treatment on survival and quality-of-life (QOL). We compared QOL in patients enrolled to SWOG-1400I, a substudy of the LungMAP biomarker-driven master protocol.<br><br>METHODS: SWOG S1400I was a randomized phase III trial comparing nivolumab/ipilimumab vs nivolumab for treatment of immunotherapy-na&#xef;ve disease in advanced squamous cell lung cancer. The primary endpoint was the MDASI-LC severity score at Week-7 and Week-13 with a target difference of 1.0 points, assessed using multivariable linear regression. A composite risk model for progression-free and overall survival was derived using best-subset selection.<br><br>RESULTS: Among 158 evaluable patients, median age was 67.6 years and most were male (66.5%). The adjusted MDASI-LC severity score was 0.04 points (95%-CI, -0.44 to 0.51, p=.89) at Week-7 and 0.12 points (95%-CI, -0.41 to 0.65, p=.66) at Week-13. A composite risk model showed that patients with high levels of both appetite loss and shortness-of-breath had a 3-fold increased risk of progression or death (HR&#x2009;=&#x2009;3.06, 95%-CI, 1.88-4.98, p<.001) - and that those with high levels of both appetite loss and work limitations had a 5-fold increased risk of death (HR&#x2009;=&#x2009;5.60, 95%-CI, 3.27-9.57, p<.001) - compared to those with neither risk category.<br><br>CONCLUSIONS: We found no evidence of a benefit of ipilimumab added to nivolumab compared to nivolumab alone for QOL in S1400I. A risk model identified patients at high risk of poor survival, demonstrating the prognostic relevance of baseline patient-reported outcomes even in those with previously-treated advanced cancer.},
}
@article {pmid36625102,
year = {2023},
author = {Nagana Gowda, GA and Raftery, D},
title = {NMR Metabolomics Methods for Investigating Disease.},
journal = {Analytical chemistry},
volume = {95},
number = {1},
pages = {83-99},
doi = {10.1021/acs.analchem.2c04606},
pmid = {36625102},
issn = {1520-6882},
}
@article {pmid36625100,
year = {2023},
author = {Singh, N and Sabo, J and Crane, DA and Doody, DR and Schiff, MA and Mueller, BA},
title = {Birth outcomes and re-hospitalizations among pregnant women with rheumatoid arthritis and systemic lupus erythematosus and their offspring.},
journal = {Arthritis care &amp; research},
volume = {},
number = {},
pages = {},
doi = {10.1002/acr.25087},
pmid = {36625100},
issn = {2151-4658},
abstract = {OBJECTIVE: To compare obstetric/birth outcomes and rehospitalization among women with and without rheumatoid arthritis (RA) or systemic lupus erythematosus (SLE) and their infants.<br><br>METHODS: This population-based retrospective cohort study identified women with RA (N=1,223) and SLE (N=1,354) and unexposed women with singleton births 1987-2014 in Washington State linked vital-hospital discharge records. Outcomes, including cause-specific hospitalizations <2&#x2009;years postpartum, were compared by estimating adjusted relative risks (RR) and cause-specific rehospitalization Hazard Ratios (HR) with 95% confidence intervals (CIs).<br><br>RESULTS: We observed increased risks of several adverse outcomes; RRs often greatest for SLE. Women with RA/SLE more often required rehospitalization, most notably <6 months postpartum (RA: 4% vs 2%, RR 2.22, 95% CI 1.62-3.04; SLE: 6% vs 2%, RR 2.78, 95% CI 2.15-3.59). Maternal postpartum rehospitalization was greatest for musculoskeletal conditions (RA: HR 19.1, 95% CI 13.6-26.8 RA; SLE: HR 29.8, 95% CI 22.1-40.1). Infants of women with SLE more often had malformations (9% vs 6%, RR 1.46, 95% CI 1.21-1.75), and increased mortality <2&#x2009;years (RR 2.11, 95% CI 1.21-3.67). Infants of women with SLE also experienced more frequent rehospitalizations in their 1[st] year of life.<br><br>CONCLUSION: Women with RA or SLE and their infants experienced adverse outcomes, particularly infants of women with SLE. Maternal/infant rehospitalization was more common; most marked in the early months postpartum. Close follow-up during these time periods is crucial to minimize adverse outcomes.},
}
@article {pmid36623515,
year = {2023},
author = {Rodler, E and Sharma, P and Barlow, WE and Gralow, JR and Puhalla, SL and Anders, CK and Goldstein, L and Tripathy, D and Brown-Glaberman, UA and Huynh, TT and Szyarto, CS and Godwin, AK and Pathak, HB and Swisher, EM and Radke, MR and Timms, KM and Lew, DL and Miao, J and Pusztai, L and Hayes, DF and Hortobagyi, GN},
title = {Cisplatin with veliparib or placebo in metastatic triple-negative breast cancer and BRCA mutation-associated breast cancer (S1416): a randomised, double-blind, placebo-controlled, phase 2 trial.},
journal = {The Lancet. Oncology},
volume = {},
number = {},
pages = {},
doi = {10.1016/S1470-2045(22)00739-2},
pmid = {36623515},
issn = {1474-5488},
abstract = {BACKGROUND: Poly(ADP-ribose) polymerase (PARP) inhibitors are effective in germline BRCA1 or BRCA2 (BRCA1/2) mutation-associated metastatic breast cancer. However, studies evaluating PARP inhibitors plus platinum-based chemotherapy in germline BRCA1/2-wildtype triple-negative breast cancer are scarce. A large proportion of germline BRCA1/2-wildtype triple-negative breast cancer shows homologous recombination deficiency (HRD), resulting in a BRCA-like phenotype that might render sensitivity to PARP inhibitors. The S1416 trial assessed the efficacy of cisplatin combined with the PARP inhibitor veliparib in three predefined groups of metastatic breast cancer: germline BRCA1/2-mutated, BRCA-like, and non-BRCA-like.<br><br>METHODS: S1416 was a randomised, double-blind, placebo-controlled, phase 2 trial conducted at 154 community and academic clinical sites across the USA. Eligible patients aged 18 years or older had metastatic or recurrent triple-negative breast cancer or germline BRCA1/2-associated metastatic or recurrent breast cancer, an Eastern Cooperative Oncology Group performance status of 0-2, and had received up to one line of chemotherapy for metastatic disease. Patients were randomly assigned (1:1) via the National Clinical Trials Network open interactive system with dynamic balancing on number of previous cytotoxic regimens for metastatic disease to receive intravenous cisplatin (75 mg/m[2], day 1) combined with either veliparib or matching placebo (300 mg orally twice a day, days 1-14) on a 21-day cycle. Investigators, patients, and the sponsors were masked to treatment assignment; the study statisticians were unmasked. Central testing after ran domisation classified patients as having mutated or wildtype germline BRCA1/2. A biomarker panel established a priori was used to classify patients with wildtype germline BRCA1/2 into BRCA-like and non-BRCA-like phenotype groups, with BRCA-like status based on at least one of the biomarkers: genomic instability score (&#x2265;42), somatic BRCA1/2 mutations, BRCA1 promoter methylation, or non-BRCA1/2 homologous recombination repair germline mutations. The primary endpoint was investigator-assessed progression-free survival, analysed separately for the three predefined biomarker groups with a prespecified &#x3b1; value for each analysis. Efficacy analyses were done by intention to treat and included all eligible patients. Safety analyses of toxicities attributed to treatment included all patients who received at least one dose of veliparib or placebo. The study is ongoing and registered with ClinicalTrials.gov, NCT02595905.<br><br>FINDINGS: Between July 7, 2016, and June 15, 2019, 335 patients were enrolled and randomly assigned. 320 patients (n=162 to cisplatin plus veliparib, all women; and n=158 to cisplatin plus placebo, 157 women and one man) were eligible for efficacy evaluation. 247 patients were classified into the three biomarker groups: germline BRCA1/2-mutated (n=37), BRCA-like (n=101), and non-BRCA-like (n=109). 73 patients could not be classified due to missing biomarker information. Median follow-up was 11&#xb7;1 months (IQR 5&#xb7;6-20&#xb7;8). In the germline BRCA1/2-mutated group, median progression-free survival was 6&#xb7;2 months (95% CI 2&#xb7;3-9&#xb7;2) in the cisplatin plus veliparib group and 6&#xb7;4 months (4&#xb7;3-8&#xb7;2) in the cisplatin plus placebo group (HR 0&#xb7;79 [95% CI 0&#xb7;38-1&#xb7;67]; log-rank p=0&#xb7;54). In the BRCA-like group, median progression-free survival was 5&#xb7;9 months (95% CI 4&#xb7;3-7&#xb7;8) in the cisplatin plus veliparib group versus 4&#xb7;2 months (2&#xb7;3-5&#xb7;0) in the cisplatin plus placebo group (HR 0&#xb7;57 [95% CI 0&#xb7;37-0&#xb7;88]; p=0&#xb7;010). In the non-BRCA-like group, median progression-free survival was 4&#xb7;0 months (95% CI 2&#xb7;5-4&#xb7;7) in the cisplatin plus veliparib group versus 3&#xb7;0 months (2&#xb7;2-4&#xb7;4) in the cisplatin plus placebo group (HR 0&#xb7;89 [95% CI 0&#xb7;60-1&#xb7;33]; p=0&#xb7;57). The most common grade 3 or worse adverse events attributed to treatment were neutropenia (71 [46%] of 155 patients in the cisplatin plus veliparib group vs 29 [20%] of 147 in the cisplatin plus placebo group), leukopenia (42 [27%] vs 11 [7%]), anaemia (35 [23%] vs 12 [8%]), and thrombocytopenia (29 [19%] vs four [3%]). Serious adverse events attributed to treatment occurred in 48 (31%) patients in the cisplatin plus veliparib group and 53 (36%) patients in the cisplatin plus placebo group. Treatment-related adverse events led to death in one patient in the cisplatin plus veliparib group (sepsis) and one patient in the cisplatin plus placebo group (acute kidney injury due to cisplatin plus heart failure from previous doxorubicin exposure).<br><br>INTERPRETATION: The addition of veliparib to cisplatin significantly improved progression-free survival in patients with BRCA-like metastatic triple-negative breast cancer, but not in patients with non-BRCA-like metastatic breast cancer. PARP inhibitors combined with platinum-based chemotherapy should be explored further in BRCA-like triple-negative breast cancer.<br><br>FUNDING: National Cancer Institute and National Institute of General Medical Sciences (US National Institutes of Health); AbbVie; Myriad Genetics; the Biomarker, Imaging, and Quality of Life Studies Funding Program (awarded by the National Cancer Institute); and The University of Kansas Cancer Center.},
}
@article {pmid36623239,
year = {2023},
author = {Cheng, HH and Sokolova, AO and Gulati, R and Bowen, D and Knerr, SA and Klemfuss, N and Grivas, P and Hsieh, A and Lee, JK and Schweizer, MT and Yezefski, T and Zhou, A and Yu, EY and Nelson, PS and Montgomery, B},
title = {Internet-Based Germline Genetic Testing for Men With Metastatic Prostate Cancer.},
journal = {JCO precision oncology},
volume = {7},
number = {},
pages = {e2200104},
doi = {10.1200/PO.22.00104},
pmid = {36623239},
issn = {2473-4284},
abstract = {PURPOSE: Germline mutations in DNA repair genes are present in approximately 10% of men with metastatic prostate cancer (mPC), and guidelines recommend genetic germline testing. Notable barriers exist, including access to genetic counseling, insurance coverage, and out-of-pocket costs. The GENTleMEN study was designed to determine the feasibility of an Internet-based, patient-driven germline genetic testing approach for men with mPC.<br><br>PATIENTS AND METHODS: In this prospective cohort study, men with mPC provided informed consent via an Internet-based platform and completed a questionnaire including demographics and family cancer history. Supporting medical data were also collected. Genetic testing was performed using the Color Genomics 30-gene targeted panel of cancer predisposition genes on a mailed saliva sample. Men whose test results identified a germline pathogenic or likely pathogenic variant received results by phone or telehealth genetic counseling; other participants received results by email with an option for phone-based or telehealth genetic counseling.<br><br>RESULTS: As of August 18, 2021, 816 eligible men were consented, of whom 68% (551) completed genetic testing, and 8.7% (48 of 551) were found to carry a pathogenic or likely pathogenic variant in a germline DNA repair gene: CHEK2 (17), BRCA2 (15), ATM (6), NBN1 (3), BRCA1 (2), PALB2 (2), PMS2 (2), and MSH6 (1). Participants were more likely to complete the testing process if they were non-Hispanic White, married, highly educated, or from a higher-income bracket.<br><br>CONCLUSION: Here, we show the feasibility of delivering germline (inherited) genetic testing by a voluntary, patient-driven, Internet-based platform to men with mPC. Preliminary results show rates of germline DNA repair mutations, consistent with other cohorts. Although feasible for some, reduced steps for participation, more dedicated diverse outreach and participant support, and identification and addressing of additional barriers is needed to ensure equitable access and optimization.},
}
@article {pmid36509074,
year = {2022},
author = {Schaeffer, EM and Srinivas, S and Adra, N and An, Y and Barocas, D and Bitting, R and Bryce, A and Chapin, B and Cheng, HH and D'Amico, AV and Desai, N and Dorff, T and Eastham, JA and Farrington, TA and Gao, X and Gupta, S and Guzzo, T and Ippolito, JE and Kuettel, MR and Lang, JM and Lotan, T and McKay, RR and Morgan, T and Netto, G and Pow-Sang, JM and Reiter, R and Roach, M and Robin, T and Rosenfeld, S and Shabsigh, A and Spratt, D and Teply, BA and Tward, J and Valicenti, R and Wong, JK and Berardi, RA and Shead, DA and Freedman-Cass, DA},
title = {NCCN Guidelines® Insights: Prostate Cancer, Version 1.2023.},
journal = {Journal of the National Comprehensive Cancer Network : JNCCN},
volume = {20},
number = {12},
pages = {1288-1298},
doi = {10.6004/jnccn.2022.0063},
pmid = {36509074},
issn = {1540-1413},
mesh = {Male ; Humans ; *Prostatic Neoplasms/diagnosis/therapy ; Risk Assessment ; },
abstract = {The NCCN Guidelines for Prostate Cancer address staging and risk assessment after a prostate cancer diagnosis and include management options for localized, regional, recurrent, and metastatic disease. The NCCN Prostate Cancer Panel meets annually to reevaluate and update their recommendations based on new clinical data and input from within NCCN Member Institutions and from external entities. These NCCN Guidelines Insights summarizes much of the panel's discussions for the 4.2022 and 1.2023 updates to the guidelines regarding systemic therapy for metastatic prostate cancer.},
}
@article {pmid36509072,
year = {2022},
author = {Gajjar, A and Mahajan, A and Abdelbaki, M and Anderson, C and Antony, R and Bale, T and Bindra, R and Bowers, DC and Cohen, K and Cole, B and Dorris, K and Ermoian, R and Franson, A and Helgager, J and Landi, D and Lin, C and Metrock, L and Nanda, R and Palmer, J and Partap, S and Plant, A and Pruthi, S and Reynolds, R and Ruggieri, P and Stearns, D and Storm, P and Wang, A and Warren, K and Whipple, N and Zaky, W and McMillian, NR and Pluchino, LA},
title = {Pediatric Central Nervous System Cancers, Version 2.2023, NCCN Clinical Practice Guidelines in Oncology.},
journal = {Journal of the National Comprehensive Cancer Network : JNCCN},
volume = {20},
number = {12},
pages = {1339-1362},
doi = {10.6004/jnccn.2022.0062},
pmid = {36509072},
issn = {1540-1413},
mesh = {Adolescent ; Child ; Humans ; *Central Nervous System Neoplasms/diagnosis/epidemiology/therapy ; *Glioma/diagnosis ; *Neoplasms, Germ Cell and Embryonal/diagnosis/epidemiology/therapy ; Prognosis ; Brain/pathology ; },
abstract = {Central nervous system (CNS) cancers account for approximately one quarter of all pediatric tumors and are the leading cause of cancer-related death in children. More than 4,000 brain and CNS tumors are diagnosed each year in children and teens, and the incidence rate has remained stagnant in recent years. The most common malignant pediatric CNS tumors are gliomas, embryonal tumors consisting of predominately medulloblastomas, and germ cell tumors. The inaugural version of the NCCN Guidelines for Pediatric Central Nervous System Cancers focuses on the diagnosis and management of patients with pediatric diffuse high-grade gliomas. The information contained in the NCCN Guidelines is designed to help clinicians navigate the complex management of pediatric patients with diffuse high-grade gliomas. The prognosis for these highly aggressive tumors is generally poor, with 5-year survival rates of <20% despite the use of combined modality therapies of surgery, radiation therapy and systemic therapy. Recent advances in molecular profiling has expanded the use of targeted therapies in patients whose tumors harbor certain alterations. However, enrollment in a clinical trial is the preferred treatment for eligible patients.},
}
@article {pmid36622766,
year = {2023},
author = {Su, YR and Sakoda, LC and Jeon, J and Thomas, M and Lin, Y and Schneider, JL and Udaltsova, N and Lee, JK and Lansdorp-Vogelaar, I and Peterse, EFP and Zauber, AG and Zheng, J and Zheng, Y and Hauser, E and Baron, JA and Barry, EL and Bishop, DT and Brenner, H and Buchanan, DD and Burnett-Hartman, A and Campbell, PT and Casey, G and Castellví-Bel, S and Chan, AT and Chang-Claude, J and Figueiredo, JC and Gallinger, SJ and Giles, GG and Gruber, SB and Gsur, A and Gunter, MJ and Hampe, J and Hampel, H and Harrison, TA and Hoffmeister, M and Hua, X and Huyghe, JR and Jenkins, MA and Keku, TO and Le Marchand, L and Li, L and Lindblom, A and Moreno, V and Newcomb, PA and Pharoah, PDP and Platz, EA and Potter, JD and Qu, C and Rennert, G and Schoen, RE and Slattery, ML and Song, M and van Duijnhoven, FJB and Van Guelpen, B and Vodicka, P and Wolk, A and Woods, MO and Wu, AH and Hayes, RB and Peters, U and Corley, DA and Hsu, L},
title = {Validation of a genetic-enhanced risk prediction model for colorectal cancer in a large community-based cohort.},
journal = {Cancer epidemiology, biomarkers &amp; prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology},
volume = {},
number = {},
pages = {},
doi = {10.1158/1055-9965.EPI-22-0817},
pmid = {36622766},
issn = {1538-7755},
abstract = {BACKGROUND: Polygenic risk scores (PRS) which summarize individuals' genetic risk profile may enhance targeted colorectal cancer (CRC) screening. A critical step towards clinical implementation is rigorous external validations in large community-based cohorts. This study externally validated a PRS-enhanced CRC risk model comprising 140 known CRC loci to provide a comprehensive assessment on prediction performance.<br><br>METHODS: The model was developed using 20,338 individuals and externally validated in a community-based cohort (n=85,221). We validated predicted 5-year absolute CRC risk, including calibration using expected-to-observed case ratios (E/O) and calibration plots, and discriminatory accuracy using time-dependent AUC. The PRS-related improvement in AUC, sensitivity and specificity were assessed in individuals of age 45-74 years (screening-eligible age group) and 40-49 years with no endoscopy history (younger-age group).<br><br>RESULTS: In European-ancestral individuals, the predicted 5-year risk calibrated well (E/O=1.01 (95%CI 0.91-1.13)) and had high discriminatory accuracy (AUC=0.73 (95%CI 0.71-0.76)). Adding the PRS to a model with age, sex, family and endoscopy history improved the 5-year AUC by 0.06 (p-value<0.001) and 0.14 (p-value=0.05) in the screening-eligible age and younger-age groups, respectively. Using a risk-threshold of 5-year SEER CRC-incidence rate at age 50 years, adding the PRS had a similar sensitivity but improved the specificity by 11% (p-value<0.001) in the screening-eligible age group. In the younger-age group it improved the sensitivity by 27% (p-value=0.04) with similar specificity.<br><br>CONCLUSIONS: The proposed PRS-enhanced model provides a well-calibrated 5-year CRC risk prediction and improves discriminatory accuracy in the external cohort.<br><br>IMPACT: The proposed model has potential utility in risk-stratified CRC prevention.},
}
@article {pmid36622694,
year = {2023},
author = {Cranmer, LD and Lu, Y and Heise, RS and Ballman, KV and Loggers, ET and Pollack, SM and Wagner, MJ and Reinke, DK and Schöffski, P and Tap, WD},
title = {Bolus versus Continuous Intravenous Delivery of Doxorubicin in Soft Tissue Sarcomas: Post Hoc Analysis of a Prospective Randomized Trial (SARC021/TH CR-406).},
journal = {Clinical cancer research : an official journal of the American Association for Cancer Research},
volume = {},
number = {},
pages = {},
doi = {10.1158/1078-0432.CCR-22-1564},
pmid = {36622694},
issn = {1557-3265},
abstract = {PURPOSE: Continuous intravenous infusion (CIV) of doxorubicin (DOX), versus bolus (BOL), may minimize dose-dependent DOX cardiomyopathy, but it is unclear whether this advantage is evident as employed in typical soft tissue sarcoma (STS) treatment. The impact of administration mode on adverse events (AEs) and efficacy were compared using data from a randomized trial of DOX-based therapy (SARC021/TH CR-406).<br><br>EXPERIMENTAL DESIGN: In this post hoc analysis, CIV vs. BOL was at discretion of the treating physician. Likelihood of AEs, and objective responses were assessed by adjusted logistic regression. Progression-free (PFS) and overall survival (OS) were compared using Kaplan-Meier, log-rank test, and adjusted Cox regression.<br><br>RESULTS: DOX was administered by BOL to 556 and by CIV to 84 patients. Proportions experiencing hematologic, non-hematologic or cardiac AEs did not differ by administration mode. Hematologic AEs were associated with age, performance status, and cumulative DOX. Non-hematologic AEs were associated with age, performance status, and cumulative evofosfamide. Cardiac AEs were only associated with cumulative DOX; there was no interaction between DOX dose and delivery mode. PFS and OS were similar (median 6.14 months BOL vs. 6.11 months CIV, p=0.47; mOS 18.4 months BOL vs. 21.4 months CIV, p=0.62). PFS, OS, and objective responses were not associated with delivery mode.<br><br>CONCLUSIONS: CIV was not associated with superior outcomes over BOL within DOX dosing limits of SARC021. Cardiac AEs were associated with increasing cumulative DOX dose. While not randomized with respect to DOX delivery mode, the results indicate that continued investigation of AE mitigation strategies is warranted.},
}
@article {pmid36622692,
year = {2022},
author = {Poore, HA and Stuart, YE and Rennison, DJ and Roesti, M and Hendry, AP and Bolnick, DI and Peichel, CL},
title = {Repeated genetic divergence plays a minor role in repeated phenotypic divergence of lake-stream stickleback.},
journal = {Evolution; international journal of organic evolution},
volume = {},
number = {},
pages = {},
doi = {10.1093/evolut/qpac025},
pmid = {36622692},
issn = {1558-5646},
abstract = {Recent studies have shown that the repeated evolution of similar phenotypes in response to similar ecological conditions (here "parallel evolution") often occurs through mutations in the same genes. However, many previous studies have focused on known candidate genes in a limited number of systems. Thus, the question of how often parallel phenotypic evolution is due to parallel genetic changes remains open. Here, we used quantitative trait locus (QTL) mapping in F2 intercrosses between lake and stream threespine stickleback (Gasterosteus aculeatus) from four independent watersheds on Vancouver Island, Canada to determine whether the same QTL underlie divergence in the same phenotypes across, between, and within watersheds. We find few parallel QTL, even in independent crosses from the same watershed or for phenotypes that have diverged in parallel. These findings suggest that different mutations can lead to similar phenotypes. The low genetic repeatability observed in these lake-stream systems contrasts with the higher genetic repeatability observed in other stickleback systems. We speculate that differences in evolutionary history, gene flow, and/or the strength and direction of selection might explain these differences in genetic parallelism and emphasize that more work is needed to move beyond documenting genetic parallelism to identifying the underlying causes.},
}
@article {pmid36622529,
year = {2023},
author = {Gholami, S and Colby, S and Horowitz, DP and Guthrie, KA and Ben-Josef, E and El-Khoueiry, AB and Blanke, CD and Philip, PA and Kachnic, LA and Ahmad, SA and Rocha, FG},
title = {Adjuvant Chemoradiation in Patients with Lymph Node-Positive Biliary Tract Cancers: Secondary Analysis of a Single-Arm Clinical Trial (SWOG 0809).},
journal = {Annals of surgical oncology},
volume = {},
number = {},
pages = {},
pmid = {36622529},
issn = {1534-4681},
abstract = {BACKGROUND: SWOG 0809 is the only prospective study of adjuvant chemotherapy followed by chemoradiation focusing on margin status in patients with extrahepatic cholangiocarcinoma (EHCC) and gallbladder cancer (GBCA); however, the effects of adjuvant therapy by nodal status have never been reported in this population.<br><br>METHODS: Patients with resected EHCC and GBCA, stage pT2-4, node-positive (N+) or margin-positive (R1) who completed four cycles of chemotherapy followed by radiotherapy were included. Cox regression was used to compare overall survival (OS), disease-free survival (DFS), local recurrence, and distant metastasis by nodal status. DFS rates were compared with historical data via a one-sample t-test.<br><br>RESULTS: Sixty-nine patients [EHCC, n&#xa0;=&#xa0;46 (66%); GBCA, n&#xa0;=&#xa0;23 (33%)] were evaluated, with a median age of 61.7 years and an R0 rate of 66.7% and R1 rate of 33.3%. EHCC versus GBCA was more likely to be N+ (73.9% vs. 47.8%, p&#xa0;=&#xa0;0.03). Nodal status did not significantly impact OS (hazard ratio [HR] 1.98, 95% confidence interval [CI] 0.86-4.54, p&#xa0;=&#xa0;0.11) or DFS (HR 1.63, 95% CI 0.77-3.44, p&#xa0;=&#xa0;0.20). Two-year OS was 70.6% for node-negative (N0) disease and 60.9% for N+ disease, while 2-year DFS was 62.5% for N0 tumors and 49.8% for N+ tumors. N+ versus N0 tumors showed higher rates of distant failure (42.2% vs. 25.0%, p&#xa0;=&#xa0;0.04). The 2-year DFS rate in N+ tumors was significantly higher than in historical controls (49.8% vs. 29.7%, p&#xa0;=&#xa0;0.004).<br><br>CONCLUSIONS: Adjuvant therapy is associated with favorable outcome independent of nodal status and may impact local control in N+ patients. These data could serve as a benchmark for future adjuvant trials, including molecular-targeted agents.},
}
@article {pmid36621992,
year = {2023},
author = {Schweizer, MT and True, L and Gulati, R and Zhao, Y and Ellis, W and Schade, G and Montgomery, B and Goyal, S and Nega, K and Hakansson, AK and Liu, Y and Davicioni, E and Pienta, K and Nelson, PS and Lin, D and Wright, J},
title = {Reply by Authors.},
journal = {The Journal of urology},
volume = {209},
number = {2},
pages = {362-363},
doi = {10.1097/JU.0000000000003038.02},
pmid = {36621992},
issn = {1527-3792},
}
@article {pmid36621991,
year = {2023},
author = {Schweizer, MT and True, L and Gulati, R and Zhao, Y and Ellis, W and Schade, G and Montgomery, B and Goyal, S and Nega, K and Hakansson, AK and Liu, Y and Davicioni, E and Pienta, K and Nelson, PS and Lin, D and Wright, J},
title = {Pathological Effects of Apalutamide in Lower-risk Prostate Cancer: Results From a Phase II Clinical Trial.},
journal = {The Journal of urology},
volume = {209},
number = {2},
pages = {354-363},
doi = {10.1097/JU.0000000000003038},
pmid = {36621991},
issn = {1527-3792},
abstract = {PURPOSE: Active surveillance is a safe and effective strategy for men with lower-risk prostate cancer who want to avoid local therapy; however, many patients on active surveillance progress to active treatment (eg, prostatectomy or radiation). We hypothesized that apalutamide would decrease active surveillance attrition rates through downstaging low-grade tumors.<br><br>MATERIALS AND METHODS: This was an open-label, single-arm, phase II study testing 90 days of oral apalutamide 240 mg daily in men with low- to intermediate-risk prostate cancer on active surveillance. The primary objective was to determine the percentage of patients with a negative biopsy immediately following treatment. Secondary objectives were to assess long-term clinical outcomes, quality of life, safety, and biomarkers of response/resistance.<br><br>RESULTS: Twenty-three patients enrolled and 22 completed 90 days of apalutamide with post-treatment biopsy. Fifteen (65%) had Grade Group 1 disease, and all others had Grade Group 2 disease. Seven (30%) had favorable- to intermediate-risk disease. Of 22 evaluable patients, 13 (59%) had no residual cancer on post-treatment biopsy. The median time to first positive biopsy was 364 days (95% CI: 91-742 days). The impact of apalutamide on quality of life was minimal and transient. Decipher risk classifier revealed a greater number of negative post-treatment biopsies in those with higher baseline genomic risk score (P = .01).<br><br>CONCLUSIONS: The negative repeat biopsy rate following 90 days of apalutamide was high in men with prostate cancer followed on active surveillance. Apalutamide was safe, well tolerated, and had minimal impact on quality of life. Randomized studies evaluating the effects of apalutamide in men enrolled on active surveillance are warranted.},
}
@article {pmid36618897,
year = {2023},
author = {Stansfield, SE and Moore, M and Boily, MC and Hughes, JP and Donnell, DJ and Dimitrov, DT},
title = {Estimating benefits of using on-demand oral prep by MSM: A comparative modeling study of the US and Thailand.},
journal = {EClinicalMedicine},
volume = {56},
number = {},
pages = {101776},
pmid = {36618897},
issn = {2589-5370},
abstract = {BACKGROUND: Daily and on-demand pre-exposure prophylaxis (PrEP) are effective at preventing HIV acquisition among men who have sex with men (MSM), but only daily PrEP is approved in the US. On-demand PrEP may improve uptake and adherence. We identify sub-groups of MSM who would benefit from on-demand PrEP and determine effectiveness achieved if individuals used their optimal regimens.<br><br>METHODS: Using data from the HPTN 067 study (study period 2012-2014), we created an individual-based stochastic model of HIV risk in two synthetic MSM populations with parameters separately estimated using data from Harlem, US, and Bangkok, Thailand. Agents were assigned daily and on-demand PrEP for six months each. Two personalized PrEP assignments: optimal, based on improved predicted effectiveness and reduced pill burden, and adherence-based, using daily PrEP adherence, were simulated for another six months.<br><br>FINDINGS: Simulated on-demand PrEP was optimal for approximately one-third of MSM. It was assigned mainly to those with low daily PrEP adherence (88% (Harlem), 95% (Bangkok) of MSM with daily PrEP adherence <40%). Mean effectiveness was slightly higher in the full synthetic population with optimal PrEP assignment compared to universal daily PrEP. Among MSM for whom on-demand PrEP was optimal, mean effectiveness improved by 18 (Harlem) and 7 percentage points (Bangkok). Comparable predicted effectiveness was achieved if on-demand PrEP was assigned to the population with daily PrEP adherence <50%. There was no advantage in assigning on-demand PrEP by sex act frequency.<br><br>INTERPRETATION: On-demand PrEP could benefit many MSM by increasing effectiveness or decreasing pill burden with similar effectiveness. On-demand PrEP may be an effective alternative to daily PrEP for individuals with difficulty taking daily PrEP consistently. Results were similar for Harlem and Bangkok, indicating that these conclusions were robust in populations with different overall adherence levels and may inform future public-health policies.<br><br>FUNDING: US NIH grant UM1 AI068617.},
}
@article {pmid36612132,
year = {2022},
author = {Palmieri, R and Maurillo, L and Del Principe, MI and Paterno, G and Walter, RB and Venditti, A and Buccisano, F},
title = {Time for Dynamic Assessment of Fitness in Acute Myeloid Leukemia.},
journal = {Cancers},
volume = {15},
number = {1},
pages = {},
doi = {10.3390/cancers15010136},
pmid = {36612132},
issn = {2072-6694},
abstract = {Informed treatment decision-making in acute myeloid leukemia (AML) requires a comprehensive evaluation of all clinical and biological features that may affect the outcome with any given type or intensity of therapy [...].},
}
@article {pmid36612116,
year = {2022},
author = {Khosla, AA and Saxena, S and Ozair, A and Venur, VA and Peereboom, DM and Ahluwalia, MS},
title = {Novel Therapeutic Approaches in Neoplastic Meningitis.},
journal = {Cancers},
volume = {15},
number = {1},
pages = {},
doi = {10.3390/cancers15010119},
pmid = {36612116},
issn = {2072-6694},
abstract = {Central nervous system (CNS) metastasis from systemic cancers can involve the brain parenchyma, leptomeninges, or the dura. Neoplastic meningitis (NM), also known by different terms, including leptomeningeal carcinomatosis and carcinomatous meningitis, occurs due to solid tumors and hematologic malignancies and is associated with a poor prognosis. The current management paradigm entails a multimodal approach focused on palliation with surgery, radiation, and chemotherapy, which may be administered systemically or directly into the cerebrospinal fluid (CSF). This review focuses on novel therapeutic approaches, including targeted and immunotherapeutic agents under investigation, that have shown promise in NM arising from solid tumors.},
}
@article {pmid36610687,
year = {2023},
author = {Wojcik, KY and Hawkins, M and Anderson-Mellies, A and Hall, E and Wysong, A and Milam, J and Hamilton, AS and Cockburn, MG},
title = {Melanoma Survival by Age Group: Population-Based Disparities for Adolescent and Young Adult Patients by Stage, Tumor Thickness, and Insurance Type.},
journal = {Journal of the American Academy of Dermatology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jaad.2022.10.063},
pmid = {36610687},
issn = {1097-6787},
abstract = {BACKGROUND: Melanoma survival literature predominantly represents patients >65 years of age. Study of younger patients may reveal potential age-group-specific differences in survival outcome.<br><br>OBJECTIVE: Identify factors associated with differences in melanoma survival in two age groups, adolescents and young adults (AYAs; ages 15-39) and older adults (ages 40-64).<br><br>METHODS: This population-based registry study included all cases (n=81,597) of cutaneous melanoma diagnosed at ages 15-64 from 2004-2015 in California. Age-group-specific multivariable Cox hazard regressions were used.<br><br>RESULTS: In the adjusted, age-group-specific models, AYA patients with Stage IV melanoma had worse survival (HR: 20.39, 95%CI: 13.30-31.20) than was observed among older adults (HR: 10.79, 95%CI: 9.33-12.48). Thicker tumors and public insurance were also associated with worse survival for AYAs than observed in models for older adults. AYAs experienced better survival when detected at earlier stages.<br><br>LIMITATIONS: Registry data does not routinely collect behavioral information or family history of melanoma.<br><br>CONCLUSIONS: Survival was much worse for AYAs with stage IV melanoma than observed among older adults. To improve AYA survival, early melanoma detection is critical. Greater awareness, suspicion, and screening for AYA melanoma may disrupt delays in diagnosis and reduce the excess burden of mortality from Stage IV melanoma in young patients.},
}
@article {pmid36610232,
year = {2023},
author = {Wu, Z and Han, Y and Wan, Y and Hua, X and Chill, SS and Teshome, K and Zhou, W and Liu, J and Wu, D and Hutchinson, A and Jones, K and Dagnall, CL and Hicks, BD and Liao, L and Hallen-Adams, H and Shi, J and Abnet, CC and Sinha, R and Chaturvedi, A and Vogtmann, E},
title = {Oral microbiome and risk of incident head and neck cancer: A nested case-control study.},
journal = {Oral oncology},
volume = {137},
number = {},
pages = {106305},
doi = {10.1016/j.oraloncology.2022.106305},
pmid = {36610232},
issn = {1879-0593},
abstract = {OBJECTIVES: This nested case-control study in the NIH-AARP Diet and Health Study was carried out to prospectively investigate the relationship of oral microbiome with head and neck cancer (HNC).<br><br>MATERIALS AND METHODS: 56 incident HNC cases were identified, and 112 controls were incidence-density matched to cases. DNA extracted from pre-diagnostic oral wash samples was whole-genome shotgun metagenomic sequenced to measure the overall oral microbiome. ITS2 gene qPCR was used to measure the presence of fungi. ITS2 gene sequencing was performed on ITS2 gene qPCR positive samples. We computed taxonomic and functional alpha-diversity and beta-diversity metrics. The presence and relative abundance of groups of red-complex (e.g., Porphyromonas gingivalis) and/or orange-complex (e.g., Fusobacterium nucleatum) periodontal pathogens were compared between cases and controls using conditional logistic regression models and MiRKAT.<br><br>RESULTS: Participants with higher taxonomic microbial alpha-diversity had a non-statistically significant decreased risk of HNC. No case-control differences were found for beta diversity by MiRKAT model (all p&#xa0;>&#xa0;0.05). A greater relative abundance of red-complex periodontal pathogens (OR&#xa0;=&#xa0;0.51, 95&#xa0;% CI&#xa0;=&#xa0;0.26-1.00), orange-complex (OR&#xa0;=&#xa0;0.38, 95&#xa0;% CI&#xa0;=&#xa0;0.18-0.83), and both complexes' pathogens (OR&#xa0;=&#xa0;0.32, 95&#xa0;% CI&#xa0;=&#xa0;0.14-0.75), were associated with reduced risk of HNC. The presence of oral fungi was also strongly associated with reduced risk of HNC compared with controls (OR&#xa0;=&#xa0;0.39, 95&#xa0;% CI&#xa0;=&#xa0;0.17-0.92).<br><br>CONCLUSION: Greater taxonomic alpha-diversity, the presence of oral fungi, and the presence or relative abundance of multiple microbial species, including the red- and orange-complex periodontal pathogens, were associated with reduced risk of HNC. Future studies with larger sample sizes are needed to evaluate these associations.},
}
@article {pmid36610058,
year = {2023},
author = {Rogers, JH and Casto, AM and Nwanne, G and Link, AC and Martinez, MA and Nackviseth, C and Wolf, CR and Hughes, JP and Englund, JA and Sugg, N and Uyeki, TM and Han, PD and Pfau, B and Shendure, J and Chu, HY},
title = {Results from a test-and-treat study for influenza among residents of homeless shelters in King County, WA: A stepped-wedge cluster-randomized trial.},
journal = {Influenza and other respiratory viruses},
volume = {},
number = {},
pages = {},
doi = {10.1111/irv.13092},
pmid = {36610058},
issn = {1750-2659},
support = {75D30120C09322/CC/CDC HHS/United States ; },
abstract = {BACKGROUND: Persons experiencing homelessness face increased risk of influenza as overcrowding in congregate shelters can facilitate influenza virus spread. Data regarding on-site influenza testing and antiviral treatment within homeless shelters remain limited.<br><br>METHODS: We conducted a cluster-randomized stepped-wedge trial of point-of-care molecular influenza testing coupled with antiviral treatment with baloxavir or oseltamivir in residents of 14 homeless shelters in Seattle, WA, USA. Residents &#x2265;3&#x2009;months with cough or &#x2265;2 acute respiratory illness (ARI) symptoms and onset <7&#x2009;days were eligible. In control periods, mid-nasal swabs were tested for influenza by reverse transcription polymerase chain reaction (RT-PCR). The intervention period included on-site rapid molecular influenza testing and antiviral treatment for influenza-positives if symptom onset was <48&#x2009;h. The primary endpoint was monthly influenza virus infections in the control versus intervention periods. Influenza whole genome sequencing was performed to assess transmission and antiviral resistance.<br><br>RESULTS: During 11/15/2019-4/30/2020 and 11/2/2020-4/30/2021, 1283 ARI encounters from 668 participants were observed. Influenza virus was detected in 51 (4%) specimens using RT-PCR (A&#x2009;=&#x2009;14; B&#x2009;=&#x2009;37); 21 influenza virus infections were detected from 269 (8%) intervention-eligible encounters by rapid molecular testing and received antiviral treatment. Thirty-seven percent of ARI-participant encounters reported symptom onset&#x2009;<&#x2009;48&#x2009;h. The intervention had no effect on influenza virus transmission (adjusted relative risk 1.73, 95% confidence interval [CI] 0.50-6.00). Of 23 influenza genomes, 86% of A(H1N1)pdm09 and 81% of B/Victoria sequences were closely related.<br><br>CONCLUSION: Our findings suggest feasibility of influenza test-and-treat strategies in shelters. Additional studies would help discern an intervention effect during periods of increased influenza activity.},
}
@article {pmid36609093,
year = {2023},
author = {Huguet, N and Green, BB and Voss, RW and Larson, AE and Angier, H and Miguel, M and Liu, S and Latkovic-Taber, M and DeVoe, JE},
title = {Factors Associated With Blood Pressure Control Among Patients in Community Health Centers.},
journal = {American journal of preventive medicine},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.amepre.2022.11.002},
pmid = {36609093},
issn = {1873-2607},
abstract = {INTRODUCTION: Understanding the multilevel factors associated with controlled blood pressure is important to determine modifiable factors for future interventions, especially among populations living in poverty. This study identified clinically important factors associated with blood pressure control among patients receiving care in community health centers.<br><br>METHODS: This study includes 31,089 patients with diagnosed hypertension by 2015 receiving care from 103 community health centers; aged 19-64 years; and with &#x2265;1 yearly visit with &#x2265;1 recorded blood pressure in 2015, 2016, and 2017. Blood pressure control was operationalized as an average of all blood pressure measurements during all the 3 years and categorized as controlled (blood pressure <140/90), partially controlled (mixture of controlled and uncontrolled blood pressure), or never controlled. Multinomial mixed-effects logistic regression models, conducted in 2022, were used to calculate unadjusted ORs and AORs of being in the never- or partially controlled blood pressure groups versus in the always-controlled group.<br><br>RESULTS: A total of 50.5% had always controlled, 39.7% had partially controlled, and 9.9% never had controlled blood pressure during the study period. The odds of being partially or never in blood pressure control were higher for patients without continuous insurance (AOR=1.09; 95% CI=1.03, 1.16; AOR=1.18; 95% CI=1.07, 1.30, respectively), with low provider continuity (AOR=1.24; 95% CI=1.15, 1.34; AOR=1.28; 95% CI=1.13, 1.45, respectively), with a recent diagnosis of hypertension (AOR=1.34; 95% CI=1.20, 1.49; AOR=1.19; 95% CI=1.00, 1.42), with inconsistent antihypertensive medications (AOR=1.19; 95% CI=1.11, 1.27; AOR=1.26; 95% CI=1.13, 1.41, respectively), and with fewer blood pressure checks (AOR=2.14; 95% CI=1.97, 2.33; AOR=2.17; 95% CI=1.90, 2.48, respectively) than for their counterparts.<br><br>CONCLUSIONS: Efforts targeting continuous and consistent access to care, antihypertensive medications, and regular blood pressure monitoring may improve blood pressure control among populations living in poverty.},
}
@article {pmid36608310,
year = {2023},
author = {Miklos, DB and Abu Zaid, M and Cooney, JP and Albring, JC and Flowers, M and Skarbnik, AP and Yakoub-Agha, I and Ko, BS and Bruno, B and Waller, EK and Yared, J and Sohn, SK and Bulabois, CE and Teshima, T and Jacobsohn, D and Greinix, H and Mokatrin, A and Lee, Y and Wahlstrom, JT and Styles, L and Socie, G},
title = {Ibrutinib for First-Line Treatment of Chronic Graft-Versus-Host Disease: Results From the Randomized Phase III iNTEGRATE Study.},
journal = {Journal of clinical oncology : official journal of the American Society of Clinical Oncology},
volume = {},
number = {},
pages = {JCO2200509},
doi = {10.1200/JCO.22.00509},
pmid = {36608310},
issn = {1527-7755},
abstract = {PURPOSE: To present primary and final analyses from the randomized, double-blind, placebo-controlled, phase III iNTEGRATE study, which evaluated the safety and efficacy of ibrutinib with prednisone in previously untreated patients with chronic graft-versus-host disease (cGVHD).<br><br>METHODS: Patients (age &#x2265; 12 years) with newly diagnosed moderate or severe cGVHD, requiring systemic corticosteroid therapy, and with no prior systemic treatment for cGVHD were randomly assigned 1:1 to receive ibrutinib 420 mg once daily plus prednisone, starting at 1 mg/kg once daily or placebo plus prednisone. The primary end point was response rate at 48 weeks according to 2014 National Institutes of Health Consensus Development Project Criteria. Other end points included event-free survival, duration of response, time to withdrawal of immunosuppressants, improvement in Lee cGVHD Symptom Scale score, overall survival (OS), and safety.<br><br>RESULTS: Ninety-five and 98 patients enrolled in the ibrutinib-prednisone and placebo-prednisone arms, respectively. At 48 weeks, response rates were 41% (ibrutinib-prednisone) and 37% (placebo-prednisone; P = .54). At 33 months of follow-up, median duration of response was 19 months (ibrutinib-prednisone) and 10 months (placebo-prednisone; P = .10). Median event-free survival was 15 months (ibrutinib-prednisone) and 8 months (placebo-prednisone; hazard ratio, 0.76; 95% CI, 0.54 to 1.1; P = .11). Improvement in overall Lee cGVHD Symptom Scale was 43% (ibrutinib-prednisone) and 31% (placebo-ibrutinib; P = .07). Median OS was not reached in either arm. The 24-month Kaplan-Meier OS estimates were 80% for both arms (hazard ratio, 1.06; 95% CI, 0.59 to 1.90). Grade &#x2265; 3 serious adverse events occurred in 49% (ibrutinib-prednisone) and 47% (placebo-prednisone) of patients.<br><br>CONCLUSION: There was no statistical difference observed in the primary and secondary end points with ibrutinib-prednisone treatment. No new safety signals were observed with ibrutinib treatment in previously untreated patients with cGVHD. The primary end point of iNTEGRATE was not met.},
}
@article {pmid36606713,
year = {2023},
author = {Guru Murthy, GS and Logan, BR and Bo-Subait, S and Beitinjaneh, A and Devine, S and Farhadfar, N and Gowda, L and Hashmi, S and Lazarus, H and Nathan, S and Sharma, A and Yared, JA and Stefanski, HE and Pulsipher, MA and Hsu, JW and Switzer, GE and Panch, SR and Shaw, BE},
title = {Association of ABO mismatch with the outcomes of allogeneic hematopoietic cell transplantation for acute leukemia.},
journal = {American journal of hematology},
volume = {},
number = {},
pages = {},
doi = {10.1002/ajh.26834},
pmid = {36606713},
issn = {1096-8652},
abstract = {Allogeneic hematopoietic cell transplantation (allo-HCT) is a potentially curative treatment for acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL). While many factors influence the outcomes of allo-HCT, the independent impact of donor-recipient ABO mismatching remains unclear. Using the Center for International Blood and Marrow Transplant Research (CIBMTR) database, we identified patients aged ≥18 years with AML or ALL who underwent allo-HCT between 2008-2018. Our objectives were to analyze the outcomes of allo-HCT based on the donor-recipient ABO status (match, minor mismatch, major mismatch, bidirectional mismatch). Among 4946 eligible patients, 2741 patients (55.4%) were ABO matched, 1030 patients (20.8%) had a minor ABO mismatch, 899 patients (18.1%) had a major ABO mismatch, and 276 patients (5.6%) had a bidirectional ABO mismatch. In multivariable analyses, compared to ABO matched allo-HCT, the presence of a major ABO mismatch was associated with worse overall survival (HR 1.16, 95% CI 1.05-1.29; p=0.005), inferior platelet engraftment (HR 0.83, 95% CI 0.77-0.90; p<0.001), and higher primary graft failure (HR 1.60, 95% CI 1.12-2.30, p=0.01). Relapse, acute graft versus host disease (GVHD) grades III-IV, and chronic GVHD were not significantly associated with ABO status. While donor age was not significantly associated with outcomes, older recipient age was associated with worse survival and non-relapse mortality. Our study demonstrates that donor-recipient ABO status is independently associated with survival and other post-transplantation outcomes in acute leukemia. This underscores the importance of considering the ABO status in donor selection algorithms and its impact in acute leukemia. This article is protected by copyright. All rights reserved.},
}
@article {pmid36603329,
year = {2022},
author = {Mills, MG and Juergens, KB and Gov, JP and McCormick, CJ and Sampoleo, R and Kachikis, A and Amory, JK and Fang, FC and Pérez-Osorio, AC and Lieberman, NAP and Greninger, AL},
title = {Evaluation and clinical validation of monkeypox (mpox) virus real-time PCR assays.},
journal = {Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology},
volume = {159},
number = {},
pages = {105373},
pmid = {36603329},
issn = {1873-5967},
abstract = {BACKGROUND: In spring of 2022, an outbreak of monkeypox (mpox) spread worldwide. Here, we describe performance characteristics of monkeypox virus (MPXV)-specific and pan-orthopoxvirus qPCR assays for clinical use.<br><br>METHODS: We validated probe-based qPCR assays targeting MPXV-specific loci F3L and G2R (genes MPXVgp052/OPG065 and MPXVgp002 and gp190/OPG002, respectively) and a pan-orthopoxvirus assay targeting the E9L locus (MPXVgp057/OPG071). Clinical samples and synthetic controls were extracted using the Roche MP96 or Promega Maxwell 48 instrument. qPCR was performed on the AB7500 thermocycler. Synthetic control DNA and high concentration clinical samples were quantified by droplet PCR. Cross-reactivity was evaluated for camelpox and cowpox genomic DNA, vaccinia culture supernatant, and HSV- and VZV-positive clinical specimens. We also tested the performance of the F3L assay using dry swabs, Aptima vaginal and rectal swabs, nasopharyngeal, rectal, and oral swabs, cerebrospinal fluid, plasma, serum, whole blood, breastmilk, urine, saliva, and semen.<br><br>RESULTS: The MPXV-F3L assay is reproducible at a limit of detection (LoD) of 65.6 copies/mL of viral DNA in viral transport medium/universal transport medium (VTM/UTM), or 3.3 copies/PCR reaction. No cross-reactivity with herpesviruses or other poxviruses was observed. MPXV-F3L detects MPXV DNA in alternative specimen types, with an LoD ranging between 260-1000 copies/mL, or 5.7-10 copies/PCR reaction. In clinical swab VTM specimens, MPXV-F3L and MPXV-G2R assays outperformed OPXV-E9L by an average of 2.4 and 2.8 Cts, respectively. MPXV-G2R outperformed MPXV-F3L by 0.4 Cts, consistent with presence of two copies of G2R present in labile inverted terminal repeats (ITRs) of MPXV genome.<br><br>CONCLUSIONS: MPXV is readily detected by qPCR using three clinically validated assays.},
}
@article {pmid36601980,
year = {2023},
author = {Harrison, C and Yacoub, A and Scott, B and Mead, A and Gerds, AT and Kiladjian, JJ and Mesa, R and Egyed, M and Scheid, C and Gutierrez, VG and O'Sullivan, J and Buckley, S and Kanellopoulos, K and Mascarenhas, J},
title = {Long-term treatment with pacritinib on a compassionate use basis in patients with advanced myelofibrosis.},
journal = {Haematologica},
volume = {},
number = {},
pages = {},
doi = {10.3324/haematol.2022.282089},
pmid = {36601980},
issn = {1592-8721},
abstract = {Not available.},
}
@article {pmid36601742,
year = {2022},
author = {Zinsli, KA and Srinivasan, S and Balkus, JE and Chambers, LC and Lowens, MS and Morgan, J and Rowlinson, E and Robinson, TS and Romano, SS and Munch, MM and Manhart, LE and Fredricks, DN},
title = {Bacterial vaginosis-associated bacteria in cisgender men who have sex with women: prevalence, association with non-gonococcal urethritis and natural history.},
journal = {Sexually transmitted infections},
volume = {},
number = {},
pages = {},
doi = {10.1136/sextrans-2022-055494},
pmid = {36601742},
issn = {1472-3263},
abstract = {OBJECTIVES: Bacterial vaginosis-associated bacterium 2 (BVAB2), Mageeibacillus indolicus and Sneathia spp are highly predictive of bacterial vaginosis (BV) in cisgender women. They have been associated with non-gonococcal urethritis (NGU) in cisgender men in some but not all populations. We evaluated this association in a cross-sectional study of cisgender men who have sex with women only (MSW).<br><br>METHODS: MSW without gonorrhoea attending a sexual health clinic (SHC) from 2014 to 2018 completed a computer-assisted self-interview, clinical interview and examination. NGU was defined as &#x2265;5 polymorphonuclear leucocytes/high-power field in urethral exudates plus either urethral symptoms or visible discharge. Urine was tested for Chlamydia trachomatis and Mycoplasma genitalium using Aptima (Hologic) and for BVAB2, M. indolicus, Sneathia spp, Trichomonas vaginalis, Ureaplasma urealyticum, Haemophilus influenzae, herpes simplex virus and adenovirus using quantitative PCR.<br><br>RESULTS: Of 317 MSW age 17-71, 67 (21.1%) had Sneathia spp, 36 (11.4%) had BVAB2, and 17 (5.4%) had M. indolicus at enrolment. Having &#x2265;3 partners in the past 2 months was the only characteristic that was more common among MSW with than those without these bacteria (BVAB2: 47% vs 23%, M. indolicus: 53% vs 24%, Sneathia spp: 42% vs 22%; p&#x2264;0.03 for all). One-hundred seventeen men (37%) were diagnosed with NGU at enrolment. There was no significant association of BVAB2, M. indolicus or Sneathia spp with NGU (adjusted OR=0.59, 95% CI 0.14 to 2.43; aOR=3.40, 95% CI 0.68 to 17.06; aOR=0.46, 95% CI 0.16 to 1.27). Of 109 MSW with monthly samples, 34 (31.2%) had one of the bacteria at one or more follow-up visits, 22 of which were co-colonised with >1. Median persistence over 6 months did not differ significantly (BVAB2=30.5 days, IQR=28-87; M. indolicus=87 days, IQR=60-126; Sneathia spp=70 days, IQR=30-135; p&#x2265;0.20 for each comparison).<br><br>CONCLUSIONS: Neither BVAB2, M. indolicus nor Sneathia spp were associated with increased risk of prevalent NGU in MSW attending an SHC.},
}
@article {pmid36601043,
year = {2023},
author = {Ghali, F and Zhao, Y and Patel, D and Jewell, T and Yu, EY and Grivas, P and Montgomery, RB and Gore, JL and Etzioni, RB and Wright, JL},
title = {Surrogate Endpoints as Predictors of Overall Survival in Metastatic Urothelial Cancer: A Trial-level Analysis.},
journal = {European urology open science},
volume = {47},
number = {},
pages = {58-64},
pmid = {36601043},
issn = {2666-1683},
abstract = {BACKGROUND: Surrogate endpoints (SEs), such as progression-free survival (PFS) and objective response rate (ORR), are frequently used in clinical trials. The relationship between SEs and overall survival (OS) has not been well described in metastatic urothelial cancer (MUC).<br><br>OBJECTIVE: We evaluated trial-level data to assess the relationship between SEs and OS. We hypothesize a moderate surrogacy relationship between both PFS and ORR with OS.<br><br>We systematically reviewed phase 2/3 trials in MUC with two or more treatment arms, and report PFS and/or ORR, and OS.<br><br>Linear regression was performed, and the coefficient of determination (R[2]) and surrogate threshold effect (STE) estimate were determined between PFS/ORR and OS.<br><br>RESULTS AND LIMITATIONS: Of 3791 search results, 59 trials and 62 comparisons met the inclusion criteria. Of the 53 trials that reported PFS, 31 (58%) reported proportional hazard regression for PFS and OS. Linear regression across trials demonstrated an R[2] of 0.60 between hazard ratio (HR) for PFS (HR[PFS]) and HR for OS (HR[OS]), and an STE of 0.41. Linear regression of &#x394;PFS (median PFS in months of the treatment arm - that of the control arm) and &#x394;OS demonstrated an R[2] of 0.12 and an STE of 14.1 mo. Thirty trials reported ORRs. Linear regression for ORR[ratio] and HR[OS] among all trials found an R[2] of 0.08; an STE of 95% was not reached at any value and &#x394;ORR and HR[OS] similarly demonstrated a poor correlation with an R[2] value of 0.03.<br><br>CONCLUSIONS: PFS provides only a moderate level of surrogacy for OS; An HR[PFS] of &#x2264;0.41 provides 95% confidence of OS improvement. ORR is weakly correlated with OS and should be de-emphasized in MUC clinical trials. When PFS is discussed, proportional hazard regression should be reported.<br><br>PATIENT SUMMARY: We examined the relationship between surrogate endpoints, common outcomes in clinical trials, with survival in urothelial cancer trials. Progression-free survival is moderately correlated, while objective response rate had a poor correlation with survival and should be de-emphasized as a primary endpoint.},
}
@article {pmid36600297,
year = {2023},
author = {Papadimitriou, N and Bull, CJ and Jenab, M and Hughes, DJ and Bell, JA and Sanderson, E and Timpson, NJ and Smith, GD and Albanes, D and Campbell, PT and Küry, S and Le Marchand, L and Ulrich, CM and Visvanathan, K and Figueiredo, JC and Newcomb, PA and Pai, RK and Peters, U and Tsilidis, KK and Boer, JMA and Vincent, EE and Mariosa, D and Gunter, MJ and Richardson, TG and Murphy, N},
title = {Separating the effects of early and later life adiposity on colorectal cancer risk: a Mendelian randomization study.},
journal = {BMC medicine},
volume = {21},
number = {1},
pages = {5},
pmid = {36600297},
issn = {1741-7015},
support = {C18281/A29019/CRUK_/Cancer Research UK/United Kingdom ; PPRCPJT\100005/CRUK_/Cancer Research UK/United Kingdom ; 17/0005587/DUK_/Diabetes UK/United Kingdom ; 202802/Z/16/Z/WT_/Wellcome Trust/United Kingdom ; },
abstract = {BACKGROUND: Observational studies have linked childhood obesity with elevated risk of colorectal cancer; however, it is unclear if this association is causal or independent from the effects of obesity in adulthood on colorectal cancer risk.<br><br>METHODS: We conducted Mendelian randomization (MR) analyses to investigate potential causal relationships between self-perceived body size (thinner, plumper, or about average) in early life (age 10) and measured body mass index in adulthood (mean age 56.5) with risk of colorectal cancer. The total and independent effects of body size exposures were estimated using univariable and multivariable MR, respectively. Summary data were obtained from a genome-wide association study of 453,169 participants in UK Biobank for body size and from a genome-wide association study meta-analysis of three colorectal cancer consortia of 125,478 participants.<br><br>RESULTS: Genetically predicted early life body size was estimated to increase odds of colorectal cancer (odds ratio [OR] per category change: 1.12, 95% confidence interval [CI]: 0.98-1.27), with stronger results for colon cancer (OR: 1.16, 95% CI: 1.00-1.35), and distal colon cancer (OR: 1.25, 95% CI: 1.04-1.51). After accounting for adult body size using multivariable MR, effect estimates for early life body size were attenuated towards the null for colorectal cancer (OR: 0.97, 95% CI: 0.77-1.22) and colon cancer (OR: 0.97, 95% CI: 0.76-1.25), while the estimate for distal colon cancer was of similar magnitude but more imprecise (OR: 1.27, 95% CI: 0.90-1.77). Genetically predicted adult life body size was estimated to increase odds of colorectal (OR: 1.27, 95% CI: 1.03, 1.57), colon (OR: 1.32, 95% CI: 1.05, 1.67), and proximal colon (OR: 1.57, 95% CI: 1.21, 2.05).<br><br>CONCLUSIONS: Our findings suggest that the positive association between early life body size and colorectal cancer risk is likely due to large body size retainment into adulthood.},
}
@article {pmid36599192,
year = {2023},
author = {Vitanza, NA and Ronsley, R and Choe, M and Henson, C and Breedt, M and Barrios-Anderson, A and Wein, A and Brown, C and Beebe, A and Kong, A and Kirkey, D and Lee, BM and Leary, SES and Crotty, EE and Hoeppner, C and Holtzclaw, S and Wilson, AL and Gustafson, JA and Foster, JB and Iliff, JJ and Goldstein, HE and Browd, SR and Lee, A and Ojemann, JG and Pinto, N and Gust, J and Gardner, RA and Jensen, MC and Hauptman, JS and Park, JR},
title = {Locoregional CAR T cells for children with CNS tumors: Clinical procedure and catheter safety.},
journal = {Neoplasia (New York, N.Y.)},
volume = {36},
number = {},
pages = {100870},
doi = {10.1016/j.neo.2022.100870},
pmid = {36599192},
issn = {1476-5586},
abstract = {Central nervous system (CNS) tumors are the most common solid malignancy in the pediatric population. Based on adoptive cellular therapy's clinical success against childhood leukemia and the preclinical efficacy against pediatric CNS tumors, chimeric antigen receptor (CAR) T cells offer hope of improving outcomes for recurrent tumors and universally fatal diseases such as diffuse intrinsic pontine glioma (DIPG). However, a major obstacle for tumors of the brain and spine is ineffective T cell chemotaxis to disease sites. Locoregional CAR T cell delivery via infusion through an intracranial catheter is currently under study in multiple early phase clinical trials. Here, we describe the Seattle Children's single-institution experience including the multidisciplinary process for the preparation of successful, repetitive intracranial T cell infusion for children and the catheter-related safety of our 307 intracranial CAR T cell doses.},
}
@article {pmid36599183,
year = {2022},
author = {Foley, GR and Marthick, JR and Ostrander, EA and Stanford, JL and Dickinson, JL and FitzGerald, LM},
title = {Association of a novel BRCA2 mutation with prostate cancer risk further supports germline genetic testing.},
journal = {European journal of cancer (Oxford, England : 1990)},
volume = {180},
number = {},
pages = {155-157},
doi = {10.1016/j.ejca.2022.11.034},
pmid = {36599183},
issn = {1879-0852},
}
@article {pmid36598808,
year = {2023},
author = {Hui, J and Nakamura, M and Dubrulle, J and Parkhurst, SM},
title = {Coordinated efforts of different actin filament populations are needed for optimal cell wound repair.},
journal = {Molecular biology of the cell},
volume = {},
number = {},
pages = {mbcE22050155},
doi = {10.1091/mbc.E22-05-0155},
pmid = {36598808},
issn = {1939-4586},
abstract = {Cells are subjected to a barrage of daily insults that often lead to their cortex being ripped open and requiring immediate repair. An important component of the cell's repair response is the formation of an actomyosin ring at the wound periphery to mediate its closure. Here we show that inhibition of myosin or the linear actin nucleation factors Diaphanous and/or DAAM results in a disrupted contractile apparatus and delayed wound closure. We also show that the branched actin nucleators WASp and SCAR function non-redundantly as scaffolds to assemble and maintain this contractile actomyosin cable. Removing branched actin leads to the formation of smaller circular actin-myosin structures at the cell cortex and slow wound closure. Removing linear and branched actin simultaneously results in failed wound closure. Surprisingly, removal of branched actin and myosin results in the formation of parallel linear F-actin filaments that undergo a chiral swirling movement to close the wound, thereby uncovering a new mechanism of cell wound closure. [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text].},
}
@article {pmid36598261,
year = {2023},
author = {O'Brien, VP and Jackson, LK and Frick, JP and Rodriguez Martinez, AE and Jones, DS and Johnston, CD and Salama, NR},
title = {Helicobacter pylori Chronic Infection Selects for Effective Colonizers of Metaplastic Glands.},
journal = {mBio},
volume = {},
number = {},
pages = {e0311622},
doi = {10.1128/mbio.03116-22},
pmid = {36598261},
issn = {2150-7511},
abstract = {Chronic gastric infection with Helicobacter pylori can lead to progressive tissue changes that culminate in cancer, but how H. pylori adapts to the changing tissue environment during disease development is not fully understood. In a transgenic mouse gastric metaplasia model, we found that strains from unrelated individuals differed in their ability to infect the stomach, to colonize metaplastic glands, and to alter the expression of the metaplasia-associated protein TFF3. H. pylori isolates from different stages of disease from a single individual had differential ability to colonize healthy and metaplastic gastric glands. Exposure to the metaplastic environment selected for high gastric colonization by one of these strains. Complete genome sequencing revealed a unique alteration in the frequency of a variant allele of the putative adhesin sabB, arising from a recombination event with the related sialic acid binding adhesin (SabA) gene. Mutation of sabB in multiple H. pylori strain backgrounds strongly reduced adherence to both normal and metaplastic gastric tissue, and highly attenuated stomach colonization in mice. Thus, the changing gastric environment during disease development promotes bacterial adhesin gene variation associated with enhanced gastric colonization. IMPORTANCE Chronic infection with Helicobacter pylori is the primary risk factor for developing stomach cancer. As disease progresses H. pylori must adapt to a changing host tissue environment that includes induction of new cell fates in the cells that line the stomach. We tested representative H. pylori isolates collected from the same patient during early and later stages of disease in a mouse model where we can rapidly induce disease-associated tissue changes. Only the later-stage H. pylori strains could robustly colonize the diseased stomach environment. We also found that the ability to colonize the diseased stomach was associated with genetic variation in a putative cell surface adhesin gene called sabB. Additional experiments revealed that SabB promotes binding to stomach tissue and is critical for stomach colonization by the late-stage strains. Thus, H. pylori diversifies its genome during disease progression and these genomic changes highlight critical factors for bacterial persistence.},
}
@article {pmid36596894,
year = {2023},
author = {Gondré-Lewis, TA and Jiang, C and Ford, ML and Koelle, DM and Sette, A and Shalek, AK and Thomas, PG},
title = {NIAID workshop on T cell technologies.},
journal = {Nature immunology},
volume = {24},
number = {1},
pages = {14-18},
pmid = {36596894},
issn = {1529-2916},
}
@article {pmid36596255,
year = {2023},
author = {Reddi, DM and Barner, LA and Burke, W and Gao, G and Grady, WM and Liu, JTC},
title = {Nondestructive 3D Pathology Image Atlas of Barrett Esophagus With Open-Top Light-Sheet Microscopy.},
journal = {Archives of pathology &amp; laboratory medicine},
volume = {},
number = {},
pages = {},
doi = {10.5858/arpa.2022-0133-OA},
pmid = {36596255},
issn = {1543-2165},
abstract = {CONTEXT.&#x2014;: Anatomic pathologists render diagnosis on tissue samples sectioned onto glass slides and viewed under a bright-field microscope. This approach is destructive to the sample, which can limit its use for ancillary assays that can inform patient management. Furthermore, the subjective interpretation of a relatively small number of 2D tissue sections per sample contributes to low interobserver agreement among pathologists for the assessment (diagnosis and grading) of various lesions.<br><br>OBJECTIVE.&#x2014;: To evaluate 3D pathology data sets of thick formalin-fixed Barrett esophagus specimens imaged nondestructively with open-top light-sheet (OTLS) microscopy.<br><br>DESIGN.&#x2014;: Formalin-fixed, paraffin-embedded Barrett esophagus samples (N = 15) were deparaffinized, stained with a fluorescent analog of hematoxylin-eosin, optically cleared, and imaged nondestructively with OTLS microscopy. The OTLS microscopy images were subsequently compared with archived hematoxylin-eosin histology sections from each sample.<br><br>RESULTS.&#x2014;: Barrett esophagus samples, both small endoscopic forceps biopsies and endoscopic mucosal resections, exhibited similar resolvable structures between OTLS microscopy and conventional light microscopy with up to a &#xd7;20 objective (&#xd7;200 overall magnification). The 3D histologic images generated by OTLS microscopy can enable improved discrimination of cribriform and well-formed gland morphologies. In addition, a much larger amount of tissue is visualized with OTLS microscopy, which enables improved assessment of clinical specimens exhibiting high spatial heterogeneity.<br><br>CONCLUSIONS.&#x2014;: In esophageal specimens, OTLS microscopy can generate images comparable in quality to conventional light microscopy, with the advantages of providing 3D information for enhanced evaluation of glandular morphologies and enabling much more of the tissue specimen to be visualized nondestructively.},
}
@article {pmid36595657,
year = {2023},
author = {Lindley, CL and Gigic, B and Peoples, AR and Han, CJ and Lin, T and Himbert, C and Warby, CA and Boehm, J and Hardikar, S and Ashworth, A and Schneider, M and Ulrich, A and Schrotz-King, P and Figueiredo, JC and Li, CI and Shibata, D and Siegel, EM and Toriola, AT and Ulrich, CM and Syrjala, KL and Ose, J},
title = {Pre-surgery inflammatory and angiogenesis biomarkers as predictors of 12-month cancer-related distress: Results from the ColoCare Study.},
journal = {Cancer epidemiology, biomarkers &amp; prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology},
volume = {},
number = {},
pages = {},
doi = {10.1158/1055-9965.EPI-22-0882},
pmid = {36595657},
issn = {1538-7755},
abstract = {BACKGROUND: Colorectal cancer (CRC) patients commonly suffer from complex psychological distress. Elevated distress may be linked to systemic biomarkers. We investigated associations of biomarkers of inflammation and angiogenesis with cancer-related distress (CTXD) score.<br><br>METHODS: N=315 patients (stage I-IV) from 2 centers of the ColoCare Study were included: Huntsman Cancer Institute and University of Heidelberg. Biomarkers (e.g., IL-6, VEGF-A, VEGF-D) were measured in serum collected pre-surgery and 12 months thereafter. The CTXD overall score and 4 subscales were collected 12 months after surgery and dichotomized to investigate biomarkers as predictors of distress 12 months after surgery; adjusted for age, sex, body mass index, tumor stage, center, and baseline levels of biomarkers.<br><br>RESULTS: Doubling of IL-6 predicted future increased risk of overall distress (Odds Ratio (OR) = 1.20; 95%Confidence Interval (CI) = 1.02-1.41; p = 0.03). VEGF-A predicted future increased risk of high family strain (VEGF-A: OR=1.21; 95%CI=1.01-1.44; p=0.04) and VEGF-D was associated with medical and financial demands (OR=1.34; 95%CI=1.01-1.74; p=0.03).<br><br>CONCLUSIONS: This is the first study to show that systemic biomarkers are significantly associated with future CTXD score. Distress was not measured at baseline; we cannot rule out ongoing associations of inflammation and distress throughout treatment versus a direct effect of inflammation on distress. Nonetheless these data add to evidence that biobehavioral processes interact and that systemic biomarkers are associated with cancer-related distress one year after surgery.<br><br>IMPACT: Exercise and diet interventions that lower systemic cytokine levels may impact longer term CTXD score and improve quality of life of CRC patients.},
}
@article {pmid36595478,
year = {2023},
author = {Ueda Oshima, M and Xie, H and Zamora, D and Flowers, ME and Hill, GR and Mielcarek, M and Sandmaier, BM and Gooley, TA and Boeckh, MJ},
title = {Impact of GVHD prophylaxis on CMV reactivation and disease after HLA-matched peripheral blood stem cell transplantation.},
journal = {Blood advances},
volume = {},
number = {},
pages = {},
doi = {10.1182/bloodadvances.2022009112},
pmid = {36595478},
issn = {2473-9537},
abstract = {The kinetics of early and late CMV reactivation after hematopoietic cell transplantation using various methods of graft-versus-host-disease (GVHD) prophylaxis are poorly defined. We retrospectively compared CMV reactivation and disease among 780 seropositive patients given HLA-matched peripheral blood stem cell (PBSC) grafts and calcineurin-inhibitor plus post-transplantation cyclophosphamide (PTCy; n=44), mycophenolate mofetil (MMF; n=414) or methotrexate (MTX; n=322). Transplantation occurred between 2007-2018; CMV-monitoring/management followed uniform standard practice. Hazards of CMV reactivation at various thresholds were compared. Spline curves were fit over average daily viral load, and areas under the curve (AUC) within one-year were calculated. PTCy and MMF were associated with an increased risk of early ((?)day 100) CMV reactivation ≥250 IU/mL after multivariable adjustment (PTCy vs. MTX: HR=1.64; 95% CI: 1.03-2.61; p=0.039; MMF vs. MTX: HR=1.50; 95% CI: 0.97-2.32; p=0.067). The viral load AUC at one-year was highest with MMF (mean difference 0.125 units vs. MTX; 95% CI 0.061-0.189; p<.001) and similar between PTCy vs. MTX (mean difference 0.016 units vs. MTX group; 95% CI, -0.126-0.158, p=0.827). CMV disease risk was similar across groups. There was no interaction between GVHD prophylaxis and CMV reactivation on chronic GVHD risk. Despite PTCy-associated increased risk of early CMV reactivation, the CMV disease risk by 1 year was low in HLA-matched PBSC transplant recipients. In contrast, MMF was associated with higher overall CMV viral burden in the 1-year posttransplant. While different mechanisms of immunosuppressive agents may impact CMV reactivation risk, effective prevention of GVHD may reduce corticosteroid exposure and mitigate infection risk over time.},
}
@article {pmid36595452,
year = {2023},
author = {Le, QH and Tang, T and Leonti, AR and Castro, SK and McKay, CN and Perkins, L and Pardo, L and Kirkey, DC and Hylkema, T and Call, L and Manselle, M and Abrahams, C and Bedard, K and Molina, A and Eidenschink Brodersen, L and Loken, MR and Tarlock, K and Meshinchi, S and Loeb, KR},
title = {Preclinical studies targeting CD74 with STRO-001 antibody-drug conjugate in acute leukemia.},
journal = {Blood advances},
volume = {},
number = {},
pages = {},
doi = {10.1182/bloodadvances.2022008303},
pmid = {36595452},
issn = {2473-9537},
}
@article {pmid36595185,
year = {2023},
author = {Jones, SMW and Ton, M and Heffner, JL and Malen, RC and Cohen, SA and Newcomb, PA},
title = {Association of financial worry with substance use, mental health, and quality of life in cancer patients.},
journal = {Journal of cancer survivorship : research and practice},
volume = {},
number = {},
pages = {},
pmid = {36595185},
issn = {1932-2267},
support = {P30 CA015704/CA/NCI NIH HHS/United States ; P30 CA015704/CA/NCI NIH HHS/United States ; P30 CA015704/CA/NCI NIH HHS/United States ; P30 CA015704/CA/NCI NIH HHS/United States ; P30 CA015704/CA/NCI NIH HHS/United States ; },
abstract = {PURPOSE: Financial worry is an under-appreciated negative effect of cancer. The relationship of financial worry and health behaviors in cancer is poorly characterized and has important clinical implications. This study examined the association of financial worry with substance misuse, mood, and quality of life.<br><br>METHODS: People with cancer (n&#x2009;=&#x2009;1473; 6 to 20&#xa0;months after diagnosis) were recruited from a SEER cancer registry in the Pacific Northwest. Participants completed an online survey assessing financial worry; misuse of cannabis, alcohol, and prescription drugs; tobacco smoking status; quality of life (physical and mental dimensions); anxiety; and depression. Multivariable regressions tested the association of financial worry to each health indicator and outcome.<br><br>RESULTS: In adjusted analyses, financial worry was associated with being a current vs. never smoker (odds ratio (OR)&#x2009;=&#x2009;1.91, 95% confidence interval (CI): 1.01, 3.60), and a positive screen for an anxiety (OR&#x2009;=&#x2009;3.01, 95% CI: 1.93, 4.68) and depressive (OR&#x2009;=&#x2009;3.08, 95% CI: 1.89, 5.00) disorder. Financial worry was not associated with cannabis, alcohol, or prescription drug misuse (all ps&#x2009;>&#x2009;0.05), but was associated with a decrease in physical (&#x3b2;&#x2009;=&#x2009;&#x2009;-&#x2009;2.97, 95% CI:&#x2009;-&#x2009;4.15,&#x2009;-&#x2009;1.79) and mental (&#x3b2;&#x2009;=&#x2009;&#x2009;-&#x2009;5.27, 95% CI:&#x2009;-&#x2009;6.59,&#x2009;-&#x2009;3.96) quality of life.<br><br>CONCLUSION: Financial worry among cancer survivors is associated with anxiety, depression, and worse quality of life. Of the evaluated substances, there was only an increased odds of current tobacco use with financial worry. Future longitudinal studies should inform the relationships between these factors.<br><br>Financial worry and material hardship may both need to be addressed in cancer survivorship.},
}
@article {pmid36594463,
year = {2023},
author = {Edwards, CL and Ng, SS and de Labastida Rivera, F and Corvino, D and Engel, JA and Montes de Oca, M and Bukali, L and Frame, TC and Bunn, PT and Chauhan, SB and Singh, SS and Wang, Y and Na, J and Amante, FH and Loughland, JR and Soon, MS and Waddell, N and Mukhopadhay, P and Koufariotis, LT and Johnston, RL and Lee, JS and Kuns, R and Zhang, P and Boyle, MJ and Hill, GR and McCarthy, JS and Kumar, R and Engwerda, CR},
title = {Human IL-10-producing Th1 cells exhibit a molecular signature distinct from Tr1 cells in malaria.},
journal = {The Journal of clinical investigation},
volume = {133},
number = {1},
pages = {},
doi = {10.1172/JCI153733},
pmid = {36594463},
issn = {1558-8238},
abstract = {Control of intracellular parasites responsible for malaria requires host IFN-γ+T-bet+CD4+ T cells (Th1 cells) with IL-10 produced by Th1 cells to mitigate the pathology induced by this inflammatory response. However, these IL-10-producing Th1 (induced type I regulatory [Tr1]) cells can also promote parasite persistence or impair immunity to reinfection or vaccination. Here, we identified molecular and phenotypic signatures that distinguished IL-10-Th1 cells from IL-10+Tr1 cells in Plasmodium falciparum-infected people who participated in controlled human malaria infection studies, as well as C57BL/6 mice with experimental malaria caused by P. berghei ANKA. We also identified a conserved Tr1 cell molecular signature shared between patients with malaria, dengue, and graft-versus-host disease. Genetic manipulation of primary human CD4+ T cells showed that the transcription factor cMAF played an important role in the induction of IL-10, while BLIMP-1 promoted the development of human CD4+ T cells expressing multiple coinhibitory receptors. We also describe heterogeneity of Tr1 cell coinhibitory receptor expression that has implications for targeting these molecules for clinical advantage during infection. Overall, this work provides insights into CD4+ T cell development during malaria that offer opportunities for creation of strategies to modulate CD4+ T cell functions and improve antiparasitic immunity.},
}
@article {pmid36593337,
year = {2023},
author = {Visvanathan, K and Mondul, AM and Zeleniuch-Jacquotte, A and Wang, M and Gail, MH and Yaun, SS and Weinstein, SJ and McCullough, ML and Eliassen, AH and Cook, NR and Agnoli, C and Almquist, M and Black, A and Buring, JE and Chen, C and Chen, Y and Clendenen, T and Dossus, L and Fedirko, V and Gierach, GL and Giovannucci, EL and Goodman, GE and Goodman, MT and Guénel, P and Hallmans, G and Hankinson, SE and Horst, RL and Hou, T and Huang, WY and Jones, ME and Joshu, CE and Kaaks, R and Krogh, V and Kühn, T and Kvaskoff, M and Lee, IM and Mahamat-Saleh, Y and Malm, J and Manjer, J and Maskarinec, G and Millen, AE and Mukhtar, TK and Neuhouser, ML and Robsahm, TE and Schoemaker, MJ and Sieri, S and Sund, M and Swerdlow, AJ and Thomson, CA and Ursin, G and Wactawski-Wende, J and Wang, Y and Wilkens, LR and Wu, Y and Zoltick, E and Willett, WC and Smith-Warner, SA and Ziegler, RG},
title = {Circulating vitamin D and breast cancer risk: an international pooling project of 17 cohorts.},
journal = {European journal of epidemiology},
volume = {},
number = {},
pages = {},
pmid = {36593337},
issn = {1573-7284},
support = {R01 CA152071/CA/NCI NIH HHS/United States ; },
abstract = {Laboratory and animal research support a protective role for vitamin D in breast carcinogenesis, but epidemiologic studies have been inconclusive. To examine comprehensively the relationship of circulating 25-hydroxyvitamin D [25(OH)D] to subsequent breast cancer incidence, we harmonized and pooled participant-level data from 10 U.S. and 7 European prospective cohorts. Included were 10,484 invasive breast cancer cases and 12,953 matched controls. Median age (interdecile range) was 57 (42-68) years at blood collection and 63 (49-75) years at breast cancer diagnosis. Prediagnostic circulating 25(OH)D was either newly measured using a widely accepted immunoassay and laboratory or, if previously measured by the cohort, calibrated to this assay to permit using a common metric. Study-specific relative risks (RRs) for season-standardized 25(OH)D concentrations were estimated by conditional logistic regression and combined by random-effects models. Circulating 25(OH)D increased from a median of 22.6 nmol/L in consortium-wide decile 1 to 93.2 nmol/L in decile 10. Breast cancer risk in each decile was not statistically significantly different from risk in decile 5 in models adjusted for breast cancer risk factors, and no trend was apparent (P-trend = 0.64). Compared to women with sufficient 25(OH)D based on Institute of Medicine guidelines (50- < 62.5 nmol/L), RRs were not statistically significantly different at either low concentrations (< 20 nmol/L, 3% of controls) or high concentrations (100- < 125 nmol/L, 3% of controls; ≥ 125 nmol/L, 0.7% of controls). RR per 25 nmol/L increase in 25(OH)D was 0.99 [95% confidence intervaI (CI) 0.95-1.03]. Associations remained null across subgroups, including those defined by body mass index, physical activity, latitude, and season of blood collection. Although none of the associations by tumor characteristics reached statistical significance, suggestive inverse associations were seen for distant and triple negative tumors. Circulating 25(OH)D, comparably measured in 17 international cohorts and season-standardized, was not related to subsequent incidence of invasive breast cancer over a broad range in vitamin D status.},
}
@article {pmid36593127,
year = {2023},
author = {Duggan, C and Cushing-Haugen, KL and Cole, AM and Allen, J and Gilles, R and Hornecker, JR and Gutierrez, AI and Warner, J and Baker, KS and Ceballos, RM and Chow, EJ},
title = {Feasibility of delivering survivorship care via lay health educators: A pilot randomized controlled trial among rural cancer survivors.},
journal = {The Journal of rural health : official journal of the American Rural Health Association and the National Rural Health Care Association},
volume = {},
number = {},
pages = {},
doi = {10.1111/jrh.12736},
pmid = {36593127},
issn = {1748-0361},
support = {R21 CA258105/NH/NIH HHS/United States ; P30 CA015704/NH/NIH HHS/United States ; UL1TR002319/NH/NIH HHS/United States ; 75N91020C00005/NH/NIH HHS/United States ; },
abstract = {PURPOSE: We tested the feasibility of survivorship care plan (SCP) delivery with/without a lay health educator (LHE) telephone-delivered information session among rural cancer survivors, and their effects on health-related self-efficacy and knowledge of cancer history.<br><br>METHODS: Randomized trial of cancer survivors from 3 rural oncology clinics featuring either SCP alone (control) or SCP plus LHE-delivered information session (intervention). Participants completed a questionnaire on health-related self-efficacy and knowledge of cancer-specific medical history. Responses were compared to medical records for accuracy. SCPs were then mailed to participants. Approximately 5 months later, participants completed a follow-up questionnaire. A subset of participants took part in subsequent qualitative interviews about their study experience.<br><br>FINDINGS: Of 301 survivors approached, 72 (23.9%) were randomized (mean age 66.4 years; 3.1 years from diagnosis; 62.5% female), and 65 (90.3%) completed the study. Global mental and physical health or self-efficacy scores did not change significantly from baseline to follow-up for either group. In exploratory analyses, self-efficacy increased in participants with inadequate/marginal health literacy in the intervention arm (+0.7, 95% CI = 0.1-1.2; P = .01). Accuracy of knowledge did not improve but was high at baseline (mean 76.0&#xb1;14.5%). 60.1% and 48.4% of control and intervention participants, respectively, found SCPs definitely/somewhat useful. Qualitative data (n = 20) suggested that SCPs were helpful to patients when primary and oncology care were less integrated.<br><br>CONCLUSIONS: An LHE-delivered informational session was feasible but had limited benefit to rural cancer survivors versus delivery of SCP alone but may be of benefit to patients with low health literacy or with less integrated care.},
}
@article {pmid36591224,
year = {2022},
author = {Duffy, FJ and Hertoghs, N and Du, Y and Neal, ML and Oyong, D and McDermott, S and Minkah, N and Carnes, J and Schwedhelm, KV and McElrath, MJ and De Rosa, SC and Newell, E and Aitchison, JD and Stuart, K},
title = {Longitudinal immune profiling after radiation-attenuated sporozoite vaccination reveals coordinated immune processes correlated with malaria protection.},
journal = {Frontiers in immunology},
volume = {13},
number = {},
pages = {1042741},
pmid = {36591224},
issn = {1664-3224},
abstract = {BACKGROUND: Identifying immune processes required for liver-stage sterilizing immunity to malaria remains an open problem. The IMRAS trial comprised 5x immunizations with radiation-attenuated sporozoites resulting in 55% protection from subsequent challenge.<br><br>METHODS: To identify correlates of vaccination and protection, we performed detailed systems immunology longitudinal profiling of the entire trial time course including whole blood transcriptomics, detailed PBMC cell phenotyping and serum antigen array profiling of 11 IMRAS radiation-attenuated sporozoite (RAS) vaccinees at up to 21 timepoints each.<br><br>RESULTS: RAS vaccination induced serum antibody responses to CSP, TRAP, and AMA1 in all vaccinees. We observed large numbers of differentially expressed genes associated with vaccination response and protection, with distinctly differing transcriptome responses elicited after each immunization. These included inflammatory and proliferative responses, as well as increased abundance of monocyte and DC subsets after each immunization. Increases in V&#x3b4;2 &#x3b3;&#x3b4;; T cells and MAIT cells were observed in response to immunization over the course of study, and CD1c+ CD40+ DC abundance was significantly associated with protection. Interferon responses strongly differed between protected and non-protected individuals with high interferon responses after the 1[st] immunization, but not the 2[nd]-5[th]. Blood transcriptional interferon responses were correlated with abundances of different circulating classical and non-classical monocyte populations.<br><br>CONCLUSIONS: This study has revealed multiple coordinated immunological processes induced by vaccination and associated with protection. Our work represents the most detailed immunological profiling of a RAS vaccine trial performed to date and will guide the design and interpretation of future malaria vaccine trials.},
}
@article {pmid36585573,
year = {2022},
author = {Bhatt, NS and Brazauskas, R and Torres, AP and Phelan, R and Shaw, BE},
title = {Relationship between work performance and quality of life in long-term survivors of pediatric and adolescent hematopoietic cell transplant.},
journal = {Journal of cancer survivorship : research and practice},
volume = {},
number = {},
pages = {},
pmid = {36585573},
issn = {1932-2267},
abstract = {PURPOSE: To assess work status, missed time at work (absenteeism), work performance (presenteeism), and their relationship with quality of life (QOL) among long-term survivors of childhood hematopoietic cell transplant (HCT).<br><br>METHODS: A single-center cross-sectional survey study of adult survivors of childhood allogeneic HCT (performed between 1985 and 2010). Work and QOL data were captured using the World Health Organization Health and Work Performance Questionnaire and the National Institutes of Health Patient Reported Outcomes Measurement Information System (PROMIS), respectively. Higher absenteeism and presenteeism scores meant higher missed time at work and productivity, respectively. PROMIS domains were scored on a T-score metric with a mean score of reference population at 50 and standard deviation of 10. Univariate linear regression was performed to study factors associated with increase in PROMIS scores.<br><br>RESULTS: Forty-four survivors completed the survey. Median ages at HCT and survey were 11&#xa0;years (interquartile range [IQR] 7-13) and 30&#xa0;years (IQR 26-34), respectively. Seventy-three percent were working, 23% were unemployed, and 4% were students. Employed survivors reported less pain and sleep disturbance. Higher absolute presenteeism was associated with less pain interference and more satisfaction with social roles and activities and physical function. Higher relative presenteeism was associated with less cognitive concerns.<br><br>We found significant associations between survivors' work status, performance, and QOL. Our findings provide an important insight on the implications of work outcomes on HCT survivors' physical, mental, and social health and emphasize the importance of longitudinal assessment of work status, performance, and QOL.},
}
@article {pmid36590676,
year = {2021},
author = {Liu, H and Plantinga, AM and Xiang, Y and Wu, MC},
title = {A Kernel-based Test of Independence for Cluster-correlated Data.},
journal = {Advances in neural information processing systems},
volume = {34},
number = {},
pages = {9869-9881},
pmid = {36590676},
issn = {1049-5258},
abstract = {The Hilbert-Schmidt Independence Criterion (HSIC) is a powerful kernel-based statistic for assessing the generalized dependence between two multivariate variables. However, independence testing based on the HSIC is not directly possible for cluster-correlated data. Such a correlation pattern among the observations arises in many practical situations, e.g., family-based and longitudinal data, and requires proper accommodation. Therefore, we propose a novel HSIC-based independence test to evaluate the dependence between two multivariate variables based on cluster-correlated data. Using the previously proposed empirical HSIC as our test statistic, we derive its asymptotic distribution under the null hypothesis of independence between the two variables but in the presence of sample correlation. Based on both simulation studies and real data analysis, we show that, with clustered data, our approach effectively controls type I error and has a higher statistical power than competing methods.},
}
@article {pmid36585541,
year = {2022},
author = {McDonnell, E and Lampe, JW and Nuding, M and Lee, D},
title = {Children With Celiac Disease Consume Specific Food Additives More Frequently Compared to Children Without Celiac Disease.},
journal = {Digestive diseases and sciences},
volume = {},
number = {},
pages = {},
pmid = {36585541},
issn = {1573-2568},
abstract = {BACKGROUND: Gluten-free foods often contain food additives to improve palatability, but the long-term effects on the human gastrointestinal tract are not well known.<br><br>AIMS: This study aimed to quantify frequency of food additive exposure in children with and without celiac disease (CD).<br><br>METHODS: Children with and without CD were enrolled and demographic data and three-day diet records were obtained. Foods were classified as gluten-free products (GFP) and "processed food", and were evaluated for presence of select food additives: polysorbate 80, carboxymethylcellulose, xanthan gum, guar gum, soy lecithin, titanium dioxide, carrageenan, maltodextrin, and aluminosilicates. The frequency of exposure was described.<br><br>RESULTS: Twenty-eight participants were included in final analysis. Children with CD had a higher number of daily exposures to xanthan gum (5.3&#xa0;&#xb1;&#xa0;3.1 vs 2.3&#xa0;&#xb1;&#xa0;2.4; p&#xa0;=&#xa0;0.009), but similar exposures to the other additives. GFP contributed 29% of total calories in the GF diet. Both groups had similar intake of processed foods. Comparing GFP and gluten-containing processed foods, 68% vs. 25% contained at least one food additive of interest (p&#xa0;<&#xa0;0.0001); in the celiac group, those with higher consumption of GFP tended to have a higher frequency of exposure to food additives (p&#xa0;=&#xa0;0.09).<br><br>CONCLUSION: A gluten-free diet and consumption of GFP may contribute to differences in food additive intake; quantifying food additive exposures and their effect on humans requires further study.},
}
@article {pmid36585521,
year = {2022},
author = {Aid, Z and Robert, E and Lopez, CK and Bourgoin, M and Boudia, F and Le Mene, M and Riviere, J and Baille, M and Benbarche, S and Renou, L and Fagnan, A and Thirant, C and Federici, L and Touchard, L and Lecluse, Y and Jetten, A and Geoerger, B and Lapillonne, H and Solary, E and Gaudry, M and Meshinchi, S and Pflumio, F and Auberger, P and Lobry, C and Petit, A and Jacquel, A and Mercher, T},
title = {High caspase 3 and vulnerability to dual BCL2 family inhibition define ETO2::GLIS2 pediatric leukemia.},
journal = {Leukemia},
volume = {},
number = {},
pages = {},
pmid = {36585521},
issn = {1476-5551},
abstract = {Pediatric acute myeloid leukemia expressing the ETO2::GLIS2 fusion oncogene is associated with dismal prognosis. Previous studies have shown that ETO2::GLIS2 can efficiently induce leukemia development associated with strong transcriptional changes but those amenable to pharmacological targeting remained to be identified. By studying an inducible ETO2::GLIS2 cellular model, we uncovered that de novo ETO2::GLIS2 expression in human cells led to increased CASP3 transcription, CASP3 activation, and cell death. Patient-derived ETO2::GLIS2[+] leukemic cells expressed both high CASP3 and high BCL2. While BCL2 inhibition partly inhibited ETO2::GLIS2[+] leukemic cell proliferation, BH3 profiling revealed that it also sensitized these cells to MCL1 inhibition indicating a functional redundancy between BCL2 and MCL1. We further show that combined inhibition of BCL2 and MCL1 is mandatory to abrogate disease progression using in vivo patient-derived xenograft models. These data reveal that a transcriptional consequence of ETO2::GLIS2 expression includes a positive regulation of the pro-apoptotic CASP3 and associates with a vulnerability to combined targeting of two BCL2 family members providing a novel therapeutic perspective for this aggressive pediatric AML subgroup.},
}
@article {pmid36585488,
year = {2022},
author = {Hwang, JP and Arnold, KB and Unger, JM and Chugh, R and Tincopa, MA and Loomba, R and Hershman, D and Ramsey, SD},
title = {Antiviral therapy use and related outcomes in patients with cancer and viral infections: results from SWOG S1204.},
journal = {Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer},
volume = {31},
number = {1},
pages = {93},
pmid = {36585488},
issn = {1433-7339},
support = {UG1CA189974/CA/NCI NIH HHS/United States ; },
abstract = {PURPOSE: Information is limited about adherence to practice guidelines in patients with hepatitis B virus (HBV), hepatitis C virus (HCV), or HIV infection receiving anticancer treatment.<br><br>METHODS: Newly diagnosed adult cancer patients were enrolled in a multicenter, prospective cohort study (SWOG S1204) during 2013-2017 to evaluate the prevalence of HBV, HCV, or HIV in patients initiating anticancer treatment. At 6&#xa0;months, records of virus-positive patients were reviewed for antiviral therapy use; anticancer treatment dose reduction; and HBV reactivation (elevated viral load). Categorical variables were compared using chi-square or Fisher's exact test.<br><br>RESULTS: Of 3055 enrolled patients with viral testing, 230 had chronic or past HBV, HCV, or HIV with 6-month follow-up data (chronic HBV, 15 patients; past HBV, 158; HCV, 49; HIV, 30). Twenty percent (3/15) of chronic HBV and 11% (17/158) of past HBV patients were co-infected with HCV and/or HIV. Rates of antiviral therapy use by 6&#xa0;months were as follows: chronic HBV, 85% (11/13); past HBV receiving anti-B cell therapy, 60% (3/5); past HBV receiving systemic anticancer therapy without anti-B cell therapy, 8% (8/105); HCV, 6% (2/35); and HIV, 90% (19/21). Among patients with available data, anticancer treatment dose was reduced in 1 of 145 patients with past HBV and 1 of 42 with HCV. HBV reactivation occurred in 1 of 15 patients with chronic HBV; this patient was not receiving antiviral therapy.<br><br>CONCLUSION: Many patients with cancer and viral infections either do not receive guideline-recommended antiviral treatment or receive antiviral treatment that is not recommended in guidelines. Further education is needed to improve adherence to guidelines.},
}
@article {pmid36585450,
year = {2022},
author = {Garcia-Recio, S and Hinoue, T and Wheeler, GL and Kelly, BJ and Garrido-Castro, AC and Pascual, T and De Cubas, AA and Xia, Y and Felsheim, BM and McClure, MB and Rajkovic, A and Karaesmen, E and Smith, MA and Fan, C and Ericsson, PIG and Sanders, ME and Creighton, CJ and Bowen, J and Leraas, K and Burns, RT and Coppens, S and Wheless, A and Rezk, S and Garrett, AL and Parker, JS and Foy, KK and Shen, H and Park, BH and Krop, I and Anders, C and Gastier-Foster, J and Rimawi, MF and Nanda, R and Lin, NU and Isaacs, C and Marcom, PK and Storniolo, AM and Couch, FJ and Chandran, U and Davis, M and Silverstein, J and Ropelewski, A and Liu, MC and Hilsenbeck, SG and Norton, L and Richardson, AL and Symmans, WF and Wolff, AC and Davidson, NE and Carey, LA and Lee, AV and Balko, JM and Hoadley, KA and Laird, PW and Mardis, ER and King, TA and , and Perou, CM},
title = {Multiomics in primary and metastatic breast tumors from the AURORA US network finds microenvironment and epigenetic drivers of metastasis.},
journal = {Nature cancer},
volume = {},
number = {},
pages = {},
pmid = {36585450},
issn = {2662-1347},
abstract = {The AURORA US Metastasis Project was established with the goal to identify molecular features associated with metastasis. We assayed 55 females with metastatic breast cancer (51 primary cancers and 102 metastases) by RNA sequencing, tumor/germline DNA exome and low-pass whole-genome sequencing and global DNA methylation microarrays. Expression subtype changes were observed in ~30% of samples and were coincident with DNA clonality shifts, especially involving HER2. Downregulation of estrogen receptor (ER)-mediated cell-cell adhesion genes through DNA methylation mechanisms was observed in metastases. Microenvironment differences varied according to tumor subtype; the ER[+]/luminal subtype had lower fibroblast and endothelial content, while triple-negative breast cancer/basal metastases showed a decrease in B and T cells. In 17% of metastases, DNA hypermethylation and/or focal deletions were identified near HLA-A and were associated with reduced expression and lower immune cell infiltrates, especially in brain and liver metastases. These findings could have implications for treating individuals with metastatic breast cancer with immune- and HER2-targeting therapies.},
}
@article {pmid36585434,
year = {2022},
author = {Tosoian, JJ and Sessine, MS and Trock, BJ and Ross, AE and Xie, C and Zheng, Y and Samora, NL and Siddiqui, J and Niknafs, Y and Chopra, Z and Tomlins, S and Kunju, LP and Palapattu, GS and Morgan, TM and Wei, JT and Salami, SS and Chinnaiyan, AM},
title = {MyProstateScore in men considering repeat biopsy: validation of a simple testing approach.},
journal = {Prostate cancer and prostatic diseases},
volume = {},
number = {},
pages = {},
pmid = {36585434},
issn = {1476-5608},
abstract = {BACKGROUND: Men with persistent risk of Grade Group (GG) ≥ 2 cancer after a negative biopsy present a unique clinical challenge. The validated MyProstateScore test is clinically-available for pre-biopsy risk stratification. In biopsy-naïve patients, we recently validated a straightforward testing approach to rule-out GG ≥ 2 cancer with 98% negative predictive value (NPV) and 97% sensitivity. In the current study, we established a practical MPS-based testing approach in men with a previous negative biopsy being considered for repeat biopsy.<br><br>METHODS: Patients provided post-digital rectal examination urine prior to repeat biopsy. MyProstateScore was calculated using the validated, locked model including urinary PCA3 and TMPRSS2:ERG scores with serum PSA. In a clinically-appropriate primary (i.e., training) cohort, we identified a lower (rule-out) threshold approximating 90% sensitivity and an upper (rule-in) threshold approximating 80% specificity for GG&#x2009;&#x2265;&#x2009;2 cancer. These thresholds were applied to an external validation cohort, and performance measures and clinical outcomes associated with their use were calculated.<br><br>RESULTS: MyProstateScore thresholds of 15 and 40 met pre-defined performance criteria in the primary cohort (422 patients; median PSA 6.4, IQR 4.3-9.1). In the 268-patient validation cohort, 25 men (9.3%) had GG&#x2009;&#x2265;&#x2009;2 cancer on repeat biopsy. The rule-out threshold of 15 provided 100% NPV and sensitivity for GG&#x2009;&#x2265;&#x2009;2 cancer and would have prevented 23% of unnecessary biopsies. Use of MyProstateScore >40 to rule-in biopsy would have prevented 67% of biopsies while maintaining 95% NPV. In the validation cohort, the prevalence of GG&#x2009;&#x2265;&#x2009;2 cancer was 0% for MyProstateScore 0-15, 6.5% for MyProstateScore 15-40, and 19% for MyProstateScore >40.<br><br>CONCLUSIONS: In patients who previously underwent a negative prostate biopsy, the MyProstateScore values of 15 and 40 yielded clinically-actionable rule-in and rule-out risk groups. Using this straightforward testing approach, MyProstateScore can meaningfully inform patients and physicians weighing the need for repeat biopsy.},
}
@article {pmid36582502,
year = {2022},
author = {Yu, TC and Thornton, ZT and Hannon, WW and DeWitt, WS and Radford, CE and Matsen, FA and Bloom, JD},
title = {A biophysical model of viral escape from polyclonal antibodies.},
journal = {Virus evolution},
volume = {8},
number = {2},
pages = {veac110},
pmid = {36582502},
issn = {2057-1577},
abstract = {A challenge in studying viral immune escape is determining how mutations combine to escape polyclonal antibodies, which can potentially target multiple distinct viral epitopes. Here we introduce a biophysical model of this process that partitions the total polyclonal antibody activity by epitope and then quantifies how each viral mutation affects the antibody activity against each epitope. We develop software that can use deep mutational scanning data to infer these properties for polyclonal antibody mixtures. We validate this software using a computationally simulated deep mutational scanning experiment and demonstrate that it enables the prediction of escape by arbitrary combinations of mutations. The software described in this paper is available at https://jbloomlab.github.io/polyclonal.},
}
@article {pmid36582473,
year = {2022},
author = {Tettamanti Boshier, FA and Reeves, DB and Duke, ER and Swan, DA and Prlic, M and Cardozo-Ojeda, EF and Schiffer, JT},
title = {Substantial uneven proliferation of CD4[+] T cells during recovery from acute HIV infection is sufficient to explain the observed expanded clones in the HIV reservoir.},
journal = {Journal of virus eradication},
volume = {8},
number = {4},
pages = {100091},
pmid = {36582473},
issn = {2055-6640},
abstract = {The HIV reservoir is a population of 1-10 million anatomically dispersed, latently infected memory CD4[+] T cells in which HIV DNA is quiescently integrated into human chromosomal DNA. When antiretroviral therapy (ART) is stopped and HIV replication initiates in one of these cells, systemic viral spread resumes, rekindling progression to AIDS. Therefore, HIV latency prevents cure. The detection of many populations of identical HIV sequences at unique integration sites implicates CD4[+] T cell proliferation as the critical driver of reservoir sustainment after a prolonged period of effective ART. Initial reservoir formation occurs during the first week of primary infection usually before ART is started. While empirical data indicates that both de novo infection and cellular proliferation generate latently infected cells during early untreated infection, it is not known which of these mechanisms is predominant. We developed a mathematical model that recapitulates the profound depletion and brisk recovery of CD4[+] T cells, reservoir creation, and viral load trajectory during primary HIV infection. We extended the model to stochastically simulate individual HIV reservoir clones. This model predicts the first detection of HIV infected clones approximately 5 weeks after infection as has recently been shown in vivo and suggests that substantial, uneven proliferation among clones during the recovery from CD4[+] lymphopenia is the most plausible explanation for the observed clonal reservoir distribution during the first year of infection.},
}
@article {pmid36582175,
year = {2022},
author = {Stimatze, T and Ruiz, RA and Garcia, I and Kelly, MM and Serfozo, E and Reilly, ED and Kim, D and Scout, N and Karekla, M and Heffner, JL},
title = {Intersectionality in Intervention Development: Insights From Formative Work on a Tailored Tobacco Cessation Program for LGBTQIA+ Young Adults.},
journal = {Health promotion practice},
volume = {},
number = {},
pages = {15248399221141693},
doi = {10.1177/15248399221141693},
pmid = {36582175},
issn = {1524-8399},
abstract = {Tailored tobacco cessation interventions focusing on minoritized communities are proliferating, but the extent to which these interventions address the needs of individuals with multiple minoritized social identities is unclear. We developed Empowered, Queer, Quitting, and Living (EQQUAL), an avatar-led digital smoking cessation intervention tailored for lesbian, gay, bisexual, transgender, queer or questioning, intersex, asexual, and more (LGBTQIA+) young adults based on acceptance and commitment therapy (ACT), via a multistage user-centered design process. The purpose was to evaluate feedback from EQQUAL development activities using an intersectional lens. Intersectionality is a paradigm created by Kimberlé Crenshaw illustrating the multiple social identities each person possesses along with the marginalization of these different social identities. We conducted a rapid deductive content analysis focused on intersectional design gaps using interviewer notes from user testing (n = 7), a diary study (n = 8), and treatment satisfaction responses from a single-arm trial of the EQQUAL intervention (n = 22). Feedback related to intersectional design fell under three broad themes: (a) inadequate representativeness of the avatar, (2) inadequate representativeness within the program broadly, and (3) non-inclusive ACT intervention content. Feedback on inclusiveness included reference to socioeconomic status, race/ethnicity, religious/cultural affiliation, and ability/disability. Although we previously found that EQQUAL was highly acceptable and showed promise in terms of efficacy in a single-arm pilot trial, we identified several gaps in intersectional design as the iterative intervention development proceeded. Because intersectional design is a critical part of developing interventions with a health equity focus, applying standardized procedures for intersectional design and analysis could improve intervention design and better address tobacco cessation treatment needs of individuals who may experience multiple forms of marginalization.},
}
@article {pmid36580020,
year = {2022},
author = {Moore, RE and Wang, T and Duvvuri, B and Feser, ML and Deane, KD and Solomon, JJ and Nelson, JL and Demoruelle, MK and Lood, C},
title = {Anti-mitochondrial antibodies predict erosive disease development in rheumatoid arthritis.},
journal = {Arthritis &amp; rheumatology (Hoboken, N.J.)},
volume = {},
number = {},
pages = {},
doi = {10.1002/art.42428},
pmid = {36580020},
issn = {2326-5205},
abstract = {OBJECTIVE: Mitochondria are found in the extracellular space in rheumatoid arthritis (RA). However, whether mitochondria are a source of autoantigens in RA has not been carefully addressed. Thus, we investigated the presence and significance of anti-mitochondrial antibodies (AMA) in patients with RA.<br><br>METHODS: AMAs were measured in sera from three cross-sectional RA cohorts (n=95, n=192, and n=117) and healthy individuals (n=38, n=72, n=50) using a flow cytometry-based assay. Further, AMAs were detected using anti-mitofusin-1 (MFN1) IgG ELISA and Western blot. A longitudinal inception cohort, followed for a median of 8&#x2009;years, was used to study disease progression.<br><br>RESULTS: AMA levels were elevated in all three RA cohorts as compared to healthy individuals (p<0.001, p<0.05, and p<0.01), with a range of 14-26% positivity. Levels of anti-MFN1 antibodies correlated with AMA levels (r=0.31, p=0.006) and were elevated in RA as compared to healthy individuals (p<0.001). Presence of AMA was associated with erosive disease (p<0.05) and interstitial lung disease (p<0.01). Further, AMA levels could predict erosive disease (OR=4.59, p=0.006) and joint space narrowing (OR=3.08, p=0.02) independent of anti-citrullinated protein antibodies. Finally, anti-MFN1 antibodies identified seronegative patients developing erosive disease (OR=9.33, p=0.02).<br><br>CONCLUSION: Our findings demonstrate the presence of novel autoantibodies targeting mitochondria in RA. AMAs stratified patients based on disease phenotype and predicted development of erosive disease, including in patients with seronegative disease. Our results highlight the essential role of mitochondria in RA pathogenesis and suggest a possible benefit of therapies targeting mitochondrial-mediated inflammation and clearance in these patients. This article is protected by copyright. All rights reserved.},
}
@article {pmid36577856,
year = {2022},
author = {Walter, RB and Sandmaier, BM and Othus, M and Orvain, C and Rodríguez-Arbolí, E and Oshima, MU and Schoch, G and Davis, C and Joachim Deeg, H and Storb, R},
title = {Comparison of reduced intensity and nonmyeloablative conditioning for adults with acute myeloid leukemia undergoing allogeneic hematopoietic cell transplantation in first or second remission.},
journal = {Bone marrow transplantation},
volume = {},
number = {},
pages = {},
pmid = {36577856},
issn = {1476-5365},
abstract = {Reduced intensity conditioning (RIC) and nonmyeloablative (NMA) conditioning regimens have expanded use of allogeneic hematopoietic cell transplantation (HCT) in AML to include older and medically less-fit patients, but relative efficacies and toxicities remain poorly defined. Here, we analyzed outcomes from 343 adults transplanted in remission after RIC (n = 137) or NMA (n = 206) conditioning between 2006 and 2021. The characteristics of RIC and NMA HCT patients were similar except that RIC patients were younger and their time between most recent remission achievement and allografting was shorter. There were no significant differences in relapse risk, relapse-free survival (RFS), overall survival (OS), and non-relapse mortality (NRM) between RIC and NMA HCT patients, both overall (relapse: hazard ratio [HR] = 0.80, P = 0.27; RFS: HR = 0.93, P = 0.61; OS: HR = 0.93, P = 0.66; NRM: HR = 1.13, P = 0.59) and when patients were stratified by pre-HCT measurable residual disease (MRD) status. After multivariable adjustment, there was no statistically significant association between conditioning intensity and relapse (HR = 0.69, P = 0.088), RFS (HR = 0.86, P = 0.37), OS (HR = 0.89, P = 0.49), or NRM (HR = 1.37, P = 0.19). In this non-randomized cohort of adults undergoing allografting for AML in first or second remission at our center, we could not detect statistically significant differences in outcomes between those assigned to RIC and those assigned to NMA conditioning.},
}
@article {pmid36577482,
year = {2022},
author = {Mussetti, A and Kanate, AS and Wang, T and He, M and Hamadani, M and Sr, HF and Boumendil, A and Glass, B and Castagna, L and Dominietto, A and McGuirk, J and Blaise, D and Gülbas, Z and Diez-Martin, J and Marsh, SGE and Paczesny, S and Gadalla, SM and Dreger, P and Zhang, MJ and Spellman, SR and Lee, SJ and Bolon, YT and Sureda, A},
title = {Haploidentical versus matched unrelated donor transplants using post-transplant cyclophosphamide for lymphomas.},
journal = {Transplantation and cellular therapy},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jtct.2022.11.028},
pmid = {36577482},
issn = {2666-6367},
abstract = {BACKGROUND: when using post-transplant cyclophosphamide (PTCy) graft-versus-host-disease (GVHD) prophylaxis for lymphoma patients, it is currently unknown whether a matched unrelated donor (MUD) or a haploidentical related donor is preferable if both are available.<br><br>OBJECTIVE: In this study we wanted to test if using a haploidentical donor has the same results of a MUD.<br><br>STUDY DESIGN: a total of 2140 adults (34% CIBMTR, 66% EBMT registry) aged &#x2265;18 years who received their first haploidentical hematopoietic cell transplant (haplo-HCT) or MUD-HCT (8/8 match at HLA-loci A, B, C, and DRB1) for lymphoma using PTCy-based GVHD prophylaxis from 2010-2019 were retrospectively analyzed.<br><br>RESULTS: The majority of both MUD and haploidentical HCTs received reduced intensity/non-myeloablative conditioning (74% and 77%, respectively), used a peripheral blood stem cell graft (91% and 60%, respectively) and a three-drug GVHD prophylaxis (PTCy&#x202f;+&#x202f;calcineurin inhibitor&#x202f;+&#x202f;MMF in 54% and 90%, respectively). Haploidentical HCT has less favorable results versus MUD cohort in terms of overall mortality (HR=1.69, 95%CI=1.30-2.27, p<0.001), progression-free survival (HR=1.39, 95%CI=1.10 - 1.79, p=0.008), non-relapse mortality (HR=1.93, 95% CI=1.21 - 3.07, p=0.006), platelets engraftment (HR=0.69, 95%CI=0.59 - 0.80, p<0.001), acute grade 2-4 GVHD incidence (HR=1.65, 95%CI=1.28 - 2.14, p<0.001) and chronic GVHD (HR=1.79, 95%CI=1.30 - 2.48, p<0.001). No significant differences were observed in terms of relapse and neutrophil engraftment. Adjusting for propensity score yielded similar results.<br><br>CONCLUSION: whenever MUD is available in a timely manner, it should be preferred over a haploidentical donor when using PTCy-based GVHD prophylaxis for patients with lymphoma.},
}
@article {pmid36576985,
year = {2022},
author = {Carreras-Torres, R and Kim, AE and Lin, Y and Díez-Obrero, V and Bien, SA and Qu, C and Wang, J and Dimou, N and Aglago, EK and Albanes, D and Arndt, V and Baurley, JW and Berndt, SI and Bézieau, S and Bishop, DT and Bouras, E and Brenner, H and Budiarto, A and Campbell, PT and Casey, G and Chan, AT and Chang-Claude, J and Chen, X and Conti, DV and Dampier, CH and Devall, MA and Drew, DA and Figueiredo, JC and Gallinger, S and Giles, GG and Gruber, SB and Gsur, A and Gunter, MJ and Harrison, TA and Hidaka, A and Hoffmeister, M and Huyghe, JR and Jenkins, MA and Jordahl, KM and Kawaguchi, E and Keku, TO and Kundaje, A and Le Marchand, L and Lewinger, JP and Li, L and Mahesworo, B and Morrison, JL and Murphy, N and Nan, H and Nassir, R and Newcomb, PA and Obón-Santacana, M and Ogino, S and Ose, J and Pai, RK and Palmer, JR and Papadimitriou, N and Pardamean, B and Peoples, AR and Pharoah, PDP and Platz, EA and Rennert, G and Ruiz-Narvaez, E and Sakoda, LC and Scacheri, PC and Schmit, SL and Schoen, RE and Shcherbina, A and Slattery, ML and Stern, MC and Su, YR and Tangen, CM and Thomas, DC and Tian, Y and Tsilidis, KK and Ulrich, CM and van Duijnhoven, FJB and Van Guelpen, B and Visvanathan, K and Vodicka, P and Cenggoro, TW and Weinstein, SJ and White, E and Wolk, A and Woods, MO and Hsu, L and Peters, U and Moreno, V and Gauderman, WJ},
title = {Genome-wide interaction study with smoking for colorectal cancer risk identifies novel genetic loci related to tumor suppression, inflammation and immune response.},
journal = {Cancer epidemiology, biomarkers &amp; prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology},
volume = {},
number = {},
pages = {},
doi = {10.1158/1055-9965.EPI-22-0763},
pmid = {36576985},
issn = {1538-7755},
abstract = {BACKGROUND: Tobacco smoking is an established risk factor for colorectal cancer (CRC). However, genetically-defined population subgroups may have increased susceptibility to smoking-related effects on CRC.<br><br>METHODS: A genome-wide interaction scan was performed including 33,756 CRC cases and 44,346 controls from three genetic consortia.<br><br>RESULTS: Evidence of an interaction was observed between smoking status (ever vs never smokers) and a locus on 3p12.1 (rs9880919, p=4.58x10-8), with higher associated risk in subjects carrying the GG genotype (OR 1.25, 95%CI 1.20-1.30) compared with the other genotypes (OR <1.17 for GA and AA). Among ever smokers, we observed interactions between smoking intensity (increase in 10 cigarettes smoked per day) and two loci on 6p21.33 (rs4151657, p=1.72x10-8) and 8q24.23 (rs7005722, p=2.88x10-8). Subjects carrying the rs4151657 TT genotype showed higher risk (OR 1.12, 95%CI 1.09-1.16) compared with the other genotypes (OR <1.06 for TC and CC). Similarly, higher risk was observed among subjects carrying the rs7005722 AA genotype (OR 1.17, 95%CI 1.07-1.28) compared with the other genotypes (OR <1.13 for AC and CC). Functional annotation revealed that SNPs in 3p12.1 and 6p21.33 loci were located in regulatory regions, and were associated with expression levels of nearby genes. Genetic models predicting gene expression revealed that smoking parameters were associated with lower CRC risk with higher expression levels of CADM2 (3p12.1) and ATF6B (6p21.33).<br><br>CONCLUSIONS: Our study identified novel genetic loci that may modulate the risk for CRC of smoking status and intensity, linked to tumor suppression and immune response.<br><br>IMPACT: These findings can guide potential prevention treatments.},
}
@article {pmid36576660,
year = {2022},
author = {Storb, R},
title = {Allogeneic bone marrow transplantation for aplastic anemia.},
journal = {International journal of hematology},
volume = {},
number = {},
pages = {},
pmid = {36576660},
issn = {1865-3774},
support = {P01 HL122173/HL/NHLBI NIH HHS/United States ; P30 CA015704/CA/NCI NIH HHS/United States ; },
abstract = {After more than 60 years of intense research in allogeneic hematopoietic cell transplantation (HCT), this therapy has progressed from one that was fraught with seemingly insurmountable complications to a standard treatment of patients with aplastic anemia. During the 1970s and 1980s, HCT donors were almost exclusively HLA-identical siblings. Subsequent advances in the understanding of the complexity of the HLA region along with the development of molecular HLA typing and the establishment of unrelated volunteer donor registries have resulted in an ever-increasing use of such donors. Most recent breakthroughs have enabled HLA-haploidentical HCT and, thereby, finding donors for nearly every patient. The outstanding outcomes reported with any of the donor options have made allogeneic HCT the preferred treatment over immunosuppressive therapy.},
}
@article {pmid36575737,
year = {2022},
author = {Breeden, L and Miles, S},
title = {A common SSD1 truncation is toxic to cells entering quiescence and promotes sporulation.},
journal = {microPublication biology},
volume = {2022},
number = {},
pages = {},
pmid = {36575737},
issn = {2578-9430},
abstract = {Ssd1p is an RNA binding protein in Saccharomyces cerevisiae that plays an important role in cell division, cell fate decisions, stress response and virulence. Lab strain W303 encodes the terminal truncation ssd1-2, which is typically interpreted to be a loss of function allele. We have shown that ssd1-2 is toxic to mpt5-Δ mutants and to diploids entering stationary phase and quiescence. The ssd1-Δ null shows no toxicity, indicating that ssd1-2 is disrupting an essential function that does not solely require Ssd1p. ssd1-2 cells are also more sensitive to stress than ssd1-Δ . These phenotypes are recessive to SSD1-1 . In contrast, ssd1-2 plays a dominant role in promoting sporulation.},
}
@article {pmid36575460,
year = {2022},
author = {Kanoni, S and Graham, SE and Wang, Y and Surakka, I and Ramdas, S and Zhu, X and Clarke, SL and Bhatti, KF and Vedantam, S and Winkler, TW and Locke, AE and Marouli, E and Zajac, GJM and Wu, KH and Ntalla, I and Hui, Q and Klarin, D and Hilliard, AT and Wang, Z and Xue, C and Thorleifsson, G and Helgadottir, A and Gudbjartsson, DF and Holm, H and Olafsson, I and Hwang, MY and Han, S and Akiyama, M and Sakaue, S and Terao, C and Kanai, M and Zhou, W and Brumpton, BM and Rasheed, H and Havulinna, AS and Veturi, Y and Pacheco, JA and Rosenthal, EA and Lingren, T and Feng, Q and Kullo, IJ and Narita, A and Takayama, J and Martin, HC and Hunt, KA and Trivedi, B and Haessler, J and Giulianini, F and Bradford, Y and Miller, JE and Campbell, A and Lin, K and Millwood, IY and Rasheed, A and Hindy, G and Faul, JD and Zhao, W and Weir, DR and Turman, C and Huang, H and Graff, M and Choudhury, A and Sengupta, D and Mahajan, A and Brown, MR and Zhang, W and Yu, K and Schmidt, EM and Pandit, A and Gustafsson, S and Yin, X and Luan, J and Zhao, JH and Matsuda, F and Jang, HM and Yoon, K and Medina-Gomez, C and Pitsillides, A and Hottenga, JJ and Wood, AR and Ji, Y and Gao, Z and Haworth, S and Yousri, NA and Mitchell, RE and Chai, JF and Aadahl, M and Bjerregaard, AA and Yao, J and Manichaikul, A and Hwu, CM and Hung, YJ and Warren, HR and Ramirez, J and Bork-Jensen, J and Kårhus, LL and Goel, A and Sabater-Lleal, M and Noordam, R and Mauro, P and Matteo, F and McDaid, AF and Marques-Vidal, P and Wielscher, M and Trompet, S and Sattar, N and Møllehave, LT and Munz, M and Zeng, L and Huang, J and Yang, B and Poveda, A and Kurbasic, A and Lamina, C and Forer, L and Scholz, M and Galesloot, TE and Bradfield, JP and Ruotsalainen, SE and Daw, E and Zmuda, JM and Mitchell, JS and Fuchsberger, C and Christensen, H and Brody, JA and Vazquez-Moreno, M and Feitosa, MF and Wojczynski, MK and Wang, Z and Preuss, MH and Mangino, M and Christofidou, P and Verweij, N and Benjamins, JW and Engmann, J and Tsao, NL and Verma, A and Slieker, RC and Lo, KS and Zilhao, NR and Le, P and Kleber, ME and Delgado, GE and Huo, S and Ikeda, DD and Iha, H and Yang, J and Liu, J and Demirkan, A and Leonard, HL and Marten, J and Frank, M and Schmidt, B and Smyth, LJ and Cañadas-Garre, M and Wang, C and Nakatochi, M and Wong, A and Hutri-Kähönen, N and Sim, X and Xia, R and Huerta-Chagoya, A and Fernandez-Lopez, JC and Lyssenko, V and Nongmaithem, SS and Bayyana, S and Stringham, HM and Irvin, MR and Oldmeadow, C and Kim, HN and Ryu, S and Timmers, PRHJ and Arbeeva, L and Dorajoo, R and Lange, LA and Prasad, G and Lorés-Motta, L and Pauper, M and Long, J and Li, X and Theusch, E and Takeuchi, F and Spracklen, CN and Loukola, A and Bollepalli, S and Warner, SC and Wang, YX and Wei, WB and Nutile, T and Ruggiero, D and Sung, YJ and Chen, S and Liu, F and Yang, J and Kentistou, KA and Banas, B and Nardone, GG and Meidtner, K and Bielak, LF and Smith, JA and Hebbar, P and Farmaki, AE and Hofer, E and Lin, M and Concas, MP and Vaccargiu, S and van der Most, PJ and Pitkänen, N and Cade, BE and van der Laan, SW and Chitrala, KN and Weiss, S and Bentley, AR and Doumatey, AP and Adeyemo, AA and Lee, JY and Petersen, ERB and Nielsen, AA and Choi, HS and Nethander, M and Freitag-Wolf, S and Southam, L and Rayner, NW and Wang, CA and Lin, SY and Wang, JS and Couture, C and Lyytikäinen, LP and Nikus, K and Cuellar-Partida, G and Vestergaard, H and Hidalgo, B and Giannakopoulou, O and Cai, Q and Obura, MO and van Setten, J and Li, X and Liang, J and Tang, H and Terzikhan, N and Shin, JH and Jackson, RD and Reiner, AP and Martin, LW and Chen, Z and Li, L and Kawaguchi, T and Thiery, J and Bis, JC and Launer, LJ and Li, H and Nalls, MA and Raitakari, OT and Ichihara, S and Wild, SH and Nelson, CP and Campbell, H and Jäger, S and Nabika, T and Al-Mulla, F and Niinikoski, H and Braund, PS and Kolcic, I and Kovacs, P and Giardoglou, T and Katsuya, T and de Kleijn, D and de Borst, GJ and Kim, EK and Adams, HHH and Ikram, MA and Zhu, X and Asselbergs, FW and Kraaijeveld, AO and Beulens, JWJ and Shu, XO and Rallidis, LS and Pedersen, O and Hansen, T and Mitchell, P and Hewitt, AW and Kähönen, M and Pérusse, L and Bouchard, C and Tönjes, A and Chen, YI and Pennell, CE and Mori, TA and Lieb, W and Franke, A and Ohlsson, C and Mellström, D and Cho, YS and Lee, H and Yuan, JM and Koh, WP and Rhee, SY and Woo, JT and Heid, IM and Stark, KJ and Zimmermann, ME and Völzke, H and Homuth, G and Evans, MK and Zonderman, AB and Polasek, O and Pasterkamp, G and Hoefer, IE and Redline, S and Pahkala, K and Oldehinkel, AJ and Snieder, H and Biino, G and Schmidt, R and Schmidt, H and Bandinelli, S and Dedoussis, G and Thanaraj, TA and Kardia, SLR and Peyser, PA and Kato, N and Schulze, MB and Girotto, G and Böger, CA and Jung, B and Joshi, PK and Bennett, DA and De Jager, PL and Lu, X and Mamakou, V and Brown, M and Caulfield, MJ and Munroe, PB and Guo, X and Ciullo, M and Jonas, JB and Samani, NJ and Kaprio, J and Pajukanta, P and Tusié-Luna, T and Aguilar-Salinas, CA and Adair, LS and Bechayda, SA and de Silva, HJ and Wickremasinghe, AR and Krauss, RM and Wu, JY and Zheng, W and Hollander, AI and Bharadwaj, D and Correa, A and Wilson, JG and Lind, L and Heng, CK and Nelson, AE and Golightly, YM and Wilson, JF and Penninx, B and Kim, HL and Attia, J and Scott, RJ and Rao, DC and Arnett, DK and Hunt, SC and Walker, M and Koistinen, HA and Chandak, GR and Mercader, JM and Costanzo, MC and Jang, D and Burtt, NP and Villalpando, CG and Orozco, L and Fornage, M and Tai, E and van Dam, RM and Lehtimäki, T and Chaturvedi, N and Yokota, M and Liu, J and Reilly, DF and McKnight, AJ and Kee, F and Jöckel, KH and McCarthy, MI and Palmer, CNA and Vitart, V and Hayward, C and Simonsick, E and van Duijn, CM and Jin, ZB and Qu, J and Hishigaki, H and Lin, X and März, W and Gudnason, V and Tardif, JC and Lettre, G and Hart, LM' and Elders, PJM and Damrauer, SM and Kumari, M and Kivimaki, M and van der Harst, P and Spector, TD and Loos, RJF and Province, MA and Parra, EJ and Cruz, M and Psaty, BM and Brandslund, I and Pramstaller, PP and Rotimi, CN and Christensen, K and Ripatti, S and Widén, E and Hakonarson, H and Grant, SFA and Kiemeney, LALM and de Graaf, J and Loeffler, M and Kronenberg, F and Gu, D and Erdmann, J and Schunkert, H and Franks, PW and Linneberg, A and Jukema, JW and Khera, AV and Männikkö, M and Jarvelin, MR and Kutalik, Z and Francesco, C and Mook-Kanamori, DO and van Dijk, KW and Watkins, H and Strachan, DP and Grarup, N and Sever, P and Poulter, N and Chuang, LM and Rotter, JI and Dantoft, TM and Karpe, F and Neville, MJ and Timpson, NJ and Cheng, CY and Wong, TY and Khor, CC and Li, H and Sabanayagam, C and Peters, A and Gieger, C and Hattersley, AT and Pedersen, NL and Magnusson, PKE and Boomsma, DI and Willemsen, AHM and Cupples, L and van Meurs, JBJ and Ghanbari, M and Gordon-Larsen, P and Huang, W and Kim, YJ and Tabara, Y and Wareham, NJ and Langenberg, C and Zeggini, E and Kuusisto, J and Laakso, M and Ingelsson, E and Abecasis, G and Chambers, JC and Kooner, JS and de Vries, PS and Morrison, AC and Hazelhurst, S and Ramsay, M and North, KE and Daviglus, M and Kraft, P and Martin, NG and Whitfield, JB and Abbas, S and Saleheen, D and Walters, RG and Holmes, MV and Black, C and Smith, BH and Baras, A and Justice, AE and Buring, JE and Ridker, PM and Chasman, DI and Kooperberg, C and Tamiya, G and Yamamoto, M and van Heel, DA and Trembath, RC and Wei, WQ and Jarvik, GP and Namjou, B and Hayes, MG and Ritchie, MD and Jousilahti, P and Salomaa, V and Hveem, K and Åsvold, BO and Kubo, M and Kamatani, Y and Okada, Y and Murakami, Y and Kim, BJ and Thorsteinsdottir, U and Stefansson, K and Zhang, J and Chen, Y and Ho, YL and Lynch, JA and Rader, DJ and Tsao, PS and Chang, KM and Cho, K and O'Donnell, CJ and Gaziano, JM and Wilson, PWF and Frayling, TM and Hirschhorn, JN and Kathiresan, S and Mohlke, KL and Sun, YV and Morris, AP and Boehnke, M and Brown, CD and Natarajan, P and Deloukas, P and Willer, CJ and Assimes, TL and Peloso, GM},
title = {Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis.},
journal = {Genome biology},
volume = {23},
number = {1},
pages = {268},
pmid = {36575460},
issn = {1474-760X},
abstract = {BACKGROUND: Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery.<br><br>RESULTS: To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N&#x2009;=&#x2009;1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3-5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism.<br><br>CONCLUSIONS: Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk.},
}
@article {pmid36575360,
year = {2022},
author = {Portuguese, AJ and Gauthier, J and Tykodi, SS and Hall, ET and Hirayama, AV and Yeung, CCS and Blosser, CD},
title = {CD19 CAR-T therapy in solid organ transplant recipients: case report and systematic review.},
journal = {Bone marrow transplantation},
volume = {},
number = {},
pages = {},
pmid = {36575360},
issn = {1476-5365},
support = {T32 HL007093/HL/NHLBI NIH HHS/United States ; },
abstract = {Post-transplant lymphoproliferative disorder (PTLD) is a leading cause of cancer death in solid organ transplant recipients (SOTRs). Relapsed or refractory (R/R) PTLD portends a high risk of death and effective management is not well established. CD19-targeted CAR-T cell therapy has been utilized, but the risks and benefits are unknown. We report the first case of diffuse large B-cell lymphoma (DLBCL) PTLD treated with lisocabtagene maraleucel and present a systematic literature review of SOTRs with PTLD treated with CD19 CAR-T therapy. Our patient achieved a complete response (CR) with limited toxicity but experienced a CD19[+] relapse 8 months after infusion despite CAR-T persistence. Literature review revealed 14 DLBCL and 2 Burkitt lymphoma PTLD cases treated with CD19 CAR-T cells. Kidney (n = 12), liver (n = 2), heart (n = 2), and pancreas after kidney (n = 1) transplant recipients were analyzed. The objective response rate (ORR) was 82.4% (14/17), with 58.5% (10/17) CRs and a 6.5-month median duration of response. Among kidney transplant recipients, the ORR was 91.7% (11/12). Allograft rejection occurred in 23.5% (4/17). No graft failure occurred. Our analysis suggests that CD19 CAR-T therapy offers short-term effectiveness and manageable toxicity in SOTRs with R/R PTLD. Further investigation through larger datasets and prospective study is needed.},
}
@article {pmid36573929,
year = {2022},
author = {Lin, DW},
title = {Point-Counterpoint: Active Surveillance Should Still be Preferred Management for All (or Nearly All) Men with Low Risk Prostate Cancer.},
journal = {The Journal of urology},
volume = {},
number = {},
pages = {101097JU0000000000003134},
doi = {10.1097/JU.0000000000003134},
pmid = {36573929},
issn = {1527-3792},
}
@article {pmid36572838,
year = {2022},
author = {Palin, AC and Alter, G and Crotty, S and Ellebedy, AH and Lane, MC and Lee, FE and Locci, M and Malaspina, A and Mallia, C and McElrath, MJ and Pulendran, B and Singh, A and D'Souza, MP},
title = {Author Correction: The persistence of memory: defining, engineering, and measuring vaccine durability.},
journal = {Nature immunology},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41590-022-01414-9},
pmid = {36572838},
issn = {1529-2916},
}
@article {pmid36083121,
year = {2022},
author = {DeFilipp, Z and Kim, HT and Yang, Z and Noonan, J and Blazar, BR and Lee, SJ and Pavletic, SZ and Cutler, C},
title = {Clinical response to belumosudil in bronchiolitis obliterans syndrome: a combined analysis from 2 prospective trials.},
journal = {Blood advances},
volume = {6},
number = {24},
pages = {6263-6270},
doi = {10.1182/bloodadvances.2022008095},
pmid = {36083121},
issn = {2473-9537},
abstract = {Chronic graft-versus-host disease (cGVHD) of the lung, or bronchiolitis obliterans syndrome (BOS), is a high-risk disease manifestation associated with poor outcomes. Currently available treatments have demonstrated limited clinical efficacy in this setting. Belumosudil is a novel oral selective rho-associated coiled-coil-containing protein kinase-2 inhibitor that was recently approved by the US Food and Drug Administration in the treatment of cGVHD. We identified 59 subjects with BOS who were enrolled and treated in 2 prospective clinical trials of belumosudil. Patients with BOS had a percentage predicted forced expiratory volume in 1 second (FEV1) of ≤79% at enrollment and clinician attribution of lung disease owing to cGVHD. The National Institutes of Health (NIH) cGVHD lung scores at enrollment were 1 (n = 30, 59%), 2 (n = 23, 39%), or 3 (n = 6, 10%). According to NIH response criteria, the best overall response rate (ORR) for lung cGVHD was 32% (partial response: 17%; complete response: 15%). Response rates were inversely proportional to baseline NIH GVHD lung score at enrollment (lung score 1: ORR 50%; lung score 2: ORR 17%, lung score 3: ORR 0%) (P = .006). In multivariable analysis, male sex, lower baseline NIH cGVHD lung score, and partial response to previous line of cGVHD therapy before enrollment were associated with higher rates of lung-specific response. No significant correlation was identified between pulmonary function evaluations and measures of patient symptoms (NIH lung symptom score or Lee Symptom Scale score for lung). In conclusion, belumosudil treatment was associated with lung-specific clinical responses for subjects with BOS, which were more commonly observed in less advanced disease. Optimization of treatment response evaluations remains a challenge in patients with BOS.},
}
@article {pmid36572384,
year = {2022},
author = {Tokaz, MC and Baldomero, H and Cowan, AJ and Saber, W and Greinix, H and Koh, MB and Kröger, N and Mohty, M and Galeano, S and Okamoto, S and Chaudhri, N and Karduss, AJ and Ciceri, F and Colturato, VAR and Corbacioglu, S and Elhaddad, A and Force, LM and Frutos, C and León, AG and Hamad, N and Hamerschlak, N and He, N and Ho, A and Huang, XJ and Jacobs, B and Kim, HJ and Lida, M and Lehmann, L and de Latour, RP and Percival, MM and Perdomo, M and Rasheed, W and Schultz, KR and Seber, A and Ko, BS and Simione, AJ and Srivastava, A and Szer, J and Wood, WA and Kodera, Y and Nagler, A and Snowden, JA and Weisdorf, D and Passweg, J and Pasquini, MC and Sureda, A and Atsuta, Y and Aljurf, M and Niederwieser, D},
title = {An Analysis of the Worldwide Utilization of Hematopoietic Stem Cell Transplantation for Acute Myeloid Leukemia.},
journal = {Transplantation and cellular therapy},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jtct.2022.12.013},
pmid = {36572384},
issn = {2666-6367},
abstract = {BACKGROUND: Acute myeloid leukemia (AML) has an aggressive course and a historically dismal prognosis. For many patients, hematopoietic stem cell transplantation (HSCT) represents the best option for cure, but access, utilization and health inequities on a global scale remain poorly elucidated.<br><br>OBJECTIVE: To describe patterns of global HSCT use in AML for a better understanding of global access, practices, and unmet needs internationally.<br><br>STUDY DESIGN: Estimates of AML incident cases in 2016 were obtained from the Global Burden of Disease (GBD) 2019 study. HSCT activities were collected from 2009-2016 by the Worldwide Network for Blood and Marrow Transplantation (WBMT) through its member organizations. The primary endpoint was global and regional use (number of HSCT) and utilization of HSCT (number of HSCT/ number of incident cases) for AML. Secondary outcomes included trends from 2009 to 2016 in donor type, stem cell source and remission status at time of HSCT.<br><br>RESULTS: Global AML incidence has steadily increased, from 102,000 (95% uncertainty interval (UI): 90,200-108,000) in 2009 to 118,000 (104,000-126,000) in 2016 (+16.2%). Over the same period, a +54.9% increase from 9,659 to 14,965 HSCT/year was observed globally, driven by an increase in allogeneic (+64.9%) with a reduction in autologous (-34.9%) HSCT. While the highest numbers of HSCT continue to be performed in high-resource regions, the largest increases were seen in resource-constrained regions [+94.6% in Africa/East Mediterranean Region (AFR/EMR); +34.7% in America-Nord Region (AMR-N)]. HSCT utilization was skewed towards high-resource regions [in 2016: AMR-N 18.4%, Europe (EUR) 17.9%, South-East Asia/Western Pacific Region (SEAR/WPR) 11.7%, America-South Region (AMR-S) 4.5% and AFR/EMR 2.8%]. For patients <70 years of age, this difference in utilization was widened; AMR-N had the highest allogeneic utilization rate, increasing from 2009 to 2016 (30.6% to 39.9%) with continued low utilization observed in AFR/EMR (1.7% to 2.9%) and AMR-S (3.5% to 5.4%). Across all regions, total HSCT for AML in 1[st] complete remission (CR1) increased (from 44.1% to 59.0%). Patterns of donor stem cell source from related versus unrelated donors varied widely by geographic region. SEAR/WPR had a +130.2% increase in related donor from 2009 to 2016 and >95% HSCT donors in AFR/EMR were from related; in comparison, AMR-N and EUR have a predilection for unrelated HSCT. Globally, allogeneic HSCT stem cell source was predominantly peripheral blood (69.7% of total HSCT in 2009 increased to 78.6% in 2016). Autologous HSCT decreased in all regions from 2009 to 2016 except in SEAR/WPR (+18.9%).<br><br>CONCLUSIONS: HSCT remains a central curative treatment modality in AML. Allogeneic HSCT for AML is rising globally but there are marked variations in regional utilization and practices, including types of graft source. Resource-constrained regions have the largest growth in HSCT use, but utilization rates remain low with a predilection for familial related donor sources and are typically offered in CR1. Further studies are necessary to elucidate the reasons, including economic factors, to understand and address these health inequalities and improve discrepancies in use of HSCT as a potentially curative treatment globally.},
}
@article {pmid36570695,
year = {2023},
author = {Shadman, M and Liu, C and Eakle, K and Hiew, HJ and Biondo, JML and Ghia, P and Mato, AR},
title = {COVID-19 Vaccination Response and Its Practical Application in Patients With Chronic Lymphocytic Leukemia.},
journal = {HemaSphere},
volume = {7},
number = {1},
pages = {e811},
pmid = {36570695},
issn = {2572-9241},
abstract = {Patients with chronic lymphocyticleukemia (CLL) typically have innate/adaptive immune system dysregulation, thus the protective effect of coronavirus disease 2019 (COVID-19) vaccination remains uncertain. This prospective review evaluates vaccination response in these patients, including seropositivity rates by CLL treatment status, type of treatment received, and timing of vaccination. Antibody persistence, predictors of poor vaccine response, and severity of COVID-19 infection in vaccinated patients were also analyzed. Practical advice on the clinical management of patients with CLL is provided. Articles reporting COVID-19 vaccination in patients with CLL, published January 1, 2021-May 1, 2022, were included. Patients with CLL displayed the lowest vaccination responses among hematologic malignancies; however, seropositivity increased with each vaccination. One of the most commonly reported independent risk factors for poor vaccine response was active CLL treatment; others included hypogammaglobulinemia and age >65-70 years. Patients who were treatment-naive, off therapy, in remission, or who had a prior COVID-19 infection displayed the greatest responses. Further data are needed on breakthrough infection rates and a heterologous booster approach in patients with hematologic malignancies. Although vaccine response was poor for patients on active therapy regardless of treatment type, CLL management in the context of COVID-19 should aim to avoid delays in antileukemic treatment, especially with the advent of numerous strategies to mitigate risk of severe COVID-19 such as pre-exposure prophylaxis, and highly effective antivirals and monoclonal antibody therapy upon confirmed infection. Patients with CLL should remain vigilant in retaining standard prevention measures such as masks, social distancing, and hand hygiene.},
}
@article {pmid36568030,
year = {2023},
author = {Young, KL and Fisher, V and Deng, X and Brody, JA and Graff, M and Lim, E and Lin, BM and Xu, H and Amin, N and An, P and Aslibekyan, S and Fohner, AE and Hidalgo, B and Lenzini, P and Kraaij, R and Medina-Gomez, C and Prokić, I and Rivadeneira, F and Sitlani, C and Tao, R and van Rooij, J and Zhang, D and Broome, JG and Buth, EJ and Heavner, BD and Jain, D and Smith, AV and Barnes, K and Boorgula, MP and Chavan, S and Darbar, D and De Andrade, M and Guo, X and Haessler, J and Irvin, MR and Kalyani, RR and Kardia, SLR and Kooperberg, C and Kim, W and Mathias, RA and McDonald, ML and Mitchell, BD and Peyser, PA and Regan, EA and Redline, S and Reiner, AP and Rich, SS and Rotter, JI and Smith, JA and Weiss, S and Wiggins, KL and Yanek, LR and Arnett, D and Heard-Costa, NL and Leal, S and Lin, D and McKnight, B and Province, M and van Duijn, CM and North, KE and Cupples, LA and Liu, CT},
title = {Whole-exome sequence analysis of anthropometric traits illustrates challenges in identifying effects of rare genetic variants.},
journal = {HGG advances},
volume = {4},
number = {1},
pages = {100163},
pmid = {36568030},
issn = {2666-2477},
abstract = {Anthropometric traits, measuring body size and shape, are highly heritable and significant clinical risk factors for cardiometabolic disorders. These traits have been extensively studied in genome-wide association studies (GWASs), with hundreds of genome-wide significant loci identified. We performed a whole-exome sequence analysis of the genetics of height, body mass index (BMI) and waist/hip ratio (WHR). We meta-analyzed single-variant and gene-based associations of whole-exome sequence variation with height, BMI, and WHR in up to 22,004 individuals, and we assessed replication of our findings in up to 16,418 individuals from 10 independent cohorts from Trans-Omics for Precision Medicine (TOPMed). We identified four trait associations with single-nucleotide variants (SNVs; two for height and two for BMI) and replicated the LECT2 gene association with height. Our expression quantitative trait locus (eQTL) analysis within previously reported GWAS loci implicated CEP63 and RFT1 as potential functional genes for known height loci. We further assessed enrichment of SNVs, which were monogenic or syndromic variants within loci associated with our three traits. This led to the significant enrichment results for height, whereas we observed no Bonferroni-corrected significance for all SNVs. With a sample size of ∼20,000 whole-exome sequences in our discovery dataset, our findings demonstrate the importance of genomic sequencing in genetic association studies, yet they also illustrate the challenges in identifying effects of rare genetic variants.},
}
@article {pmid36567516,
year = {2022},
author = {Levy, S and Abd Alhadi, M and Azulay, A and Kahana, A and Bujanover, N and Gazit, R and McGargill, MA and Friedman, LM and Hertz, T},
title = {FLU-LISA: High throughput antibody profiling using antigen microarrays.},
journal = {Immunology and cell biology},
volume = {},
number = {},
pages = {},
doi = {10.1111/imcb.12618},
pmid = {36567516},
issn = {1440-1711},
abstract = {Vaccination and natural infection both elicit potent humoral responses that provide protection from subsequent infections. The immune-history of an individual following such exposures is in part encoded by antibodies. While there are multiple immunoassays for measuring antibody responses, the majority of these methods measure responses to a single antigen. A commonly used method for measuring antibody responses is the enzyme-linked immunosorbent assay (ELISA) - a semi-quantitative assay that is simple to perform in research and clinical settings. Here, we present FLU-LISA (fluorescence-linked immunosorbent assay) - a novel antigen microarray based assay for rapid high-throughput antibody profiling. The assay can be used for profiling IgG, IgA and IgM responses to multiple antigens simultaneously, requiring minimal amounts of sample and antigens. Using several influenza and SARS-CoV-2 antigen microarrays, we demonstrated the specificity and sensitivity of our novel assay and compared it to the traditional ELISA, using samples from mice, chickens and humans. We also showed that our assay can be readily used with dried blood spots, which can be collected from humans and wild birds. The FLU-LISA can be readily used to profile hundreds of samples against dozens of antigens in a single day, and therefore offers an attractive alternative to the traditional ELISA.},
}
@article {pmid36565698,
year = {2022},
author = {Hägglöf, T and Cipolla, M and Loewe, M and Chen, ST and Mesin, L and Hartweger, H and ElTanbouly, MA and Cho, A and Gazumyan, A and Ramos, V and Stamatatos, L and Oliveira, TY and Nussenzweig, MC and Viant, C},
title = {Continuous germinal center invasion contributes to the diversity of the immune response.},
journal = {Cell},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.cell.2022.11.032},
pmid = {36565698},
issn = {1097-4172},
abstract = {Antibody responses are characterized by increasing affinity and diversity over time. Affinity maturation occurs in germinal centers by a mechanism that involves repeated cycles of somatic mutation and selection. How antibody responses diversify while also undergoing affinity maturation is not as well understood. Here, we examined germinal center (GC) dynamics by tracking B cell entry, division, somatic mutation, and specificity. Our experiments show that naive B cells continuously enter GCs where they compete for T cell help and undergo clonal expansion. Consistent with late entry, invaders carry fewer mutations but can contribute up to 30% or more of the cells in late-stage germinal centers. Notably, cells entering the germinal center at later stages of the reaction diversify the immune response by expressing receptors that show low affinity to the immunogen. Paradoxically, the affinity threshold for late GC entry is lowered in the presence of high-affinity antibodies.},
}
@article {pmid36567810,
year = {2021},
author = {Beieler, AM and Yoke, LH and Liu, C and Pergam, SA and Wald, A and Dhanireddy, S},
title = {Advanced practice providers in the infectious disease workforce: A nationwide utilization survey.},
journal = {Journal of interprofessional education &amp; practice},
volume = {24},
number = {},
pages = {100448},
pmid = {36567810},
issn = {2405-4526},
abstract = {BACKGROUND: Shortages of infectious disease (ID) physicians is an identified workforce problem. The COVID-19 pandemic has exacerbated this care gap, leaving many communities without access to an ID physician. More advanced practice providers (APPs), specifically nurse practitioners and physician assistants, work as healthcare extenders, yet are not well described in ID.<br><br>PURPOSE: Evaluate collaboration between ID physicians and APPs, and potential barriers to utilization of APPs.<br><br>METHODS: Anonymous and voluntary surveys; one for physicians, another for APPs. We collected experience, practice setting, familiarity regarding APPs in ID, use of APPs, and perceived barriers/concerns for utilization of APPs.<br><br>DISCUSSION: Nationwide, 218 ID physicians and 93 APPs in ID responded. 71% (155) of ID physicians use APPs. Of APPs, 53% (49) had&#xa0;>&#xa0;5 years ID experience. Responses highlighted opportunities for dedicated ID education, collaboration, and clarification of practice scope.<br><br>CONCLUSION: APPs are an experienced group who provide ID care, working alongside physicians to meet ID workforce needs.},
}
@article {pmid36564740,
year = {2022},
author = {Eastment, MC and Wanje, G and Richardson, BA and Mwaringa, E and Patta, S and Sherr, K and Barnabas, RV and Mandaliya, K and Jaoko, W and McClelland, RS},
title = {A cross-sectional study of the prevalence, barriers, and facilitators of cervical cancer screening in family planning clinics in Mombasa County, Kenya.},
journal = {BMC health services research},
volume = {22},
number = {1},
pages = {1577},
pmid = {36564740},
issn = {1472-6963},
support = {K08-CA228761/NH/NIH HHS/United States ; K24-HD88229/NH/NIH HHS/United States ; },
abstract = {BACKGROUND: Cervical cancer is the most common cancer in sub-Saharan Africa. With appropriate screening and treatment, cervical cancer can be prevented. In Kenya, cervical cancer screening is recommended for all women of reproductive age who visit a health facility. In particular, the Kenyan Ministry of Health has tasked family planning clinics and HIV clinics with implementing cervical cancer screening as part of the overall cervical cancer screening strategy. A cross-sectional survey was conducted to understand cervical cancer screening practices and explore clinic-level barriers and facilitators to screening in family planning clinics (FP) in Mombasa County, Kenya.<br><br>METHODS: Structured interviews were conducted with randomly sampled FP clinic managers to collect information about clinic size, location, type, management support, infrastructure, screening practices, and availability of screening commodities. Data were abstracted from FP registers for a 15-month period from October 1, 2017 until December 31, 2018 to understand cervical cancer screening prevalence. Generalized linear models were used to calculate prevalence ratios (PR) and identify clinic-level correlates of reporting any cervical cancer screening.<br><br>RESULTS: A total of 70 clinics were sampled, 54% (38) were urban and 27% (19) were public facilities. The median number of staff in a clinic was 4 (interquartile range [IQR] 2-6) with a median of 1 provider trained to perform screening (IQR 0-3). Fifty-four percent (38/70) of clinic managers reported that their clinics performed cervical cancer screening. Of these, only 87% (33) and 71% (27) had dependable access to speculums and acetic acid, respectively. Being a public FP clinic was associated with higher prevalence of reported screening (14/38 [37%] vs 6/32 [16%]; prevalence rate ratio [PR] 1.57, 95%CI 1.05-2.33). Clinics that reported cervical cancer screening were much more likely to have at least one provider trained to perform cervical cancer screening (84%, 32/38) compared to clinics that did not report screening (28%, 9/32; PR 3.77, 95%CI&#xa0;1.82-7.83).<br><br>CONCLUSION: Integration of cervical cancer screening into FP clinics offers great potential to reach large numbers of reproductive-aged women. Increasing training of healthcare providers and ensuring adequate commodity supplies in FP clinics offer concrete solutions to increase screening in a largely unscreened population.},
}
@article {pmid36564505,
year = {2022},
author = {Li, X and Quick, C and Zhou, H and Gaynor, SM and Liu, Y and Chen, H and Selvaraj, MS and Sun, R and Dey, R and Arnett, DK and Bielak, LF and Bis, JC and Blangero, J and Boerwinkle, E and Bowden, DW and Brody, JA and Cade, BE and Correa, A and Cupples, LA and Curran, JE and de Vries, PS and Duggirala, R and Freedman, BI and Göring, HHH and Guo, X and Haessler, J and Kalyani, RR and Kooperberg, C and Kral, BG and Lange, LA and Manichaikul, A and Martin, LW and McGarvey, ST and Mitchell, BD and Montasser, ME and Morrison, AC and Naseri, T and O'Connell, JR and Palmer, ND and Peyser, PA and Psaty, BM and Raffield, LM and Redline, S and Reiner, AP and Reupena, MS and Rice, KM and Rich, SS and Sitlani, CM and Smith, JA and Taylor, KD and Vasan, RS and Willer, CJ and Wilson, JG and Yanek, LR and Zhao, W and , and Rotter, JI and Natarajan, P and Peloso, GM and Li, Z and Lin, X},
title = {Powerful, scalable and resource-efficient meta-analysis of rare variant associations in large whole genome sequencing studies.},
journal = {Nature genetics},
volume = {},
number = {},
pages = {},
pmid = {36564505},
issn = {1546-1718},
support = {HHSN268201700001I/HL/NHLBI NIH HHS/United States ; HHSN268201700002I/HL/NHLBI NIH HHS/United States ; HHSN268201700003I/HL/NHLBI NIH HHS/United States ; HHSN268201700005I/HL/NHLBI NIH HHS/United States ; HHSN268201700004I/HL/NHLBI NIH HHS/United States ; HHSN268201800010I/HB/NHLBI NIH HHS/United States ; HHSN268201800011I/HB/NHLBI NIH HHS/United States ; HHSN268201800012I/HB/NHLBI NIH HHS/United States ; HHSN268201800013I/MD/NIMHD NIH HHS/United States ; HHSN268201800014I/HB/NHLBI NIH HHS/United States ; HHSN268201800015I/HB/NHLBI NIH HHS/United States ; HHSN268201500001I/HL/NHLBI NIH HHS/United States ; HHSN268201500003I/HL/NHLBI NIH HHS/United States ; HHSN268201600018C/HL/NHLBI NIH HHS/United States ; HHSN268201600001C/HL/NHLBI NIH HHS/United States ; HHSN268201600002C/HL/NHLBI NIH HHS/United States ; HHSN268201600003C/HL/NHLBI NIH HHS/United States ; HHSN268201600004C/HL/NHLBI NIH HHS/United States ; HHSN268201500001I/HL/NHLBI NIH HHS/United States ; 75N92019D00031/HL/NHLBI NIH HHS/United States ; HHSN268201500003I/HL/NHLBI NIH HHS/United States ; 75N92019D00031/HL/NHLBI NIH HHS/United States ; },
abstract = {Meta-analysis of whole genome sequencing/whole exome sequencing (WGS/WES) studies provides an attractive solution to the problem of collecting large sample sizes for discovering rare variants associated with complex phenotypes. Existing rare variant meta-analysis approaches are not scalable to biobank-scale WGS data. Here we present MetaSTAAR, a powerful and resource-efficient rare variant meta-analysis framework for large-scale WGS/WES studies. MetaSTAAR accounts for relatedness and population structure, can analyze both quantitative and dichotomous traits and boosts the power of rare variant tests by incorporating multiple variant functional annotations. Through meta-analysis of four lipid traits in 30,138 ancestrally diverse samples from 14 studies of the Trans Omics for Precision Medicine (TOPMed) Program, we show that MetaSTAAR performs rare variant meta-analysis at scale and produces results comparable to using pooled data. Additionally, we identified several conditionally significant rare variant associations with lipid traits. We further demonstrate that MetaSTAAR is scalable to biobank-scale cohorts through meta-analysis of TOPMed WGS data and UK Biobank WES data of ~200,000 samples.},
}
@article {pmid36564459,
year = {2022},
author = {Schweizer, MT and Gulati, R and Yezefski, T and Cheng, HH and Mostaghel, E and Haffner, MC and Patel, RA and De Sarkar, N and Ha, G and Dumpit, R and Woo, B and Lin, A and Panlasigui, P and McDonald, N and Lai, M and Nega, K and Hammond, J and Grivas, P and Hsieh, A and Montgomery, B and Nelson, PS and Yu, EY},
title = {Bipolar androgen therapy plus olaparib in men with metastatic castration-resistant prostate cancer.},
journal = {Prostate cancer and prostatic diseases},
volume = {},
number = {},
pages = {},
pmid = {36564459},
issn = {1476-5608},
support = {R50 CA221836/CA/NCI NIH HHS/United States ; P30 CA015704/CA/NCI NIH HHS/United States ; P30 CA015704/CA/NCI NIH HHS/United States ; P50 CA097186/CA/NCI NIH HHS/United States ; },
abstract = {BACKGROUND: Bipolar androgen therapy (BAT) results in rapid fluctuation of testosterone (T) between near-castrate and supraphysiological levels and has shown promise in metastatic castration-resistant prostate cancer (mCRPC). Its clinical effects may be mediated through induction of DNA damage, and preclinical studies suggest synergy with PARP inhibitors.<br><br>PATIENTS AND METHODS: This was a single-center, Phase II trial testing olaparib plus BAT (T cypionate/enanthate 400&#x2009;mg every 28 days) with ongoing androgen deprivation. Planned recruitment was 30 subjects (equal proportions with/without homologous recombination repair [HRR] gene mutations) with mCRPC post abiraterone and/or enzalutamide. The primary objective was to determine PSA50 response (PSA decline &#x2265;50% from baseline) rate at 12-weeks. The primary analysis utilized the entire (intent-to-treat [ITT]) cohort, with those dropping out early counted as non-responders. Secondary/exploratory analyses were in those treated beyond 12-weeks (response-evaluable cohort).<br><br>RESULTS: Thirty-six patients enrolled and 6 discontinued prior to response assessment. In the ITT cohort, PSA50 response rate at 12-weeks was 11/36 (31%; 95% CI 17-48%), and 16/36 (44%, 95% CI 28-62%) had a PSA50 response at any time on-study. After a median follow-up of 19 months, the median clinical/radiographic progression-free survival in the ITT cohort was 13.0 months (95% CI 7-17). Clinical outcomes were similar regardless of HRR gene mutational status.<br><br>CONCLUSIONS: BAT plus olaparib is associated with high response rates and long PFS. Clinical benefit was observed regardless of HRR gene mutational status.},
}
@article {pmid36563837,
year = {2022},
author = {Hall, MS and Holt, VL and Holzman, C and Vazquez, AI and Harris, HR and As-Sanie, S and Upson, K},
title = {Breastfeeding history and adenomyosis risk using a novel case-control study design.},
journal = {Fertility and sterility},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.fertnstert.2022.12.028},
pmid = {36563837},
issn = {1556-5653},
abstract = {OBJECTIVE: To evaluate the association between breastfeeding history, including lifetime exclusive breastfeeding, and adenomyosis risk.<br><br>DESIGN: We used data from a case-control study designed with two control groups to address the challenge of selecting non-cases for a valid epidemiologic study when cases are identified by hysterectomy. The case-control study was conducted among pre- and post-menopausal enrollees ages 18-59 years of a large, integrated healthcare system in western Washington State.<br><br>SUBJECTS: Cases were enrollees with incident, pathology-confirmed adenomyosis diagnosed 2001-2006 (n=386). The two control groups were: 1) randomly selected age-matched enrollees with intact uteri ("population controls", n=323) and 2) hysterectomy controls (n=233).<br><br>EXPOSURE: Data on breastfeeding history were collected by in-person interview. For each live birth reported, participants were asked if they breastfed, along with infant age at supplemental feeding introduction and breastfeeding discontinuation.<br><br>MAIN OUTCOME MEASURES: Among participants with at least one live birth (330 cases, 246 population controls, and 198 hysterectomy controls), we used unconditional logistic regression to estimate adjusted odds ratios and 95% confidence intervals (CI) for the associations between 1) ever breastfeeding, 2) ever breastfeeding for &#x2265; 8 weeks, 3) lifetime breastfeeding, and 4) lifetime exclusive breastfeeding and adenomyosis. Analyses were adjusted for age, reference year, smoking, education, and parity.<br><br>RESULTS: In analyses comparing cases to population controls, we observed a 40% decreased odds of adenomyosis with history of ever breastfeeding (adjusted odds ratio 0.6, 95% CI: 0.3-1.0) and breastfeeding &#x2265; 8 weeks (adjusted odds ratio 0.6, 95% CI: 0.4-0.8). The strongest associations, 60-70% decreased odds of adenomyosis, were observed with &#x2265;12 months of lifetime breastfeeding (vs. <3 months) (adjusted odds ratio 0.4, 95% CI: 0.2-0.6; P<0.001 for trend) and 9-<12 months of lifetime exclusive breastfeeding (vs. <3 months) (adjusted odds ratio 0.3, 95% CI: 0.2-0.6; P<0.001 for trend), comparing cases to population controls. In analyses using hysterectomy controls, we observed similar patterns of associations slightly attenuated in magnitude.<br><br>CONCLUSION: Breastfeeding history was associated with a 40% decreased odds of adenomyosis, a condition that can confer substantial morbidity and requires hysterectomy for definitive treatment. The consistency of our findings with that of a prior study lend support that breastfeeding may modify adenomyosis risk.},
}
@article {pmid36563682,
year = {2022},
author = {Wang, E and Pineda, JMB and Kim, WJ and Chen, S and Bourcier, J and Stahl, M and Hogg, SJ and Bewersdorf, JP and Han, C and Singer, ME and Cui, D and Erickson, CE and Tittley, SM and Penson, AV and Knorr, K and Stanley, RF and Rahman, J and Krishnamoorthy, G and Fagin, JA and Creger, E and McMillan, E and Mak, CC and Jarvis, M and Bossard, C and Beaupre, DM and Bradley, RK and Abdel-Wahab, O},
title = {Modulation of RNA splicing enhances response to BCL2 inhibition in leukemia.},
journal = {Cancer cell},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.ccell.2022.12.002},
pmid = {36563682},
issn = {1878-3686},
abstract = {Therapy resistance is a major challenge in the treatment of cancer. Here, we performed CRISPR-Cas9 screens across a broad range of therapies used in acute myeloid leukemia to identify genomic determinants of drug response. Our screens uncover a selective dependency on RNA splicing factors whose loss preferentially enhances response to the BCL2 inhibitor venetoclax. Loss of the splicing factor RBM10 augments response to venetoclax in leukemia yet is completely dispensable for normal hematopoiesis. Combined RBM10 and BCL2 inhibition leads to mis-splicing and inactivation of the inhibitor of apoptosis XIAP and downregulation of BCL2A1, an anti-apoptotic protein implicated in venetoclax resistance. Inhibition of splicing kinase families CLKs (CDC-like kinases) and DYRKs (dual-specificity tyrosine-regulated kinases) leads to aberrant splicing of key splicing and apoptotic factors that synergize with venetoclax, and overcomes resistance to BCL2 inhibition. Our findings underscore the importance of splicing in modulating response to therapies and provide a strategy to improve venetoclax-based treatments.},
}
@article {pmid36561732,
year = {2022},
author = {Psutka, SP and Veleber, S and Siman, J and Jannat, S and Holt, S and Wright, JL and Greenlee, H},
title = {Effects of acupuncture to decrease adverse events in patients with high-risk non-muscle invasive bladder cancer receiving induction intravesical BCG therapy: Study protocol for a randomized, controlled pilot and feasibility study.},
journal = {Contemporary clinical trials communications},
volume = {30},
number = {},
pages = {101044},
pmid = {36561732},
issn = {2451-8654},
abstract = {BACKGROUND: Treatment-related serious adverse events (SAEs) are common in patients receiving intravesical Bacillus Calmette-Guerin (BCG) for the treatment of high-risk nonmuscle-invasive bladder cancer (NMIBC). Here we describe the protocol of a randomized, attention/waitlist-controlled feasibility pilot study testing the use of acupuncture to decrease SAEs and treatment interruptions in this population. The primary objectives are to evaluate the feasibility and efficacy of conducting pre-procedure acupuncture in a Urology Clinic.<br><br>METHODS: A total of 45 patients will be recruited and randomized in a 2:1 ratio (treatment arm: attention/waitlist control). Eligibility criteria include 1) age 18 years or older, 2) English-speaking, 3) high-risk NMIBC, 4) no acupuncture in the previous 3 months, and 5) willing and able to participate in trial activities. Patients in the treatment arm will receive acupuncture prior to weekly BCG for a total of six weeks. Methods were developed to train and monitor research acupuncturists and included online and in-person training, study manuals, and monthly meetings throughout the study period. Feasibility assessments include evaluation of the recruitment, retention and protocol adherence to acupuncture treatment, and measurement of CTCAE v5.0 adverse events specific to acupuncture, and clinic staff surveys regarding the intervention impact on clinic workflow. Efficacy measures will be compared between treatment and control groups including: EORTC-QLQ-NMIBC-24, EORTC-QLQ-C30, CTCAE v5.0, medication journal, healthcare utilization, current use of complementary, alternative, and integrative therapies, and acupuncture expectancy and treatment preference. Trial results will inform the design of a multi-center trial to expand testing of the protocol to a larger patient cohort.},
}
@article {pmid36550769,
year = {2022},
author = {Parkin, N and Gao, F and Grebe, E and Cutrell, A and Das, M and Donnell, D and Duerr, A and Glidden, DV and Hughes, JP and Murray, J and Robertson, MN and Zinserling, J and Lau, J and Miller, V and , },
title = {Facilitating next-generation pre-exposure prophylaxis (PrEP) clinical trials using HIV recent infection assays: a consensus statement from the Forum HIV Prevention Trial Design Project.},
journal = {Clinical pharmacology and therapeutics},
volume = {},
number = {},
pages = {},
doi = {10.1002/cpt.2830},
pmid = {36550769},
issn = {1532-6535},
abstract = {Standard-of-care HIV pre-exposure prophylaxis (PrEP) is highly efficacious, but uptake of and persistence on a daily oral pill is low in many settings. Evaluation of alternate PrEP products will require innovation to avoid the unpractically large sample sizes in non-inferiority trials. We propose estimating HIV incidence in people not on PrEP as an external counterfactual to which on-PrEP incidence in trial subjects can be compared. HIV recent infection testing algorithms (RITAs) such as the limiting antigen avidity assay plus viral load used on specimens from untreated, HIV positive people identified during screening is one possible approach. Its feasibility is partly dependent on the sample size needed to ensure adequate power, which is impacted by RITA performance, the number of recent infections identified, the expected efficacy of the intervention, and other factors. Screening sample sizes to support detection of an 80% reduction in incidence for three key populations are more modest, and comparable to the number of participants in recent phase 3 PrEP trials. Sample sizes would be significantly larger in populations with lower incidence, where the false recency rate is higher or if PrEP efficacy is expected to be lower. Our proposed counterfactual approach appears to be feasible, offers high statistical power, and is nearly contemporaneous with the on-PrEP population. It will be important to monitor the performance of this approach during new product development for HIV prevention. If successful, it could be a model for preventive HIV vaccines and prevention of other infectious diseases.},
}
@article {pmid36549781,
year = {2022},
author = {Rini, BI and Signoretti, S and Choueiri, TK and McDermott, DF and Motzer, RJ and George, S and Powles, T and Donskov, F and Tykodi, SS and Pal, SK and Gupta, S and Lee, CW and Jiang, R and Tannir, NM},
title = {Long-term outcomes with nivolumab plus ipilimumab versus sunitinib in first-line treatment of patients with advanced sarcomatoid renal cell carcinoma.},
journal = {Journal for immunotherapy of cancer},
volume = {10},
number = {12},
pages = {},
doi = {10.1136/jitc-2022-005445},
pmid = {36549781},
issn = {2051-1426},
abstract = {BACKGROUND: Patients with advanced renal cell carcinoma with sarcomatoid features (sRCC) have a poor prognosis and limited therapeutic options. First-line nivolumab plus ipilimumab (NIVO+IPI) provided efficacy benefits over sunitinib (SUN) in patients with intermediate/poor-risk sRCC at 42 months minimum follow-up in the phase 3 CheckMate 214 trial. In this exploratory post hoc analysis, we report clinical efficacy of NIVO+IPI in sRCC after a minimum follow-up of 5 years.<br><br>METHODS: In CheckMate 214, patients with clear cell advanced RCC were randomized to NIVO 3&#x2009;mg/kg plus IPI 1&#x2009;mg/kg every 3 weeks (four doses), then NIVO 3&#x2009;mg/kg every 2 weeks versus SUN 50&#x2009;mg once daily (4 weeks; 6-week cycles). Randomized patients with sRCC were identified via independent central pathology review of archival tumor tissue or histological classification per local pathology report. Overall survival (OS), as well as progression-free survival (PFS) and objective response rate (ORR) per independent radiology review using Response Evaluation Criteria in Solid Tumors V.1.1, were evaluated in all International Metastatic Renal Cell Carcinoma Database Consortium intermediate/poor-risk sRCC patients and by baseline tumor PD-L1 expression level (&#x2265;1%&#x2009;vs <1%). Safety outcomes are reported using descriptive statistics.<br><br>RESULTS: In total, 139 patients with intermediate/poor-risk sRCC were identified (NIVO+IPI, n=74; SUN, n=65). At 5 years minimum follow-up, more patients remained on treatment with NIVO+IPI versus SUN (12% vs zero). Efficacy benefits with NIVO+IPI versus SUN were maintained with median OS of 48.6 vs 14.2 months (HR 0.46), median PFS of 26.5 vs 5.5 months (HR 0.50), and ORR 60.8% vs 23.1%. In addition, median duration of response was longer (not reached vs 25.1 months), and more patients had complete responses (23.0% vs 6.2%) with NIVO+IPI versus SUN, respectively. Efficacy was better with NIVO+IPI versus SUN regardless of tumor PD-L1 expression, but the magnitude of OS, PFS, and ORR benefits with NIVO+IPI was greater for sRCC patients with tumor PD-L1 &#x2265;1%. No new safety signals emerged in either arm with longer follow-up.<br><br>CONCLUSIONS: Among patients with intermediate/poor-risk sRCC, NIVO+IPI maintained long-term survival benefits and demonstrated durable and deep responses over SUN at minimum follow-up of 5 years, supporting NIVO+IPI as a preferred first-line therapy in this population.<br><br>TRIAL REGISTRATION NUMBER: NCT02231749.},
}
@article {pmid36549742,
year = {2022},
author = {Gigic, B and van Roekel, E and Holowatyj, AN and Brezina, S and Geijsen, AJMR and Ulvik, A and Ose, J and Koole, JL and Damerell, V and Kiblawi, R and Gumpenberger, T and Lin, T and Kvalheim, G and Koelsch, T and Kok, DE and van Duijnhoven, FJ and Bours, MJ and Baierl, A and Li, CI and Grady, W and Vickers, K and Habermann, N and Schneider, M and Kampman, E and Ueland, PM and Ulrich, A and Weijenberg, M and Gsur, A and Ulrich, C and , },
title = {Cohort profile: Biomarkers related to folate-dependent one-carbon metabolism in colorectal cancer recurrence and survival - the FOCUS Consortium.},
journal = {BMJ open},
volume = {12},
number = {12},
pages = {e062930},
doi = {10.1136/bmjopen-2022-062930},
pmid = {36549742},
issn = {2044-6055},
abstract = {PURPOSE: The overarching goal of the FOCUS (biomarkers related to folate-dependent one-carbon metabolism in colorectal cancer (CRC) recurrence and survival) Consortium is to unravel the effect of folate and folate-mediated one-carbon metabolism (FOCM) biomarkers on CRC prognosis to provide clinically relevant advice on folate intake to cancer patients and define future tertiary prevention strategies.<br><br>PARTICIPANTS: The FOCUS Consortium is an international, prospective cohort of 2401&#x2009;women and men above 18 years of age who were diagnosed with a primary invasive non-metastatic (stages I-III) CRC. The consortium comprises patients from Austria, two sites from the Netherlands, Germany and two sites from the USA. Patients are recruited after CRC diagnosis and followed at 6 and 12 months after enrolment. At each time point, sociodemographic data, data on health behaviour and clinical data are collected, blood samples are drawn.<br><br>FINDINGS TO DATE: An increased risk of cancer recurrences was observed among patients with higher compared with lower circulating folic acid concentrations. Furthermore, specific folate species within the FOCM pathway were associated with both inflammation and angiogenesis pathways among patients with CRC. In addition, higher vitamin B6 status was associated with better quality of life at 6&#x2009;months post-treatment.<br><br>FUTURE PLANS: Better insights into the research on associations between folate and FOCM biomarkers and clinical outcomes in patients with CRC will facilitate the development of guidelines regarding folate intake in order to provide clinically relevant advice to patients with cancer, health professionals involved in patient care, and ultimately further tertiary prevention strategies in the future. The FOCUS Consortium offers an excellent infrastructure for short-term and long-term research projects and for combining additional biomarkers and data resulting from the individual cohorts within the next years, for example, microbiome data, omics and multiomics data or CT-quantified body composition data.},
}
@article {pmid36549565,
year = {2022},
author = {Titcomb, TJ and Liu, B and Wahls, TL and Snetselaar, LG and Shadyab, AH and Tabung, FK and Saquib, N and Arcan, C and Tinker, LF and Wallace, RB and Bao, W},
title = {Comparison of the ketogenic ratio of macronutrients with the low-carbohydrate diet score and their association with risk of type 2 diabetes in postmenopausal women: A secondary analysis of the women's health initiative.},
journal = {Journal of the Academy of Nutrition and Dietetics},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jand.2022.12.004},
pmid = {36549565},
issn = {2212-2672},
abstract = {BACKGROUND: Previous attempts to identify low-carbohydrate diets (LCDs) in epidemiological studies relied on the LCD score, which is unable to identify ketogenic dieters. Ketogenic ratios of macronutrients are clinical equations proposed to predict ketogenic diets; however, their utility in epidemiological studies is unknown.<br><br>OBJECTIVE: To determine the number of participants consuming a ketogenic diet, compare ketogenic ratios to the LCD score, and evaluate their association with type 2 diabetes mellitus (T2DM).<br><br>DESIGN: Secondary analysis of the Women's Health Initiative (WHI) with 17.9 &#xb1; 6.03 years of follow-up. Baseline food frequency questionnaires were used to calculate the ketogenic ratio as follows: (0.9*grams fat + 0.46*grams protein) divided by (0.1*grams fat + 0.58*grams protein + grams net carbohydrate), a value &#x2265;1.5 is the minimum threshold for a ketogenic diet.<br><br>PARTICIPANTS/SETTING: 125,982 postmenopausal women without diabetes (age 50-79 years) enrolled in the multicenter WHI observational study and clinical trials were included.<br><br>MAIN OUTCOME MEASURES: Risk of self-reported incident T2DM.<br><br>Cox proportional hazards models, adjusted for age, race, ethnicity, education, income, health insurance, relationship status, geographic region, WHI study component, female hormone use, smoking status, alcohol use, recreational physical activity, total energy intake, diet quality, body mass index, hyperlipidemia, and hypertension, were used to compare hazard ratios (HRs) and 95% confidence intervals (CIs) for T2DM between quintiles of the ketogenic ratio.<br><br>RESULTS: 18,775 incident cases of T2DM occurred. The median ketogenic ratio was 0.35 (interquartile range 0.28-0.42) and 15 individuals (0.01%) exceeded the threshold for a ketogenic diet. Higher ketogenic ratio quintiles were associated with increased risk of T2DM in a dose-dependent manner. Comparing extreme quintiles of the ketogenic ratio, the HR and 95% CI for diabetes was 1.24 (1.18-1.31; Ptrend < 0.001) in fully adjusted models. Similarly, comparing extreme quintiles, the HR (95% CI) for diabetes was 1.36 (1.29-1.43; Ptrend < 0.001) for the LCD score and 1.13 (1.07-1.19; Ptrend < 0.001) for the simplified ketogenic ratio in fully adjusted models.<br><br>CONCLUSION: Increasing ketogenic ratio values are associated with increased risk of T2DM and align well with LCD scores; however, too few participants consumed a ketogenic diet to determine its association with T2DM.},
}
@article {pmid36549469,
year = {2022},
author = {Liu, JJ and DeCuir, N and Kia, L and Peterson, J and Miller, C and Issaka, R},
title = {Tools to Measure the Impact of Structural Racism and Discrimination on Gastrointestinal and Hepatology Disease Outcomes: A Scoping Review.},
journal = {Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.cgh.2022.12.002},
pmid = {36549469},
issn = {1542-7714},
abstract = {BACKGROUND AND AIMS: Structural racism and discrimination (SRD) are important upstream determinants of health perpetuated by discriminatory laws and policies. Therefore, measuring SRD and its impact on health is critical to developing interventions that address resultant health disparities. We aimed to identify gastrointestinal (GI) or liver studies that report measures of SRD or interventions to achieve health equity in these domains by addressing upstream determinants of health.<br><br>METHODS: We conducted a scoping review according to PRISMA-ScR guidelines. Studies that used an SRD measure or examined an upstream intervention in GI or liver disease were included. Studies that described health disparities in GI or liver conditions without mentioning SRD were excluded. Study characteristics, findings and limitations were extracted.<br><br>RESULTS: Forty-six articles (19 studies using SRD measures and 27 studies of upstream interventions) were identified. Measures of residential racial segregation were most frequently reported. SRD was associated with poorer health outcomes for racial and ethnic minority populations. While upstream intervention studies primarily focused on policies related to colon cancer screening and organ graft allocation, racial and ethnic disparities often persisted post-intervention.<br><br>CONCLUSION: To achieve health equity in GI and liver conditions, there is an urgent need for research that goes beyond describing health disparities to incorporating measures of SRD and implementing interventions that address this understudied determinant of health.},
}
@article {pmid36549440,
year = {2022},
author = {Davis, CP and Garzia, NA and Cushing-Haugen, K and Terry, KL and Chiu, YH and Sandoval-Insausti, H and Chavarro, JE and Missmer, SA and Harris, HR},
title = {Fruit and vegetable consumption, pesticide residue intake from consumption of fruits and vegetables, and risk of uterine fibroids.},
journal = {F&amp;S science},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.xfss.2022.12.001},
pmid = {36549440},
issn = {2666-335X},
abstract = {OBJECTIVE: To examine the association between the consumption of fruits and vegetables and pesticide residue intake from consumption of fruits and vegetables and risk of ultrasound or hysterectomy-confirmed fibroids. Only a few studies have evaluated the association of fruit and vegetable intake with uterine fibroids with inconsistent results. No studies have examined pesticide exposure through fruits and vegetables with fibroid risk.<br><br>DESIGN: Prospective cohort study. Cox proportional hazards models were used to calculate hazard ratios (HR) and 95% confidence intervals (CI).<br><br>SETTING: Not applicable.<br><br>PATIENT(S): 81,782 premenopausal participants from the Nurses' Health Study II cohort were followed from 1991-2009 for the fruits and vegetable analysis, and 49,927 participants were followed from 1999-2009 for the pesticide residue burden analysis. Diet was assessed every four years with a food frequency questionnaire. Fruits and vegetables were classified into high- or low-pesticide-residues using a validated method based on surveillance data from the U.S. Department of Agriculture.<br><br>INTERVENTION(S): Not applicable MAIN OUTCOME MEASURE(S): Cases of ultrasound or hysterectomy-confirmed fibroids were identified from self-reports to validated questionnaires.<br><br>RESULTS: From 1991-2009, 9,706 incident cases of ultrasound or hysterectomy-confirmed fibroids were reported, and 4,195 incident cases were identified from 1999-2009. No association was observed between total fruit and vegetable consumption and uterine fibroid risk. Participants who consumed the highest intake of total fruits (&#x2265;4/day) were 10% less likely to develop uterine fibroids compared to participants who consumed <1/day (95% CI=0.80-1.01; ptrend=0.03). No associations were observed with any other fruit or vegetable groups. An inverse association was observed between intake of high-pesticide-residue fruits and vegetables and fibroid risk (HR for 5[th] vs 1[st] quintile=0.87; 95% CI=0.77-0.99; ptrend=0.04) while no association with low-pesticide-residue fruits and vegetables was observed (HR for 5[th] vs 1[st] quintile=1.08; 95% CI=0.95-1.23; ptrend=0.26).<br><br>CONCLUSION: Our findings suggest that pesticide residues on fruits and vegetables are not associated with a higher risk of uterine fibroids. Further, our results suggest that intake of fruits may be associated with a lower risk of fibroids. Future research in this area should focus on dietary exposures across the life course as well as assessment of class-specific pesticides.},
}
@article {pmid36547666,
year = {2022},
author = {Sweet, KL and Cortes, JE and Apperley, JF and Mann, M and Mauro, MJ and Oehler, VG and Ruiz, C and Schiffer, CA and Ehrlich, LA and Pamuk, GE and Wynne, J and Mehta, GU and de Claro, RA and Theoret, MR and Smith, BD and Norsworthy, KJ},
title = {Project Confirm: Accelerated Drug Approvals for Chronic Myeloid Leukemia.},
journal = {Clinical cancer research : an official journal of the American Association for Cancer Research},
volume = {},
number = {},
pages = {},
doi = {10.1158/1078-0432.CCR-22-2628},
pmid = {36547666},
issn = {1557-3265},
abstract = {The Food and Drug Administration (FDA) has an accelerated approval program for drugs which have been identified as promising treatments for serious conditions when the available data suggests that the benefits outweigh the foreseeable risks. All of the currently available treatment options for chronic myeloid leukemia (CML) initially went through the accelerated approval program. Here a group of academic CML experts, patient panelists and members from the FDA convened to discuss the utility of the accelerated approval program as it pertains to CML, and the utility of this program in future drug development in this disease. The results of that discussion are summarized here.},
}
@article {pmid36546651,
year = {2022},
author = {Strickler, JH and Satake, H and George, TJ and Yaeger, R and Hollebecque, A and Garrido-Laguna, I and Schuler, M and Burns, TF and Coveler, AL and Falchook, GS and Vincent, M and Sunakawa, Y and Dahan, L and Bajor, D and Rha, SY and Lemech, C and Juric, D and Rehn, M and Ngarmchamnanrith, G and Jafarinasabian, P and Tran, Q and Hong, DS},
title = {Sotorasib in KRAS p.G12C-Mutated Advanced Pancreatic Cancer.},
journal = {The New England journal of medicine},
volume = {},
number = {},
pages = {},
doi = {10.1056/NEJMoa2208470},
pmid = {36546651},
issn = {1533-4406},
abstract = {BACKGROUND: KRAS p.G12C mutation occurs in approximately 1 to 2% of pancreatic cancers. The safety and efficacy of sotorasib, a KRAS G12C inhibitor, in previously treated patients with KRAS p.G12C-mutated pancreatic cancer are unknown.<br><br>METHODS: We conducted a single-group, phase 1-2 trial to assess the safety and efficacy of sotorasib treatment in patients with KRAS p.G12C-mutated pancreatic cancer who had received at least one previous systemic therapy. The primary objective of phase 1 was to assess safety and to identify the recommended dose for phase 2. In phase 2, patients received sotorasib at a dose of 960 mg orally once daily. The primary end point for phase 2 was a centrally confirmed objective response (defined as a complete or partial response). Efficacy end points were assessed in the pooled population from both phases and included objective response, duration of response, time to objective response, disease control (defined as an objective response or stable disease), progression-free survival, and overall survival. Safety was also assessed.<br><br>RESULTS: The pooled population from phases 1 and 2 consisted of 38 patients, all of whom had metastatic disease at enrollment and had previously received chemotherapy. At baseline, patients had received a median of 2 lines (range, 1 to 8) of therapy previously. All 38 patients received sotorasib in the trial. A total of 8 patients had a centrally confirmed objective response (21%; 95% confidence interval [CI], 10 to 37). The median progression-free survival was 4.0 months (95% CI, 2.8 to 5.6), and the median overall survival was 6.9 months (95% CI, 5.0 to 9.1). Treatment-related adverse events of any grade were reported in 16 patients (42%); 6 patients (16%) had grade 3 adverse events. No treatment-related adverse events were fatal or led to treatment discontinuation.<br><br>CONCLUSIONS: Sotorasib showed anticancer activity and had an acceptable safety profile in patients with KRAS p.G12C-mutated advanced pancreatic cancer who had received previous treatment. (Funded by Amgen and others; CodeBreaK 100 ClinicalTrials.gov number, NCT03600883.).},
}
@article {pmid36544274,
year = {2023},
author = {Hopkins, SE and Orr, E and Boyer, BB and Thompson, B},
title = {Culturally adapting an evidence-based intervention to promote a healthy diet and lifestyle for Yup'ik Alaska native communities.},
journal = {International journal of circumpolar health},
volume = {82},
number = {1},
pages = {2159888},
doi = {10.1080/22423982.2022.2159888},
pmid = {36544274},
issn = {2242-3982},
abstract = {Underserved populations are at increased risk for obesity and related cardiovascular disease, type 2 diabetes, and other chronic diseases. Lack of access to healthy foods, sedentary behaviour, and other social environmental factors contribute to disease risk. Yup'ik Alaska Native communities are experiencing lifestyle changes that are likely to affect their cardiometabolic risks. Barrera &amp; Castro's Cultural Adaptation Framework was used to adapt an evidence-based intervention (EBI) originally designed for Latino communities for use in Yup'ik communities. Focus groups and key informant interviews were held in two Yup'ik communities. Major themes included causes of obesity, barriers and facilitators to healthy foods and physical activity, and intervention ideas. The adaptation process was guided by a Community Planning Group of Yup'ik women and included information gathering, preliminary adaptation design, preliminary adaptation tests, and adaptation refinement. Two of the adapted educational modules were pilot tested. Involving community members as co-researchers in cultural adaptation is vital for an EBI to be effective in another population. Small group gatherings led by local lay health workers are culturally appropriate and may be an effective health promotion model in Yup'ik communities. Social environmental factors affecting healthy food availability and physical activity need further exploration.},
}
@article {pmid36543503,
year = {2022},
author = {Lin, JY and Larson, J and Schoenberg, J and Sepulveda, A and Tinker, L and Wheeler, M and Albert, C and Manson, JE and Wells, G and Martin, LW and Froelicher, V and LaMonte, M and Kooperberg, C and Hlatky, MA and Greenland, P and Stefanick, ML and Perez, MV},
title = {Serial 7-Day Electrocardiogram Patch Screening for AF in High-Risk Older Women by the CHARGE-AF Score.},
journal = {JACC. Clinical electrophysiology},
volume = {8},
number = {12},
pages = {1523-1534},
doi = {10.1016/j.jacep.2022.08.024},
pmid = {36543503},
issn = {2405-5018},
abstract = {BACKGROUND: Asymptomatic atrial fibrillation (AF) is associated with an increased risk of stroke. The yield of serial electrocardiographic (ECG) screening for AF is unknown.<br><br>OBJECTIVES: The aim of this study was to determine the frequency of AF detected by serial, 7-day ECG patch screenings in older women identified as having an elevated risk of AF according to the CHARGE (Cohorts for Heart and Aging Research in Genomic Epidemiology)-AF clinical prediction score.<br><br>METHODS: Postmenopausal women with a 5-year predicted risk of new-onset AF&#xa0;&#x2265;5% according to CHARGE-AF were recruited from the ongoing WHISH (Women's Health Initiative Strong and Healthy) randomized trial of a physical activity intervention. Participants with AF at baseline by self-report or medical records review were excluded. Screening with 7-day ECG patch monitors was performed at baseline, 6&#xa0;months, and 12&#xa0;months from study enrollment.<br><br>RESULTS: On baseline monitoring, 2.5% of the cohort had AF detected, increasing to 3.7% by 6&#xa0;months and 4.9% cumulatively by 12&#xa0;months. Yield of patch screening was higher among participants with a higher (&#x2265;10%) CHARGE-AF score: 4.2% had AF detected at baseline, 5.9% at 6&#xa0;months, and 7.2% at 12&#xa0;months. Most participants with patch-identified AF never had a clinical diagnosis of AF (36 of 46 [78%]).<br><br>CONCLUSIONS: Older women with an elevated CHARGE-AF score had a high prevalence of AF on 7-day ECG patch screening. Serial screening over 12&#xa0;months substantially increased the detection of AF. These data can be useful in helping identify high-risk participants for enrollment in future studies of the management of asymptomatic AF.(Women's&#xa0;Health Initiative Silent Atrial Fibrillation Recording Study [WHISH STAR]; NCT05366803.).},
}
@article {pmid36542251,
year = {2022},
author = {Gholami, S and Colby, S and Horowitz, DP and Guthrie, KA and Ben-Josef, E and El-Khoueiry, AB and Blanke, CD and Philip, PA and Kachnic, LA and Ahmad, SA and Rocha, FG},
title = {ASO Visual Abstract: Adjuvant Chemoradiation in Patients with Lymph Node-Positive Biliary Tract Cancers - Secondary Analysis of a Single-Arm Clinical Trial (SWOG 0809).},
journal = {Annals of surgical oncology},
volume = {},
number = {},
pages = {},
doi = {10.1245/s10434-022-12927-w},
pmid = {36542251},
issn = {1534-4681},
}
@article {pmid36541636,
year = {2023},
author = {Remien, RH and Dacus, JD and Farley, JE and Hughes, JP and Gamble, T and Wang, ZZ and Batey, DS and Mayer, KH and Del Rio, C and Balán, IC and Irvin, R and Mitchell, KM and Cummings, V and Eshleman, SH and Conserve, DF and Knox, J and Yu, K and Beyrer, C and , },
title = {HTPN 078: an enhanced case management study to achieve viral suppression among viremic HIV-positive men who have sex with men in the United States.},
journal = {AIDS (London, England)},
volume = {37},
number = {2},
pages = {217-231},
doi = {10.1097/QAD.0000000000003411},
pmid = {36541636},
issn = {1473-5571},
abstract = {OBJECTIVES: After identifying and recruiting men who have sex with men living with HIV and virally unsuppressed, this study attempted to enhance treatment and care via case management to increase the proportion who achieved viral suppression.<br><br>DESIGN: Participants were randomized into one of two study arms: standard of care (SOC) or enhanced case management (CM) intervention. Participants were followed for 12&#x200a;months with quarterly study assessments, with blood collected for CD4+ cell count testing, HIV viral load testing (primary prespecified outcome), and plasma storage.<br><br>METHODS: Participants identified via respondent-driven sampling and direct recruitment and were invited to participate in the randomized controlled trial. The CM intervention provided a wide range of support services including, health education, clinical care coordination, medication adherence support, and social service assistance. The month-12 assessment included questions about healthcare utilization, stigma, substance use, and mental health.<br><br>RESULTS: Among the 144 participants virally unsuppressed at baseline, most had had a previous positive HIV test result; were Black, non-Hispanic, gay and bisexual men, aged 22-50. Among the 128 participants at the last study visit, 68 were virally suppressed, with no statistically significant difference between the CM and SOC arms (viral suppression 42% and 53%, respectively; adjusted odds ratio = 0.62 [P&#x200a;=&#x200a;0.15; 95% confidence interval: 0.32, 1.2]).<br><br>CONCLUSIONS: Reaching targets of at least 90% sustained viral suppression among all people with HIV will likely require more than an individual-level CM approach that addresses barriers to optimal care and treatment at multiple levels.},
}
@article {pmid36539908,
year = {2022},
author = {Lopci, E and Aide, N and Dimitrakopoulou-Strauss, A and Dercle, L and Iravani, A and Seban, RD and Sachpekidis, C and Humbert, O and Gheysens, O and Glaudemans, AWJM and Weber, WA and Van den Abbeele, AD and Wahl, RL and Scott, AM and Pandit-Taskar, N and Hicks, RJ},
title = {Perspectives on joint EANM/SNMMI/ANZSNM practice guidelines/procedure standards for [[18]F]FDG PET/CT imaging during immunomodulatory treatments in patients with solid tumors.},
journal = {Cancer imaging : the official publication of the International Cancer Imaging Society},
volume = {22},
number = {1},
pages = {73},
pmid = {36539908},
issn = {1470-7330},
abstract = {Response assessment in the context of immunomodulatory treatments represents a major challenge for the medical imaging community and requires a multidisciplinary approach with involvement of oncologists, radiologists, and nuclear medicine specialists. There is evolving evidence that [[18]F]FDG PET/CT is a useful diagnostic modality for this purpose. The clinical indications for, and the principal aspects of its standardization in this context have been detailed in the recently published "Joint EANM/SNMMI/ANZSNM practice guidelines/procedure standards on recommended use of [[18]F]FDG PET/CT imaging during immunomodulatory treatments in patients with solid tumors version 1.0". These recommendations arose from a fruitful collaboration between international nuclear medicine societies and experts in cancer treatment. In this perspective, the key elements of the initiative are reported, summarizing the core aspects of the guidelines for radiologists and nuclear medicine physicians. Beyond the previous guidelines, this perspective adds further commentary on how this technology can advance development of novel therapeutic approaches and guide management of individual patients.},
}
@article {pmid36539618,
year = {2022},
author = {Fernandez-Rozadilla, C and Timofeeva, M and Chen, Z and Law, P and Thomas, M and Schmit, S and Díez-Obrero, V and Hsu, L and Fernandez-Tajes, J and Palles, C and Sherwood, K and Briggs, S and Svinti, V and Donnelly, K and Farrington, S and Blackmur, J and Vaughan-Shaw, P and Shu, XO and Long, J and Cai, Q and Guo, X and Lu, Y and Broderick, P and Studd, J and Huyghe, J and Harrison, T and Conti, D and Dampier, C and Devall, M and Schumacher, F and Melas, M and Rennert, G and Obón-Santacana, M and Martín-Sánchez, V and Moratalla-Navarro, F and Oh, JH and Kim, J and Jee, SH and Jung, KJ and Kweon, SS and Shin, MH and Shin, A and Ahn, YO and Kim, DH and Oze, I and Wen, W and Matsuo, K and Matsuda, K and Tanikawa, C and Ren, Z and Gao, YT and Jia, WH and Hopper, J and Jenkins, M and Win, AK and Pai, R and Figueiredo, J and Haile, R and Gallinger, S and Woods, M and Newcomb, P and Duggan, D and Cheadle, J and Kaplan, R and Maughan, T and Kerr, R and Kerr, D and Kirac, I and Böhm, J and Mecklin, LP and Jousilahti, P and Knekt, P and Aaltonen, L and Rissanen, H and Pukkala, E and Eriksson, J and Cajuso, T and Hänninen, U and Kondelin, J and Palin, K and Tanskanen, T and Renkonen-Sinisalo, L and Zanke, B and Männistö, S and Albanes, D and Weinstein, S and Ruiz-Narvaez, E and Palmer, J and Buchanan, D and Platz, E and Visvanathan, K and Ulrich, C and Siegel, E and Brezina, S and Gsur, A and Campbell, P and Chang-Claude, J and Hoffmeister, M and Brenner, H and Slattery, M and Potter, J and Tsilidis, K and Schulze, M and Gunter, M and Murphy, N and Castells, A and Castellví-Bel, S and Moreira, L and Arndt, V and Shcherbina, A and Stern, M and Pardamean, B and Bishop, T and Giles, G and Southey, M and Idos, G and McDonnell, K and Abu-Ful, Z and Greenson, J and Shulman, K and Lejbkowicz, F and Offit, K and Su, YR and Steinfelder, R and Keku, T and van Guelpen, B and Hudson, T and Hampel, H and Pearlman, R and Berndt, S and Hayes, R and Martinez, ME and Thomas, S and Corley, D and Pharoah, P and Larsson, S and Yen, Y and Lenz, HJ and White, E and Li, L and Doheny, K and Pugh, E and Shelford, T and Chan, A and Cruz-Correa, M and Lindblom, A and Hunter, D and Joshi, A and Schafmayer, C and Scacheri, P and Kundaje, A and Nickerson, D and Schoen, R and Hampe, J and Stadler, Z and Vodicka, P and Vodickova, L and Vymetalkova, V and Papadopoulos, N and Edlund, C and Gauderman, W and Thomas, D and Shibata, D and Toland, A and Markowitz, S and Kim, A and Chanock, S and van Duijnhoven, F and Feskens, E and Sakoda, L and Gago-Dominguez, M and Wolk, A and Naccarati, A and Pardini, B and FitzGerald, L and Lee, SC and Ogino, S and Bien, S and Kooperberg, C and Li, C and Lin, Y and Prentice, R and Qu, C and Bézieau, S and Tangen, C and Mardis, E and Yamaji, T and Sawada, N and Iwasaki, M and Haiman, C and Le Marchand, L and Wu, A and Qu, C and McNeil, C and Coetzee, G and Hayward, C and Deary, I and Harris, S and Theodoratou, E and Reid, S and Walker, M and Ooi, LY and Moreno, V and Casey, G and Gruber, S and Tomlinson, I and Zheng, W and Dunlop, M and Houlston, R and Peters, U},
title = {Deciphering colorectal cancer genetics through multi-omic analysis of 100,204 cases and 154,587 controls of European and east Asian ancestries.},
journal = {Nature genetics},
volume = {},
number = {},
pages = {},
pmid = {36539618},
issn = {1546-1718},
abstract = {Colorectal cancer (CRC) is a leading cause of mortality worldwide. We conducted a genome-wide association study meta-analysis of 100,204 CRC cases and 154,587 controls of European and east Asian ancestry, identifying 205 independent risk associations, of which 50 were unreported. We performed integrative genomic, transcriptomic and methylomic analyses across large bowel mucosa and other tissues. Transcriptome- and methylome-wide association studies revealed an additional 53 risk associations. We identified 155 high-confidence effector genes functionally linked to CRC risk, many of which had no previously established role in CRC. These have multiple different functions and specifically indicate that variation in normal colorectal homeostasis, proliferation, cell adhesion, migration, immunity and microbial interactions determines CRC risk. Crosstissue analyses indicated that over a third of effector genes most probably act outside the colonic mucosa. Our findings provide insights into colorectal oncogenesis and highlight potential targets across tissues for new CRC treatment and chemoprevention strategies.},
}
@article {pmid36539002,
year = {2022},
author = {Hanna, M and Dey, N and Grady, WM},
title = {Emerging Tests for Non-Invasive Colorectal Cancer Screening.},
journal = {Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.cgh.2022.12.008},
pmid = {36539002},
issn = {1542-7714},
abstract = {Colorectal cancer (CRC) is among the most common cancers globally and a major cause of cancer-related deaths. The American Cancer Society estimates that CRC will kill 1 in 60 Americans and CRC screening is recommended for all Americans ≥45 years of age. Current CRC screening methods are effective for preventing CRC and have been shown to reduce CRC-related mortality. However, none of the currently available tests is ideal, and many people are not compliant with CRC screening. Novel CRC screening tests based on advances in CRC molecular biology, genetics, and epigenetics combined with developments in sequencing technologies and computational analytic methods, have been developed to address the shortcomings of current CRC screening tests. These emerging tests include blood-based assays that use plasma-derived circulating tumor DNA and serum proteins to detect early CRC and advanced adenomas, assays that use stool DNA or mRNA, and methods for profiling the gut microbiome. Here we review current screening modalities, and we discuss the principles behind the most promising emerging CRC screening tests and the data supporting their potential to be used in clinical practice .},
}
@article {pmid36536032,
year = {2022},
author = {Brochu, H and Wang, R and Tollison, T and Pyo, CW and Thomas, A and Tseng, E and Law, L and Picker, LJ and Gale, M and Geraghty, DE and Peng, X},
title = {Alternative splicing and genetic variation of mhc-e: implications for rhesus cytomegalovirus-based vaccines.},
journal = {Communications biology},
volume = {5},
number = {1},
pages = {1387},
pmid = {36536032},
issn = {2399-3642},
abstract = {Rhesus cytomegalovirus (RhCMV)-based vaccination against Simian Immunodeficiency virus (SIV) elicits MHC-E-restricted CD8+ T cells that stringently control SIV infection in ~55% of vaccinated rhesus macaques (RM). However, it is unclear how accurately the RM model reflects HLA-E immunobiology in humans. Using long-read sequencing, we identified 16 Mamu-E isoforms and all Mamu-E splicing junctions were detected among HLA-E isoforms in humans. We also obtained the complete Mamu-E genomic sequences covering the full coding regions of 59 RM from a RhCMV/SIV vaccine study. The Mamu-E gene was duplicated in 32 (54%) of 59 RM. Among four groups of Mamu-E alleles: three ~5% divergent full-length allele groups (G1, G2, G2_LTR) and a fourth monomorphic group (G3) with a deletion encompassing the canonical Mamu-E exon 6, the presence of G2_LTR alleles was significantly (p = 0.02) associated with the lack of RhCMV/SIV vaccine protection. These genomic resources will facilitate additional MHC-E targeted translational research.},
}
@article {pmid35702158,
year = {2022},
author = {Banerjee, S and Smith, C and Geballe, A and Rothenburg, S and Kitzman, JO and Brennan, G},
title = {Gene amplification acts as a molecular foothold to facilitate cross-species adaptation and evasion of multiple antiviral pathways.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {35702158},
abstract = {Cross-species spillover events are responsible for many of the pandemics in human history including COVID-19; however, the evolutionary mechanisms that enable these events are poorly understood. We have previously modeled this process using a chimeric vaccinia virus expressing the rhesus cytomegalovirus-derived PKR antagonist RhTRS1 in place of its native PKR antagonists; E3L and K3L (VACVΔEΔK+RhTRS1). Using this virus, we demonstrated that gene amplification of rhtrs1 occurred early during experimental evolution and was sufficient to fully rescue virus replication in partially resistant African green monkey (AGM) fibroblasts. Notably, this rapid gene amplification also allowed limited virus replication in otherwise completely non-permissive human fibroblasts, suggesting that gene amplification may act as a "molecular foothold" to facilitate viral adaptation to multiple species. In this study, we demonstrate that there are multiple barriers to VACVΔEΔK+RhTRS1 replication in human cells, mediated by both PKR and RNase L. We experimentally evolved three AGM-adapted virus populations in human fibroblasts. Each population adapted to human cells bimodally, via an initial 10-fold increase in replication after only two passages followed by a second 10-fold increase in replication by passage nine. Using our Illumina-based pipeline, we found that some SNPs which had evolved during the prior AGM adaptation were rapidly lost, while 13 single-base substitutions and short indels increased over time, including two SNPs unique to HFF adapted populations. Many of these changes were associated with components of the viral RNA polymerase, although no variant was shared between all three populations. Taken together, our results demonstrate that rhtrs1 amplification was sufficient to increase viral tropism after passage in an "intermediate species" and subsequently enabled the virus to adopt different, species-specific adaptive mechanisms to overcome distinct barriers to viral replication in AGM and human cells.},
}
@article {pmid22161569,
year = {2011},
author = {Eckels, J and Hussey, P and Nelson, EK and Myers, T and Rauch, A and Bellew, M and Connolly, B and Law, W and Eng, JK and Katz, J and McIntosh, M and Mallick, P and Igra, M},
title = {Installation and use of LabKey Server for proteomics.},
journal = {Current protocols in bioinformatics},
volume = {Chapter 13},
number = {},
pages = {13.5.1-13.5.25},
doi = {10.1002/0471250953.bi1305s36},
pmid = {22161569},
issn = {1934-340X},
mesh = {Chromatography, Liquid/methods ; Data Mining ; Databases, Protein ; Mass Spectrometry/methods ; Proteomics/instrumentation/*methods ; *Software ; },
abstract = {LabKey Server (formerly CPAS, the Computational Proteomics Analysis System) provides a Web-based platform for mining data from liquid chromatography-tandem mass spectrometry (LC-MS/MS) proteomic experiments. This open source platform supports systematic proteomic analyses and secure data management, integration, and sharing. LabKey Server incorporates several tools currently used in proteomic analysis, including the X! Tandem search engine, the ProteoWizard toolkit, and the PeptideProphet and ProteinProphet data mining tools. These tools and others are integrated into LabKey Server, which provides an extensible architecture for developing high-throughput biological applications. The LabKey Server analysis pipeline acts on data in standardized file formats, so that researchers may use LabKey Server with other search engines, including Mascot or SEQUEST, that follow a standardized format for reporting search engine results. Supported builds of LabKey Server are freely available at http://www.labkey.com/. Documentation and source code are available under the Apache License 2.0 at http://www.labkey.org.},
}
@article {pmid36534128,
year = {2022},
author = {Radtke, S and Pande, D and Enstrom, MR and Kiem, HP},
title = {Safe and efficient lentiviral vector integration with HSC-targeted gene therapy.},
journal = {Blood advances},
volume = {},
number = {},
pages = {},
doi = {10.1182/bloodadvances.2022009087},
pmid = {36534128},
issn = {2473-9537},
}
@article {pmid36530463,
year = {2022},
author = {Nagana Gowda, GA and Pascua, V and Raftery, D},
title = {A new limit for blood metabolite analysis using [1]H NMR spectroscopy.},
journal = {Journal of magnetic resonance open},
volume = {12-13},
number = {},
pages = {},
pmid = {36530463},
issn = {2666-4410},
abstract = {Human blood is the most widely used biospecimen in the clinic and the metabolomics field. While both mass spectrometry and NMR spectroscopy are the two premier analytical platforms in the metabolomics field, NMR exhibits several unsurpassed characteristics for blood metabolite analysis, the most important of which are its ability to identify unknown metabolites and its quantitative nature. However, the relatively small number of metabolites accessible by NMR has restricted the scope of its applications. Enhancing the limit of identified metabolites in blood will therefore greatly impact NMR-based metabolomics. Continuing our efforts to address this major issue, our current study describes the identification of 12 metabolites, which expands the number of quantifiable blood metabolites by ~15%. These results, in combination with our earlier efforts, now provide access to nearly 90 metabolites, which is the highest to date for a simple 1D [1]H NMR experiment that is widely used in the metabolomics field. Metabolites were identified based on the comprehensive investigation of human blood and plasma using 1D/2D NMR techniques. The newly identified metabolites were validated based on chemical shift databases, spectra of authentic compounds obtained under conditions identical to blood/plasma, and, finally, spiking experiments using authentic compounds. Considering the high reproducibility of NMR and the sensitivity of chemical shifts to altered sample conditions, experimental protocols and peak annotations are provided for the newly identified metabolites, which serve as a template for identification of blood metabolites for routine applications. Separately, the identified metabolites were evaluated for their sensitivity to preanalytical conditions. The results reveal that among the newly identified metabolites, inosine monophosphate (IMP) and nicotinamide are associated with labile coenzymes and their levels are sensitive to preanalytical conditions. The study demonstrates the expansion of quantifiable blood metabolites using NMR to a new height and is expected to greatly impact blood metabolomics.},
}
@article {pmid36529006,
year = {2022},
author = {Placidi, L and Righetto, R and Vecchi, C and Zara, S and Alparone, A and Moretti, R and Amelio, D and Scartoni, D and Schwarz, M},
title = {Automation of pencil beam scanning proton treatment planning for intracranial tumours.},
journal = {Physica medica : PM : an international journal devoted to the applications of physics to medicine and biology : official journal of the Italian Association of Biomedical Physics (AIFB)},
volume = {105},
number = {},
pages = {102503},
doi = {10.1016/j.ejmp.2022.11.007},
pmid = {36529006},
issn = {1724-191X},
abstract = {PURPOSE: To evaluate the feasibility of comprehensive automation of an intra-cranial proton treatment planning.<br><br>MATERIALS AND METHODS: Class solution (CS) beam configuration selection allows the user to identify predefined beam configuration based on target localization; automatic CS (aCS) will then explore all the possible CS beam geometries. Ten patients, already used for the e