@article {pmid39838067,
year = {2025},
author = {Haseli, S and Park, C and Azhideh, A and Karande, G and Chalian, M},
title = {Performance and reliability comparison: original vs. revised bone reporting and data system (Bone-RADS).},
journal = {Skeletal radiology},
volume = {},
number = {},
pages = {},
pmid = {39838067},
issn = {1432-2161},
abstract = {OBJECTIVE: To propose a revised bone reporting and data system (Bone-RADS) and evaluate its diagnostic performance and inter-reader reliability compared to the original Bone-RADS for solitary bone lesions on CT.

MATERIALS AND METHODS: This retrospective study included 159 adult patients (mean age: 56 ± 19 years; 88 men) who underwent bone biopsy for solitary bone lesions between March 2005 and September 2021. Two radiologists (R1/2) independently categorized the lesions twice, once using the original Bone-RADS and once using the revised version. Lesions were classified as follows: (1, benign; 2, incompletely assessed; 3, indeterminate; 4, malignancy or requiring treatment). The revised Bone-RADS excluded the original criteria for lesion related pain and history of malignancy. Diagnostic performance was assessed using histopathology as the reference standard, and inter-reader reliability was analyzed.

RESULTS: The bone lesions included 96 lucent and 63 sclerotic/mixed lesions. Sensitivity showed no significant difference between the original and revised Bone-RADS for both readers across lucent and sclerotic/mixed lesions (all P ≥ .05). However, the specificity of the revised Bone-RADS was significantly higher than that of the original (lucent: 11% vs. 50% [R1], 11% vs. 46% [R2]; sclerotic/mixed: 32% vs. 92% [R1], 32% vs. 86% [R2]). Other performance metrics, including positive/negative predictive value and accuracy, were also higher in the revised Bone-RADS. Inter-reader reliability was higher for the revised Bone-RADS compared to the original (κ = .744 vs .854).

CONCLUSION: The revised Bone-RADS significantly improved specificity while maintaining sensitivity compared to the original version.},
}

@article {pmid39834946,
year = {2024},
author = {O'Halloran, K and Crotty, EE and Christodoulou, E and Leary, SE and Miller, A and Paulson, VA and Lockwood, CM and Margol, AS and Biegel, JA},
title = {Targeted detection of sequence variants in cell-free DNA from cerebrospinal fluid in pediatric central nervous system tumors.},
journal = {Frontiers in oncology},
volume = {14},
number = {},
pages = {1513073},
pmid = {39834946},
issn = {2234-943X},
abstract = {The emergence of liquid biopsy technologies holds great promise in the cancer setting, including in pediatric central nervous system (CNS) tumors. In contrast to broad lower-depth sequencing, commonly referred to as low pass whole genome sequencing (WGS), targeted platforms with a higher depth of coverage have also been established. Here, we review targeted liquid biopsy techniques with applicability to pediatric CNS tumors. These include polymerase chain reaction (PCR), both droplet digital PCR and reverse transcription-based PCR, Sanger sequencing, and next-generation sequencing approaches that incorporate amplicon- and hybrid capture-based methods. The goal of this paper is to facilitate an understanding of these targeted techniques and provide a context for clinical relevance within disease categories, as well as a discussion on optimizing real-world implementation for pediatric CNS tumors.},
}

@article {pmid39831734,
year = {2025},
author = {Moussa, MJ and Tabet, GC and Siefker-Radtke, AO and Xiao, L and Wilson, NR and Gao, J and Logothetis, CJ and Grivas, P and Lee, B and Shah, AY and Msaouel, P and Li, R and Clemente, LC and Zhao, J and Tannir, NM and Kamat, AM and Hansel, DE and Guo, CC and Campbell, MT and Alhalabi, O},
title = {Histopathologic Progression and Metastatic Relapse Outcomes in Small Cell Neuroendocrine Carcinomas of the Urinary Tract.},
journal = {Cancer medicine},
volume = {14},
number = {2},
pages = {e70594},
pmid = {39831734},
issn = {2045-7634},
support = {//Ingram Family Fund/ ; },
mesh = {Humans ; Male ; Female ; *Carcinoma, Neuroendocrine/pathology/therapy/drug therapy/surgery ; Aged ; Middle Aged ; *Neoplasm Recurrence, Local/pathology ; *Carcinoma, Small Cell/pathology/therapy ; Disease Progression ; Urologic Neoplasms/pathology/therapy/mortality ; Neoadjuvant Therapy ; Prognosis ; Adult ; Retrospective Studies ; Aged, 80 and over ; },
abstract = {INTRODUCTION: Small cell neuroendocrine carcinoma of the urinary tract (SCNEC-URO) has an inferior prognosis compared to conventional urothelial carcinoma (UC). Here, we evaluate the predictors and patterns of relapse after surgery.

MATERIALS AND METHODS: We identified a definitive-surgery cohort (n = 224) from an institutional database of patients with cT1-T4NxM0 SCNEC-URO treated in 1985-2021. Histopathologic review was conducted by independent pathologists. Relapse event was the time-to-event outcome, and relapse probabilities were estimated using a competing risk method with cumulative incidence functions (CIFs). Fine-Gray distribution models assessed covariate associations.

RESULTS: Most patients (161, 71.9%) received neoadjuvant chemotherapy (neoCTX). Ninety two (41%) patients had relapse with 77 (83.7%) having distant organs as first metastatic sites, including 10 (10.9%) with exclusive central nervous system (CNS) metastases, mostly (9/10) within 1 year of surgery. Patients with pathologic complete response (pCR) after neoCTx had the lowest 5-year CIF (16.5% [95% CI 9.3%-25.6%]). Patients with remaining exclusively small cell (SC) histology had the highest CIF (85.7% [95% CI 46.6-96.9]). Patients with eradicated SCNEC but remaining UC components had an intermediate-risk CIF (32.5% [95% CI 18.6-47.2]). Multivariable analysis adjusting for neoCTx, clinical stage at diagnosis (T3/4, N0/N+ vs. T1/T2, N0), and pathologic stage (pN+ vs. pN0) demonstrated that any SCNEC histology at resection (vs. pCR) was associated with relapse risk (hazard ratio = 3.69 [95% CI 1.91-7.13], p = 0.0001).

CONCLUSIONS: SCNEC-URO is a systemic disease with high risk of distant relapse including CNS. Our findings highlight unmet needs for neoadjuvant/adjuvant approaches targeting the rare SCNEC subtype and suggest adding CNS surveillance within the first year after definitive surgery to high-risk patients. PRÉCIS (CONDENSED ABSTRACT): Alongside neoadjuvant chemotherapy and cancer stage, histology at resection strongly impacts relapse risk in small cell neuroendocrine carcinomas of the urinary tract. The incidence of brain metastasis is notably higher than in "traditional" urothelial cancer within the first year after surgery, especially if small cell cancer persists, thus necessitating close neurological monitoring during this period.},
}

Humans
Male
Female
*Carcinoma, Neuroendocrine/pathology/therapy/drug therapy/surgery
Aged
Middle Aged
*Neoplasm Recurrence, Local/pathology
*Carcinoma, Small Cell/pathology/therapy
Disease Progression
Urologic Neoplasms/pathology/therapy/mortality
Neoadjuvant Therapy
Prognosis
Adult
Retrospective Studies
Aged, 80 and over

@article {pmid39831552,
year = {2025},
author = {Lichauco, C and Foss, EJ and Gatbonton-Schwager, T and Athow, NF and Lofts, B and Acob, R and Taylor, E and Marquez, JJ and Lao, U and Miles, S and Bedalov, A},
title = {Sir2 and Fun30 regulate ribosomal DNA replication timing via MCM helicase positioning and nucleosome occupancy.},
journal = {eLife},
volume = {13},
number = {},
pages = {},
pmid = {39831552},
issn = {2050-084X},
support = {R01GM117446/NH/NIH HHS/United States ; },
mesh = {*Silent Information Regulator Proteins, Saccharomyces cerevisiae/metabolism/genetics ; *Saccharomyces cerevisiae Proteins/metabolism/genetics ; *Sirtuin 2/metabolism/genetics ; *Saccharomyces cerevisiae/genetics/metabolism ; *Nucleosomes/metabolism ; *DNA, Ribosomal/genetics/metabolism ; DNA Replication Timing ; Transcription Factors/metabolism/genetics ; DNA Replication ; DNA Helicases/metabolism/genetics ; Gene Expression Regulation, Fungal ; },
abstract = {The association between late replication timing and low transcription rates in eukaryotic heterochromatin is well known, yet the specific mechanisms underlying this link remain uncertain. In Saccharomyces cerevisiae, the histone deacetylase Sir2 is required for both transcriptional silencing and late replication at the repetitive ribosomal DNA (rDNA) arrays. We have previously reported that in the absence of SIR2, a de-repressed RNA PolII repositions MCM replicative helicases from their loading site at the ribosomal origin, where they abut well-positioned, high-occupancy nucleosomes, to an adjacent region with lower nucleosome occupancy. By developing a method that can distinguish activation of closely spaced MCM complexes, here we show that the displaced MCMs at rDNA origins have increased firing propensity compared to the nondisplaced MCMs. Furthermore, we found that both activation of the repositioned MCMs and low occupancy of the adjacent nucleosomes critically depend on the chromatin remodeling activity of FUN30. Our study elucidates the mechanism by which Sir2 delays replication timing, and it demonstrates, for the first time, that activation of a specific replication origin in vivo relies on the nucleosome context shaped by a single chromatin remodeler.},
}

*Silent Information Regulator Proteins, Saccharomyces cerevisiae/metabolism/genetics
*Saccharomyces cerevisiae Proteins/metabolism/genetics
*Sirtuin 2/metabolism/genetics
*Saccharomyces cerevisiae/genetics/metabolism
*Nucleosomes/metabolism
*DNA, Ribosomal/genetics/metabolism
DNA Replication Timing
Transcription Factors/metabolism/genetics
DNA Replication
DNA Helicases/metabolism/genetics
Gene Expression Regulation, Fungal

@article {pmid39830606,
year = {2025},
author = {Adsul, P and Sanchez-Youngman, S and Dickson, E and Jacquez, B and Kuhlemeier, A and Muhammad, M and Briant, KJ and Hempstead, B and Mendoza, JA and Rosas, LG and Patel, A and Rodriguez Espinosa, P and Akintobi, T and Castro-Reyes, P and Carter-Edwards, L and Wallerstein, N},
title = {Assessing the context within academic health institutions toward improving equity-based, community and patient-engaged research.},
journal = {Journal of clinical and translational science},
volume = {9},
number = {1},
pages = {e6},
pmid = {39830606},
issn = {2059-8661},
abstract = {INTRODUCTION: The continued momentum toward equity-based, patient/community-engaged research (P/CenR) is pushing health sciences to embrace principles of community-based participatory research. Much of this progress has hinged on individual patient/community-academic partnered research projects and partnerships with minimal institutional support from their academic health institutions.

METHODS: We partnered with three academic health institutions and used mixed methods (i.e., institution-wide survey (n = 99); qualitative interviews with institutional leadership (n = 11); and focus group discussions (6 focus groups with patients and community members (n = 22); and researchers and research staff (n = 9)) to gain a deeper understanding of the institutional context.

RESULTS: Five key themes emerged that were supported by quantitative data. First, the global pandemic and national events highlighting social injustices sparked a focus on health equity in academic institutions; however, (theme 2) such a focus did not always translate to support for P/CenR nor align with institutional reputation. Only 52% of academics and 79% of community partners believed that the institution is acting on the commitment to health equity (Χ[2] = 6.466, p < 0.05). Third, institutional structures created power imbalances and community mistrust which were identified as key barriers to P/CenR. Fourth, participants reported that institutional resources and investments are necessary for recruitment and retention of community-engaged researchers. Finally, despite challenges, participants were motivated to transform current paradigms of research and noted that accountability, communication, and training were key facilitators.

CONCLUSIONS: Triangulating findings from this mixed-methods study revealed critical barriers which provide important targets for interventions to improving supportive policies and practices toward equity-based P/CenR.},
}

@article {pmid39828431,
year = {2025},
author = {Begnel, ER and Ojee, E and Adhiambo, J and Mabele, E and Wandika, B and Ogweno, V and Lim, ES and Gantt, S and Kinuthia, J and Lehman, DA and Slyker, J and Wamalwa, D},
title = {The Linda Kizazi study: a comparison of morbidity and mortality from birth to 2 years between children who are HIV-unexposed and HIV-exposed, uninfected in the era of universal antiretroviral therapy.},
journal = {BMJ global health},
volume = {10},
number = {1},
pages = {},
pmid = {39828431},
issn = {2059-7908},
support = {R01 HD092311/HD/NICHD NIH HHS/United States ; },
mesh = {Humans ; *HIV Infections/drug therapy/mortality/epidemiology ; Female ; Infant ; Kenya/epidemiology ; Infant, Newborn ; Pregnancy ; Male ; Adult ; Child, Preschool ; Malaria/mortality/drug therapy/epidemiology ; Cohort Studies ; Diarrhea/epidemiology/mortality ; Respiratory Tract Infections/mortality/epidemiology ; Hospitalization/statistics & numerical data ; Morbidity ; Pregnancy Complications, Infectious/drug therapy/epidemiology ; Anti-Retroviral Agents/therapeutic use ; },
abstract = {BACKGROUND: Historically, children who are HIV-exposed, uninfected (CHEU) have been found to have greater morbidity and mortality than children who are HIV-unexposed, uninfected (CHUU). To assess whether this difference persists in the era of universal antiretroviral therapy (ART), we conducted a cohort study to compare the risk of acute diarrhoea, respiratory tract infections (RTI), malaria, hospitalisation, and all-cause mortality between Kenyan CHEU and CHUU from birth to 2 years.

METHODS: From December 2018 to March 2020 at Mathare North Health Centre in Nairobi, we recruited pregnant women living with HIV on ART for ≥6 months and pregnant women without HIV from the same community. We followed the mother-infant pairs for 2 years post partum and collected data on symptoms of illness, clinical visits and diagnoses, and infant feeding every 3 months; a self-selected subset of participants also received weekly data collection for up to 1 year. We compared the risk of each outcome between CHEU versus CHUU using HRs from Andersen-Gill (recurrent morbidity outcomes) and Cox proportional hazards (mortality) regression models adjusted for maternal age, marital status and education level.

RESULTS: Among 187 mother-infant pairs with postpartum data, 86 (46%) infants were CHEU and 101 (54%) were CHUU. All initiated breastfeeding, and 88% of CHEU and 57% of CHUU were exclusively breastfed (EBF) for ≥6 months. There was no significant difference in risk of diarrhoea (HR=0.79, 95% CI 0.52 to 1.22), malaria (HR=0.44, 95% CI 0.16 to 1.21), hospitalisation (HR=1.11, 95% CI 0.30 to 4.14), or mortality (HR=1.87, 95% CI 0.17 to 20.5). However, CHEU had lower risk of any RTI (HR=0.60, 95% CI 0.44 to 0.82) and pneumonia (HR=0.29, 95% CI 0.091 to 0.89).

CONCLUSIONS: CHEU born to women on effective long-term ART experienced similar overall morbidity and mortality as CHUU. However, CHEU had substantially lower risk of pneumonia and other RTI, possibly due to longer EBF in this group.},
}

Humans
*HIV Infections/drug therapy/mortality/epidemiology
Female
Infant
Kenya/epidemiology
Infant, Newborn
Pregnancy
Male
Adult
Child, Preschool
Malaria/mortality/drug therapy/epidemiology
Cohort Studies
Diarrhea/epidemiology/mortality
Respiratory Tract Infections/mortality/epidemiology
Hospitalization/statistics & numerical data
Morbidity
Pregnancy Complications, Infectious/drug therapy/epidemiology
Anti-Retroviral Agents/therapeutic use

@article {pmid39827422,
year = {2025},
author = {Sierra, J and de León, UA and Padilla-Longoria, P},
title = {Tumor microenvironment noise-induced polarization: the main challenge in macrophages' immunotherapy for cancer.},
journal = {Molecular and cellular biochemistry},
volume = {},
number = {},
pages = {},
pmid = {39827422},
issn = {1573-4919},
abstract = {Disturbance of epigenetic processes can lead to altered gene function and malignant cellular transformation. In particular, changes in the epigenetic landscape are a central topic in cancer biology. The initiation and progression of cancer are now recognized to involve both epigenetic and genetic alterations. In this paper, we study the epigenetic mechanism (related to the tumor microenvironment) responsible for increasing tumor-associated macrophages that promote the occurrence and metastasis of tumor cells, support tumor angiogenesis, inhibit T-cell-mediated anti-tumor immune response, and lead to tumor progression. We show that the tumor benefits from the macrophages' high degree of plasticity and larger epigenetic basins corresponding to phenotypes that favor cancer development through a process that we call noise-induced polarization. Moreover, we propose a mechanism to promote the appropriate epigenetic stability for immunotherapies involving macrophages, which includes p53 and APR-246 (eprenetapopt). Our results show that a combination therapy may be necessary to ensure the proper epigenetic stability of macrophages, which otherwise will contribute to cancer progression. On the other hand, we conclude that macrophages may remain in the anti-tumoral state in types of cancer that exhibit less TP53 mutation, like colorectal cancer; in these cases, macrophages' immunotherapy may be more suitable. We finally mention the relevance of the epigenetic potential (Waddington's landscape) as the backbone for our study, which encapsulates the biological information of the system.},
}

@article {pmid39826256,
year = {2025},
author = {Lim, FY and Lea, HG and Dostie, AM and Kim, SY and van Neel, TL and Hassan, GW and Takezawa, MG and Starita, LM and Adams, KN and Boeckh, M and Schiffer, JT and Hyrien, O and Waghmare, A and Berthier, E and Theberge, AB},
title = {homeRNA self-blood collection enables high-frequency temporal profiling of presymptomatic host immune kinetics to respiratory viral infection: a prospective cohort study.},
journal = {EBioMedicine},
volume = {112},
number = {},
pages = {105531},
doi = {10.1016/j.ebiom.2024.105531},
pmid = {39826256},
issn = {2352-3964},
abstract = {BACKGROUND: Early host immunity to acute respiratory infections (ARIs) is heterogenous, dynamic, and critical to an individual's infection outcome. Due to limitations in sampling frequency/timepoints, kinetics of early immune dynamics in natural human infections remain poorly understood. In this nationwide prospective cohort study, we leveraged a Tasso-SST based self-blood collection and stabilization tool (homeRNA) to profile detailed kinetics of the presymptomatic to convalescence host immunity to contemporaneous respiratory pathogens.

METHODS: We enrolled non-symptomatic adults with recent exposure to ARIs who subsequently tested negative (exposed-uninfected) or positive for respiratory pathogens. Participants self-collected blood and nasal swabs daily for seven consecutive days followed by weekly blood collection for up to seven additional weeks. Symptom burden was assessed during each collection. Nasal swabs were tested for SARS-CoV-2 and common respiratory pathogens. 92 longitudinal blood samples spanning the presymptomatic to convalescence phase of eight participants with SARS-CoV-2 infection and 40 interval-matched samples from four exposed-uninfected participants were subjected to high-frequency longitudinal profiling of 785 immune genes. Generalized additive mixed models (GAMM) were used to identify temporally dynamic genes from the longitudinal samples and linear mixed models (LMM) were used to identify baseline differences between exposed-infected (n = 8), exposed-uninfected (n = 4), and uninfected (n = 13) participant groups.

FINDINGS: Between June 2021 and April 2022, 68 participants across 26 U.S. states completed the study and self-collected a total of 691 and 466 longitudinal blood and nasal swab samples along with 688 symptom surveys. SARS-CoV-2 was detected in 17 out of 22 individuals with study-confirmed respiratory infection, of which five were still presymptomatic or pre-shedding, enabling us to profile detailed expression kinetics of the earliest blood transcriptional response to contemporaneous variants of concern. 51% of the genes assessed were found to be temporally dynamic during COVID-19 infection. During the pre-shedding phase, a robust but transient response consisting of genes involved in cell migration, stress response, and T cell activation were observed. This is followed by a rapid induction of many interferon-stimulated genes (ISGs), concurrent to onset of viral shedding and increase in nasal viral load and symptom burden. Finally, elevated baseline expression of antimicrobial peptides was observed in exposed-uninfected individuals.

INTERPRETATION: We demonstrated that unsupervised self-collection and stabilization of capillary blood can be applied to natural infection studies to characterize detailed early host immune kinetics at a temporal resolution comparable to that of human challenge studies. The remote (decentralized) study framework enables conduct of large-scale population-wide longitudinal mechanistic studies.

FUNDING: This study was funded by R35GM128648 to ABT for in-lab developments of homeRNA and data analysis, a Packard Fellowship for Science and Engineering from the David and Lucile Packard Foundation to ABT for the study execution, sample collection, and analysis, and R01AI153087 to AW for data analysis.},
}

@article {pmid39826253,
year = {2025},
author = {Montaño, MA and Jatho, A and Nassolo, C and Mugisha, N and Bula, A and Chagomerana, MB and Borok, M and Mtisi, TJ and Joffe, M and Bender Ignacio, RA and Ndlovu, N},
title = {Healthcare provider perspectives on integrating HIV care into cancer centers in Malawi, South Africa, Uganda, and Zimbabwe.},
journal = {Translational oncology},
volume = {53},
number = {},
pages = {102273},
doi = {10.1016/j.tranon.2025.102273},
pmid = {39826253},
issn = {1936-5233},
abstract = {BACKGROUND: In East and Southern Africa, treatment of people with concomitant cancer and HIV is complicated by siloed service delivery pathways, which exacerbate barriers to care and impact clinical decision-making. Integrating HIV care into cancer treatment centers may improve service delivery and overall patient outcomes.

METHODS: We administered a questionnaire to clinicians and support staff at tertiary cancer referral centers in Malawi, Zimbabwe, Uganda, and South Africa to assess level of concern about clinical management of people with HIV (PWH) and cancer, barriers to integrating HIV service delivery into cancer treatment delivery, and beliefs related to HIV, antiretroviral therapy (ART), and integrated care.

RESULTS: Of 195 clinician and support staff participants, 165 (85 %) were direct providers of cancer-associated care. Over 50 % indicated that they held concerns about survival, treatment complications, co-morbidities, and drug-drug interactions in PWH compared to patients without HIV. Over 80 % agreed that knowing cancer patients' HIV status, ART status, and ART regimen would facilitate better care and should be considered in cancer care decision-making. Overall, respondents were optimistic that HIV-related care could be easily integrated into cancer care provision. The most-frequently endorsed barriers to integrated care were workspace limitations, disruptions to workflow, availability of staff, and cost to the hospital and to patients.

CONCLUSIONS: Cancer clinicians and support staff report overall positive attitudes toward integrating HIV and cancer service delivery. Research to elucidate service delivery pathways and contextualize system-based barriers to integrating care are critical next steps to optimize linked HIV and cancer care delivery.},
}

@article {pmid39825826,
year = {2025},
author = {Mughal, TI and Mascarenhas, J and Rampal, RK and Bose, P and Lion, T and Ajufo, H and Yacoub, A and Meshinchi, S and Masarova, L and Mesa, R and Jamieson, C and Barbui, T and Saglio, G and Van Etten, RA},
title = {Impact of Recent Translational and Therapeutic Developments on Clinical Course of BCR::ABL1-Positive and -Negative Myeloproliferative Neoplasms.},
journal = {Hematological oncology},
volume = {43},
number = {1},
pages = {e70013},
doi = {10.1002/hon.70013},
pmid = {39825826},
issn = {1099-1069},
support = {//Alpine Oncology Foundation/ ; },
mesh = {Humans ; *Myeloproliferative Disorders/therapy/genetics/diagnosis/metabolism/drug therapy ; Protein Kinase Inhibitors/therapeutic use ; Proto-Oncogene Proteins c-abl/genetics/metabolism ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/therapy/genetics/drug therapy/pathology ; Fusion Proteins, bcr-abl/genetics/antagonists & inhibitors ; },
abstract = {Despite the study of BCR::ABL1-positive and -negative myeloproliferative neoplasms (MPNs) providing seminal insights into cancer biology, tumor evolution and precision oncology over the past half century, significant challenges remain. MPNs are clonal hematopoietic stem cell-derived neoplasms with heterogenous clinical phenotypes and a clonal architecture which impacts the often-complex underlying genetics and microenvironment. The major driving molecular abnormalities have been well characterized, but debate on their role as disease-initiating molecular lesions continues. The introduction of the ABL1 tyrosine kinase inhibitors have been extremely successful in the treatment of chronic myeloid leukemia with most patients having a near-normal life expectancy. Similar success has, however, not been achieved for BCR::ABL1-negative MPNs in terms of disease course modification and most patients remain incurable. In both disease categories, genomic instability seems to increase the risk of disease progression to accelerated/blast phase, which is resistant/refractory to conventional treatment and associated with a poor prognosis. To address some of these issues, the late John Goldman and Tariq Mughal founded a scientific and clinical platform in 2006, the Post-American Society of Hematology (ASH) MPN workshop, to appraise novel cancer biology, candidate therapeutic targets, treatments and other clinical challenges and pay tribute to all the many scientists and clinicians around the world instrumental to the progress made and continuing advances being made. This paper summarizes some of the recent data discussed at the 18[th] edition of the workshop and includes reference to some data presented or published after the workshop, including the 26[th] John Goldman CML conference.},
}

Humans
*Myeloproliferative Disorders/therapy/genetics/diagnosis/metabolism/drug therapy
Protein Kinase Inhibitors/therapeutic use
Proto-Oncogene Proteins c-abl/genetics/metabolism
Leukemia, Myelogenous, Chronic, BCR-ABL Positive/therapy/genetics/drug therapy/pathology
Fusion Proteins, bcr-abl/genetics/antagonists & inhibitors

@article {pmid39825500,
year = {2025},
author = {Prizment, A and Standafer, A and Qu, C and Beutel, KM and Wang, S and Huang, WY and Lindblom, A and Pearlman, R and Van Guelpen, B and Wolk, A and Buchanan, DD and Grant, RC and Schmit, SL and Platz, EA and Joshu, CE and Couper, DJ and Peters, U and Starr, TK and Scott, P and Pankratz, N},
title = {Functional variants in the cystic fibrosis transmembrane conductance regulator (CFTR) gene are associated with increased risk of colorectal cancer.},
journal = {Human molecular genetics},
volume = {},
number = {},
pages = {},
doi = {10.1093/hmg/ddaf007},
pmid = {39825500},
issn = {1460-2083},
support = {/NH/NIH HHS/United States ; R21CA256749/CA/NCI NIH HHS/United States ; //University of Minnesota Academic Health Center/ ; //Whiteside Institute for Clinical Research/ ; },
abstract = {BACKGROUND: Individuals with cystic fibrosis (CF; a recessive disorder) have an increased risk of colorectal cancer (CRC). Evidence suggests individuals with a single CFTR variant may also have increased CRC risk.

METHODS: Using population-based studies (GECCO, CORECT, CCFR, and ARIC; 53 785 CRC cases and 58 010 controls), we tested for an association between the most common CFTR variant (Phe508del) and CRC risk. For replication, we used whole exome sequencing data from UK Biobank (UKB; 5126 cases and 20 504 controls matched 4:1 based on genetic distance, age, and sex), and extended our analyses to all other heterozygous CFTR variants annotated as CF-causing.

RESULTS: In our meta-analysis of GECCO-CORECT-CCFR-ARIC, the odds ratio (OR) for CRC risk associated with Phe508del was 1.11 (P = 0.010). In our UKB replication, the OR for CRC risk associated with Phe508del was 1.28 (P = 0.002). The sequencing data from UKB also revealed an association between the presence of any other single CF-causing variant (excluding Phe508del) and CRC risk (OR = 1.33; P = 0.030). When stratifying CFTR variants by functional class, class I variants (no protein produced) had a stronger association (OR = 1.77; p = 0.002), while class II variants (misfolding and retention of the protein in the endoplasmic reticulum) other than Phe508del (OR = 1.75; p = 0.107) had similar effect size as Phe508del, and variants in classes III-VI had non-significant ORs less than 1.0 and/or were not present in cases.

CONCLUSIONS: CF-causing heterozygous variants, especially class I variants, are associated with a modest but statistically significant increased CRC risk. More research is needed to explain the biology underlying these associations.},
}

@article {pmid39819674,
year = {2025},
author = {Bordeaux, J and Blitzblau, R and Aasi, SZ and Alam, M and Amini, A and Bibee, K and Bolotin, D and Chen, PL and Contreras, CM and DiMaio, D and Donigan, JM and Farma, JM and Ghosh, K and Harms, K and LeBoeuf, N and Lukens, JN and Manber, S and Mark, L and Medina, T and Nehal, KS and Nghiem, P and Olino, K and Paragh, G and Park, S and Patel, T and Rich, J and Shaha, AR and Sharma, B and Sokumbi, Y and Srivastava, D and Thomas, V and Tomblinson, C and Venkat, P and Xu, YG and Yu, S and Yusuf, M and McCullough, B and Espinosa, S},
title = {Dermatofibrosarcoma Protuberans, Version 1.2025, NCCN Clinical Practice Guidelines In Oncology.},
journal = {Journal of the National Comprehensive Cancer Network : JNCCN},
volume = {23},
number = {1},
pages = {},
doi = {10.6004/jnccn.2025.0001},
pmid = {39819674},
issn = {1540-1413},
mesh = {*Dermatofibrosarcoma/therapy/diagnosis/pathology ; Humans ; *Skin Neoplasms/therapy/diagnosis/pathology ; Medical Oncology/standards/methods ; Combined Modality Therapy/methods ; Neoplasm Recurrence, Local/therapy ; },
abstract = {Dermatofibrosarcoma protuberans (DFSP) is a rare cutaneous soft tissue sarcoma and affects an estimated 1,500 people annually in the United States. DFSP frequently exhibits extensive local infiltration. Initial treatment is through surgical excision, and care should be taken to ensure that negative margins are achieved to minimize recurrence. Although DFSP has a reported high rate of recurrence, metastasis is more uncommon. Fibrosarcomatous DFSP is an aggressive variant with an increased risk for local recurrence and metastasis. If achieving negative margins or resection is not feasible, radiation therapy or systemic treatment are options that may be considered by a multidisciplinary team. The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) outline recommended treatment options available for DFSP.},
}

*Dermatofibrosarcoma/therapy/diagnosis/pathology
Humans
*Skin Neoplasms/therapy/diagnosis/pathology
Medical Oncology/standards/methods
Combined Modality Therapy/methods
Neoplasm Recurrence, Local/therapy

@article {pmid39819601,
year = {2025},
author = {Wood, DE and Kazerooni, EA and Aberle, DR and Argento, C and Baines, J and Boer, B and Brown, LM and Donington, J and Eapen, GA and Ferguson, JS and Hou, L and Klippenstein, D and Kolansky, AS and Kumar, R and Leard, LE and Leung, ANC and Mazzone, P and Merritt, RE and Norris, K and Onaitis, M and Pipavath, S and Puri, V and Raz, D and Reddy, C and Reid, ME and Sandler, KL and Sands, J and Schabath, MB and Sears, CR and Studts, JL and Tanoue, L and Thacker, AL and Tong, BC and Travis, WD and Wei, B and Westover, K and McCullough, B and Ramakrishnan, S},
title = {NCCN Guidelines® Insights: Lung Cancer Screening, Version 1.2025.},
journal = {Journal of the National Comprehensive Cancer Network : JNCCN},
volume = {23},
number = {1},
pages = {},
doi = {10.6004/jnccn.2025.0002},
pmid = {39819601},
issn = {1540-1413},
mesh = {Humans ; *Lung Neoplasms/diagnosis ; *Early Detection of Cancer/standards/methods ; Mass Screening/standards/methods ; },
abstract = {The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Lung Cancer Screening provide criteria for selecting individuals for screening and offer recommendations for evaluating and managing lung nodules detected during initial and subsequent annual screening. These NCCN Guidelines Insights focus on recent updates to the NCCN Guidelines for Lung Cancer Screening.},
}

Humans
*Lung Neoplasms/diagnosis
*Early Detection of Cancer/standards/methods
Mass Screening/standards/methods

@article {pmid39825152,
year = {2025},
author = {Okines, AFC and Curigliano, G and Mizuno, N and Oh, DY and Rorive, A and Soliman, H and Takahashi, S and Bekaii-Saab, T and Burkard, ME and Chung, KY and Debruyne, PR and Fox, JR and Gambardella, V and Gil-Martin, M and Hamilton, EP and Monk, BJ and Nakamura, Y and Nguyen, D and O'Malley, DM and Olawaiye, AB and Pothuri, B and Reck, M and Sudo, K and Sunakawa, Y and Van Marcke, C and Yu, EY and Ramos, J and Tan, S and Bieda, M and Stinchcombe, TE and Pohlmann, PR},
title = {Tucatinib and trastuzumab in HER2-mutated metastatic breast cancer: a phase 2 basket trial.},
journal = {Nature medicine},
volume = {},
number = {},
pages = {},
pmid = {39825152},
issn = {1546-170X},
abstract = {Human epidermal growth factor receptor 2 (HER2, also known as ERBB2) signaling promotes cell growth and differentiation, and is overexpressed in several tumor types, including breast, gastric and colorectal cancer. HER2-targeted therapies have shown clinical activity against these tumor types, resulting in regulatory approvals. However, the efficacy of HER2 therapies in tumors with HER2 mutations has not been widely investigated. SGNTUC-019 is an open-label, phase 2 basket study evaluating tucatinib, a HER2-targeted tyrosine kinase inhibitor, in combination with trastuzumab in patients with HER2-altered solid tumors. The study included a cohort of 31 heavily pretreated female patients with HER2-mutated metastatic breast cancer who were also HER2 negative per local testing. Hormone receptor (HR)-positive patients also received fulvestrant. The overall response rate (primary endpoint) was 41.9% (90% confidence interval (CI): 26.9-58.2). Secondary endpoints of duration of response and progression-free survival were 12.6 months (90% CI: 4.7 to not estimable) and 9.5 months (90% CI: 5.4-13.8), respectively. No new safety signals were detected. Responses were observed across various HER2 mutations, including mutations in the tyrosine kinase and extracellular domains. The chemotherapy-free regimen of tucatinib and trastuzumab showed clinically meaningful antitumor activity with durable responses and favorable tolerability in heavily pretreated patients with HER2 mutations. These data support further investigation of HER2-targeted therapies in this patient population. ClinicalTrials.gov registration: NCT04579380 .},
}

@article {pmid39824819,
year = {2025},
author = {Zhang, B and Fong, Y and Dang, L and Fintzi, J and Chen, S and Wang, J and Rouphael, NG and Branche, AR and Diemert, DJ and Falsey, AR and Graciaa, DS and Baden, LR and Frey, SE and Whitaker, JA and Little, SJ and Kamidani, S and Walter, EB and Novak, RM and Rupp, R and Jackson, LA and Yu, C and Magaret, CA and Molitor, C and Borate, B and Busch, S and Benkeser, D and Netzl, A and Smith, DJ and Babu, TM and Kottkamp, AC and Luetkemeyer, AF and Immergluck, LC and Presti, RM and Bäcker, M and Winokur, PL and Mahgoub, SM and Goepfert, PA and Fusco, DN and Atmar, RL and Posavad, CM and Mu, J and Makowski, M and Makhene, MK and Nayak, SU and Roberts, PC and Gilbert, PB and Follmann, D and , },
title = {Neutralizing antibody immune correlates in COVAIL trial recipients of an mRNA second COVID-19 vaccine boost.},
journal = {Nature communications},
volume = {16},
number = {1},
pages = {759},
pmid = {39824819},
issn = {2041-1723},
support = {contract 75N910D00024, task order 75N91022F00007//U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (NIAID)/ ; contract 75N910D00024, task order no. 75N91022F00007//U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (NIAID)/ ; 75N93021C00012/AI/NIAID NIH HHS/United States ; UM1AI148684//U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (NIAID)/ ; 75N93021C00014/AI/NIAID NIH HHS/United States ; R37AI054165//U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (NIAID)/ ; Contract no. 75A50122C00008//U.S. Department of Health & Human Services | Biomedical Advanced Research and Development Authority (BARDA)/ ; 75A50122C00008//U.S. Department of Health & Human Services | Biomedical Advanced Research and Development Authority (BARDA)/ ; 75N93021D00021/AI/NIAID NIH HHS/United States ; },
mesh = {Humans ; *Antibodies, Neutralizing/immunology/blood ; *COVID-19/prevention & control/immunology/virology ; *COVID-19 Vaccines/immunology/administration & dosage ; *SARS-CoV-2/immunology ; *Antibodies, Viral/immunology/blood ; *Immunization, Secondary ; Female ; Male ; Adult ; Middle Aged ; Spike Glycoprotein, Coronavirus/immunology ; mRNA Vaccines/immunology ; },
abstract = {Neutralizing antibody titer has been a surrogate endpoint for guiding COVID-19 vaccine approval and use, although the pandemic's evolution and the introduction of variant-adapted vaccine boosters raise questions as to this surrogate's contemporary performance. For 985 recipients of an mRNA second bivalent or monovalent booster containing various Spike inserts [Prototype (Ancestral), Beta, Delta, and/or Omicron BA.1 or BA.4/5] in the COVAIL trial (NCT05289037), titers against 5 strains were assessed as correlates of risk of symptomatic COVID-19 ("COVID-19") and as correlates of relative (Pfizer-BioNTech Omicron vs. Prototype) booster protection against COVID-19 over 6 months of follow-up during the BA.2-BA.5 Omicron-dominant period. Consistently across the Moderna and Pfizer-BioNTech vaccine platforms and across all variant Spike inserts assessed, both peak and exposure-proximal ("predicted-at-exposure") titers correlated with lower Omicron COVID-19 risk in individuals previously infected with SARS-CoV-2, albeit significantly less so in naïve individuals [e.g., exposure-proximal hazard ratio per 10-fold increase in BA.1 titer 0.74 (95% CI 0.59, 0.94) for naïve vs. 0.41 (95% CI 0.23, 0.64) for non-naïve; interaction p = 0.013]. Neutralizing antibody titer was a strong inverse correlate of Omicron COVID-19 in non-naïve individuals and a weaker correlate in naïve individuals, posing questions about how prior infection alters the neutralization correlate.},
}

Humans
*Antibodies, Neutralizing/immunology/blood
*COVID-19/prevention & control/immunology/virology
*COVID-19 Vaccines/immunology/administration & dosage
*SARS-CoV-2/immunology
*Antibodies, Viral/immunology/blood
*Immunization, Secondary
Female
Male
Adult
Middle Aged
Spike Glycoprotein, Coronavirus/immunology
mRNA Vaccines/immunology

@article {pmid39822915,
year = {2025},
author = {Cooper, DJ and Karten, J and Hoffe, SE and King, DA and Weiss, M and DePeralta, DK and Coveler, AL and Hingorani, SR and Shefter, T and Meguid, C and Roberts, H and Hong, TS and Narang, A and Hacker-Prietz, A and Fisher, GA and Sandler, J and Singer, L and Korah, B and Hoos, W and Stricker, CT and Herman, JM},
title = {The power of personas: Exploring an innovative model for understanding stakeholder perspectives in an oncology learning health network.},
journal = {Learning health systems},
volume = {9},
number = {1},
pages = {e10422},
pmid = {39822915},
issn = {2379-6146},
abstract = {INTRODUCTION: Learning health networks (LHNs) improve clinical outcomes by applying core tenets of continuous quality improvements (QI) to reach community-defined outcomes, data-sharing, and empowered interdisciplinary teams including patients and caregivers. LHNs provide an ideal environment for the rapid adoption of evidence-based guidelines and translation of research and best practices at scale. When an LHN is established, it is critical to understand the needs of all stakeholders. To accomplish this, we used ethnographic methods to develop personas of different stakeholders within The Canopy Cancer Collective, the first oncology LHN.

METHODS: We partnered with a firm experienced in qualitative research and human-centered design to conduct interviews with stakeholders of The Canopy Cancer Collective, a newly developed pancreatic cancer LHN. Together with the firm, we developed a personas model approach to represent the wide range of diverse perspectives among the representative stakeholders, which included care team members, patients, and caregivers.

RESULTS: Thirty-one stakeholders from all facets of pancreatic cancer care were interviewed, including 20 care team members, 8 patients, and 3 caregivers. Interview transcripts were analyzed to construct 10 personas felt to represent the broad spectrum of stakeholders within The Cancer Canopy Collective. These personas were used as a foundation for the design and development of The Cancer Canopy Cancer Collective key drivers and aims.

CONCLUSIONS: As LHNs continue to facilitate comprehensive approaches to patient-centered care, interdisciplinary teams who understand each other's needs can improve Network unity and cohesion. We present the first model utilizing personas for LHNs, demonstrating this framework holds significant promise for further study. If validated, such an approach could be used as a dynamic foundation for understanding individual stakeholder needs in similar LHN ecosystems in the future.},
}

@article {pmid39820690,
year = {2025},
author = {Nascimento de Lima, P and Matrajt, L and Coronado, G and Escaron, AL and Rutter, CM},
title = {Cost-Effectiveness of Noninvasive Colorectal Cancer Screening in Community Clinics.},
journal = {JAMA network open},
volume = {8},
number = {1},
pages = {e2454938},
pmid = {39820690},
issn = {2574-3805},
mesh = {Humans ; *Colorectal Neoplasms/diagnosis/economics ; *Cost-Benefit Analysis ; Middle Aged ; *Early Detection of Cancer/economics/methods/statistics & numerical data ; Female ; Male ; *Colonoscopy/economics/statistics & numerical data ; California ; Occult Blood ; Aged ; Mass Screening/economics/methods ; Quality-Adjusted Life Years ; },
abstract = {IMPORTANCE: Several noninvasive tests for colorectal cancer screening are available, but their effectiveness in settings with low adherence to screening and follow-up colonoscopy is not well documented.

OBJECTIVE: To assess the cost-effectiveness of and outcomes associated with noninvasive colorectal cancer screening strategies, including new blood-based tests, in a population with low adherence to screening and ongoing surveillance colonoscopy.

The validated microsimulation model used for the decision analytical modeling study projected screening outcomes from 2025 to 2124 for a simulated cohort of 10 million individuals aged 50 years in 2025 and representative of a predominantly Hispanic or Latino patient population served by a Federally Qualified Health Center in Southern California. The simulated population had low adherence to first-step noninvasive testing (45%), second-step follow-up colonoscopy after an abnormal noninvasive test result (40%), and ongoing surveillance colonoscopy among patients with high-risk findings at follow-up colonoscopy (80%).

EXPOSURES: Colorectal cancer screening strategies included no screening, an annual or biennial fecal immunochemical test, a triennial multitarget stool DNA test, and a triennial blood-based test. Using a blood-based test was assumed to increase first-step adherence by 17.5 percentage points.

MAIN OUTCOMES AND MEASURES: Outcomes included colorectal cancer incidence and mortality, life-years gained and quality-adjusted life-years gained relative to no screening, costs, and net monetary benefit assuming a willingness to pay of $100 000 per quality-adjusted life-year gained.

RESULTS: Under realistic adherence assumptions, a program of annual fecal immunochemical testing was the most effective and cost-effective strategy, yielding 121 life-years gained per 1000 screened individuals and a net monetary benefit of $5883 per person. Triennial blood testing was the least effective, yielding 23 life-years gained per 1000, and was not cost-effective, with a negative net monetary benefit. Annual fecal immunochemical testing with 45% first-step adherence and 80% adherence to follow-up and surveillance colonoscopy yielded greater benefit than triennial blood testing with perfect adherence (88 vs 77 life-years gained per 1000).

CONCLUSIONS AND RELEVANCE: This study suggests that in a federally qualified health care setting, prioritizing the convenience of blood tests over less costly and more effective existing stool-based tests could result in higher costs and worse population-level outcomes. Novel screening modalities should be carefully evaluated for performance in community settings before widespread adoption.},
}

Humans
*Colorectal Neoplasms/diagnosis/economics
*Cost-Benefit Analysis
Middle Aged
*Early Detection of Cancer/economics/methods/statistics & numerical data
Female
Male
*Colonoscopy/economics/statistics & numerical data
California
Occult Blood
Aged
Mass Screening/economics/methods
Quality-Adjusted Life Years

@article {pmid39820359,
year = {2025},
author = {Gauthier, J and Liang, EC and Huang, JJ and Kimble, EL and Hirayama, AV and Fiorenza, S and Voutsinas, JM and Wu, QV and Jaeger-Ruckstuhl, CA and Pender, BS and Kirchmeier, DR and Torkelson, A and Braathen, K and Basom, R and Shadman, M and Kopmar, NE and Cassaday, RD and Riddell, SR and Maloney, DG and Turtle, CJ},
title = {Phase I study of CD19 CAR T-cell therapy harboring a fully human scFv in CAR-naïve adult B-ALL patients.},
journal = {Blood advances},
volume = {},
number = {},
pages = {},
doi = {10.1182/bloodadvances.2024015314},
pmid = {39820359},
issn = {2473-9537},
abstract = {CD19-directed chimeric antigen receptor-engineered (CD19 CAR) T-cell therapy elicits high response rates but fails to induce durable responses in most adults with relapsed or refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL). In a previous clinical trial (NCT01865617), we observed anti-CAR immune responses associated with impaired in vivo CAR T-cell expansion after second infusions. Because these CD8+ T-cell responses were predominantly directed at peptides derived from the murine single chain variable fragment (scFv) in the CAR, we conducted a clinical trial investigating the safety and efficacy of CD19 CAR T-cells engineered with a CAR incorporating a fully human scFv (JCAR021) in adults with R/R B-ALL (NCT03103971). Twenty-three patients received lymphodepletion chemotherapy and JCAR021 infusion. Nineteen patients developed CRS (any grade, 83%; grade 2, 61%) and 12 developed neurotoxicity (52%; grade ≥3, 35%). The overall response and CR/CRi rates were 82% and 64%, respectively. We observed MRD-negative marrow responses in 82% of those with marrow disease and extramedullary responses by PET-CT in 79% (CR, 50%) of those with measurable FDG-avid disease. The median duration of remission (DOR) was 10 months with a 4-year DOR probability of 29%. Four patients underwent allo-HCT while in CR/CRi after JCAR021. Durable remissions were observed in patients with low marrow disease burden. In contrast, the DOR was limited in those with high marrow burden, highlighting a remaining critical need to identify new strategies to prolong remissions. We observed similar outcomes in CAR-naïve adult B-ALL patients receiving CD19 CAR T-cells expressing a fully human or murine scFv-containing CAR.},
}

@article {pmid39818460,
year = {2025},
author = {Daneshmand, S and Kamat, AM and Shore, ND and Meeks, JJ and Galsky, MD and Jacob, JM and van der Heijden, MS and Williams, SB and Powles, T and Chang, SS and Catto, JWF and Psutka, SP and Guerrero-Ramos, F and Xylinas, E and Miyake, M and Simone, G and Daniel, K and Sweiti, H and Cutie, C and Necchi, A},
title = {Development of TAR-200: A novel targeted releasing system designed to provide sustained delivery of gemcitabine for patients with bladder cancer.},
journal = {Urologic oncology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.urolonc.2024.12.264},
pmid = {39818460},
issn = {1873-2496},
abstract = {Treatment options for recurrent high-risk non-muscle-invasive bladder cancer (HR NMIBC) and muscle-invasive bladder cancer (MIBC) are limited, highlighting a need for clinically effective, accessible, and better-tolerated alternatives. In this review we examine the clinical development program of TAR-200, a novel targeted releasing system designed to provide sustained intravesical delivery of gemcitabine to address the needs of patients with NMIBC and of those with MIBC. We describe the concept and design of TAR-200 and the clinical development of this gemcitabine intravesical system in the SunRISe portfolio of studies. This includes 3 phase I studies evaluating the safety and initial tumor activity of TAR-200 and 5 phase II/III studies assessing the efficacy and safety of TAR-200, with or without systemic cetrelimab, as a treatment option for patients with HR NMIBC (bacillus Calmette-Guérin naive [papillary and carcinoma in situ] and MIBC (neoadjuvant and patients ineligible for or refusing radical cystectomy). Pharmacokinetics demonstrate intravesical gemcitabine delivery via TAR-200 over a prolonged period without detectable plasma levels. Phase I studies showed that TAR-200 is well tolerated, with preliminary antitumor activity in intermediate-risk NMIBC and MIBC. Preliminary data from the phase IIb SunRISe-1 study demonstrate that TAR-200 monotherapy is safe and effective in patients with bacillus Calmette-Guérin-unresponsive high-risk NMIBC. TAR-200 represents an innovative approach to the local treatment of bladder cancer.},
}

@article {pmid39817910,
year = {2025},
author = {Termote, M and Marques, RC and Hyllner, E and Guryleva, MV and Henskens, M and Brutscher, A and Baken, IJL and Dopico, XC and Gasull, AD and Murrell, B and Stamatatos, L and Westerberg, LS and Dosenovic, P},
title = {Antigen affinity and site of immunization dictate B cell recall responses.},
journal = {Cell reports},
volume = {44},
number = {1},
pages = {115221},
doi = {10.1016/j.celrep.2024.115221},
pmid = {39817910},
issn = {2211-1247},
abstract = {Protective antibodies against HIV-1 require unusually high levels of somatic mutations introduced in germinal centers (GCs). To achieve this, a sequential vaccination approach was proposed. Using HIV-1 antibody knockin mice with fate-mapping genes, we examined if antigen affinity affects the outcome of B cell recall responses. Compared to a high-affinity boost, a low-affinity boost resulted in decreased numbers of memory-derived B cells in secondary GCs but with higher average levels of somatic mutations, indicating an affinity threshold for memory B cells to enter GCs. Furthermore, upon boosting local lymph nodes (LNs), the composition of primary GCs was modified in an antigen-affinity-dependent manner to constitute less somatically mutated B cells. Our results demonstrate that antigen affinity and location of the boost affect the outcome of the B cell recall response. These results can help guide the design of vaccine immunogens aiming to selectively engage specific B cell clones for further diversification.},
}

@article {pmid39817771,
year = {2025},
author = {Cohen, P and Lambson, BE and Mkhize, NN and Moodley, C and Yssel, AEJ and Moyo-Gwete, T and York, T and Gwashu-Nyangiwe, A and Ndabambi, N and Thebus, R and Juraska, M and deCamp, AC and Williamson, BD and Magaret, CA and Gilbert, PB and Westfall, D and Deng, W and Mullins, JI and Morris, L and Williamson, C and Moore, PL},
title = {Resistance mutations that distinguish HIV-1 envelopes with discordant VRC01 phenotypes from multi-lineage infections in the HVTN703/HPTN081 trial: implications for cross-resistance.},
journal = {Journal of virology},
volume = {},
number = {},
pages = {e0173024},
doi = {10.1128/jvi.01730-24},
pmid = {39817771},
issn = {1098-5514},
abstract = {The Antibody Mediated Prevention (AMP) trials showed that passively infused VRC01, a broadly neutralizing antibody (bNAb) targeting the CD4 binding site (CD4bs) on the HIV-1 envelope protein (Env), protected against neutralization-sensitive viruses. We identified six individuals from the VRC01 treatment arm with multi-lineage breakthrough HIV-1 infections from HVTN703, where one variant was sensitive to VRC01 (IC50 < 25 ug/mL) but another was resistant. By comparing Env sequences of resistant and sensitive clones from each participant, we identified sites predicted to affect VRC01 neutralization and assessed the effect of their reversion in the VRC01-resistant clone on neutralization sensitivity. In four pairs, a single mutation restored partial or full sensitivity to VRC01, whereas in the fifth participant, transfer of the entire [Formula: see text]23-V5 loop was required. No VRC01 resistance mutations could be identified in the sixth participant, with the discordant clones differing by >100 amino acids. Mutations responsible for the differential neutralization phenotypes occurred at distinct sites across Env, including residues in loop D, the CD4-binding loop, and between the [Formula: see text]23 and V5 loops. Analysis of deep sequencing env data showed that VRC01 resistance was likely the property of the acquired virus, rather than occurring through post-acquisition evolution. Although VRC01-resistant parental clones generally retained sensitivity to other CD4-binding site bNAbs, they were less potently neutralized than the VRC01-sensitive clones. In conclusion, VRC01 resistance mutations occurred through multiple mutational pathways, but sensitivity to second-generation CD4bs bNAbs was retained even in VRC01-resistant transmitted viruses, confirming the potential of these bNAbs for HIV-1 prevention studies.IMPORTANCEThe Antibody Mediated Prevention (AMP) trials provided proof of principle that VRC01, a CD4-binding site (CD4bs) HIV-1 broadly neutralizing antibody (bNAb), prevented the acquisition of antibody-sensitive viruses. However, understanding common mutations that confer resistance to different bNAbs provides important insights into the genetic barrier to resistance. Here we studied six AMP trial participants with breakthrough infections mediated by multiple viral lineages with discordant VRC01 sensitivity. We identified different mutations across the CD4-binding site that conferred resistance to VRC01 and showed that these mutations were a property of the acquired virus, rather than a result of post-acquisition evolution. We found that although VRC01 resistance was associated with reduced neutralization potency of second-generation CD4-binding site bNAbs, overall neutralization sensitivity was generally retained, which is promising for future use of such bNAbs in clinical trials.},
}

@article {pmid39817189,
year = {2025},
author = {Kundel, V and Devarakonda, K and Khan, S and Suarez-Farinas, M and Cohen, O and Santos-Gallego, C and Menegus, MA and Kini, A and Vengrenyuk, Y and Okamoto, N and Ueda, H and Gidwani, U and Kizer, JR and Redline, S and Kaplan, R and Shah, N},
title = {Exploring the Relationship Between Sleep Apnea, Myocardial Infarct Size, and Coronary Collaterals in Acute Myocardial Infarction: A Multidisciplinary Study.},
journal = {Nature and science of sleep},
volume = {17},
number = {},
pages = {27-42},
pmid = {39817189},
issn = {1179-1608},
support = {K23 HL125923/HL/NHLBI NIH HHS/United States ; K23 HL161324/HL/NHLBI NIH HHS/United States ; },
abstract = {PURPOSE: We designed a study investigating the cardioprotective role of sleep apnea (SA) in patients with acute myocardial infarction (AMI), focusing on its association with infarct size and coronary collateral circulation.

METHODS: We recruited adults with AMI, who underwent Level-III SA testing during hospitalization. Delayed-enhancement cardiac magnetic resonance (CMR) imaging was performed to quantify AMI size (percent-infarcted myocardium). Rentrop Score quantified coronary collateralization (scores 0-3, higher scores indicating augmented collaterals). Group differences in Rentrop grade and infarct size were compared using the Wilcoxon Rank-Sum test and Fisher's Exact test as appropriate, with a significance threshold set at p <0.05.

RESULTS: Among 33 adults, mean age was 54.4±11.5 and mean BMI was 28.4±5.9. 8 patients (24%) had no SA, and 25 (76%) had SA (mild n=10, moderate n=8, severe n=7). 66% (n=22) underwent CMR, and all patients had Rentrop scores. Median infarct size in the no-SA group was 22% versus 28% in the SA group (p=0.79). While we did not find statistically significant differences, moderate SA had a trend toward a smaller infarct size (median 15.5%; IQR 9.23) compared to the other groups (no SA [22.0%; 16.8,31.8], mild SA [27%; 23.8,32.5], and severe SA [34%; 31.53], p=0.12). A higher proportion of moderate SA patients had a Rentrop grade >0, with a trend toward significance (moderate SA versus other groups: 62.5% versus 28%, p=0.08).

CONCLUSION: Our study did not find statistically significant differences in cardiac infarct size and the presence of coronary collaterals by sleep apnea severity among patients with AMI. However, our results are hypothesis-generating, and suggest that moderate SA may potentially offer cardioprotective benefits through enhanced coronary collaterals. These insights call for future research to explore the heterogeneity in ischemic preconditioning by SA severity and hypoxic burden to guide tailored clinical strategies for SA management in patients with AMI.},
}

@article {pmid39817081,
year = {2024},
author = {Tereshchenko, LG and Haq, KT and Howell, SJ and Mitchell, EC and Hyde, J and Martínez, J and Ahmed, CA and Briceno, G and Patel, H and Pena, J and Khan, A and Soliman, EZ and Lima, JAC and Kapadia, SR and Misra-Hebert, AD and Kattan, MW and Kansal, MM and Daviglus, ML and Kaplan, R},
title = {Electrical Heterogeneity in Hispanic Background Subpopulations: The HCHS/SOL.},
journal = {JACC. Advances},
volume = {3},
number = {12},
pages = {101225},
pmid = {39817081},
issn = {2772-963X},
abstract = {BACKGROUND: The Hispanic/Latino population is not uniform. Prevalence and clinical outcomes of cardiac arrhythmias in ethnic background subgroups are variable, but the reasons for differences are unclear. Vectorcardiographic Global Electrical Heterogeneity (GEH) has been shown to be associated with adverse cardiovascular outcomes.

OBJECTIVES: The purpose of this study was to compare GEH in Hispanic/Latino background subpopulations. We hypothesized that ethnicity category moderates an association of prevalent cardiovascular disease (CVD) with GEH.

METHODS: Cross-sectional analysis of the HCHS/SOL (Hispanic Community Health Study/Study of Latinos) included 15,684 participants (mean age 41 years; 38% Mexican, 20% Cuban, 16% Puerto Rican, 10% Dominican, 7% Central American, 5% South American, 4% mixed Hispanic/Latino background). Acculturation and socioeconomic data were collected. GEH was measured as spatial QRS-T angle, spatial ventricular gradient (SVG) azimuth, SVG elevation, SVG magnitude, and sum absolute QRST integral. Linear regression models included interaction terms of ethnic background category by CVD and were adjusted for age, sex, education attainment, hypertension, diabetes, smoking, dyslipidemia, obesity, chronic kidney disease, physical activity, diet quality, heart rate, and rhythm.

RESULTS: The adjusted spatial QRS-T angle was significantly (P < 0.0001) narrower in Dominican background (-3.4°[95% CI -5.0° to -1.7°]) as compared to a total mean. SVG azimuth pointed farther posteriorly in Dominican (+2.9 [95% CI: 1.6-4.2]) and Puerto Rican (+3.8 [2.4-5.2]), but farther anteriorly in South American (-2.9 [95% CI: -4.4 to -1.4]) and Mexican (-3.5 [95% CI: -4.3 to -2.6]) vs total mean. An association of coronary heart disease with GEH was especially strong in Cuban background subpopulation.

CONCLUSIONS: In CVD-free Hispanic/Latino subpopulations, cardiovascular risk factors do not fully explain GEH differences across ethnic background categories, which likely reflect unmeasured health disparities.},
}

@article {pmid39817038,
year = {2025},
author = {Bradley, J and Floyd, S and Piwowar-Manning, E and Laeyendecker, O and Baker, OR and Bell-Mandla, N and Bwalya, J and Moore, A and Eshleman, SH and Donnell, D and Bock, P and Fidler, S and Ayles, H and Hayes, RJ},
title = {Strong Association Between HIV Incidence and Herpes Simplex Virus Type 2 in Zambia and South Africa: Prospective Data From the HPTN 071 (PopART) Trial.},
journal = {Open forum infectious diseases},
volume = {12},
number = {1},
pages = {ofae721},
pmid = {39817038},
issn = {2328-8957},
abstract = {BACKGROUND: Herpes simplex virus type 2 (HSV2) is an important cofactor for HIV acquisition and transmission. Associations between the infections are reexamined in longitudinal data from an HIV prevention trial.

METHODS: The HPTN 071 (PopART) trial evaluated a combination prevention intervention in 21 urban communities in Zambia and South Africa. HIV incidence was measured in a cohort of approximately 2000 adults (age, 18-44 years) selected randomly from each community and followed up for 36 months. Incidence of HSV2 infection was estimated, and the effects of risk factors were examined. The association between HIV incidence and HSV2 infection was examined at individual and community levels.

RESULTS: An overall 10 539 participants were HSV2 negative at baseline and retested after 36 months. Estimated HSV2 incidence was 5.4 per 100 person-years (95% CI, 5.0-5.7) for women and 2.9 per 100 person-years (95% CI, 2.6-3.2) for men. When compared with those remaining HSV2 negative, HIV incidence was higher in those who were HSV2 positive at baseline (women: adjusted rate ratio [aRR], 3.24 [95% CI, 2.50-4.20]; men: aRR, 2.57 [95% CI, 1.60-4.11]) and even higher in those who seroconverted to HSV2 during follow-up (women: aRR, 5.94 [95% CI, 4.42-7.98]; men: aRR, 8.37 [95% CI, 5.18-13.52]). At the community level, strong associations were seen between HIV incidence and HSV2 prevalence (R [2] = 0.48, P < .001) and incidence (R [2] = 0.36, P = .004).

CONCLUSIONS: There were strong associations between HIV incidence and HSV2 prevalence and incidence at individual and community levels. HSV2 control could contribute to HIV prevention.},
}

@article {pmid39815807,
year = {2025},
author = {Lim, SYT and Cole, FM and Laszlo, GS and Lunn-Halbert, MC and Huo, J and Li, J and Kehret, AR and Walter, RB},
title = {Targeting the membrane-proximal domain of CD33 to maximize the efficacy of natural killer cell-based immunotherapies.},
journal = {Haematologica},
volume = {},
number = {},
pages = {},
doi = {10.3324/haematol.2024.286593},
pmid = {39815807},
issn = {1592-8721},
abstract = {Not available.},
}

@article {pmid39815460,
year = {2025},
author = {Moseley, A and LeBlanc, M and Freidlin, B and Shallis, RM and Zeidan, AM and Sallman, DA and Erba, HP and Little, RF and Othus, M},
title = {Evaluating the impact of stratification on the power and cross-arm balance of randomized phase 2 clinical trials.},
journal = {Clinical trials (London, England)},
volume = {},
number = {},
pages = {17407745241304065},
doi = {10.1177/17407745241304065},
pmid = {39815460},
issn = {1740-7753},
abstract = {BACKGROUND/AIMS: Randomized clinical trials often use stratification to ensure balance between arms. Analysis of primary endpoints of these trials typically uses a "stratified analysis," in which analyses are performed separately in each subgroup defined by the stratification factors, and those separate analyses are weighted and combined. In the phase 3 setting, stratified analyses based on a small number of stratification factors can provide a small increase in power. The impact on power and type-1 error of stratification in the setting of smaller sample sizes as in randomized phase 2 trials has not been well characterized.

METHODS: We performed computational studies to characterize the power and cross-arm balance of modestly sized clinical trials (less than 170 patients) with varying numbers of stratification factors (0-6), sample sizes, randomization ratios (1:1 vs 2:1), and randomization methods (dynamic balancing vs stratified block).

RESULTS: We found that the power of unstratified analyses was minimally impacted by the number of stratification factors used in randomization. Analyses stratified by 1-3 factors maintained power over 80%, while power dropped below 80% when four or more stratification factors were used. These trends held regardless of sample size, randomization ratio, and randomization method. For a given randomization ratio and sample size, increasing the number of factors used in randomization had an adverse impact on cross-arm balance. Stratified block randomization performed worse than dynamic balancing with respect to cross-arm balance when three or more stratification factors were used.

CONCLUSION: Stratified analyses can decrease power in the setting of phase 2 trials when the number of patients in a stratification subgroup is small.},
}

@article {pmid39763725,
year = {2024},
author = {Aditham, AK and Radford, CE and Carr, CR and Jasti, N and King, NP and Bloom, JD},
title = {Deep mutational scanning of rabies glycoprotein defines mutational constraint and antibody-escape mutations.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {39763725},
issn = {2692-8205},
support = {P30 CA015704/CA/NCI NIH HHS/United States ; R01 AI141707/AI/NIAID NIH HHS/United States ; },
abstract = {Rabies virus causes nearly 60,000 human deaths annually. Antibodies that target the rabies glycoprotein (G) are being developed as post-exposure prophylactics, but mutations in G can render such antibodies ineffective. Here, we use pseudovirus deep mutational scanning to measure how all single amino-acid mutations to G affect cell entry and neutralization by a panel of antibodies. These measurements identify sites critical for rabies G's function, and define constrained regions that are attractive epitopes for clinical antibodies, including at the apex and base of the protein. We provide complete maps of escape mutations for eight monoclonal antibodies, including some in clinical use or development. Escape mutations for most antibodies are present in some natural rabies strains. Overall, this work provides comprehensive information on the functional and antigenic effects of G mutations that can help inform development of stabilized vaccine antigens and antibodies that are resilient to rabies genetic variation.},
}

@article {pmid38088119,
year = {2024},
author = {Brown, JR and Eichhorst, B and Hillmen, P and Jurczak, W and Kaźmierczak, M and Lamanna, N and O'Brien, SM and Tam, CS and Qiu, L and Zhou, K and Simkovic, M and Mayer, J and Gillespie-Twardy, A and Ferrajoli, A and Ganly, PS and Weinkove, R and Grosicki, S and Mital, A and Robak, T and Osterborg, A and Yimer, HA and Salmi, T and Wang, MD and Fu, L and Li, J and Wu, K and Cohen, A and Shadman, M},
title = {Plain language summary of zanubrutinib or ibrutinib in chronic lymphocytic leukemia that is resistant to treatment or has come back after treatment.},
journal = {Future oncology (London, England)},
volume = {20},
number = {12},
pages = {717-726},
doi = {10.2217/fon-2023-0849},
pmid = {38088119},
issn = {1744-8301},
mesh = {Humans ; *Adenine/analogs & derivatives ; *Leukemia, Lymphocytic, Chronic, B-Cell/drug therapy/pathology ; *Lymphoma, B-Cell/drug therapy ; Piperidines/therapeutic use ; Pyrazoles/adverse effects ; *Pyrimidines ; },
abstract = {WHAT IS THIS SUMMARY ABOUT?: This is a plain language summary of a research study called ALPINE. The study involved people who had been diagnosed with, and previously treated at least once for, relapsed or refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL). Lymphocytes help to find and fight off viruses and infections in the body, but when someone has CLL or SLL, the body creates abnormal lymphocytes, leaving the patient with a weakened immune system and susceptible to illness. In CLL, these lymphocytes are in the bone marrow and bloodstream, whereas for SLL, they are mostly found in the lymph nodes, such as those in the neck.

HOW WAS THE RESEARCH DONE?: The ALPINE study was designed to directly compare the cancer-fighting effects and side effects of zanubrutinib and ibrutinib as treatment for patients with relapsed or refractory CLL/SLL.

WHAT WERE THE RESULTS?: After 30 months, zanubrutinib was more effective than ibrutinib at reducing and keeping the cancer from coming back. Clinical Trial Registration: NCT03734016 (ClinicalTrials.gov).},
}

Humans
*Adenine/analogs & derivatives
*Leukemia, Lymphocytic, Chronic, B-Cell/drug therapy/pathology
*Lymphoma, B-Cell/drug therapy
Piperidines/therapeutic use
Pyrazoles/adverse effects
*Pyrimidines

@article {pmid39815416,
year = {2025},
author = {Powles, T and Park, SH and Gurney, H and Loriot, Y and Sridhar, SS and Bellmunt, J and di Pietro, A and Grivas, P},
title = {Avelumab maintenance treatment for advanced urothelial cancer: plain language summary of long-term results from the JAVELIN Bladder 100 study.},
journal = {Future oncology (London, England)},
volume = {},
number = {},
pages = {1-12},
doi = {10.1080/14796694.2024.2435208},
pmid = {39815416},
issn = {1744-8301},
}

@article {pmid39814501,
year = {2025},
author = {Karvonen, KA},
title = {Challenging the Status Quo: Multi-level Solutions for Equitable Hematopoietic Cell Transplantation Clinical Trial Representation.},
journal = {Transplantation and cellular therapy},
volume = {31},
number = {1},
pages = {7-9},
doi = {10.1016/j.jtct.2024.12.014},
pmid = {39814501},
issn = {2666-6367},
}

@article {pmid39814200,
year = {2025},
author = {Rangelova, E and Stoop, TF and van Ramshorst, TME and Ali, M and van Bodegraven, EA and Javed, AA and Hashimoto, D and Steyerberg, E and Banerjee, A and Jain, A and Sauvanet, A and Serrablo, A and Giani, A and Giardino, A and Zerbi, A and Arshad, A and Wijma, AG and Coratti, A and Zironda, A and Socratous, A and Rojas, A and Halimi, A and Ejaz, A and Oba, A and Patel, BY and Björnsson, B and Reames, BN and Tingstedt, B and Goh, BKP and Payá-Llorente, C and Domingo Del Pozo, C and González-Abós, C and Medin, C and van Eijck, CHJ and de Ponthaud, C and Takishita, C and Schwabl, C and Månsson, C and Ricci, C and Thiels, CA and Douchi, D and Hughes, DL and Kilburn, D and Flanking, D and Kleive, D and Sousa Silva, D and Edil, BH and Pando, E and Moltzer, E and Kauffman, EF and Warren, E and Bozkurt, E and Sparrelid, E and Thoma, E and Verkolf, E and Ausania, F and Giannone, F and Hüttner, FJ and Burdio, F and Souche, FR and Berrevoet, F and Daams, F and Motoi, F and Saliba, G and Kazemier, G and Roeyen, G and Nappo, G and Butturini, G and Ferrari, G and Kito Fusai, G and Honda, G and Sergeant, G and Karteszi, H and Takami, H and Suto, H and Matsumoto, I and Mora-Oliver, I and Frigerio, I and Fabre, JM and Chen, J and Sham, JG and Davide, J and Urdzik, J and de Martino, J and Nielsen, K and Okano, K and Kamei, K and Okada, K and Tanaka, K and Labori, KJ and Goodsell, KE and Alberici, L and Webber, L and Kirkov, L and de Franco, L and Miyashita, M and Maglione, M and Gramellini, M and Ramera, M and João Amaral, M and Ramaekers, M and Truty, MJ and van Dam, MA and Stommel, MWJ and Petrikowski, M and Imamura, M and Hayashi, M and D'Hondt, M and Brunner, M and Hogg, ME and Zhang, C and Ángel Suárez-Muñoz, M and Luyer, MD and Unno, M and Mizuma, M and Janot, M and Sahakyan, MA and Jamieson, NB and Busch, OR and Bilge, O and Belyaev, O and Franklin, O and Sánchez-Velázquez, P and Pessaux, P and Strandberg Holka, P and Ghorbani, P and Casadei, R and Sartoris, R and Schulick, RD and Grützmann, R and Sutcliffe, R and Mata, R and Patel, RB and Takahashi, R and Rodriguez Franco, S and Sánchez Cabús, S and Hirano, S and Gaujoux, S and Festen, S and Kozono, S and Maithel, SK and Chai, SM and Yamaki, S and van Laarhoven, S and Mieog, JSD and Murakami, T and Codjia, T and Sumiyoshi, T and Karsten, TM and Nakamura, T and Sugawara, T and Boggi, U and Hartman, V and de Meijer, VE and Bartholomä, W and Kwon, W and Koh, YX and Cho, Y and Takeyama, Y and Inoue, Y and Nagakawa, Y and Kawamoto, Y and Ome, Y and Soonawalla, Z and Uemura, K and Wolfgang, CL and Jang, JY and Padbury, R and Satoi, S and Messersmith, W and Wilmink, JW and Abu Hilal, M and Besselink, MG and Del Chiaro, M and , },
title = {The impact of neoadjuvant therapy in patients with left-sided resectable pancreatic cancer: an international multicenter study.},
journal = {Annals of oncology : official journal of the European Society for Medical Oncology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.annonc.2024.12.015},
pmid = {39814200},
issn = {1569-8041},
abstract = {PURPOSE: To assess the association between neoadjuvant therapy and overall survival (OS) in patients with left-sided resectable pancreatic cancer (RPC) compared to upfront surgery.

BACKGROUND: Left-sided pancreatic cancer is associated with worse OS compared to right-sided pancreatic cancer. Although neoadjuvant therapy is currently seen as not effective in patients with RPC, current randomized trials included mostly patients with right-sided RPC.

METHODS: International multicenter retrospective study including consecutive patients after left-sided pancreatic resection for pathology-proven RPC, either after neoadjuvant therapy or upfront surgery in 76 centers from 18 countries on 4 continents (2013-2019). Primary endpoint is OS from diagnosis. Time-dependent Cox regression analysis was performed to investigate the association of neoadjuvant therapy with OS, adjusting for confounders at time of diagnosis. Adjusted OS probabilities were calculated.

RESULTS: Overall, 2,282 patients after left-sided pancreatic resection for RPC were included of whom 290 patients (13%) received neoadjuvant therapy. The most common neoadjuvant regimens were (m)FOLFIRINOX (38%) and gemcitabine-nab-paclitaxel (22%). After upfront surgery, 72% of patients received adjuvant chemotherapy, mostly a single-agent regimen (74%). Neoadjuvant therapy was associated with prolonged OS compared to upfront surgery (adjusted HR=0.69 [95%CI 0.58-0.83]) with an adjusted median OS of 53 vs. 37 months (P=0.0003) and adjusted 5-year OS rates of 47% vs. 35% (P=0.0001) compared to upfront surgery. Interaction analysis demonstrated a stronger effect of neoadjuvant therapy in patients with a larger tumor (Pinteraction=0.003) and higher serum CA19-9 (Pinteraction=0.005). In contrast, the effect of neoadjuvant therapy was not enhanced for splenic artery (Pinteraction=0.43), splenic vein (Pinteraction=0.30), retroperitoneal (Pinteraction=0.84), and multivisceral (Pinteraction=0.96) involvement.

CONCLUSIONS: Neoadjuvant therapy in patients with left-sided RPC was associated with improved OS compared to upfront surgery. The impact of neoadjuvant therapy increased with larger tumor size and higher serum CA19-9 at diagnosis. Randomized controlled trials on neoadjuvant therapy specifically in patients with left-sided RPC are needed.},
}

@article {pmid39813621,
year = {2025},
author = {Gore, S and Blyth, E and Bleakley, M and Lee, K and Micklethwaite, KP and Gowrishankar, K},
title = {Current developments in T-cell receptor therapy for Acute Myeloid Leukaemia.},
journal = {Blood advances},
volume = {},
number = {},
pages = {},
doi = {10.1182/bloodadvances.2024014105},
pmid = {39813621},
issn = {2473-9537},
abstract = {T-cell receptor (TCR) therapies are a promising modality for the treatment of cancers, with significant efforts being directed towards acute myeloid leukaemia (AML), a particularly challenging disease. Chimeric antigen receptor (CAR) T-cells targeting single surface antigens have shown remarkable efficacy for B-cell lymphoblastic leukaemia, lymphomas and multiple myeloma. However, AML presents formidable obstacles to the effectiveness of CAR T-cells due to the widespread expression of heterogenous leukaemia immunophenotypes and surface antigen targets additionally present on normal myeloid cells. TCR therapies are an evolving field of cell therapies that allow targeting intracellular antigenic peptides presented via HLA molecules. The development of TCR therapy for AML is progressing rapidly through preclinical research and successful clinical trials. This review specifically explores the antigens targeted in AML, the diverse methodologies and strategies employed in TCR identification and preclinical TCR T-cell development. The review also discusses innovative molecular designs to improve functional efficacy, mitigate safety concerns and overcome HLA restriction. Specific outcomes of early clinical trials targeting important antigens WT1, PRAME and HA-1 are also highlighted. Ultimately, this review underscores why TCR therapy is poised to become an indispensable component of AML immunotherapy.},
}

@article {pmid39812506,
year = {2025},
author = {Little, A and Zhao, N and Mikhaylova, A and Zhang, A and Ling, W and Thibord, F and Johnson, AD and Raffield, LM and Curran, JE and Blangero, J and O'Connell, JR and Xu, H and Rotter, JI and Rich, SS and Rice, KM and Chen, MH and Reiner, A and Kooperberg, C and Vu, T and Hou, L and Fornage, M and Loos, RJF and Kenny, E and Mathias, R and Becker, L and Smith, AV and Boerwinkle, E and Yu, B and Thornton, T and Wu, MC},
title = {General Kernel Machine Methods for Multi-Omics Integration and Genome-Wide Association Testing With Related Individuals.},
journal = {Genetic epidemiology},
volume = {49},
number = {1},
pages = {e22610},
doi = {10.1002/gepi.22610},
pmid = {39812506},
issn = {1098-2272},
support = {//U.S. Department of Health and Human Services, National Institute on Minority Health and Health Disparities, National Institutes of Health, National Human Genome Research Institute, National Center for Research Resources, COPD Foundation, National Heart, Lung, and Blood Institute, National Science Foundation, National Institute on Aging, and National Institute of Neurological Disorders and Stroke./ ; },
mesh = {Humans ; *Genome-Wide Association Study/methods ; *Genomics/methods ; Phenotype ; Algorithms ; Models, Genetic ; Polymorphism, Single Nucleotide ; Genotype ; Computer Simulation ; Machine Learning ; Multiomics ; },
abstract = {Integrating multi-omics data may help researchers understand the genetic underpinnings of complex traits and diseases. However, the best ways to integrate multi-omics data and use them to address pressing scientific questions remain a challenge. One important and topical problem is how to assess the aggregate effect of multiple genomic data types (e.g. genotypes and gene expression levels) on a phenotype, particularly while accommodating routine issues, such as having related subjects' data in analyses. In this paper, we extend an existing composite kernel machine regression model to integrate two multi-omics data types, while accommodating for general correlation structures amongst outcomes. Due to the kernel machine regression framework, our methods allow for the integration of high-dimensional omics data with small, nonlinear, and interactive effects, and accommodation of general study designs. Here, we focus on scientific questions that aim to assess the association between a functional grouping (such as a gene or a pathway) and a quantitative trait of interest. We use a kernel machine regression to integrate the two multi-omics data types, as they may relate to the trait, and perform a global test of association. We demonstrate the advantage of this approach over single data type association tests via simulation. Finally, we apply this method to a large, multi-ethnic data set to investigate how predicted gene expression and rare genetic variation may be related to two platelet traits.},
}

Humans
*Genome-Wide Association Study/methods
*Genomics/methods
Phenotype
Algorithms
Models, Genetic
Polymorphism, Single Nucleotide
Genotype
Computer Simulation
Machine Learning
Multiomics

@article {pmid39809874,
year = {2025},
author = {Mao, JJ and Bryl, K and Gillespie, EF and Green, A and Hung, TKW and Baser, R and Panageas, K and Postow, MA and Daly, B},
title = {Randomized clinical trial of a digital integrative medicine intervention among patients undergoing active cancer treatment.},
journal = {NPJ digital medicine},
volume = {8},
number = {1},
pages = {29},
pmid = {39809874},
issn = {2398-6352},
support = {P30 CA008748/CA/NCI NIH HHS/United States ; K08 CA252640/CA/NCI NIH HHS/United States ; 1P50CA271357-01//U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)/ ; },
abstract = {Exercise and mindfulness-based interventions have growing evidence for managing fatigue and comorbid symptoms; however, packaging them in a cohesive digital way for patients undergoing cancer treatment has not been evaluated. We conducted a randomized controlled trial to assess the impact of a 12 week digital integrative medicine program, Integrative Medicine at Home (IM@Home), versus enhanced usual care on fatigue severity (primary outcome), comorbid symptoms and acute healthcare utilization (secondary outcomes), in 200 patients with solid tumors experiencing fatigue during treatment. Fatigue severity decreased more in IM@Home than in the control (1.99 vs. 1.51 points; p = 0.04). IM@Home participants also had reduced symptom distress (p = 0.003), anxiety (p = 0.03), and depression (p = 0.02). Acute healthcare utilization was lower with IM@Home, with fewer emergency department visits (rate ratio 0.49; p = 0.04), hospitalizations (4% vs. 12.9%; p = 0.03), and shorter hospital stays (4.25 vs. 10 days; p < 0.001). These promising findings should be confirmed in phase III clinical trials. "Study registered at clinicaltrials.gov (NCT05053230) on 09-20-2021".},
}

@article {pmid39809842,
year = {2025},
author = {Popchock, AR and Hedouin, S and Mao, Y and Asbury, CL and Stergachis, AB and Biggins, S},
title = {Stable centromere association of the yeast histone variant Cse4 requires its essential N-terminal domain.},
journal = {The EMBO journal},
volume = {},
number = {},
pages = {},
pmid = {39809842},
issn = {1460-2075},
support = {NIH 1DP5OD029630//HHS | National Institutes of Health (NIH)/ ; P30 CA015704/CA/NCI NIH HHS/United States ; NIH R35GM134842//HHS | National Institutes of Health (NIH)/ ; R35 GM149357/GM/NIGMS NIH HHS/United States ; NIH R35 GM149357//HHS | National Institutes of Health (NIH)/ ; NIH F32GM136010//HHS | National Institutes of Health (NIH)/ ; },
abstract = {Chromosome segregation relies on kinetochores that assemble on specialized centromeric chromatin containing a histone H3 variant. In budding yeast, a single centromeric nucleosome containing Cse4 assembles at a sequence-defined 125 bp centromere. Yeast centromeric sequences are poor templates for nucleosome formation in vitro, suggesting the existence of mechanisms that specifically stabilize Cse4 nucleosomes in vivo. The extended Cse4 N-terminal tail binds to the chaperone Scm3, and a short essential region called END within the N-terminal tail binds the inner kinetochore complex Okp1/Ame1. To address the roles of these interactions, we utilized single-molecule fluorescence assays to monitor Cse4 during kinetochore assembly. We found that Okp1/Ame1 and Scm3 independently stabilize Cse4 at centromeres via their END interaction. Scm3 and Cse4 stability at the centromere are enhanced by Ipl1/Aurora B phosphorylation of the Cse4 END, identifying a previously unknown role for Ipl1 in ensuring Cse4 stability. Strikingly, a phosphomimetic mutation in the Cse4 END restores Cse4 recruitment in mutants defective in Okp1/Ame1 binding. Together, these data suggest that a key function of the essential Cse4 N-terminus is to ensure Cse4 localization at centromeres.},
}

@article {pmid39808799,
year = {2025},
author = {Baumrin, E and Pidala, JA and Mitchell, S and Onstad, L and Lee, SJ},
title = {Development of the Lee Symptom Scale-Skin Sclerosis for chronic GVHD-associated sclerosis.},
journal = {Blood},
volume = {},
number = {},
pages = {},
doi = {10.1182/blood.2024027334},
pmid = {39808799},
issn = {1528-0020},
abstract = {Sclerosis is a highly morbid manifestation of chronic GVHD (cGVHD), associated with distressing symptoms and significant long-term disability. A patient-reported outcome measure (PRO) for cGVHD-associated sclerosis is essential to advance therapeutic trials. We aimed to develop a PRO for adults with cGVHD-associated sclerosis and evaluate and refine its content validity. Adults age ≥18 years with cGVHD-associated sclerosis participated in semi-structured interviews to identify salient symptoms and functions. Sclerosis-relevant symptoms and functions from existing PROs were also used to prompt discussion of topics not spontaneously mentioned. Symptoms and functions (subcodes) of importance were clustered and mapped to overarching domains (codes) using inductive analysis, and candidate items were developed. Cognitive interviews were employed to evaluate content validity of the items, response options, recall period, and respondent instructions.Thirty-five open-ended interviews, conducted to saturation, revealed the breadth of the patient experience with cGVHD-associated sclerosis including 5 overarching domains: (1) skin changes, (2) symptoms, (3) emotional and social functioning, (4) mobility restrictions, and (4) activity limitations. A pool of 54 items was tested and iteratively refined through cognitive debriefing interviews (n=25). Phrasing changes were made to improve relevance and comprehension. One item was removed and two items were added to address respondent feedback, resulting in 55 items. Results support the relevance, comprehensibility, and comprehensiveness of the provisional Lee Symptom Scale-Skin Sclerosis. Concept elicitation and cognitive interviewing have informed the development of the Lee Symptom Scale-Skin Sclerosis. Psychometric testing and determination of minimal clinically important difference are underway in an external cohort to validate the PRO.},
}

@article {pmid39808648,
year = {2025},
author = {Friedland, BA and Gundacker, H and Achilles, SL and Chen, BA and Hoesley, C and Richardson, BA and Kelly, CW and Piper, J and Johnson, S and Devlin, B and Steytler, J and Kleinbeck, K and Dangi, B and Friend, C and Song, M and Mensch, B and van der Straten, A and Jacobson, C and Hendrix, CW and Brown, J and Blithe, D and Hiller, SL and , },
title = {Acceptability of a dapivirine levonorgestrel vaginal ring in two Phase 1 trials (MTN-030/IPM 041 and MTN-044/IPM 053/CCN019): Implications for multipurpose prevention technology development.},
journal = {PloS one},
volume = {20},
number = {1},
pages = {e0312957},
pmid = {39808648},
issn = {1932-6203},
mesh = {Humans ; Female ; Adult ; *Levonorgestrel/administration & dosage ; *Pyrimidines/administration & dosage/therapeutic use ; *Contraceptive Devices, Female ; *HIV Infections/prevention & control ; Young Adult ; Adolescent ; Middle Aged ; Patient Acceptance of Health Care ; Anti-HIV Agents/administration & dosage/therapeutic use ; Contraceptive Agents, Female/administration & dosage ; Pregnancy ; },
abstract = {End-user feedback early in product development is important for optimizing multipurpose prevention technologies for HIV and pregnancy prevention. We evaluated the acceptability of the 90-day dapivirine levonorgestrel ring (DPV-LNG ring) used for 14 days compared to a dapivirine-only ring (DVR-200mg) in MTN-030/IPM 041 (n = 23), and when used for 90 days cyclically or continuously in MTN-044/IPM 053/CCN019 (n = 25). We enrolled healthy, non-pregnant, HIV-negative women aged 18-45 in Pittsburgh, PA and Birmingham, AL (MTN-030 only). Self-reports of vaginal bleeding and adherence (ring removals, expulsions) were collected via daily short message service. Acceptability data were recorded in face-to-face interviews at study exit. We assessed differences in acceptability by product characteristics and adherence; and associations between baseline characteristics/demographics, number of bleeding days, adherence, and overall acceptability. Most (21/23) women in the 14-day MTN-030 study and about half (13/25) in the 90-day MTN-044 study liked their assigned rings. In MTN-030 there were no significant associations between any variables and overall acceptability of either ring. In MTN-044, women who disliked the DPV-LNG ring had a significantly higher incidence of unanticipated vaginal bleeding, and reporting that vaginal bleeding changes were unacceptable than those who liked it. Although we found no overall association between adherence and acceptability, significantly more women who disliked (versus liked) the DPV-LNG ring reported expulsions during toileting. The DPV-LNG ring could meet the needs of women seeking simultaneous protection from HIV and unintended pregnancy. Addressing issues related to vaginal bleeding and expulsions early in product development will likely enhance acceptability of the DPV-LNG ring. Trial registration: Clinical Trial Registration: MTN-030/IPM 041: ClinicalTrials.gov NCT02855346; MTN-044/IPM 053/CCN019: ClinicalTrials.gov NCT03467347.},
}

Humans
Female
Adult
*Levonorgestrel/administration & dosage
*Pyrimidines/administration & dosage/therapeutic use
*Contraceptive Devices, Female
*HIV Infections/prevention & control
Young Adult
Adolescent
Middle Aged
Patient Acceptance of Health Care
Anti-HIV Agents/administration & dosage/therapeutic use
Contraceptive Agents, Female/administration & dosage
Pregnancy

@article {pmid39764024,
year = {2024},
author = {Arends, T and Bennett, SR and Tapscott, SJ},
title = {DUX4-induced HSATII RNA accumulation drives protein aggregation impacting RNA processing pathways.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {39764024},
issn = {2692-8205},
support = {P30 CA015704/CA/NCI NIH HHS/United States ; R01 AR045203/AR/NIAMS NIH HHS/United States ; T32 CA009657/CA/NCI NIH HHS/United States ; },
abstract = {RNA-driven protein aggregation leads to cellular dysregulation by sequestering regulatory proteins, disrupting normal cellular processes, and contributing to the development of diseases and tumorigenesis. Here, we show that double homeobox 4 (DUX4), an early embryonic transcription factor and causative gene of facioscapulohumeral muscular dystrophy (FSHD), induces the accumulation of stable intranuclear RNAs, including nucleolar-associated RNA and human satellite II (HSATII) repeat RNA. Stable intranuclear RNAs drive protein aggregation in DUX4-expressing muscle cells. Specifically, HSATII RNA sequesters m[6]A and m[5]C RNA methylation factors. Furthermore, HSATII-YBX1 ribonucleoprotein (RNP) complex formation is mediated by HSATII RNA accumulation, NSUN2 activity and RNA methylation. YBX-1 specifically associates with HSATII double-stranded RNA. Aberrant HSATII-RNP complexes affect key RNA processing pathways, including mRNA splicing. Differential splicing of genes mediated by HSATII-RNP complexes are associated with pathways known to be dysregulated by DUX4 expression. These findings highlight the broader influence of DUX4 on nuclear RNA dynamics and suggest that HSATII RNA could be a critical mediator of RNA processing regulation in DUX4-expressing cells. Understanding the impact of HSATII-RNP formation on RNA processing pathways provides valuable insight into the molecular mechanisms underlying FSHD.},
}

@article {pmid39763963,
year = {2024},
author = {Frouard, J and Telwatte, S and Luo, X and Elphick, N and Thomas, R and Arneson, D and Roychoudhury, P and Butte, AJ and Wong, JK and Hoh, R and Deeks, SG and Lee, SA and Roan, NR and Yukl, S},
title = {HIV-SEQ REVEALS GLOBAL HOST GENE EXPRESSION DIFFERENCES BETWEEN HIV-TRANSCRIBING CELLS FROM VIREMIC AND SUPPRESSED PEOPLE WITH HIV.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {39763963},
issn = {2692-8205},
support = {P01 AI169606/AI/NIAID NIH HHS/United States ; UM1 AI164559/AI/NIAID NIH HHS/United States ; R01 AI183286/AI/NIAID NIH HHS/United States ; R01 DK120387/DK/NIDDK NIH HHS/United States ; UM1 AI164560/AI/NIAID NIH HHS/United States ; P30 AI027763/AI/NIAID NIH HHS/United States ; R21 AI170166/AI/NIAID NIH HHS/United States ; UM1 AI164567/AI/NIAID NIH HHS/United States ; R01 AI132128/AI/NIAID NIH HHS/United States ; R01 DK131526/DK/NIDDK NIH HHS/United States ; R01 AI147777/AI/NIAID NIH HHS/United States ; },
abstract = {"Active" reservoir cells transcribing HIV can perpetuate chronic inflammation in virally suppressed people with HIV (PWH) and likely contribute to viral rebound after antiretroviral therapy (ART) interruption, so they represent an important target for new therapies. These cells, however, are difficult to study using single-cell RNA-seq (scRNA-seq) due to their low frequency and low levels of HIV transcripts, which are usually not polyadenylated. Here, we developed "HIV-seq" to enable more efficient capture of HIV transcripts - including non-polyadenylated ones - for scRNA-seq analysis of cells from PWH. By spiking in a set of custom-designed capture sequences targeting conserved regions of the HIV genome during scRNA-seq, we increased our ability to find HIV RNA+ cells from PWH by up to 44%. Implementing HIV-seq in conjunction with surface phenotyping by CITE-seq on paired blood specimens from PWH before vs. after ART suppression, we found that HIV RNA+ cells were enriched among T effector memory (Tem) cells during both viremia and ART suppression, but exhibited a cytotoxic signature during viremia only. By contrast, HIV RNA+ cells from the ART-suppressed timepoints exhibited a distinct anti-inflammatory signature involving elevated TGF-β and diminished IFN signaling. Overall, these findings demonstrate that active reservoir cells exhibit transcriptional features distinct from HIV RNA+ cells during viremia, and underscore HIV-seq as a useful tool to better understand the mechanisms by which HIV-transcribing cells can persist during ART.},
}

@article {pmid39808447,
year = {2025},
author = {Koyama, M},
title = {Control of antigen-independent T-cell migration after HSCT.},
journal = {Blood advances},
volume = {9},
number = {1},
pages = {207-208},
doi = {10.1182/bloodadvances.2024014584},
pmid = {39808447},
issn = {2473-9537},
}

@article {pmid39808074,
year = {2024},
author = {Ho, K and Hoesley, C and Anderson, PL and Fernández-Romero, JA and Friedland, BA and Kelly, CW and Jiao, Y and Edick, S and Brand, R and Kunjara Na Ayudhya, RP and Zyhowski, A and Hartman, DJ and Reddy, NB and Al-Khouja, A and Piper, J and Bauermeister, JA and Teleshova, N and Melo, C and Cornejal, N and Barnable, P and Singh, D and Scheckter, R and McClure, T and Hillier, SL and Hendrix, CW and , },
title = {Phase I Dose Volume Escalation of Rectally Administered PC-1005 to Assess Safety, Pharmacokinetics, and Antiviral Pharmacodynamics as a Multipurpose Prevention Technology (MTN-037).},
journal = {Journal of acquired immune deficiency syndromes (1999)},
volume = {97},
number = {4},
pages = {379-386},
pmid = {39808074},
issn = {1944-7884},
support = {UM1AI068633//Division of AIDS, National Institute of Allergy and Infectious Diseases/ ; },
mesh = {Humans ; Female ; Adult ; *Antiviral Agents/pharmacokinetics/administration & dosage/adverse effects ; Male ; Middle Aged ; Administration, Rectal ; Carrageenan/pharmacokinetics/administration & dosage ; HIV Infections/prevention & control/drug therapy ; Pre-Exposure Prophylaxis/methods ; Young Adult ; Rectum/virology ; Papillomavirus Infections/prevention & control ; Pyridines ; Urea/analogs & derivatives ; },
abstract = {BACKGROUND: On demand, topical PrEP is desired by those preferring episodic, nonsystemic PrEP. PC-1005 gel (MIV-150, zinc, and carrageenan) exhibits in vitro antiviral HIV-1, human papillomavirus (HPV), and herpes simplex virus type 2 (HSV-2) activity, attractive for a multipurpose prevention technology candidate. We evaluated the safety, pharmacokinetics, and antiviral effect of rectally applied PC-1005.

METHODS: HIV-uninfected adults received a series of 3 rectal PC-1005 doses-4, 16, and 32 mL separated by 2-week washout periods. Following each dose, plasma, rectal fluid and tissue, and vaginal fluid were collected over 48 hours.

RESULTS: Thirteen adults enrolled; 12 completed all 3 doses. All 13 adverse events reported were grade 1 or 2; 5 were judged study drug related. Plasma MIV-150 peaked 1-2 h after dosing with a median peak concentrations range of 0.07-0.23 ng/mL and median half-life range of 4.9-7.4 hours across dose volumes; median concentrations were below assay quantitation limits (BLQ) 24 hours after dosing. Rectal tissue MIV-150 peaked 0.5-1 hours after dosing at 1.4 ng/g (ng/mL) (0.8, 1.9), 46.0 (30.7, 831.0), and 79.7 (11.9, 116.0), respectively, after each dose volume; median tissue concentrations were BLQ beyond 5 hours for all doses. All vaginal fluid samples were BLQ. Ex vivo antiviral assays showed 5 hours of antiviral HPV and HSV effects but no anti-HIV activity.

CONCLUSIONS: MIV-150 rectal tissue concentrations were below the 100 ng/g target concentration and transient. Ex vivo assays demonstrated antiviral HSV and HPV effects but not against HIV. PC-1005 requires a more potent antiviral and longer-lasting formulation for further consideration as a multipurpose prevention technology candidate.

CLINICAL TRIALS: NCT03408899.},
}

Humans
Female
Adult
*Antiviral Agents/pharmacokinetics/administration & dosage/adverse effects
Male
Middle Aged
Administration, Rectal
Carrageenan/pharmacokinetics/administration & dosage
HIV Infections/prevention & control/drug therapy
Pre-Exposure Prophylaxis/methods
Young Adult
Rectum/virology
Papillomavirus Infections/prevention & control
Pyridines
Urea/analogs & derivatives

@article {pmid39764056,
year = {2024},
author = {Samorodnitsky, S and Campbell, K and Little, A and Ling, W and Zhao, N and Chen, YC and Wu, MC},
title = {Detecting Clinically Relevant Topological Structures in Multiplexed Spatial Proteomics Imaging Using TopKAT.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {39764056},
issn = {2692-8205},
support = {U10 CA180819/CA/NCI NIH HHS/United States ; },
abstract = {Novel multiplexed spatial proteomics imaging platforms expose the spatial architecture of cells in the tumor microenvironment (TME). The diverse cell population in the TME, including its spatial context, has been shown to have important clinical implications, correlating with disease prognosis and treatment response. The accelerating implementation of spatial proteomic technologies motivates new statistical models to test if cell-level images associate with patient-level endpoints. Few existing methods can robustly characterize the geometry of the spatial arrangement of cells and also yield both a valid and powerful test for association with patient-level outcomes. We propose a topology-based approach that combines persistent homology with kernel testing to determine if topological structures created by cells predict continuous, binary, or survival clinical endpoints. We term our method TopKAT (Topological Kernel Association Test) and show that it can be more powerful than statistical tests grounded in the spatial point process model, particularly when cells arise along the boundary of a ring. We demonstrate the properties of TopKAT through simulation studies and apply it to two studies of triple negative breast cancer where we show that TopKAT recovers clinically relevant topological structures in the spatial distribution of immune and tumor cells.},
}

@article {pmid39807974,
year = {2025},
author = {Kang, SK and Gulati, R and Moise, N and Hur, C and Elkin, EB},
title = {Multi-Cancer Early Detection Tests: State of the Art and Implications for Radiologists.},
journal = {Radiology},
volume = {314},
number = {1},
pages = {e233448},
doi = {10.1148/radiol.233448},
pmid = {39807974},
issn = {1527-1315},
mesh = {Humans ; *Early Detection of Cancer/methods ; *Neoplasms/diagnostic imaging ; Radiologists ; Biomarkers, Tumor/blood ; },
abstract = {Multi-cancer early detection (MCED) tests are already being marketed as noninvasive, convenient opportunities to test for multiple cancer types with a single blood sample. The technology varies-involving detection of circulating tumor DNA, fragments of DNA, RNA, or proteins unique to each targeted cancer. The priorities and tradeoffs of reaching diagnostic resolution in the setting of possible false positives and negatives remain under active study. Given the well-established role of imaging in lesion detection and characterization for most cancers, radiologists have an essential role to play in selecting diagnostic pathways, determining the validity of test results, resolving false-positive MCED test results, and evaluating tradeoffs for clinical policy. Appropriate access to and use of imaging tests will also factor into clinical guidelines. Thus, all clinicians potentially involved with MCED tests for cancer screening will need to weigh the benefits and harms of MCED testing, including consideration of how the tests will be used alongside or in place of other screening options, how diagnostic confirmation tests should be selected, and what the implications are for policy and reimbursement decisions. Further, patients will need regular support to make informed decisions about screening using MCED tests in the context of their personal cancer risks, health-related values, and access to care.},
}

Humans
*Early Detection of Cancer/methods
*Neoplasms/diagnostic imaging
Radiologists
Biomarkers, Tumor/blood

@article {pmid39806218,
year = {2025},
author = {Bajunaid, R and Niu, C and Hambly, C and Liu, Z and Yamada, Y and Aleman-Mateo, H and Anderson, LJ and Arab, L and Baddou, I and Bandini, L and Bedu-Addo, K and Blaak, EE and Bouten, CVC and Brage, S and Buchowski, MS and Butte, NF and Camps, SGJA and Casper, R and Close, GL and Cooper, JA and Cooper, R and Das, SK and Davies, PSW and Dabare, P and Dugas, LR and Eaton, S and Ekelund, U and Entringer, S and Forrester, T and Fudge, BW and Gillingham, M and Goris, AH and Gurven, M and El Hamdouchi, A and Haisma, HH and Hoffman, D and Hoos, MB and Hu, S and Joonas, N and Joosen, AM and Katzmarzyk, P and Kimura, M and Kraus, WE and Kriengsinyos, W and Kuriyan, R and Kushner, RF and Lambert, EV and Lanerolle, P and Larsson, CL and Leonard, WR and Lessan, N and Löf, M and Martin, CK and Matsiko, E and Medin, AC and Morehen, JC and Morton, JP and Must, A and Neuhouser, ML and Nicklas, TA and Nyström, CD and Ojiambo, RM and Pietiläinen, KH and Pitsiladis, YP and Plange-Rhule, J and Plasqui, G and Prentice, RL and Racette, SB and Raichlen, DA and Ravussin, E and Redman, LM and Reilly, JJ and Reynolds, R and Roberts, SB and Samaranayakem, D and Sardinha, LB and Silva, AM and Sjödin, AM and Stamatiou, M and Stice, E and Urlacher, SS and Van Etten, LM and van Mil, EGAH and Wilson, G and Yanovski, JA and Yoshida, T and Zhang, X and Murphy-Alford, AJ and Sinha, S and Loechl, CU and Luke, AH and Pontzer, H and Rood, J and Sagayama, H and Schoeller, DA and Westerterp, KR and Wong, WW and Speakman, JR},
title = {Predictive equation derived from 6,497 doubly labelled water measurements enables the detection of erroneous self-reported energy intake.},
journal = {Nature food},
volume = {},
number = {},
pages = {},
pmid = {39806218},
issn = {2662-1355},
support = {CAS 153E11KYSB20190015//Bureau of International Cooperation, Chinese Academy of Sciences/ ; BCS-1824466//National Science Foundation (NSF)/ ; },
abstract = {Nutritional epidemiology aims to link dietary exposures to chronic disease, but the instruments for evaluating dietary intake are inaccurate. One way to identify unreliable data and the sources of errors is to compare estimated intakes with the total energy expenditure (TEE). In this study, we used the International Atomic Energy Agency Doubly Labeled Water Database to derive a predictive equation for TEE using 6,497 measures of TEE in individuals aged 4 to 96 years. The resultant regression equation predicts expected TEE from easily acquired variables, such as body weight, age and sex, with 95% predictive limits that can be used to screen for misreporting by participants in dietary studies. We applied the equation to two large datasets (National Diet and Nutrition Survey and National Health and Nutrition Examination Survey) and found that the level of misreporting was >50%. The macronutrient composition from dietary reports in these studies was systematically biased as the level of misreporting increased, leading to potentially spurious associations between diet components and body mass index.},
}

@article {pmid39805421,
year = {2025},
author = {Ajelli, M and Muyembe, JJ and Touré, A and Diallo, A and Litvinova, M and Merler, S and Mulangu, S and Bagayoko, A and Bah, A and Bah, I and Barry, A and Barry, F and Chérif, M and Condé, D and Diallo, AA and Diallo, F and Diakité, M and Doré, K and Mapan, KA and Koundouno, T and Onivogui, PK and Lamah, F and Maneno, H and Nomou, A and Sekouba, K and Sani, I and Soumah, A and Sy, MM and Gsell, PS and Halloran, ME and Henao-Restrepo, AM and Fall, IS and Ryan, MJ and Salama, P and Vespignani, A and Longini, IM},
title = {Vaccination Strategies for Ebola in the Democratic Republic of Congo: The WHO-Ebola Modeling Collaboration.},
journal = {International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases},
volume = {},
number = {},
pages = {107779},
doi = {10.1016/j.ijid.2025.107779},
pmid = {39805421},
issn = {1878-3511},
abstract = {OBJECTIVES: Assess the effectiveness of ring vaccination in controlling an Ebola virus outbreak in the Democratic Republic of Congo.

METHODS: This analysis focuses on two areas of the Democratic Republic of Congo, Beni and Butembo/Katwa, which were affected during the 2018-2020 Ebola outbreak. To simulate Ebola virus transmission, we used a spatially explicit agent-based model with households, health care facilities, and Ebola treatment units. Model parameters were calibrated using data collected under the ring-vaccination expanded-access protocol implemented during the outbreak. The model was used to estimate the impact of the deployed ring vaccination strategy, compared to what would have happened if there had been no ring vaccination. The impact of alternative vaccination strategies (mass vaccination, targeted geographic vaccination, and ring-plus) was evaluated as well.

RESULTS: Compared to a hypothetical scenario where vaccination was not implemented, ring vaccination was estimated to have averted 54.3% (SD, 32.5%) and 62.7% (SD, 23.2%) of potential cases in Beni and Butembo/Katwa, respectively. Under ring vaccination, the average number of averted cases per 1000 vaccine doses administered was 15.1 (SD, 16.8) and 27.8 (SD, 22.9), in Beni and Butembo/Katwa, respectively. In terms of number of averted cases per vaccine dose, ring vaccination was estimated to be more efficient than any of the other evaluated vaccination strategies.

CONCLUSION: Despite some level of social instability, ring vaccination with the rVSV-ZEBOV vaccine was highly effective during the 2018-2020 Ebola outbreak in the Democratic Republic of Congo. As compared to alternative vaccination strategies, ring vaccination was estimated to be the most efficient.},
}

@article {pmid39804957,
year = {2025},
author = {Zakerzade, R and Chang, CH and Chatla, K and Krishnapura, A and Appiah, SP and Zhang, J and Unckless, RL and Blumenstiel, JP and Bachtrog, D and Wei, KH},
title = {Diversification and recurrent adaptation of the synaptonemal complex in Drosophila.},
journal = {PLoS genetics},
volume = {21},
number = {1},
pages = {e1011549},
doi = {10.1371/journal.pgen.1011549},
pmid = {39804957},
issn = {1553-7404},
abstract = {The synaptonemal complex (SC) is a protein-rich structure essential for meiotic recombination and faithful chromosome segregation. Acting like a zipper to paired homologous chromosomes during early prophase I, the complex is a symmetrical structure where central elements are connected on two sides by the transverse filaments to the chromatin-anchoring lateral elements. Despite being found in most major eukaryotic taxa implying a deeply conserved evolutionary origin, several components of the complex exhibit unusually high rates of sequence turnover. This is puzzlingly exemplified by the SC of Drosophila, where the central elements and transverse filaments display no identifiable homologs outside of the genus. Here, we exhaustively examine the evolutionary history of the SC in Drosophila taking a comparative phylogenomic approach with high species density to circumvent obscured homology due to rapid sequence evolution. Contrasting starkly against other genes involved in meiotic chromosome pairing, SC genes show significantly elevated rates of coding evolution due to a combination of relaxed constraint and recurrent, widespread positive selection. In particular, the central element cona and transverse filament c(3) G have diversified through tandem and retro-duplications, repeatedly generating paralogs with novel germline activity. In a striking case of molecular convergence, c(3) G paralogs that independently arose in distant lineages evolved under positive selection to have convergent truncations to the protein termini and elevated testes expression. Surprisingly, the expression of SC genes in the germline is prone to change suggesting recurrent regulatory evolution which, in many species, resulted in high testes expression even though Drosophila males are achiasmic. Overall, our study recapitulates the poor conservation of SC components, and further uncovers that the lack of conservation extends to other modalities including copy number, genomic locale, and germline regulation. Considering the elevated testes expression in many Drosophila species and the common ancestor, we suggest that the activity of SC genes in the male germline, while still poorly understood, may be a prime target of constant evolutionary pressures driving repeated adaptations and innovations.},
}

@article {pmid39801002,
year = {2025},
author = {Schaub, SK and Simone, CB and Lo, SS and Choi, JI},
title = {The current landscape of oncologic emergencies: the role of radiotherapy.},
journal = {Annals of palliative medicine},
volume = {},
number = {},
pages = {},
doi = {10.21037/apm-24-159},
pmid = {39801002},
issn = {2224-5839},
}

@article {pmid39800921,
year = {2025},
author = {Chen, A and Baek, G and Russell, K and Shaw, C and Othus, M and Cohen, J and Palmer, S and Rasmussen, J and Bubalo, J and Tsomo, T and Schwarz, T and Namburi, S and Halpern, A},
title = {Evaluation of the Toxicity and Outcomes of the Combination of Midostaurin and CLAG-M in Patients With FLT3-Mutated Acute Myeloid Leukemia (AML): A Multicenter Retrospective Analysis.},
journal = {The Annals of pharmacotherapy},
volume = {},
number = {},
pages = {10600280241305608},
doi = {10.1177/10600280241305608},
pmid = {39800921},
issn = {1542-6270},
abstract = {BACKGROUND: Addition of midostaurin to standard "7+3" (cytarabine and anthracycline) significantly prolongs overall and event-free survival. At University of Washington/Fred Hutchinson Cancer Center (UW/FHCC), the standard regimen for newly diagnosed (ND) and relapsed/refractory (R/R) AML is cladribine, high-dose cytarabine, GCSF, and mitoxantrone (CLAG-M); midostaurin is added if FLT3-mutated. There is limited data on the use of FLT3-inhibitors with high-dose cytarabine regimens in AML.

OBJECTIVE: This study aimed to evaluate the safety and efficacy of the combination of midostaurin with CLAG-M versus midostaurin plus 7+3 in FLT3-mutated AML patients.

METHODS: This is a retrospective, multicenter review including FLT3-mutated AML patients undergoing (re)induction chemotherapy with either CLAG-M or 7+3 at UW/FHCC, Oregon Health & Science University, and Swedish Cancer Institute. The primary outcome was incidence of adverse events. Secondary outcomes included disease response per ELN2017 criteria and 28-day mortality. Excluded were patients on clinical trials or who started midostaurin 30 days after chemotherapy.

RESULTS: Eighty patients treated from September 2016 to December 2023 were included; 36 patients received CLAG-M, and 44 patients 7+3. Baseline characteristics were similar across all institutions. Adverse event rates were similar between the 2 cohorts, except diarrhea and bleeding which were more common in the 7+3 cohort. The rate of complete remission (CR) plus CR with incomplete blood count recovery did not significantly differ between the 2 cohorts: CLAG-M, 86% versus 7+3, 70% (P = 0.11).

CONCLUSION & RELEVANCE: The toxicity profile of CLAG-M combined with midostaurin is comparable with the combination of 7+3 with midostaurin, and induces high remissions rates in adults with FLT3-mutated AML.},
}

@article {pmid39800670,
year = {2025},
author = {Najjar, R and Wang, X and Pineda, JMB and Alessi, H and Bays, A and Bradley, RK and Jarvis, JN and Mustelin, T},
title = {Altered Protein Structures and Neoepitopes in Lupus Neutrophils From Dysregulated Splicing of Messenger RNA.},
journal = {ACR open rheumatology},
volume = {7},
number = {1},
pages = {e11770},
pmid = {39800670},
issn = {2578-5745},
support = {AI188952/RG/CSR NIH HHS/United States ; AR075134, AR074939, and AR081654 to T.M./RG/CSR NIH HHS/United States ; AI-186337 and AI-183320 (to Dr Mustelin)/GF/NIH HHS/United States ; },
abstract = {OBJECTIVE: To test whether messenger RNA (mRNA) splicing is altered in neutrophils from patients with systemic lupus erythematosus (SLE) and can produce neoantigens.

METHODS: RNA sequencing of neutrophils from patients with SLE (n = 15) and healthy donors (n = 12) were analyzed for mRNA splicing using the RiboSplitter pipeline, an event-focused tool based on SplAdder with subsequent translation and protein domain annotation. RNA sequencing from SARS-CoV2-infected individuals was used as an additional comparator.

RESULTS: Neutrophils from patients with SLE contained 521 statistically significant altered mRNA splicing events compared with healthy donor neutrophils, many of them affecting important immunologic pathways, myeloid function, transcription factors, and proteins involved in mRNA splicing. A subset of splicing events were only present in SLE samples, and some of them occurred at unannotated splice acceptor or donor sites. Two patients were particularly rich in such events. Only a small number of dysregulated splicing events were more pronounced in patients with active disease or with high type I interferons but were not detected in SARS-CoV2-infected individuals, who also had high type I interferons. Besides causing a range of structural changes, 80 mRNA splice variants exclusive to SLE were predicted to translate into novel amino acid sequences. Peptides derived from these novel amino acid sequences were predicted to bind to the individual patients' class I and II major histocompatibility complex molecules with high affinity.

CONCLUSION: We conclude that aberrant mRNA splicing in SLE has the potential to affect both the function of granulocytes and to generate novel autoantigens.},
}

@article {pmid39763936,
year = {2024},
author = {Fang, A and Kumar, L and Creevy, KE and , and Promislow, DEL and Ma, J},
title = {The first comorbidity networks in companion dogs in the Dog Aging Project.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {39763936},
issn = {2692-8205},
support = {U19 AG057377/AG/NIA NIH HHS/United States ; },
abstract = {Comorbidity and its association with age are of great interest in geroscience. However, there are few model organisms that are well-suited to study comorbidities that will have high relevance to humans. In this light, we turn our attention to the companion dog. The companion dog shares many morbidities with humans. Thus, a better understanding of canine comorbidity relationships could benefit both humans and dogs. We present an analysis of canine comorbidity networks from the Dog Aging Project, a large epidemiological cohort study of companion dogs in the United States. We included owner-reported health conditions that occurred in at least 60 dogs (n=166) and included only dogs that had at least one of those health conditions (n=26,523). We constructed an undirected comorbidity network using a Poisson binomial test, adjusting for age, sex, sterilization status, breed background (i.e., purebred vs. mixed-breed), and weight. The comorbidity network reveals well-documented comorbidities, such as diabetes with blindness and hypertension with chronic kidney disease. In addition, this network also supports less well-studied comorbidity relationships, such as proteinuria with anemia. A directed comorbidity network accounting for time of reported condition onset suggests that diabetes occurs before cataracts, which is consistent with the canine literature. Analysis of age-stratified networks reveals that global centrality measures increase with age and are the highest in the Senior group compared to the Young Adult and Mature Adult groups. Our results suggest that comorbidity network analysis is a promising method to enhance clinical knowledge and canine healthcare management.},
}

@article {pmid39763889,
year = {2024},
author = {Park, J and Prokopchuk, G and Popchock, AR and Hao, J and Liao, TW and Yan, S and Hedman, DJ and Larson, JD and Walther, BK and Becker, NA and Basu, A and Maher, LJ and Wheeler, RJ and Asbury, CL and Biggins, S and Lukeš, J and Ha, T},
title = {Probing mechanical selection in diverse eukaryotic genomes through accurate prediction of 3D DNA mechanics.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {39763889},
issn = {2692-8205},
support = {R35 GM143949/GM/NIGMS NIH HHS/United States ; R35 GM149357/GM/NIGMS NIH HHS/United States ; /WT_/Wellcome Trust/United Kingdom ; R35 GM122569/GM/NIGMS NIH HHS/United States ; R35 GM134842/GM/NIGMS NIH HHS/United States ; },
abstract = {Connections between the mechanical properties of DNA and biological functions have been speculative due to the lack of methods to measure or predict DNA mechanics at scale. Recently, a proxy for DNA mechanics, cyclizability, was measured by loop-seq and enabled genome-scale investigation of DNA mechanics. Here, we use this dataset to build a computational model predicting bias-corrected intrinsic cyclizability, with near-perfect accuracy, solely based on DNA sequence. Further, the model predicts intrinsic bending direction in 3D space. Using this tool, we aimed to probe mechanical selection - that is, the evolutionary selection of DNA sequence based on its mechanical properties - in diverse circumstances. First, we found that the intrinsic bend direction of DNA sequences correlated with the observed bending in known protein-DNA complex structures, suggesting that many proteins co-evolved with their DNA partners to capture DNA in its intrinsically preferred bent conformation. We then applied our model to large-scale yeast population genetics data and showed that centromere DNA element II, whose consensus sequence is unknown, leaving its sequence-specific role unclear, is under mechanical selection to increase the stability of inner-kinetochore structure and to facilitate centromeric histone recruitment. Finally, in silico evolution under strong mechanical selection discovered hallucinated sequences with cyclizability values so extreme that they required experimental validation, yet, found in nature in the densely packed mitochondrial(mt) DNA of Namystynia karyoxenos, an ocean-dwelling protist with extreme mitochondrial gene fragmentation. The need to transmit an extraordinarily large amount of mtDNA, estimated to be > 600 Mb, in combination with the absence of mtDNA compaction proteins may have pushed mechanical selection to the extreme. Similarly extreme DNA mechanics are observed in bird microchromosomes, although the functional consequence is not yet clear. The discovery of eccentric DNA mechanics in unrelated unicellular and multicellular eukaryotes suggests that we can predict extreme natural biology which can arise through strong selection. Our methods offer a way to study the biological functions of DNA mechanics in any genome and to engineer DNA sequences with desired mechanical properties.},
}

@article {pmid39763555,
year = {2024},
author = {Li, R and Taliun, SAG and Liao, K and Flickinger, M and Sobell, JL and Genovese, G and Locke, AE and Chiu, RR and LeFaive, J and Martins, T and Chapman, S and Neumann, A and Handsaker, RE and Arnett, DK and Barnes, KC and Boerwinkle, E and Braff, D and Cade, BE and Fornage, M and Gibbs, RA and Hoth, KF and Hou, L and Kooperberg, C and Loos, RJF and Metcalf, GA and Montgomery, CG and Morrison, AC and Qin, ZS and Redline, S and Reiner, AP and Rich, SS and Rotter, JI and Taylor, KD and Viaud-Martinez, KA and , and , and Bigdeli, TB and Gabriel, S and Zollner, S and Smith, AV and Abecasis, G and McCarroll, S and Pato, MT and Pato, CN and Boehnke, M and Knowles, J and Kang, HM and Ophoff, RA and Ernst, J and Scott, LJ},
title = {Whole genome sequence-based association analysis of African American individuals with bipolar disorder and schizophrenia.},
journal = {medRxiv : the preprint server for health sciences},
volume = {},
number = {},
pages = {},
pmid = {39763555},
support = {R01 HL120393/HL/NHLBI NIH HHS/United States ; U54 HG003067/HG/NHGRI NIH HHS/United States ; DP1 DA044371/DA/NIDA NIH HHS/United States ; U01 HG012079/HG/NHGRI NIH HHS/United States ; U01 HL120393/HL/NHLBI NIH HHS/United States ; HHSN268201800001C/HL/NHLBI NIH HHS/United States ; HHSN268201500014C/HL/NHLBI NIH HHS/United States ; R01 HL117626/HL/NHLBI NIH HHS/United States ; HHSN268201600033C/HL/NHLBI NIH HHS/United States ; R01 HL055673/HL/NHLBI NIH HHS/United States ; U01 MH105653/MH/NIMH NIH HHS/United States ; R01 HL089856/HL/NHLBI NIH HHS/United States ; U54 HG003273/HG/NHGRI NIH HHS/United States ; R01 HL098433/HL/NHLBI NIH HHS/United States ; R01 HL113326/HL/NHLBI NIH HHS/United States ; HHSN268201500015C/HL/NHLBI NIH HHS/United States ; R01 MH115676/MH/NIMH NIH HHS/United States ; R01 HL104608/HL/NHLBI NIH HHS/United States ; R01 HG009976/HG/NHGRI NIH HHS/United States ; },
abstract = {In studies of individuals of primarily European genetic ancestry, common and low-frequency variants and rare coding variants have been found to be associated with the risk of bipolar disorder (BD) and schizophrenia (SZ). However, less is known for individuals of other genetic ancestries or the role of rare non-coding variants in BD and SZ risk. We performed whole genome sequencing of African American individuals: 1,598 with BD, 3,295 with SZ, and 2,651 unaffected controls (InPSYght study). We increased power by incorporating 14,812 jointly called psychiatrically unscreened ancestry-matched controls from the Trans-Omics for Precision Medicine (TOPMed) Program for a total of 17,463 controls. To identify variants and sets of variants associated with BD and/or SZ, we performed single-variant tests, gene-based tests for singleton protein truncating variants, and rare and low-frequency variant annotation-based tests with conservation and universal chromatin states and sliding windows. We found suggestive evidence of BD association with single-variants on chromosome 18 and of lower BD risk associated with rare and low-frequency variants on chromosome 11 in a region with multiple BD GWAS loci, using a sliding window approach. We also found that chromatin and conservation state tests can be used to detect differential calling of variants in controls sequenced at different centers and to assess the effectiveness of sequencing metric covariate adjustments. Our findings reinforce the need for continued whole genome sequencing in additional samples of African American individuals and more comprehensive functional annotation of non-coding variants.},
}

@article {pmid39799046,
year = {2024},
author = {Ramasamy, K and Vij, R and Kuter, D and Cella, D and Durie, BGM and Abonour, R and Rifkin, RM and Ailawadhi, S and Lee, HC and Cowan, AJ and Ho, C and Dhanasiri, S and Fish, S and Yu, E and Dhamane, AD and Fang, J and Marshall, TS and Samuel, A and Liu, L and Katz, J and Gu, T and Jagannath, S},
title = {Real-World Treatment Patterns and Clinical Outcomes in Patients With Multiple Myeloma Previously Treated With Lenalidomide and an Anti-CD38 Monoclonal Antibody.},
journal = {Clinical lymphoma, myeloma & leukemia},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.clml.2024.12.002},
pmid = {39799046},
issn = {2152-2669},
abstract = {BACKGROUND: This analysis explored real-world characteristics, treatment patterns and clinical outcomes in patients with relapsed or refractory multiple myeloma (RRMM) previously treated with lenalidomide and an anti-CD38 monoclonal antibody (mAb) and requiring subsequent treatment.

MATERIALS AND METHODS: The PREAMBLE and Connect MM prospective registries of patients with multiple myeloma (MM), and the US nationwide Flatiron Health electronic health record-derived de-identified database were analysed. MM-specific treatment patterns (prior/index therapies) and outcomes (progression-free survival [PFS]/overall survival [OS]) were assessed.

RESULTS: This analysis included: PREAMBLE n = 215; Connect MM n = 232; Flatiron Health n = 845. Median age at index was 69.0 years, median 3 prior lines of therapy; > 50% male. The most common index regimens accounted < 15% of treatments (most common PREAMBLE, Connect MM: carfilzomib±dexamethasone; Flatiron Health: pomalidomide+daratumumab+dexamethasone); most patients received classes that they had previously; ≥ 93% were triple-class exposed (immunomodulatory drug, proteasome inhibitor, anti-CD38 mAb). In PREAMBLE, Connect MM and Flatiron Health, respectively: 80.9%, 68.1% and 77.2% were lenalidomide- and anti-CD38 mAb-refractory; 69.3%, 67.2% and 71.1% were triple-class refractory (TCR); median PFS: 5.2 (95% CI 3.7-6.7), 4.4 (3.5-5.6) and 5.3 months (4.8-6.0); median OS: 19.3 (15.8-26.1), 14.2 (11.0-16.9) and 23.1 months (19.0-28.6). PFS and OS were shorter in lenalidomide- and anti-CD38 mAb-refractory patients versus those who were not refractory to both. A similar pattern was observed for TCR patients versus non-TCR patients.

CONCLUSION: There is no uniform standard of care for patients with RRMM with prior exposure to lenalidomide and anti-CD38 mAbs. Survival outcomes are poor, with a need for effective treatments for these patients.},
}

@article {pmid39798802,
year = {2025},
author = {Petersdorf, EW and McKallor, C and Malkki, M and Hsu, K and He, M and Spellman, SR and Gooley, T and Stevenson, P},
title = {The Association of HLA-E Ligand and NKG2 Receptor Variation with Relapse and Mortality after Haploidentical Related Donor Transplantation.},
journal = {Transplantation and cellular therapy},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jtct.2025.01.004},
pmid = {39798802},
issn = {2666-6367},
abstract = {BACKGROUND: Recurrence of blood malignancy is the major cause of mortality after hematopoietic cell transplantation. NKG2 receptor/HLA-E ligand complexes play a fundamental role in the surveillance and elimination of transformed cells but their role in the control of leukemia in transplantation is unknown.

OBJECTIVE: We tested the hypothesis that gene variation of patient and/or donor HLA-E ligand and donor NKG2C-NKG2A receptors are associated with the risks of relapse and mortality (primary endpoints) and GVHD and non-relapse mortality (secondary endpoints) after haploidentical transplantation.

STUDY DESIGN: We retrospectively defined donor NKG2 receptor haplotypes and patient HLA-E ligands in 1629 haploidentical related transplantations. HLA-E residue 107 was genotyped in patients and donors. Single nucleotide polymorphisms descriptive of NKG2C and NKG2A haplotypes were characterized in donors. Overall mortality, relapse, non-relapse mortality and chronic GVHD were studied using Cox regression models. Acute GVHD was studied by logistic regression.

RESULTS: The hazard of relapse for patients transplanted from NKG2C-del/del donors was 51% lower than that from wt/wt donors (hazard ratio, HR, 0.49 [95% confidence interval, CI, 0.26-0.89) contributing to a HR for mortality of 0.62 (95% CI, 0.38-1.02). The HR of mortality among patients transplanted from a donor with 2 vs. 0 copies of the NKG2A rs35909400-rs2734440-rs12824474 CCC haplotype was HR 2.28 (95% CI, 1.34-3.86). The HRs of mortality for ArgArg and ArgGly patients compared to GlyGly patients were 1.42 (95% CI, 1.11-1.82) and 1.43 (95% CI, 1.13-1.81), respectively. Hazard ratios for non-relapse mortality for patients with ArgGly or ArgArg genotypes compared to patients with GlyGly genotype were HR 1.60 (95% CI, 1.06-2.41) and HR 1.79 (95% CI, 1.21-2.66), respectively. Assessment of donor receptor/patient ligand pairings showed that among Arg-positive patients, the HR of mortality from donors with any wt-CCC/CCC haplotype was HR 2.52 (95% CI, 1.45-4.38) relative to donors with any wt-non CCC/CCC haplotype.

CONCLUSIONS: The success of haploidentical transplantation may be defined by the cumulative effects of donor NKG2 receptor and patient HLA-E ligand polymorphisms. Patient HLA-E ligand and donor NKG2C-NKG2A receptor haplotypes shed new light on their role in the control of malignancy.},
}

@article {pmid39798608,
year = {2025},
author = {Marshall, A and Kassim, S and Brown-Korsah, J and Chang, C and Hippe, DS and Kim, EJ and Shinohara, MM},
title = {Black Patients with Mycosis Fungoides and Sézary Syndrome Experience Worse Health-Related Quality of Life: A Cross-Sectional Study.},
journal = {Journal of the American Academy of Dermatology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jaad.2025.01.006},
pmid = {39798608},
issn = {1097-6787},
}

@article {pmid39798390,
year = {2024},
author = {Talukder, R and Bakaloudi, DR and Makrakis, D and Diamantopoulos, LN and Enright, T and Leary, JB and Raychaudhuri, R and Tripathi, N and Agarwal, N and Jindal, T and Brown, JR and Zakharia, Y and Rey-Cárdenas, M and Castellano, D and Nguyen, CB and Alva, A and Zakopoulou, R and Bamias, A and Barrera, RM and Marmolejo, D and Drakaki, A and Pinato, DJ and Korolewicz, J and Buznego, LA and Duran, I and Carballeira, CC and McKay, RR and Stewart, TF and Gupta, S and Barata, P and Yu, EY and Koshkin, VS and Khaki, AR and Grivas, P},
title = {Clinical Outcomes With Immune Checkpoint Inhibitors in Patients With FGFR2/3, MTAP or ERBB2 Genomic Alterations in Advanced Urothelial Carcinoma.},
journal = {Clinical genitourinary cancer},
volume = {23},
number = {1},
pages = {102284},
doi = {10.1016/j.clgc.2024.102284},
pmid = {39798390},
issn = {1938-0682},
abstract = {BACKGROUND: FGFR2/3, MTAP and ERBB2 genomic alterations have treatment targets in advanced urothelial carcinoma (aUC). These alterations may affect tumor microenvironment and outcomes with immune checkpoint inhibitors (ICIs) in aUC.

PATIENTS AND METHODS: We identified patients with available genomic data in our multi-institution cohort of patients with aUC treated with ICI. Outcomes (observed response rate [ORR], progression-free and overall survival [PFS, OS]) with ICI were compared between patients with and without FGFR 2/3, MTAP, ERBB2 alterations. We compared ORR using logistic regression and PFS/OS using Cox proportional hazards.

RESULTS: Out of 1,514 patients, 276 (18%), 174 (11%) and 208 (14%) patients had known FGFR2/3, MTAP and ERBB2 alteration status, respectively. and were treated with ICI in 1L or 2 + L. In patients with (vs. without) FGFR2/3 alteration, ORR with ICI was 21% vs. 32% (OR 0.54; [95%CI 0.32-0.91]), PFS was significantly shorter in patients with FGFR2/3 alterations (HR = 1.36 [95%CI 1.03-1.80]; P=0.03); OS was not significantly different (HR = 1.22 [95%CI 0.86-1.47]). In patients with (vs. without) MTAP alteration, ORR with ICI was 25% versus 40% (OR 0.52 [95%CI 0.20-1.38]); PFS and OS were nonsignificantly different. In patients with (vs. without) ERBB2 alteration, ORR with ICI was similar (37% vs. 35%; OR 1.06; 95%CI 0.57-1.97); PFS and OS were significantly longer in patients with ERBB2 alteration [HR 0.63 (95%CI 0.41-0.95); P=0.03; HR 0.66, [95% CI 0.44-0.97]), respectively.

CONCLUSION: Our results support further evaluation of FGFR2/3, MTAP and ERBB2 alterations as putative biomarkers in patients with aUC treated with ICI.},
}

@article {pmid39796789,
year = {2024},
author = {Dekker, SE and Deng, L},
title = {Correction: Dekker, S.E.; Deng, L. Clinical Advances and Challenges in Targeting KRAS Mutations in Non-Small Cell Lung Cancer. Cancers 2024, 16, 3885.},
journal = {Cancers},
volume = {17},
number = {1},
pages = {},
pmid = {39796789},
issn = {2072-6694},
abstract = {In the original publication [...].},
}

@article {pmid39763863,
year = {2024},
author = {Farrell-Sherman, A and de la Force, N and Prator, C and Valieris, R and Azam, W and Da Silva, I and Deeks, SG and Thanh, C and Bosch, R and Henrich, TJ and Cohn, L},
title = {Inflammatory Monocytes Increase Prior to Detectable HIV-1 Rebound Viremia.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {39763863},
issn = {2692-8205},
support = {K24 AI174971/AI/NIAID NIH HHS/United States ; P30 CA015704/CA/NCI NIH HHS/United States ; R01 AI141003/AI/NIAID NIH HHS/United States ; UM1 AI164560/AI/NIAID NIH HHS/United States ; },
abstract = {The persistence of HIV-1 proviruses in latently infected cells allows viremia to resume upon treatment cessation. To characterize the resulting immune response, we compare plasma proteomics and single-cell transcriptomics of peripheral blood mononuclear cells (PBMCs) before, during, and after detectable plasma viremia. We observe unique transcriptional signatures prior to viral rebound including a significant increase in CD16[++] monocytes with increased anti-viral gene expression. Inflammatory proteins were identified in plasma after detectable rebound. Identifying early signals of imminent viral rebound after treatment cessation will aid in the development of strategies to prolong time to viral rebound and cure HIV-1.},
}

@article {pmid39793544,
year = {2025},
author = {Wheeler, SB and Thom, B and Waters, AR and Shankaran, V},
title = {Interventions to Address Cancer-Related Financial Hardship: A Scoping Review and Call to Action.},
journal = {JCO oncology practice},
volume = {21},
number = {1},
pages = {29-40},
doi = {10.1200/OP.24.00375},
pmid = {39793544},
issn = {2688-1535},
mesh = {Humans ; *Neoplasms/therapy/economics/epidemiology ; *Financial Stress ; },
abstract = {PURPOSE: As oncology practices implement routine screening for financial hardship (FH) and health-related social needs, interventions that address these needs must be implemented. A growing body of literature has reported on FH interventions.

METHODS: We conducted a scoping review of the literature using PubMed, EMBASE, PsychInfo, and CINAHL to identify key studies (2000-2024) reporting on interventions to address cancer-related FH. Full-length manuscripts were included in the review if they detailed a research, quality improvement, or community-based intervention to address at least one element of FH and drew association with an outcome of interest. Studies were categorized by intervention type and qualitatively analyzed to identify critical components, outcomes, and limitations.

RESULTS: Forty-four publications reporting on 43 interventions were included in the final analysis and were categorized as research interventions (n = 20) and real-world programs (n = 20). Studies reporting on financial navigation programs (n = 17) and specialty pharmacy assistance programs (n = 11) were most common; enrolled patients received concrete assistance with direct medical costs and cost-of-living expenses (eg, transportation and food). In addition, several of these programs improved overall patient-reported financial toxicity, decreased appointment no-shows, and improved enrollment in clinical trials.

CONCLUSION: Interventions to address FH are feasible and can address all domains of FH-material, behavioral, and psychosocial. Future research should address the uptake and implementation of these interventions across diverse cancer care delivery settings. Such programs will be an essential part of cancer care delivery until broad social and policy changes can address the underlying factors that contribute to FH in Americans with cancer.},
}

Humans
*Neoplasms/therapy/economics/epidemiology
*Financial Stress

@article {pmid39792043,
year = {2025},
author = {Galvin, RT and Chen, Y and Yuan, Y and Cooney, T and Howell, R and Smith, S and Arnold, MA and Conces, M and Leisenring, W and Armstrong, GT and Neglia, JP and Turcotte, LM},
title = {Temporal Trends of Subsequent CNS Malignancies Among Survivors of Childhood Cancer.},
journal = {Journal of the National Cancer Institute},
volume = {},
number = {},
pages = {},
doi = {10.1093/jnci/djaf005},
pmid = {39792043},
issn = {1460-2105},
abstract = {PURPOSE: It is not known whether temporal changes in childhood cancer therapy have reduced risk of subsequent malignant neoplasms (SMNs) of the central nervous system (CNS), a frequently fatal late effect of cancer therapy.

METHODS: Five-year survivors of primary childhood cancers diagnosed between 1970-1999 in the Childhood Cancer Survivor Study with a subsequent CNS SMN were identified. Cumulative incidence rates and standardized incidence ratios (SIR) were compared among survivors diagnosed between 1970-1979 (N = 6223), 1980-1989 (N = 9680), and 1990-1999 (N = 8999). Multivariable models assessed risk factors for CNS SMN.

RESULTS: 157 CNS SMNs (1970s, 52; 1980s, 63; 1990s, 42) were identified, excluding meningiomas, which were most often malignant gliomas. The proportion of survivors receiving any cranial radiotherapy (CRT) exposure was reduced over time (1970s 77.0%, 1980s 54.3%, 1990s 33.9%), while the proportion receiving >35Gy CRT showed a smaller reduction (11.4%, 10.8%, and 8.5%, respectively). Twenty-year cumulative incidence (95% CI) and SIR (95% CI) for CNS SMN by treatment decade were 0.32% (0.18-0.46%) and 6.6 (5.0-8.7); 0.55% (0.41-0.70%) and 8.3 (6.6-10.4); and 0.43% (0.31-0.55%) and 9.2 (7.0-12.0), respectively, with no statistically significant decreases between eras. Multivariable analyses showed increased risk for CRT dose levels >10Gy and for primary diagnoses of medulloblastoma/PNET (HR 18.7, 9.2-37.9) and astrocytoma (HR 10.1, 5.3-19.5). Three-year cumulative incidence of death after CNS SMN, by treatment decade, were 76%, 74%, and 73%, respectively.

CONCLUSION: CNS SMN incidence has not decreased despite fewer survivors exposed to CNS-directed radiotherapy. CNS SMNs remain a substantial source of mortality for affected patients.},
}

@article {pmid39790992,
year = {2024},
author = {Ruiz, RA and Lehavot, K and Heffner, JL and Kava, CM and Ornelas, IJ},
title = {Coping and Social Support in Relation to Minority Stress and Cigarette Smoking Among Lesbian, Gay, and Bisexual Veterans.},
journal = {Annals of LGBTQ public and population health},
volume = {5},
number = {4},
pages = {335-352},
pmid = {39790992},
issn = {2688-4518},
support = {I01 HX002423/HX/HSRD VA/United States ; T32 CA092408/CA/NCI NIH HHS/United States ; T32 CA193193/CA/NCI NIH HHS/United States ; },
abstract = {The intersection between a minoritized sexual orientation identity and a U.S. military Veteran status places lesbian, gay, and bisexual (LGB) Veterans at increased risk for cigarette smoking. Guided by the Minority Stress Model, this study assessed whether coping and three types of social support (general, Veteran-specific, and lesbian, gay, bisexual, and transgender [LGBT]-specific) moderated the association between minority stressors and past-year smoking among LGB Veterans. Participants were recruited online for a prospective cohort study. We conducted secondary data analysis of baseline surveys collected from September 2019 to December 2020. The study sample included cisgender LGB Veterans (N = 463). Adjusted multivariable logistic regression models estimated the odds of past-year smoking with interaction terms between minority stressors and coping/social support to test for moderation. Four statistically significant interaction terms were found. Higher versus lower levels (i.e., one-point score increase) of coping buffered the relationship between victimization and past-year smoking; Veteran-specific social support buffered the relationship between interpersonal LGB military stress and past-year smoking; and LGBT-specific social support buffered the relationship between intrapersonal LGB military stress and past-year smoking. However, general social support strengthened the relationship between social exclusion and past-year smoking. Findings provide some evidence for the minority stress model; however, regarding cigarette smoking, coping and social support may mitigate stress in some cases and exacerbate stress in others. LGB Veterans may benefit from learning positive coping skills and leveraging social support linked to LGB and Veteran identities to support smoking cessation.},
}

@article {pmid39789324,
year = {2025},
author = {Du, Z and Pandey, A and Moghadas, SM and Bai, Y and Wang, L and Matrajt, L and Singer, BH and Galvani, AP},
title = {Impact of RSVpreF vaccination on reducing the burden of respiratory syncytial virus in infants and older adults.},
journal = {Nature medicine},
volume = {},
number = {},
pages = {},
pmid = {39789324},
issn = {1546-170X},
abstract = {Respiratory syncytial virus (RSV) causes a substantial health burden among infants and older adults. Prefusion F protein-based vaccines have shown high efficacy against RSV disease in clinical trials, offering promise for mitigating this burden through maternal and older adult immunization. Employing an individual-based model, we evaluated the impact of RSV vaccination on hospitalizations and deaths in 13 high-income countries, assuming that the vaccine does not prevent infection or transmission. Using country-specific vaccine uptake rates for seasonal influenza, we found that vaccination of older adults would prevent hospitalizations by a median of 35-64% across the countries studied here. Vaccination of pregnant women could avert infant hospitalizations by 5-50%. Reductions in RSV-related mortality mirrored those estimated for hospitalizations. While substantial hospitalization costs could be averted, the impact of vaccination depends critically on uptake rates. Enhancing uptake and accessibility is crucial for maximizing the real-world impact of vaccination on reducing RSV burden among vulnerable populations.},
}

@article {pmid39788927,
year = {2025},
author = {Cardle, II and Raman, J and Nguyen, DC and Wang, T and Wu, AY and Sellers, DL and Pichon, TJ and Cheng, EL and Kacherovsky, N and Salipante, SJ and Jensen, MC and Pun, SH},
title = {DNA Aptamer-Polymer Conjugates for Selective Targeting of Integrin α4β1[+] T-Lineage Cancers.},
journal = {ACS applied materials & interfaces},
volume = {},
number = {},
pages = {},
doi = {10.1021/acsami.4c17788},
pmid = {39788927},
issn = {1944-8252},
abstract = {Selective therapeutic targeting of T-cell malignancies is difficult due to the shared lineage between healthy and malignant T cells. Current front-line chemotherapy for these cancers is largely nonspecific, resulting in frequent cases of relapsed/refractory disease. The development of targeting approaches for effectively treating T-cell leukemia and lymphoma thus remains a critical goal for the oncology field. Here, we report the discovery of a DNA aptamer, named HR7A1, that displays low nanomolar affinity for the integrin α4β1 (VLA-4), a marker associated with chemoresistance and relapse in leukemia patients. After truncation of HR7A1 to a minimal binding motif, we demonstrate elevated binding of the aptamer to T-lineage cancer cells over healthy immune cells. Using cryo-EM and competition studies, we find that HR7A1 shares an overlapping binding site on α4β1 with fibronectin and VCAM-1, which has implications for sensitizing blood cancers to chemotherapy. We last characterize barriers to in vivo aptamer translation, including serum stability, temperature-sensitive binding, and short circulation half-life, and synthesize an aptamer-polymer conjugate that addresses these challenges. Future work will seek to validate in vivo targeting of α4β1[+] tumors with the conjugate, establishing an aptamer-based biomaterial that can be readily adapted for targeted treatment of T-cell malignancies.},
}

@article {pmid39787437,
year = {2025},
author = {Yu, EY and Rumble, RB and Agarwal, N and Cheng, HH and Eggener, SE and Bitting, RL and Beltran, H and Giri, VN and Spratt, D and Mahal, B and Lu, K and Crispino, T and Trabulsi, EJ},
title = {Germline and Somatic Genomic Testing for Metastatic Prostate Cancer: ASCO Guideline.},
journal = {Journal of clinical oncology : official journal of the American Society of Clinical Oncology},
volume = {},
number = {},
pages = {JCO2402608},
doi = {10.1200/JCO-24-02608},
pmid = {39787437},
issn = {1527-7755},
abstract = {PURPOSE: To evaluate evidence on germline and somatic genomic testing for patients with metastatic prostate cancer and provide recommendations.

METHODS: A systematic review by a multidisciplinary panel with patient representation was conducted. The PubMed database was searched from January 2018 to May 2024. Articles were selected for inclusion if they reported on patients with metastatic prostate cancer who received a germline or somatic genomic test and/or made comparisons between those tests, reported detection rates, prognostic information, or treatment implications.

RESULTS: A total of 1,713 papers were identified in the literature search. After applying the eligibility criteria, 14 remained: eight systematic reviews and six clinical trials.

RECOMMENDATIONS: Patients with metastatic prostate cancer should undergo both germline and somatic DNA sequencing using panel-based assays. These tests can guide the use of poly(ADP-ribose) polymerase inhibitors, which have a survival benefit in metastatic castration-resistant prostate cancer. In addition, germline testing may have screening implications for additional cancers for patients and cascade testing implications for family members. The data supporting when to perform repeat testing and optimal tissue type to use (eg, primary tumor v metastatic biopsy versus circulating tumor DNA [ctDNA] testing) are more limited, but this panel recommends considering retesting in patients whose results were previously negative or uninformative, and to consider either a metastatic biopsy or ctDNA when a significant change in clinical status occurs. Next-generation genomic sequencing findings that are associated with prognostic only (and not predictive) value should not be used to guide treatment outside of a clinical trial.Additional information is available at www.asco.org/genitourinary-cancer-guidelines.},
}

@article {pmid39787247,
year = {2025},
author = {Welti, J and Bogdan, D and Figueiredo, I and Coleman, I and Jiménez Vacas, J and Liodaki, K and Weigl, F and Buroni, L and Zeng, W and Bernett, I and Bertan, C and Roumeliotis, TI and Bhamra, A and Rekowski, J and Gurel, B and Neeb, AJ and Ning, J and Li, D and Gil, VS and Riisnaes, R and Miranda, S and Crespo, M and Ferreira, A and Tunariu, N and Pasqua, E and Chessum, N and Cheeseman, M and Te Poele, R and Powers, M and Carreira, S and Choudhary, J and Clarke, P and Banerji, U and Swain, A and Jones, K and Yuan, W and Workman, P and Nelson, PS and de Bono, JS and Sharp, A},
title = {NXP800 activates the unfolded protein response, altering AR and E2F function to impact castration-resistant prostate cancer growth.},
journal = {Clinical cancer research : an official journal of the American Association for Cancer Research},
volume = {},
number = {},
pages = {},
doi = {10.1158/1078-0432.CCR-24-2386},
pmid = {39787247},
issn = {1557-3265},
abstract = {PURPOSE: Advanced prostate cancer (PCa) is invariably fatal with the androgen receptor (AR) being a major therapeutic target. AR signaling inhibitors have improved overall survival for men with advanced PCa, but treatment resistance is inevitable and includes reactivation of AR signaling. Novel therapeutic approaches targeting these mechanisms to block tumor growth is an urgent unmet clinical need. One attractive strategy is to target heat shock proteins critical to AR functional activity.

EXPERIMENTAL DESIGN: We first did transcriptome analysis on multiple castration-resistant PCa (CRPC) cohorts to correlate the association between the GO Cellular Response to Heat gene expression signature and overall survival. Next, we analyzed the impact of targeting the heat shock factor 1 (HSF1) pathway, with an inhibitor in clinical development, namely NXP800, in models of treatment-resistant PCa. Finally, we confirmed our mechanistic and phenotypic findings using an NXP800-resistant model and an in-vivo model of CRPC.

RESULTS: We report that in multiple CRPC transcriptome cohorts the GO Cellular Response to Heat gene expression signature associates with AR signaling and worse clinical outcome. We demonstrate the effects of targeting the HSF1 pathway, central to cellular stress, with an inhibitor in clinical development, namely NXP800 (formerly CCT361814), in PCa. Targeting the HSF1 pathway with the inhibitor NXP800 decreases HSP72 expression, activates the unfolded protein response, and inhibits AR- and E2F-mediated activity, inhibiting the growth of treatment-resistant PCa models.

CONCLUSIONS: Overall, NXP800 has anti-tumor activity against treatment-resistant PCa models, including molecular subtypes with limited treatment options, supporting its consideration for PCa-specific clinical development.},
}

@article {pmid39786434,
year = {2024},
author = {Lee, SJ and Zeiser, R},
title = {FDA-approved therapies for chronic GVHD.},
journal = {Blood},
volume = {},
number = {},
pages = {},
doi = {10.1182/blood.2024026633},
pmid = {39786434},
issn = {1528-0020},
abstract = {Despite novel prophylactic regimens, chronic graft-versus-host disease (cGVHD) remains a challenging complication after allogeneic hematopoietic cell transplantation. Chronic GVHD can affect multiple organs and reduces quality of life, and treatment can cause serious side effects. In the last ten years, the drugs ibrutinib, ruxolitinib, belumosudil and axatilimab were FDA-approved for cGVHD. Here we discuss which signaling pathways and cell types are targeted, the clinical studies that were the basis for FDA-approval, and future directions for clinical research.},
}

@article {pmid39763564,
year = {2024},
author = {Huang, YJ and Kurniansyah, N and Goodman, MO and Spitzer, BW and Wang, J and Stilp, A and Laurie, C and de Vries, PS and Chen, H and Min, YI and Sims, M and Peloso, GM and Guo, X and Bis, JC and Brody, JA and Raffield, LM and Smith, JA and Zhao, W and Rotter, JI and Rich, SS and Redline, S and Fornage, M and Kaplan, R and Franceschini, N and Levy, D and Morrison, AC and Boerwinkle, E and Smith, NL and Kooperberg, C and Psaty, BM and Zöllner, S and , and Sofer, T},
title = {The expected polygenic risk score (ePRS) framework: an equitable metric for quantifying polygenetic risk via modeling of ancestral makeup.},
journal = {medRxiv : the preprint server for health sciences},
volume = {},
number = {},
pages = {},
pmid = {39763564},
support = {R56 HG013163/HG/NHGRI NIH HHS/United States ; OT2 OD026556/OD/NIH HHS/United States ; R01 HL139553/HL/NHLBI NIH HHS/United States ; U2C OD023196/OD/NIH HHS/United States ; OT2 OD025315/OD/NIH HHS/United States ; OT2 OD026551/OD/NIH HHS/United States ; U24 OD023121/OD/NIH HHS/United States ; OT2 OD026549/OD/NIH HHS/United States ; OT2 OD025337/OD/NIH HHS/United States ; OT2 OD025277/OD/NIH HHS/United States ; OT2 OD026555/OD/NIH HHS/United States ; OT2 OD026550/OD/NIH HHS/United States ; OT2 OD026553/OD/NIH HHS/United States ; OT2 OD023205/OD/NIH HHS/United States ; OT2 OD025276/OD/NIH HHS/United States ; OT2 OD026557/OD/NIH HHS/United States ; OT2 OD026554/OD/NIH HHS/United States ; U24 OD023163/OD/NIH HHS/United States ; R01 HG011031/HG/NHGRI NIH HHS/United States ; OT2 OD023206/OD/NIH HHS/United States ; R01 HL154385/HL/NHLBI NIH HHS/United States ; U24 OD023176/OD/NIH HHS/United States ; OT2 OD026548/OD/NIH HHS/United States ; OT2 OD026552/OD/NIH HHS/United States ; R01 HL161012/HL/NHLBI NIH HHS/United States ; R01 HL142711/HL/NHLBI NIH HHS/United States ; R01 AG080598/AG/NIA NIH HHS/United States ; },
abstract = {Polygenic risk scores (PRSs) depend on genetic ancestry due to differences in allele frequencies between ancestral populations. This leads to implementation challenges in diverse populations. We propose a framework to calibrate PRS based on ancestral makeup. We define a metric called "expected PRS" (ePRS), the expected value of a PRS based on one's global or local admixture patterns. We further define the "residual PRS" (rPRS), measuring the deviation of the PRS from the ePRS. Simulation studies confirm that it suffices to adjust for ePRS to obtain nearly unbiased estimates of the PRS-outcome association without further adjusting for PCs. Using the TOPMed dataset, the estimated effect size of the rPRS adjusting for the ePRS is similar to the estimated effect of the PRS adjusting for genetic PCs. Similarly, we applied the ePRS framework to six cardiovascular-related traits in the All of Us dataset, and the results are consistent with those from the TOPMed analysis. The ePRS framework can protect from population stratification in association analysis and provide an equitable strategy to quantify genetic risk across diverse populations.},
}

@article {pmid39763516,
year = {2024},
author = {Mazziotta, F and Martin, LE and Eagan, DN and Bar, M and Kinsella, S and Paulson, KG and Voillet, V and Lahman, MC and Hunter, D and Schmitt, TM and Duerkopp, N and Yeung, C and Tang, TH and Gottardo, R and Asano, Y and Wilcox, EC and Lee, B and Zhang, T and Lopedote, P and Penter, L and Wu, CJ and Milano, F and Greenberg, PD and Chapuis, AG},
title = {Acute Myeloid Leukemia Skews Therapeutic WT1-specific CD8 TCR-T Cells Towards an NK-like Phenotype that Compromises Function and Persistence.},
journal = {medRxiv : the preprint server for health sciences},
volume = {},
number = {},
pages = {},
pmid = {39763516},
support = {K08 CA169485/CA/NCI NIH HHS/United States ; P01 CA018029/CA/NCI NIH HHS/United States ; T32 CA080416/CA/NCI NIH HHS/United States ; },
abstract = {Acute myeloid leukemia (AML) that is relapsed and/or refractory post-allogeneic hematopoietic cell transplantation (HCT) is usually fatal. In a prior study, we demonstrated that AML relapse in high-risk patients was prevented by post-HCT immunotherapy with Epstein-Barr virus (EBV)-specific donor CD8[+] T cells engineered to express a high-affinity Wilms Tumor Antigen 1 (WT1)-specific T-cell receptor (TTCR-C4). However, in the present study, infusion of EBV- or Cytomegalovirus (CMV)-specific TTCR-C4 did not clearly improve outcomes in fifteen patients with active disease post-HCT. TCRC4-transduced EBV-specific T cells persisted longer post-transfer than CMV-specific T cells. Persisting TTCR-C4 skewed towards dysfunctional natural killer-like terminal differentiation, distinct from the dominant exhaustion programs reported for T-cell therapies targeting solid tumors. In one patient with active AML post-HCT, a sustained TTCR-C4 effector-memory profile correlated with long-term TTCR-C4 persistence and disease control. These findings reveal complex mechanisms underlying AML-induced T-cell dysfunction, informing future therapeutic strategies for addressing post-HCT relapse.},
}

@article {pmid39786405,
year = {2024},
author = {Reiner, AS and Watt, GP and Malone, KE and Lynch, CF and John, EM and Knight, JA and Woods, M and Liang, X and Tischkowitz, M and Conti, DV and Robson, ME and Mellemkjær, L and Teraoka, SN and Concannon, P and Bernstein, JL},
title = {Breast Cancer Susceptibility Gene Sequence Variations and Development of Contralateral Breast Cancer.},
journal = {JAMA network open},
volume = {7},
number = {12},
pages = {e2452158},
doi = {10.1001/jamanetworkopen.2024.52158},
pmid = {39786405},
issn = {2574-3805},
mesh = {Humans ; Female ; *Genetic Predisposition to Disease ; Case-Control Studies ; Middle Aged ; Adult ; *Breast Neoplasms/genetics/epidemiology ; Receptors, Estrogen/genetics ; Checkpoint Kinase 2/genetics ; BRCA2 Protein/genetics ; Ataxia Telangiectasia Mutated Proteins/genetics ; Germ-Line Mutation/genetics ; BRCA1 Protein/genetics ; },
abstract = {IMPORTANCE: Heterogeneity in development of estrogen receptor (ER)-specific first primary breast cancer exists due to deleterious germline variants in moderate- to high-penetrance breast cancer susceptibility genes, but it is unknown if these associations occur in ER-specific CBC.

OBJECTIVE: To determine the association of deleterious germline variants in breast cancer susceptibility genes with ER-specific CBC development and whether ER status of the first primary breast cancer modifies these associations.

This case-control study included CBC cases and matched unilateral breast cancer controls from The Women's Environment, Cancer, and Radiation Epidemiology (WECARE) Study, a population-based case-control study. Eligible women were diagnosed between 1985 and 2000 with data and biospecimens collected from 2001 to 2004. Eligible participants were women younger than 55 years at first invasive breast cancer diagnosis. Participants were matched on age, diagnosis year, cancer registry region, and race and ethnicity, and countermatched on radiation treatment. For cases, CBC occurred 1 year or more following first breast cancer diagnosis. Analyses were performed from May to October 2024.

EXPOSURES: CHEK2 1100delC and deleterious variants in ATM, BRCA1, and BRCA2.

MAIN OUTCOME AND MEASURE: Development of CBC, measured as a rate ratio (RR).

RESULTS: A total of 1290 women were included in analysis (median [IQR] age at first diagnosis, 47 [42-51] years). The ER-positive CBC rate for women with deleterious ATM variants was 4 times higher than for women without deleterious ATM variants (RR, 4.84; 95% CI, 1.11-21.08; P = .04); no women with ER-negative CBC carried deleterious ATM variants. The ER-positive CBC rates for women with deleterious variants in BRCA2 or CHEK2 1100delC were 5 to 6 times higher than for women without deleterious variants in BRCA2 or CHEK2 1100delC, respectively (BRCA2: RR, 5.88; 95% CI, 2.61-13.26, P < .001; CHEK2 1100delC: RR, 6.06; 95% CI, 1.26-29.04; P = .02). The ER-negative CBC rate for women with deleterious BRCA1 variants was 26 times higher than for women without deleterious BRCA1 variants (RR, 26.16; 95% CI, 8.01-85.44; P < .001). First primary breast cancer ER status did not modify associations between deleterious variants and ER-specific CBC development.

CONCLUSIONS AND RELEVANCE: In this case-control study of CBC, deleterious variants in breast cancer susceptibility genes were differentially associated with ER-specific CBC development. Germline variation profile may inform estimates of outcomes for ER-specific CBC subtypes.},
}

Humans
Female
*Genetic Predisposition to Disease
Case-Control Studies
Middle Aged
Adult
*Breast Neoplasms/genetics/epidemiology
Receptors, Estrogen/genetics
Checkpoint Kinase 2/genetics
BRCA2 Protein/genetics
Ataxia Telangiectasia Mutated Proteins/genetics
Germ-Line Mutation/genetics
BRCA1 Protein/genetics

@article {pmid39786387,
year = {2024},
author = {Mina, A and McGraw, KL and Cunningham, L and Kim, N and Jen, EY and Calvo, KR and Ehrlich, LA and Aplan, PD and Garcia-Manero, G and Foran, JM and Garcia, JS and Zeidan, AM and DeZern, AE and Komrokji, RS and Sekeres, MA and Scott, BL and Buckstein, RJ and Tinsley-Vance, S and Verma, A and Wroblewski, T and Pavletic, SZ and Norsworthy, KJ},
title = {Advancing Drug Development in Myelodysplastic Syndromes.},
journal = {Blood advances},
volume = {},
number = {},
pages = {},
doi = {10.1182/bloodadvances.2024014865},
pmid = {39786387},
issn = {2473-9537},
abstract = {Myelodysplastic syndromes/neoplasms (MDS) are heterogeneous stem cell malignancies characterized by poor prognosis and no curative therapies outside of allogeneic hematopoietic stem cell transplantation. Despite some recent approvals by the United States Food and Drug Administration (FDA), (e.g., luspatercept, ivosidenib, decitabine/cedazuridine and imetelstat), there has been little progress in the development of truly transformative therapies for the treatment of patients with MDS. Challenges to advancing drug development in MDS are multifold but may be grouped into specific categories including criteria for risk stratification and eligibility, response definitions, time-to-event endpoints, transfusion endpoints, functional assessments, and biomarker development. Strategies to address these challenges and optimize future clinical trial design for patients with MDS are presented here.},
}

@article {pmid39783874,
year = {2024},
author = {Palacios, N and Gordon, S and Wang, T and Huttenhower, C and Gonzalez, HM and Knight, R and Decarli, C and Daviglus, ML and Lamar, M and Tarraf, W and Cai, J and Burk, R and Qi, Q and Kaplan, RC},
title = {Biomarkers.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {20 Suppl 2},
number = {},
pages = {e092828},
doi = {10.1002/alz.092828},
pmid = {39783874},
issn = {1552-5279},
mesh = {Humans ; Female ; Male ; *Gastrointestinal Microbiome/physiology ; Aged ; Cross-Sectional Studies ; *Biomarkers/blood ; Feces/microbiology ; Cognition/physiology ; Middle Aged ; Alzheimer Disease/genetics/microbiology ; Hispanic or Latino ; Metagenome ; Cohort Studies ; White ; },
abstract = {BACKGROUND: Few large microbiome studies on Alzheimer's Disease and Related Dementia (AD/ADRD) have been conducted, especially among US Latinos. We conducted a study within the Study of Latinos- Investigation of Neurocognitive Aging (SOL-INCA) cohort to examine the role of the gut microbiota in cognitive function.

METHODS: We analyzed the fecal metagenomes of 2,470 SOL-INCA participants to, cross-sectionally, identify microbial taxonomic and functional features associated with cognitive function. Global cognition was defined as an aggregate score based on a cognitive battery (executive function, working memory, among others). Omnibus (PERMANOVA) and feature-wise analyses (MaAsLin2) were conducted to identify microbiome-cognition associations, and specific microbial species and pathways (Kyoto Encyclopedia of Genes and Genomes (KEGG modules) associated with cognition. We assessed the accuracy of a Random Forest classifier to distinguish SOL participants with the best (>=1SD above mean) vs. the worst (>=1SD below mean) cognition. We also tested the association of identified taxa and KEGG modules with concurrently collected serum metabolites.

RESULT: We identified several taxa and pathways significantly associated with cognitive function in SOL. B. longum was the taxa most strongly associated with worse cognition, whereas Eubacterium species (E. siraeum and E.eligens), were associated with better cognition. Several KEGG modules, most strongly Ornithine and Serine biosynthesis, were associated with worse cognition. A microbiome species-based Random Forest classifier had moderate accuracy (AUC = 0.62) to discriminate between high (1SD or more above mean) vs low (1SD or more below mean) cognition.

CONCLUSION: In a large Latino cohort, we identified several microbial taxa and KEGG pathways associated with cognition, further implicating the microbiome in AD/ADRD risk.},
}

Humans
Female
Male
*Gastrointestinal Microbiome/physiology
Aged
Cross-Sectional Studies
*Biomarkers/blood
Feces/microbiology
Cognition/physiology
Middle Aged
Alzheimer Disease/genetics/microbiology
Hispanic or Latino
Metagenome
Cohort Studies
White

@article {pmid39780444,
year = {2025},
author = {Zainal, NH and Benjet, C and Albor, Y and Nuñez-Delgado, M and Zambrano-Cruz, R and Contreras-Ibáñez, CC and Cudris-Torres, L and de la Peña, FR and González, N and Guerrero-López, JB and Gutierrez-Garcia, RA and Jiménez-Peréz, AL and Medina-Mora, ME and Patiño, P and Cuijpers, P and Gildea, SM and Kazdin, AE and Kennedy, CJ and Luedtke, A and Sampson, NA and Petukhova, MV and Zubizarreta, JR and Kessler, RC},
title = {Statistical methods to adjust for the effects on intervention compliance in randomized clinical trials where precision treatment rules are being developed.},
journal = {International journal of methods in psychiatric research},
volume = {34},
number = {1},
pages = {e70005},
doi = {10.1002/mpr.70005},
pmid = {39780444},
issn = {1557-0657},
support = {R01MH120648/MH/NIMH NIH HHS/United States ; R01MH120648/TW/FIC NIH HHS/United States ; },
mesh = {Humans ; *Cognitive Behavioral Therapy/methods ; Female ; Male ; Adult ; Young Adult ; Patient Compliance/statistics & numerical data ; Outcome Assessment, Health Care/standards ; Randomized Controlled Trials as Topic ; Data Interpretation, Statistical ; Anxiety Disorders/therapy ; },
abstract = {BACKGROUND: Heterogeneity of treatment effects (HTEs) can occur because of either differential treatment compliance or differential treatment effectiveness. This distinction is important, as it has action implications, but it is unclear how to distinguish these two possibilities statistically in precision treatment analysis given that compliance is not observed until after randomization. We review available statistical methods and illustrate a recommended method in secondary analysis in a trial focused on HTE.

METHODS: The trial randomized n = 880 anxious and/or depressed university students to guided internet-delivered cognitive behavioral therapy (i-CBT) or treatment-as-usual (TAU) and evaluated joint remission. Previously reported analyses documented superiority of i-CBT but significant HTE. In the reanalysis reported here, we used baseline (i.e., pre-randomization) covariates to predict compliance among participants randomized to guided i-CBT, generated a cross-validated within-person expected compliance score based on this model in both intervention groups, and then used this expected composite score as a predictor in an expanded HTE analysis.

RESULTS: The significant intervention effect was limited to participants with high expected compliance. Residual HTE was nonsignificant.

CONCLUSIONS: Future psychotherapy HTE trials should routinely develop and include expected compliance composite scores to distinguish the effects of differential treatment compliance from the effects of differential treatment effectiveness.},
}

Humans
*Cognitive Behavioral Therapy/methods
Female
Male
Adult
Young Adult
Patient Compliance/statistics & numerical data
Outcome Assessment, Health Care/standards
Randomized Controlled Trials as Topic
Data Interpretation, Statistical
Anxiety Disorders/therapy

@article {pmid39779669,
year = {2025},
author = {Papier, K and Bradbury, KE and Balkwill, A and Barnes, I and Smith-Byrne, K and Gunter, MJ and Berndt, SI and Le Marchand, L and Wu, AH and Peters, U and Beral, V and Key, TJ and Reeves, GK},
title = {Diet-wide analyses for risk of colorectal cancer: prospective study of 12,251 incident cases among 542,778 women in the UK.},
journal = {Nature communications},
volume = {16},
number = {1},
pages = {375},
pmid = {39779669},
issn = {2041-1723},
support = {C570/A16491 and A29186//Cancer Research UK (CRUK)/ ; },
mesh = {Humans ; Female ; *Colorectal Neoplasms/epidemiology/genetics ; United Kingdom/epidemiology ; Prospective Studies ; Middle Aged ; *Diet ; Risk Factors ; Adult ; Dairy Products ; Aged ; Incidence ; Alcohol Drinking/epidemiology/adverse effects ; Calcium, Dietary/administration & dosage ; },
abstract = {Uncertainty remains regarding the role of diet in colorectal cancer development. We examined associations of 97 dietary factors with colorectal cancer risk in 542,778 Million Women Study participants (12,251 incident cases over 16.6 years), and conducted a targeted genetic analysis in the ColoRectal Transdisciplinary Study, Colon Cancer Family Registry, and Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO). Alcohol (relative risk per 20 g/day=1.15, 95% confidence interval 1.09-1.20) and calcium (per 300 mg/day=0.83, 0.77-0.89) intakes had the strongest associations, followed by six dairy-related factors associated with calcium. We showed a positive association with red and processed meat intake and weaker inverse associations with breakfast cereal, fruit, wholegrains, carbohydrates, fibre, total sugars, folate, and vitamin C. Genetically predicted milk consumption was inversely associated with risk of colorectal, colon, and rectal cancers. We conclude that dairy products help protect against colorectal cancer, and that this is driven largely or wholly by calcium.},
}

Humans
Female
*Colorectal Neoplasms/epidemiology/genetics
United Kingdom/epidemiology
Prospective Studies
Middle Aged
*Diet
Risk Factors
Adult
Dairy Products
Aged
Incidence
Alcohol Drinking/epidemiology/adverse effects
Calcium, Dietary/administration & dosage

@article {pmid39778191,
year = {2025},
author = {Marks, DI and Cassaday, RD and Ribera, JM and Schuh, AC and Park, JH and Chiaretti, S and Stelljes, M},
title = {Characterizing the ideal patient for treatment with inotuzumab ozogamicin for relapsed/refractory acute lymphoblastic leukemia: a systematic literature review.},
journal = {Expert review of hematology},
volume = {},
number = {},
pages = {},
doi = {10.1080/17474086.2025.2450223},
pmid = {39778191},
issn = {1747-4094},
abstract = {INTRODUCTION: Inotuzumab ozogamicin(InO) is indicated for the treatment of adults with relapsed or refractory(R/R) acute lymphoblastic leukemia (ALL). This systematic literature review (CRD42022330496) assessed outcomes bybaseline characteristics for patients with R/R ALL treated with InO to identifywhich patients may benefit most.

METHODS: In adherencewith PRISMA guidelines, searches were run in Embase and MEDLINE. Inclusioncriteria were real-world evidence, observational studies, and phase 2-4 trials.The Cochrane Risk of Bias tool and Newcastle-Ottawa instrument assessedquality.

RESULTS: 34 publicationswere included; 11 described the phase 3 INO-VATE trial. Patients treated withInO who were CD22-positive, in first salvage, and eligible for subsequent hematopoieticstem cell transplant (HSCT) had improved outcomes. Reduced incidence ofveno-occlusive disease was observed in patients with normal transaminase levels and bilirubin, no priorliver disease, and who did not receive dual alkylators.

CONCLUSIONS: The idealpatient for InO treatment has CD22-positive disease (≥20% leukemic blasts), normal liverfunction, no history of liver disease, is in first salvage, hasnot previously received HSCT, prefers outpatient treatment, or has high diseaseburden. Limitations included potentially missing publications that werenon-English, not identified in the searches, or available after the date thesearches were conducted.

REGISTRATION: This systematic review was registered on theProspective Register of Systematic Reviews (PROSPERO), registration number:CRD42022330496.},
}

@article {pmid39778123,
year = {2025},
author = {Rotz, SJ and Stratton, K and Leisenring, WM and Smith, SA and Howell, RM and Bates, JE and Pappo, AS and Neglia, JP and Armstrong, GT and Turcotte, LM},
title = {Melanoma Among Adult Survivors of Childhood Cancer: 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 = {JCO2401519},
doi = {10.1200/JCO-24-01519},
pmid = {39778123},
issn = {1527-7755},
abstract = {PURPOSE: Melanoma as a subsequent malignant neoplasm has been described among childhood cancer survivors; however, the risk factors and long-term survival are not well understood.

METHODS: We assessed incidence, risk factors, and outcomes for melanoma among participants in the Childhood Cancer Survivor Study cohort. Cumulative incidence and standardized incidence ratios (SIRs) were calculated, and multivariable Cox models were used to determine hazard ratios (HRs) and associated 95% CI for melanoma risk factors. Radiation exposure to seven body regions and melanoma status for each of eight regions per survivor were integrated into the Cox model.

RESULTS: Among 25,716 participants, 177 melanomas developed in 160 survivors (110 invasive, 62 in situ cutaneous, five ocular). The 40-year melanoma cumulative incidence was 1.1% (95% CI, 0.9 to 1.4) for all participants and 1.5% (95% CI, 1.0 to 2.1) among those receiving a cumulative radiation dose of ≥40 Gy. Compared with the general population, the SIR for invasive skin or ocular melanoma was 2.0 (95% CI, 1.6 to 2.4). A cumulative radiation dose of ≥40 Gy to the corresponding body region(s) of the melanoma (HR, 2.0 [95% CI, 1.1 to 3.7]), a cumulative cyclophosphamide equivalent dose of ≥20,000 mg/m[2] (HR, 1.9 [95% CI, 1.1 to 3.6]), and bleomycin exposure (HR, 2.2 [95% CI, 1.2 to 4.1]) were associated with increased cutaneous melanoma. Invasive melanoma at any site was associated with an increased risk of death (HR, 2.4 [95% CI, 1.7 to 3.3]).

CONCLUSION: Childhood cancer survivors have more than a two-fold increased risk of melanoma compared with the general population, and those with an invasive melanoma have more than a two-fold risk of death. High-dose radiation and alkylating agent exposure, and bleomycin are important risk factors for melanoma and should be considered in future patient guidance and screening.},
}

@article {pmid39777681,
year = {2025},
author = {Hall, MS and Harris, HR and As-Sanie, S and Upson, K},
title = {Early-Life Exposures and Odds of Adenomyosis: A Population-Based Case-Control Study.},
journal = {Paediatric and perinatal epidemiology},
volume = {},
number = {},
pages = {},
doi = {10.1111/ppe.13165},
pmid = {39777681},
issn = {1365-3016},
support = {R01HD040398//Eunice Kennedy Shriver National Institute of Child Health and Human Development/ ; R00NR017191/NR/NINR NIH HHS/United States ; /NH/NIH HHS/United States ; },
abstract = {BACKGROUND: Adenomyosis can confer life-altering symptoms such as pelvic pain. Yet, the epidemiologic study of this uterine condition lags other gynaecologic conditions. This includes the investigation of intrauterine exposures that could disrupt foetal development and contribute to the presence of adenomyosis in adulthood.

OBJECTIVE: We investigated nine early-life factors and the odds of adenomyosis using data from a population-based case-control study of enrollees of an integrated healthcare system in Washington State ages 18-59.

METHODS: Cases (n = 386) had incident, pathology-confirmed adenomyosis diagnosed between 2001 and 2006. Two control groups were employed: hysterectomy controls (n = 233) and randomly selected age-matched enrollees with an intact uterus ('population controls', n = 323). The primary study activity was a structured in-person interview; participants were also mailed a family history questionnaire that included questions on early-life factors. We conducted logistic regression to estimate adjusted odds ratios (aOR) and 95% confidence intervals (CI) for the associations between early-life factors and adenomyosis.

RESULTS: Comparing cases to population controls, our data suggested an 80% increased odds of adenomyosis with younger maternal age at participant's birth (≤ 19 vs. ages 25-29) (aOR 1.81, 95% CI 0.94, 3.50) and a 50% increased odds of adenomyosis for participants who were the fourth or later live birth (vs. firstborn) (aOR 1.51, 95% CI 0.88, 2.59). Among never-smoking participants, our data suggested a 50% increased odds of adenomyosis with intrauterine exposure to cigarette smoking (aOR 1.50, 95% CI 0.92, 2.46). In analyses using hysterectomy controls, these associations were attenuated.

CONCLUSIONS: These data suggested that several intrauterine exposures were associated with increased odds of adenomyosis in adulthood. The intrauterine period may be a susceptible window for subsequent development of adenomyosis and warrants further investigation.},
}

@article {pmid39777474,
year = {2025},
author = {Tau, S and Chamberlin, MD and Yang, H and Marotti, JD and Muskus, PC and Roberts, AM and Carmichael, MM and Cressey, L and Dragnev, CPC and Demidenko, E and Hampsch, RA and Soucy, SM and Kolling, FW and Samkoe, KS and Alvarez, JV and Kettenbach, AN and Miller, TW},
title = {Oxidative Phosphorylation is a Metabolic Vulnerability of Endocrine Therapy-Tolerant Persister Cells in ER+ Breast Cancer.},
journal = {Cancer research},
volume = {},
number = {},
pages = {},
doi = {10.1158/0008-5472.CAN-24-1204},
pmid = {39777474},
issn = {1538-7445},
abstract = {Despite adjuvant treatment with endocrine therapies, estrogen receptor-positive (ER+) breast cancers recur in a significant proportion of patients. Recurrences are attributable to clinically undetectable endocrine-tolerant persister cancer cells that retain tumor-forming potential. Therefore, strategies targeting such persister cells may prevent recurrent disease. Using CRISPR-Cas9 genome-wide knockout screening in ER+ breast cancer cells, we identified a survival mechanism involving metabolic reprogramming with reliance upon mitochondrial respiration in endocrine-tolerant persister cells. Quantitative proteomic profiling showed reduced levels of glycolytic proteins in persisters. Metabolic tracing of glucose revealed an energy-depleted state in persisters where oxidative phosphorylation was required to generate ATP. A phase II clinical trial was conducted to evaluate changes in mitochondrial markers in primary ER+/HER2- breast tumors induced by neoadjuvant endocrine therapy (NCT04568616). In an analysis of tumor specimens from 32 patients, tumors exhibiting residual cell proliferation after aromatase inhibitor-induced estrogen deprivation with letrozole showed increased mitochondrial content. Genetic profiling and barcode lineage tracing showed that endocrine-tolerant persistence occurred stochastically without genetic predisposition. Pharmacological inhibition of mitochondrial complex I suppressed the tumor-forming potential of persisters in mice and synergized with the anti-estrogen fulvestrant to induce regression of patient-derived xenografts. These findings indicate that mitochondrial metabolism is essential in endocrine-tolerant persister ER+ breast cancer cells and warrant the development of treatment strategies to leverage this vulnerability for treating breast cancer.},
}

@article {pmid39777359,
year = {2024},
author = {Suraci, CM and Morrison, ML and Roth, MB},
title = {Oxygen is toxic in the cold in C. elegans.},
journal = {Frontiers in physiology},
volume = {15},
number = {},
pages = {1471249},
doi = {10.3389/fphys.2024.1471249},
pmid = {39777359},
issn = {1664-042X},
abstract = {INTRODUCTION: Temperature and oxygen are two factors that profoundly affect survival limits of animals; too much or too little of either is lethal. However, humans and other animals can exhibit exceptional survival when oxygen and temperature are simultaneously low. This research investigates the role of oxygen in the cold shock death of Caenorhabditis elegans.

METHODS: The survival of C. elegans populations in combinations of oxygen concentrations and was assayed. Additionally, the effect of cold acclimatization, mutations in the cold acclimatization pathway, compounds, and antioxidant proteins on survival in low temperatures and high oxygen were investigated.

RESULTS: We demonstrate that C. elegans have increased survival in 2°C when deprived of oxygen, and an increase to just 0.25 kPa of oxygen decreased survival. Additionally, we show that oxygen toxicity produced by a 35-fold increase above atmospheric oxygen levels was fatal for nematodes in 8 h at room temperature and 2 h at 2°C. We found that cold acclimatization and mutations in the cold acclimatization pathway improve survival in room temperature oxygen toxicity. Furthermore, we found that the compounds glucose, manganese (II), and ascorbate improve both cold shock and high oxygen survival, while the antioxidant proteins catalase and peroxiredoxin are essential to wild type survival in these conditions.

DISCUSSION: Our results suggest that oxygen toxicity contributes to the death of C. elegans during cold shock. The changes in survival induced by cold acclimatization and mutations in the cold acclimatization pathway suggest that oxygen toxicity in the cold exerts evolutionary pressure, leading to the development of protections against it. Additionally, the resistance provided by diverse compounds and antioxidant proteins in both low temperature and high oxygen suggests these conditions have similar chemical environments. We discuss evidence that similar phenomena may function in humans.},
}

@article {pmid39776913,
year = {2024},
author = {Chen, XT and Leisegang, M and Gavvovidis, I and Pollack, SM and Lorenz, FKM and Schumacher, TN and Daumke, O and Blankenstein, T},
title = {Generation of effective and specific human TCRs against tumor/testis antigen NY-ESO-1 in mice with humanized T cell recognition system.},
journal = {Frontiers in immunology},
volume = {15},
number = {},
pages = {1524629},
doi = {10.3389/fimmu.2024.1524629},
pmid = {39776913},
issn = {1664-3224},
mesh = {Animals ; Humans ; *Antigens, Neoplasm/immunology ; Mice ; *Receptors, Antigen, T-Cell/immunology/genetics ; *Mice, Transgenic ; *Membrane Proteins/immunology/genetics ; HLA-A2 Antigen/immunology ; Immunotherapy, Adoptive/methods ; T-Lymphocytes/immunology/metabolism ; Male ; Cell Line, Tumor ; },
abstract = {Generation of high avidity T cell receptors (TCRs) reactive to tumor-associated antigens (TAA) is impaired by tolerance mechanisms, which is an obstacle to effective T cell therapies for cancer treatment. NY-ESO-1, a human cancer-testis antigen, represents an attractive target for such therapies due to its broad expression in different cancer types and the restricted expression in normal tissues. Utilizing transgenic mice with a diverse human TCR repertoire, we isolated effective TCRs against NY-ESO-1157-165 restricted to HLA-A*02:01. We compared the functions of the murine-derived TCR with human-derived TCRs and an affinity matured TCR, using in vitro co-culture and in vivo adoptive T cell transfer in tumor-bearing mice. Alanine scan, x-scan, LCL assay were employed to address the cross-reactivity of the NY-ESO-1157-165 specific TCRs. We also used human tissue cDNA library and human primary cells to assess the safety of adoptive T cell therapies targeting NY-ESO-1 antigen in the clinic. One of the murine-derived human TCRs, TCR-ESO, exhibited higher functional avidity compared to human-derived NY-ESO-1157-165 specific TCRs. TCR-ESO appeared to have similar efficiency in antigen recognition as an in vitro affinity-matured TCR, TCR 1G4-α95LY, which was applied in clinical trials. TCR-ESO showed little cross-reactivity, in contrast to TCR 1G4-α95LY. Our data indicate that highly effective TCRs against NY-ESO-1 are likely deleted in humans due to tolerance mechanisms, and that the TCR gene loci transgenic mice represent a reliable source to isolate effective and highly-specific TCRs for adoptive T cell therapies.},
}

Animals
Humans
*Antigens, Neoplasm/immunology
Mice
*Receptors, Antigen, T-Cell/immunology/genetics
*Mice, Transgenic
*Membrane Proteins/immunology/genetics
HLA-A2 Antigen/immunology
Immunotherapy, Adoptive/methods
T-Lymphocytes/immunology/metabolism
Male
Cell Line, Tumor

@article {pmid39775835,
year = {2025},
author = {Wooldridge, TB and Ford, SM and Conwell, HC and Hyde, J and Harris, K and Shapiro, B},
title = {Direct Measurement of the Mutation Rate and Its Evolutionary Consequences in a Critically Endangered Mollusk.},
journal = {Molecular biology and evolution},
volume = {42},
number = {1},
pages = {},
doi = {10.1093/molbev/msae266},
pmid = {39775835},
issn = {1537-1719},
support = {2307479//National Science Foundation Ocean Science Department (NSF-OCE/ ; },
mesh = {Animals ; *Mutation Rate ; *Endangered Species ; *Gastropoda/genetics ; Biological Evolution ; Evolution, Molecular ; Germ-Line Mutation ; Mollusca/genetics ; Population Density ; },
abstract = {The rate at which mutations arise is a fundamental parameter of biology. Despite progress in measuring germline mutation rates across diverse taxa, such estimates are missing for much of Earth's biodiversity. Here, we present the first estimate of a germline mutation rate from the phylum Mollusca. We sequenced three pedigreed families of the white abalone Haliotis sorenseni, a long-lived, large-bodied, and critically endangered mollusk, and estimated a de novo mutation rate of 8.60 × 10-9 single nucleotide mutations per site per generation. This mutation rate is similar to rates measured in vertebrates with comparable generation times and longevity to abalone, and higher than mutation rates measured in faster-reproducing invertebrates. The spectrum of de novo mutations is also similar to that seen in vertebrate species, although an excess of rare C > A polymorphisms in wild individuals suggests that a modifier allele or environmental exposure may have once increased C > A mutation rates. We use our rate to infer baseline effective population sizes (Ne) across multiple Pacific abalone and find that abalone persisted over most of their evolutionary history as large and stable populations, in contrast to extreme fluctuations over recent history and small census sizes in the present day. We then use our mutation rate to infer the timing and pattern of evolution of the abalone genus Haliotis, which was previously unknown due to few fossil calibrations. Our findings are an important step toward understanding mutation rate evolution and they establish a key parameter for conservation and evolutionary genomics research in mollusks.},
}

Animals
*Mutation Rate
*Endangered Species
*Gastropoda/genetics
Biological Evolution
Evolution, Molecular
Germ-Line Mutation
Mollusca/genetics
Population Density

@article {pmid39775763,
year = {2025},
author = {Levis, MJ and Hamadani, M and Logan, BR and Jones, RJ and Singh, AK and Litzow, MR and Wingard, JR and Papadopoulos, EB and Perl, AE and Soiffer, RJ and Ustun, C and Ueda Oshima, M and Uy, GL and Waller, EK and Vasu, S and Solh, MM and Mishra, A and Muffly, L and Kim, HJ and Stelljes, M and Najima, Y and Onozawa, M and Thomson, KJ and Nagler, A and Wei, AH and Marcucci, G and Chen, C and Hasabou, N and Rosales, M and Hill, JE and Gill, SC and Nuthethi, R and King, D and Mendizabal, AM and Devine, SM and Horowitz, MM and Chen, YB},
title = {Measurable residual disease and posttransplantation gilteritinib maintenance for patients with FLT3-ITD-mutated AML.},
journal = {Blood},
volume = {},
number = {},
pages = {},
doi = {10.1182/blood.2024025154},
pmid = {39775763},
issn = {1528-0020},
abstract = {BMT CTN 1506 ("MORPHO"; NCT02997202) was a randomized phase 3 study of gilteritinib compared to placebo as maintenance therapy after hematopoietic stem cell transplantation (HCT) for patients with FLT3-ITD-mutated acute myeloid leukemia (AML). A key secondary endpoint was to determine the impact on survival of pre- and/or post-HCT measurable residual disease (MRD), as determined using a highly sensitive assay for FLT3-ITD mutations. Generally, gilteritinib maintenance therapy was associated with improved relapse-free survival (RFS) for participants with detectable peri-HCT MRD, whereas no benefit was evident for those lacking detectable MRD. We conducted a post-hoc analysis of the data and found that the level of MRD detected with this approach correlated remarkably with RFS and relapse risk, and that MRD detectable at any level negatively impacted RFS. In the placebo arm, 42.2% of participants with detectable FLT3-ITD MRD relapsed compared to 13.4% of those without detectable MRD. We found that 14.8% of participants had multiple FLT3-ITD clones detected as MRD and had worse survival irrespective of treatment arm. Finally, we examined the kinetics of FLT3-ITD clonal relapse or eradication and found that participants on the placebo arm with detectable MRD relapsed rapidly after HCT, often within a few weeks. MRD-positive participants on the gilteritinib arm relapsed either with FLT3 wild type clones (as assessed by capillary electrophoresis), after cessation of gilteritinib with persistent MRD, or on progression of multi-clonal disease. These data demonstrate the potential of using FLT3-ITD MRD to guide therapy with gilteritinib for this subtype of AML.},
}

@article {pmid39774957,
year = {2025},
author = {Liu, H and Zhang, W and Di, M and Lee, H and Shi, L and Wang, X and Xingyu, Z and Powers, CA and Sethi, V and Li, X and Xiao, Y and Crane, A and Kaltenmeier, C and Alberola, RB and Behari, J and Duarte-Rojo, A and Hughes, D and Malik, S and Jonassaint, N and Geller, D and Tohme, S and Gunabushanam, V and Tevar, A and Cruz, R and Hughes, C and Dharmayan, S and Ayloo, S and Humar, A and Molinari, M},
title = {Survival benefit associated with liver transplantation for hepatocellular carcinoma based on tumor burden scores at listing.},
journal = {Hepatology communications},
volume = {9},
number = {1},
pages = {},
doi = {10.1097/HC9.0000000000000619},
pmid = {39774957},
issn = {2471-254X},
mesh = {Humans ; *Liver Transplantation/mortality ; *Carcinoma, Hepatocellular/surgery/mortality ; *Liver Neoplasms/surgery/mortality/pathology ; Male ; Female ; Middle Aged ; *Waiting Lists/mortality ; *Tumor Burden ; United States ; Aged ; Adult ; Survival Rate ; Tissue and Organ Procurement ; Registries ; },
abstract = {INTRODUCTION: Liver transplantation (LT) provides significant survival benefits to patients with unresectable HCC. In the United States, organ allocation policies for HCCs within the United Network for Organ Sharing criteria do not prioritize patients based on their differences in oncological characteristics. This study assessed whether transplant-associated survival benefits (TASBs) vary among patients with different tumor burden scores (TBS) measured at the time of listing.

METHODS: We analyzed data from adults applying for HCC MELD exception points between 2002 and 2019, with follow-up until December 2023, using the Scientific Registry of Transplant Recipients. TBS was determined based on the largest tumor diameter and number of HCCs. Patients were categorized into low (≤3), intermediate (3.1-5), and high (>5) TBS groups. TASB was measured as the difference in 5-year survival with and without LT.

RESULTS: This study included 36,634 LT candidates. High-TBS patients had higher waitlist dropout rates and marginally lower post-transplant survival, resulting in a significantly greater TASB. The 5-year TASB for the low, intermediate, and high TBS groups were 15.7, 22.1, and 25.0 months, respectively. The adjusted survival benefit expressed in 5-year survival differences was 21.9%, 34.5%, and 39.4% in the low, intermediate, and high TBS groups, respectively (p<0.001).

CONCLUSIONS: Higher TBS during listing correlates with greater LT benefits for patients with unresectable HCC within UNOS criteria. We conclude that organ allocation policies in the United States should prioritize patients with high TBS due to their increased risk of dropout and comparable post-transplant survival when compared to patients with less advanced tumors.},
}

Humans
*Liver Transplantation/mortality
*Carcinoma, Hepatocellular/surgery/mortality
*Liver Neoplasms/surgery/mortality/pathology
Male
Female
Middle Aged
*Waiting Lists/mortality
*Tumor Burden
United States
Aged
Adult
Survival Rate
Tissue and Organ Procurement
Registries

@article {pmid39774938,
year = {2024},
author = {Munoz, FM and Beigi, R and Posavad, CM and Kelly, C and Badell, ML and Bunge, K and Mulligan, MJ and Parameswaran, L and Richardson, BA and Olsen-Chen, C and Novak, RM and Brady, RC and DeFranco, E and Gerber, JS and Shriver, M and Suthar, MS and Coler, R and Berube, BJ and Kim, SH and Piper, JM and Miedema, J and Pasetti, M and Neuzil, KM and Cardemil, CV and , },
title = {Enhanced D614G and Omicron Variants Antibody Persistence in Infants at 2 Months of Age Following Maternal mRNA Booster Vaccination During Pregnancy or Postpartum.},
journal = {The Pediatric infectious disease journal},
volume = {43},
number = {11},
pages = {1065-1073},
pmid = {39774938},
issn = {1532-0987},
mesh = {Humans ; Female ; Pregnancy ; *SARS-CoV-2/immunology ; *COVID-19/prevention & control/immunology ; *Antibodies, Viral/blood ; *Immunization, Secondary ; *Milk, Human/immunology ; Prospective Studies ; *COVID-19 Vaccines/immunology/administration & dosage ; Infant ; Adult ; *Postpartum Period ; Antibodies, Neutralizing/blood/immunology ; Immunoglobulin G/blood ; Vaccination ; Infant, Newborn ; Male ; Young Adult ; Spike Glycoprotein, Coronavirus/immunology ; },
abstract = {BACKGROUND: Following maternal COVID-19 vaccination, the persistence of antibodies in sera and breast milk for mothers and infants is not well characterized. We sought to describe the persistence of antibodies through 2 months after delivery in maternal and infant serum and breast milk following maternal COVID-19 mRNA vaccination and to examine differences by receipt of booster dose during pregnancy or postpartum.

METHODS: This is a prospective cohort study with enrollment from July 2021 to January 2022 at 9 US academic sites. Pregnant or postpartum participants and their infants were enrolled after COVID-19 mRNA monovalent vaccination during pregnancy (primary 2-dose series) with booster (third dose) vaccination during pregnancy or within 2 months post-partum. SARS-CoV-2-binding and functional antibody responses at delivery and 2 months after delivery in mothers and infants were measured by spike and receptor-binding domain immunoglobulin (Ig) G, pseudovirus and live neutralizing antibody (nAb) titers to ancestral and Omicron BA.1 and BA.5 strains. Breast milk spike and receptor-binding domain IgG and IgA titers were also measured.

RESULTS: A total of 237 maternal/infant dyads were included (110 primary series during pregnancy, 99 pregnancy booster and 28 postpartum booster). A pregnancy booster resulted in 2.2-4.7-fold higher IgG and nAb at delivery and 2 months for both mothers and infants compared to the primary series alone (P < 0.001 for all comparisons). While infant IgG and nAb titers decreased by 2 months of age, the proportion of infants with detectable nAb at 2 months was greater in infants of mothers boosted during pregnancy compared with primary series for all variants (D614G: 99% vs. 56%; BA.1: 56% vs. 4% and BA.5: 57% vs. 9%; P < 0.001 for all comparisons). Breast milk spike IgA and IgG were present in 64%-100% and 100% of participants, respectively, and those boosted during pregnancy or postpartum had 3.1-4.6-fold higher levels of breast milk antibodies at 2 months compared to primary series during pregnancy (P < 0.001).

CONCLUSIONS: mRNA COVID-19 monovalent booster vaccination during pregnancy results in significantly higher maternal and infant serum-binding IgG and nAb titers compared to a primary 2-dose series, including against Omicron variants, through 2 months of age. Breast milk antibodies following maternal vaccination during pregnancy or postpartum may provide additional protection during early infancy.},
}

Humans
Female
Pregnancy
*SARS-CoV-2/immunology
*COVID-19/prevention & control/immunology
*Antibodies, Viral/blood
*Immunization, Secondary
*Milk, Human/immunology
Prospective Studies
*COVID-19 Vaccines/immunology/administration & dosage
Infant
Adult
*Postpartum Period
Antibodies, Neutralizing/blood/immunology
Immunoglobulin G/blood
Vaccination
Infant, Newborn
Male
Young Adult
Spike Glycoprotein, Coronavirus/immunology

@article {pmid39772633,
year = {2025},
author = {Portuguese, AJ and Banerjee, R and Chen, G and Reddi, S and Cowan, AJ},
title = {Novel Treatment Options for Multiple Myeloma.},
journal = {JCO oncology practice},
volume = {},
number = {},
pages = {OP2400752},
doi = {10.1200/OP-24-00752},
pmid = {39772633},
issn = {2688-1535},
abstract = {Multiple myeloma (MM), the second most common hematologic malignancy in the United States, is characterized by repeated cycles of remission and relapse, with increasing resistance to treatment after each line of therapy. Despite the virtually incurable nature of MM, recent therapeutic breakthroughs have fundamentally reshaped its treatment landscape. This review explores evolving care paradigms, spanning from newly diagnosed MM to relapsed or refractory disease. In the frontline setting, treatment strategies have shifted beyond their traditional emphasis on autologous stem-cell transplant eligibility to a broader categorization of patients on the basis of their suitability for quadruplet therapy. In the relapsed/refractory setting, novel immunotherapies, including chimeric antigen receptor T-cell (CAR-T) therapies and bispecific antibodies, have revolutionized treatment, offering new hope for patients with previously limited options. Precision medicine is playing a growing role in MM treatment, with venetoclax showing significant efficacy in patients with t(11;14) translocation, advancing targeted therapy for this subgroup. On the horizon, investigational CAR-T products and cereblon E3 ligase modulators, such as mezigdomide and iberdomide, may provide faster, more durable responses compared with current therapies. In addition, belantamab mafodotin, an antibody-drug conjugate withdrawn from the US market in 2022, is on the verge of reapproval after positive results from recent randomized trials. While these therapies offer significant potential, challenges remain in managing toxicity, ensuring treatment accessibility, and optimizing sequencing strategies. As the therapeutic arsenal expands, the need for personalized MM treatment plans that balance efficacy with quality of life becomes even more essential.},
}

@article {pmid39767189,
year = {2024},
author = {Masroori, Z and Haseli, S and Abbaspour, E and Pouramini, A and Azhideh, A and Fathi, M and Kafi, F and Chalian, M},
title = {Patellar Non-Traumatic Pathologies: A Pictorial Review of Radiologic Findings.},
journal = {Diagnostics (Basel, Switzerland)},
volume = {14},
number = {24},
pages = {},
doi = {10.3390/diagnostics14242828},
pmid = {39767189},
issn = {2075-4418},
abstract = {Patellar pathologies are a common cause of knee dysfunction, with Patellofemoral Pain Syndrome (PFPS) alone responsible for 25% of knee-related visits to sports medicine clinics. Non-traumatic conditions, while often overlooked, can also lead to significant discomfort and functional limitations, highlighting the importance of accurate and timely diagnosis for effective management and prevention of complications. This pictorial review examines the radiologic characteristics of various non-traumatic patellar disorders, focusing on imaging modalities such as radiography, computed tomography (CT), and magnetic resonance imaging (MRI). Key diagnostic markers, including patellar tilt, tibial tuberosity-trochlear groove distance (TT-TG), and congruence angle (CA), are discussed for their significance in non-traumatic pathology identification. Furthermore, this review highlights specific radiologic features for a range of non-traumatic patellar conditions, including patellar tendinopathy, chondromalacia patellae, and trochlear dysplasia, emphasizing how distinct radiologic findings facilitate precise diagnosis and clinical assessment. Ultimately, it provides a practical guide for clinicians in diagnosing non-traumatic patellar pathologies through a comprehensive review of key radiologic features while also discussing advancements in imaging technologies and management strategies to support accurate diagnosis and effective clinical decision-making.},
}

@article {pmid39763680,
year = {2024},
author = {Thomas, CE and Takashima, Y and Wesselink, E and Ugai, T and Steinfelder, RS and Buchanan, DD and Qu, C and Hsu, L and Dias Costa, A and Gallinger, S and Grant, RC and Huyghe, JR and Thomas, SS and Ogino, S and Phipps, AI and Nowak, JA and Peters, U},
title = {Association between somatic microsatellite instability, hypermutation status, and specific T cell subsets in colorectal cancer tumors.},
journal = {Frontiers in immunology},
volume = {15},
number = {},
pages = {1505896},
pmid = {39763680},
issn = {1664-3224},
mesh = {Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; *Colorectal Neoplasms/genetics/immunology ; *Lymphocytes, Tumor-Infiltrating/immunology/metabolism ; *Microsatellite Instability ; Mutation ; *T-Lymphocyte Subsets/immunology/metabolism ; Observational Studies as Topic ; },
abstract = {BACKGROUND: Microsatellite instability-high (MSI-high) tumors comprise ~15% of sporadic colorectal cancers (CRC) and are associated with elevated T cell infiltration. However, the universality of this response across T cell subtypes with distinct functions is unknown.

METHODS: Including 1,236 CRC tumors from three observational studies, we conducted in-situ T cell profiling using a customized 9-plex (CD3, CD4, CD8, CD45RA, CD45RO, FOXP3, KRT, MKI67, and DAPI) multispectral immunofluorescence assay. MSI status was assessed through polymerase chain reaction or immunohistochemical assays. We used multivariable ordinal logistic regression to estimate odds ratios (OR per increasing quantile) and 95% confidence intervals (CIs) for the association of MSI status with quantiles of T cell densities in either tumor epithelial or stromal tissue areas.

RESULTS: Compared to microsatellite instability low or microsatellite stable (MSI-low/MSS) tumors, MSI-high status was associated with higher density for the majority of immune subsets (twelve out of eighteen) in both epithelial and stromal tissue areas. The strongest associations were for CD3[+]CD8[+] T cells in epithelial areas [OR (95% CI) for naive, memory, and regulatory subsets = 3.49 (2.57, 4.75); 2.82 (2.10, 3.78); 3.04 (2.24, 4.13), respectively]. Conversely, stromal area CD3[+]CD4[+] memory T cells were inversely associated [OR (95% CI) = 0.68 (0.51, 0.91)].

DISCUSSION: MSI-high status was strongly associated with higher densities of most T cell subsets in both epithelial and stromal tissue areas. Our investigation supports efforts to identify patients who may be more likely to respond to current immunotherapy treatments.

SIGNIFICANCE: This study helps us better understand how a clinically relevant tumor phenotype, microsatellite instability status, is related to different functioning T cell densities in colorectal tumors, which may impact future immunotherapy strategies.},
}

Adult
Aged
Female
Humans
Male
Middle Aged
*Colorectal Neoplasms/genetics/immunology
*Lymphocytes, Tumor-Infiltrating/immunology/metabolism
*Microsatellite Instability
Mutation
*T-Lymphocyte Subsets/immunology/metabolism
Observational Studies as Topic

@article {pmid39762553,
year = {2025},
author = {Granadier, D and Acenas, D and Dudakov, JA},
title = {Endogenous thymic regeneration: restoring T cell production following injury.},
journal = {Nature reviews. Immunology},
volume = {},
number = {},
pages = {},
pmid = {39762553},
issn = {1474-1741},
abstract = {Despite its importance for generating and maintaining a healthy and broad T cell repertoire, the thymus is exquisitely sensitive to acute damage. Marked thymic involution occurs in response to stimuli as diverse as infection, stress, pregnancy, malnutrition, drug use and cytoreductive chemotherapy. However, the thymus also has a remarkable capacity for repair, although this regenerative capacity declines with age. Endogenous thymic regeneration is a crucial process that allows for the recovery of immune competence after acute damage and delay to this recovery can have important clinical effects. Until recently, the mechanisms that drive endogenous thymic regeneration were not well understood, but recent work in mice has revealed multiple distinct pathways of regeneration and the molecular mechanisms that trigger these pathways after damage. In this Review, we discuss the effects of different types of damage to the thymus, with a focus on an emerging body of work in mice that provides insight into the cellular and molecular mechanisms that regulate endogenous tissue regeneration in the thymus. We also highlight some of the clinical challenges that are presented by dysregulated thymic regeneration.},
}

@article {pmid39761503,
year = {2025},
author = {Raghav, KPS and Guthrie, KA and Tan, B and Denlinger, CS and Fakih, M and Overman, MJ and Dasari, NA and Corum, LR and Hicks, LG and Patel, MS and Esparaz, BT and Kazmi, SM and Alluri, N and Colby, S and Gholami, S and Gold, PJ and Chiorean, EG and Kopetz, S and Hochster, HS and Philip, PA},
title = {Trastuzumab Plus Pertuzumab Versus Cetuximab Plus Irinotecan in Patients With RAS/BRAF Wild-Type, HER2-Positive, Metastatic Colorectal Cancer (S1613): A Randomized Phase II Trial.},
journal = {Journal of clinical oncology : official journal of the American Society of Clinical Oncology},
volume = {},
number = {},
pages = {JCO2401710},
doi = {10.1200/JCO-24-01710},
pmid = {39761503},
issn = {1527-7755},
abstract = {PURPOSE: ERBB2 overexpression/amplification in RAS/BRAF wild-type (WT) metastatic colorectal cancer (mCRC; human epidermal growth factor receptor 2 [HER2]-positive mCRC) appears to be associated with limited benefit from anti-EGFR antibodies and promising responses to dual-HER2 inhibition; however, comparative efficacy has not been investigated. We conducted a randomized phase II trial to evaluate efficacy and safety of dual-HER2 inhibition against standard-of-care anti-EGFR antibody-based therapy as second/third-line treatment in HER2-positive mCRC.

METHODS: Patients with RAS/BRAF-WT mCRC after central confirmation of HER2 positivity (immunohistochemistry 3+ or 2+ and in situ hybridization amplified [HER2/CEP17 ratio >2.0]) were assigned (1:1) to either trastuzumab plus pertuzumab (TP; trastuzumab 6 mg/kg and pertuzumab 420 mg once every 3 weeks) or cetuximab plus irinotecan (CETIRI; cetuximab 500 mg/m[2] and irinotecan 180 mg/m[2] once every 2 weeks) until progression or unacceptable toxicity. Crossover to TP was allowed after progression on CETIRI. The primary end point was progression-free survival (PFS). Secondary end points included objective response rate (ORR), overall survival, safety, and HER2 gene copy number (GCN ≥20/<20) as a predictive factor.

RESULTS: Between October 2017 and March 2022, 54 participants were assigned to TP (n = 26) and CETIRI (n = 28). Median PFS did not vary significantly by treatment: 4.7 (95% CI, 1.9 to 7.6) and 3.7 (95% CI, 1.6 to 6.7) months in the TP and CETIRI groups, respectively. Efficacy of TP versus CETIRI differed significantly by HER2 GCN (median PFS, GCN ≥20 [9.9 v 2.9 months] and GCN <20 [3.0 v 4.2 months], respectively; P interaction = .003). On TP, ORR was 34.6% (57.1% with GCN ≥20 v 9.1% with GCN <20) with median GCN of 29.7 versus 13.2 for responders and nonresponders, respectively (P = .004). Grade ≥3 adverse events occurred in 23.1% and 46.1% of participants with TP and CETIRI, respectively.

CONCLUSION: TP appears to be a safe and effective cytotoxic chemotherapy-free option for patients with RAS/BRAF-WT, HER2-positive mCRC. Higher levels of HER2 amplification were associated with greater degree of clinical benefit from TP vis-à-vis CETIRI.},
}

@article {pmid39761015,
year = {2024},
author = {Nguyen, HH and Talbot, J and Li, D and Raghavan, V and Littman, DR},
title = {Modulating intestinal neuroimmune VIPergic signaling attenuates the reduction in ILC3-derived IL-22 and hepatic steatosis in MASLD.},
journal = {Hepatology communications},
volume = {8},
number = {11},
pages = {},
pmid = {39761015},
issn = {2471-254X},
mesh = {Animals ; *Interleukin-22 ; *Interleukins ; Mice ; *Vasoactive Intestinal Peptide ; *Diet, High-Fat/adverse effects ; *Non-alcoholic Fatty Liver Disease/immunology ; *Lymphocytes/immunology/metabolism ; Disease Models, Animal ; Signal Transduction ; Male ; Mice, Inbred C57BL ; Immunity, Innate ; Fatty Liver/immunology ; Neurons/immunology/metabolism ; Neuroimmunomodulation ; },
abstract = {BACKGROUND: Metabolic dysfunction-associated steatotic liver disease (MASLD, formerly known as NAFLD) is a major driver of cirrhosis and liver-related mortality. However, therapeutic options for MASLD, including prevention of liver steatosis, are limited. We previously described that vasoactive intestinal peptide-producing neurons (VIP-neurons) regulate the efficiency of intestinal dietary fat absorption and IL-22 production by type 3 innate lymphoid cells (ILC3) in the intestine. Given the described hepatoprotective role of IL-22, we hypothesize that modulation of this neuroimmune circuit could potentially be an innovative approach for the control of liver steatosis.

METHODS: We used a model of diet-induced MASLD by exposing mice to a high-fat diet (HFD) for 16 weeks, when the development of liver steatosis was first observed in our animals. We characterized IL-22 production by intestinal ILC3 at this dietary endpoint. We then evaluated whether communication between VIP-neurons and ILC3 affected IL-22 production and MASLD development by exposing mice with a conditional genetic deletion of Vipr2 in ILC3 (Rorc(t)CreVipr2fl/fl) to the HFD. We also performed intermittent global inhibition of VIP-neurons using a chemogenetic inhibitory approach (VipIres-CrehM4DiLSL) in HFD-fed mice.

RESULTS: Production of IL-22 by intestinal ILC3 is reduced in steatotic mice that were exposed to an HFD for 16 weeks. Targeted deletion of VIP receptor 2 in ILC3 resulted in higher production of IL-22 in ILC3 and was associated with a significant reduction in liver steatosis in mice under HFD. Global inhibition of VIP-producing neurons also resulted in a significant reduction in liver steatosis.

CONCLUSIONS: Modulating VIPergic neuroimmune signaling can ameliorate the development of hepatic steatosis induced by a surplus of fat ingestion in the diet. This neuroimmune pathway should be further investigated as a potential therapeutic avenue in MASLD.},
}

Animals
*Interleukin-22
*Interleukins
Mice
*Vasoactive Intestinal Peptide
*Diet, High-Fat/adverse effects
*Non-alcoholic Fatty Liver Disease/immunology
*Lymphocytes/immunology/metabolism
Disease Models, Animal
Signal Transduction
Male
Mice, Inbred C57BL
Immunity, Innate
Fatty Liver/immunology
Neurons/immunology/metabolism
Neuroimmunomodulation

@article {pmid39760096,
year = {2024},
author = {McDougall, JA and Briant, KJ and Carosso, E and Cole, AM and Dee, C and Doody, DR and Hannon, PA and Henderson, V and Johnson, S and Parker, M and Schwartz, SM and Mendoza, JA},
title = {Data-Driven Community Engagement: Using Quantitative and Qualitative Data to Set Priorities and Launch New Initiatives in a Growing Catchment Area.},
journal = {Preventive oncology & epidemiology},
volume = {2},
number = {1},
pages = {},
pmid = {39760096},
issn = {2832-2134},
support = {P30 CA015704/CA/NCI NIH HHS/United States ; },
abstract = {In 2022, the catchment area of the Fred Hutchinson/University of Washington/Seattle Children's Cancer Consortium (the Consortium) grew from 13-counties in Western Washington State to include all 39 counties in Washington. Widening the catchment area provided new opportunities for the Consortium to monitor the cancer burden, identify cancer-related health disparities, use a bidirectional approach to develop cancer focused programming, and facilitate research in clinical and community settings. In this commentary, we describe the exploratory process of catchment area change led by the Consortium's Office of Community Outreach and Engagement and new initiatives that followed that growth. We hope that by sharing the ongoing, data-driven community engagement approach in the Consortium's current, statewide catchment area, our experience will be of value to other cancer centers looking to engage with communities and develop bidirectional partnerships in new areas.},
}

@article {pmid39759131,
year = {2024},
author = {Biswas, D and Hippe, DS and Winter, AM and Li, I and Rahbar, H and Partridge, SC},
title = {Diffusion weighted imaging for improving the diagnostic performance of screening breast MRI: impact of apparent diffusion coefficient quantitation methods and cutoffs.},
journal = {Frontiers in oncology},
volume = {14},
number = {},
pages = {1437506},
pmid = {39759131},
issn = {2234-943X},
abstract = {INTRODUCTION: Diffusion weighted MRI (DWI) has emerged as a promising adjunct to reduce unnecessary biopsies prompted by breast MRI through use of apparent diffusion coefficient (ADC) measures. The purpose of this study was to investigate the effects of different lesion ADC measurement approaches and ADC cutoffs on the diagnostic performance of breast DWI in a high-risk MRI screening cohort to identify the optimal approach for clinical incorporation.

METHODS: Consecutive screening breast MRI examinations (August 2014-Dec 2018) that prompted a biopsy for a suspicious breast lesion (BI-RADS 4 or 5) were retrospectively evaluated. On DWI, ADC (b=0/100/600/800s/mm[2]) measures were calculated with three different techniques for defining lesion region-of-interest (ROI; single slice('2D'), whole volume('3D') and lowest ADC region('hotspot')). An optimal data-derived ADC cutoff for each technique was retrospectively identified to reduce benign biopsies while avoiding any false negatives, inherently producing cutoffs with 100% sensitivity in this particular cohort. Further, diagnostic performance of these measures was validated using two prespecified ADC cutoffs: 1.53x10[-3]mm[2]/s from the ECOG-ACRIN A6702 trial and 1.30x10[-3]mm[2]/s from the international EUSOBI group. Diagnostic performance was compared between ADC maps generated with 2(0/800s/mm[2]) and 4(0/100/600/800s/mm[2]) b-values. Benign biopsy reduction rate was calculated (number of benign lesions with ADC >cutoff)/(total number of benign lesions).

RESULTS: 137 suspicious lesions (in 121 women, median age 44 years [range, 20-75yrs]) were detected on contrast-enhanced screening breast MRI and recommended for biopsy. Of those, 30(21.9%) were malignant and 107(78.1%) were benign. Hotspot ADC measures were significantly lower (p<0.001) than ADCs from both 2D and 3D ROI techniques. Applying the optimal data-derived ADC cutoffs resulted in comparable reduction in benign biopsies across ROI techniques (range:16.8% -17.8%). Applying the prespecified A6702 and EUSOBI cutoffs resulted in benign biopsy reduction rates of 11.2-19.6%(with 90.0-100% sensitivity) and 36.4-51.4%(with 70.0-83.3% sensitivity), respectively, across ROI techniques. ADC measures and benign biopsy reduction rates were similar when calculated with only 2 b-values (0,800 s/mm[2]) versus all 4 b-values.

DISCUSSION: Our findings demonstrate that with appropriate ADC thresholds, comparable reduction in benign biopsies can be achieved using lesion ADC measurements computed from a variety of approaches. Choice of ADC cutoff depends on ROI approach and preferred performance tradeoffs (biopsy reduction vs sensitivity).},
}

@article {pmid39758135,
year = {2024},
author = {Langley, BO and Rillamas-Sun, E and Huang, Y and Indorf, A and Robles, M and Feaster, R and D'Addario, L and Ergas, IJ and Roh, JM and Kushi, LH and Greenlee, H},
title = {Validation and Utility of Drug-Nutrient Interaction and Dietary Supplement Mechanistic Activity in the Natural Medicines Database.},
journal = {JCO oncology advances},
volume = {1},
number = {},
pages = {e2400062},
pmid = {39758135},
issn = {2994-9750},
abstract = {PURPOSE: The increasing use of dietary supplements by patients with cancer and other chronic diseases requires the systematized review of potential interactions between prescription drugs and nutrients from supplements by health care and clinical research teams. Dietary supplement interaction databases are positioned to fill a gap in quantifying potential risks for patients, although none have been assessed for reliability in data interpretation. The NatMed database, a source for comprehensive reports on mechanistic and safety data for dietary supplement ingredients, was evaluated for use in future investigations.

METHODS: Data from NatMed were retrieved using licensed end points for ingredient monographs with drug-nutrient interactions with doxorubicin across five pharmacokinetic and metabolic pathways, and for ingredient monographs with antioxidant activity. Interactions between dietary supplements and doxorubicin treatment and antioxidant monographs were independently reviewed and characterized by clinical pharmacists. Cohen's K was used to measure interrater reliability and the degree of agreement between pharmacists.

RESULTS: Three hundred fifteen potential interactions with doxorubicin (n = 115 monographs) and 455 other antioxidant ingredients were identified and reviewed by clinical pharmacists. There was substantial to near-perfect agreement for drug-nutrient interactions with doxorubicin (Cohen's K = 0.64-0.85) and for antioxidants (Cohen's K = 0.84). A small proportion of retrieved monographs were not validated by the clinical pharmacists for interactions with doxorubicin (n = 20 occurrences, 6.4%) or for antioxidant activity (n = 28, 6.2%).

CONCLUSION: A high degree of reliability in data on dietary supplement interactions with doxorubicin and mechanisms of action suggests NatMed may be a dependable source of data for future investigators. Additional procedures including independent data validation and use of multiple dietary supplement interaction databases will strengthen the quality of findings in future studies.},
}

@article {pmid39756456,
year = {2025},
author = {Lapen, K and Feliciano, EJG and Dee, EC and Gillespie, EF and Yahalom, J and Imber, BS},
title = {Electronic patient-reported outcomes for CAR T-cell therapies.},
journal = {The Lancet. Oncology},
volume = {26},
number = {1},
pages = {e6},
doi = {10.1016/S1470-2045(24)00644-2},
pmid = {39756456},
issn = {1474-5488},
}

@article {pmid39756444,
year = {2025},
author = {Choueiri, TK and Merchan, JR and Figlin, R and McDermott, DF and Arrowsmith, E and Michaelson, MD and Tykodi, SS and Heath, EI and Spigel, DR and D'Souza, A and Kassalow, L and Perini, RF and Vickery, D and Bauer, TM},
title = {Belzutifan plus cabozantinib as first-line treatment for patients with advanced clear-cell renal cell carcinoma (LITESPARK-003): an open-label, single-arm, phase 2 study.},
journal = {The Lancet. Oncology},
volume = {26},
number = {1},
pages = {64-73},
doi = {10.1016/S1470-2045(24)00649-1},
pmid = {39756444},
issn = {1474-5488},
mesh = {Humans ; *Anilides/therapeutic use/administration & dosage/adverse effects ; Female ; Male ; Middle Aged ; *Carcinoma, Renal Cell/drug therapy/pathology ; *Pyridines/administration & dosage/therapeutic use/adverse effects ; Aged ; *Kidney Neoplasms/drug therapy/pathology ; *Antineoplastic Combined Chemotherapy Protocols/therapeutic use/adverse effects ; Adult ; },
abstract = {BACKGROUND: Belzutifan, a first-in-class HIF-2α inhibitor, has shown antitumour activity as monotherapy and in combination with cabozantinib in patients with previously treated advanced kidney cancer. The phase 2 LITESPARK-003 study was designed to determine the antitumour activity and safety of belzutifan in combination with cabozantinib in patients with advanced clear-cell renal cell carcinoma that was previously untreated (cohort 1) or previously treated with immunotherapy (cohort 2). Here, we report results from cohort 1 of this clinical trial.

METHODS: LITESPARK-003 is an open-label, single-arm, phase 2 study at ten hospitals and cancer centres in the USA. In cohort 1, eligible patients were at least 18 years of age, had an Eastern Cooperative Oncology Group performance status of 0 or 1, and had received no previous systemic therapy for locally advanced or metastatic renal cell carcinoma. Patients received belzutifan 120 mg orally once daily and cabozantinib 60 mg orally once daily until unacceptable adverse events, disease progression, or patient withdrawal. The primary endpoint was investigator-assessed confirmed objective response according to Response Evaluation Criteria in Solid Tumors version 1.1. Antitumour activity and safety were assessed in all patients who received at least one dose of study treatment. This trial is registered with ClinicalTrials.gov, NCT03634540, and is ongoing.

FINDINGS: Between Sept 27, 2018, and Jan 10, 2023, we screened 138 patients for eligibility, and 50 (36%) were enrolled and assigned to cohort 1. The median age was 64 years (IQR 57-72). 40 (80%) of 50 patients were male and ten (20%) were female. 48 (96%) patients were White, one (2%) patient was Black or African American, and one (2%) was of a race in the other category. As of the data cutoff (May 15, 2023), median follow-up was 24·3 months (IQR 13·9-32·0). 35 (70%, 95% CI 55-82) of 50 patients had a confirmed objective response, including four (8%) who had a complete response and 31 (62%) who had a partial response. The most frequent grade 3-4 treatment-related adverse events were hypertension (six [12%] patients), anaemia (five [10%] patients), and fatigue (four [8%] patients). Seven (14%) of 50 patients had serious treatment-related adverse events. No treatment-related deaths occurred.

INTERPRETATION: Belzutifan plus cabozantinib has promising antitumour activity in treatment-naive patients with advanced clear-cell renal cell carcinoma and further investigation of an HIF-2α inhibitor in combination with a multitargeted tyrosine kinase inhibitor as a treatment option in this population is warranted.

FUNDING: Merck Sharp & Dohme LLC, a subsidiary of Merck & Co, Inc, Rahway, NJ, USA, and the National Cancer Institute.},
}

Humans
*Anilides/therapeutic use/administration & dosage/adverse effects
Female
Male
Middle Aged
*Carcinoma, Renal Cell/drug therapy/pathology
*Pyridines/administration & dosage/therapeutic use/adverse effects
Aged
*Kidney Neoplasms/drug therapy/pathology
*Antineoplastic Combined Chemotherapy Protocols/therapeutic use/adverse effects
Adult

@article {pmid39755942,
year = {2025},
author = {Yan, L and He, Q and Verma, SP and Zhang, X and Giel, AS and Maj, C and Graz, K and Naderi, E and Chen, J and Ali, MW and Gharahkhani, P and Shu, X and Offit, K and Shah, PM and Gerdes, H and Molena, D and Srivastava, A and MacGregor, S and , and Palles, C and Thieme, R and Vieth, M and Gockel, I and Vaughan, TL and Schumacher, J and Buas, MF},
title = {Biologically-targeted discovery-replication scan identifies G×G interaction in relation to risk of Barrett's esophagus and esophageal adenocarcinoma.},
journal = {HGG advances},
volume = {},
number = {},
pages = {100399},
doi = {10.1016/j.xhgg.2025.100399},
pmid = {39755942},
issn = {2666-2477},
abstract = {Inherited genetics represents an important contributor to risk of esophageal adenocarcinoma (EAC), and its precursor Barrett's esophagus (BE). Genome-wide association studies have identified ∼30 susceptibility variants for BE/EAC, yet genetic interactions remain unexamined. To address challenges in large-scale G×G scans, we combined knowledge-guided filtering and machine learning approaches, focusing on genes with (A) known/plausible links to BE/EAC pathogenesis (n=493) or (B) prior evidence of biological interactions (n=4,196). ∼75 x 10[6] SNP×SNP interactions were screened via hierarchical group lasso (glinternet) using BEACON GWAS data. The top ∼2000 interactions retained in each scan were prioritized using P values from single logistic models. Identical scans were repeated among males only (78%), with two independent GWAS datasets used for replication. In overall and male-specific primary replications, 11 of 187 and 20 of 191 interactions satisfied P<0.05, respectively. The strongest evidence for secondary replication was for rs17744726×rs3217992 among males, with consistent directionality across all cohorts (Pmeta=2.19×10[-8]); rs3217992 "T" was associated with reduced risk only in individuals homozygous for rs17744726 "G". Rs3217992 maps to the CDKN2B 3'UTR and reportedly disrupts microRNA-mediated repression. Rs17744726 maps to an intronic enhancer region in BLK. Through in-silico prioritization and experimental validation, we identified a nearby proxy variant (rs4841556) as a functional modulator of enhancer activity. Enhancer-gene mapping and eQTLs implicated BLK and FAM167A as targets. The first systematic G×G investigation in BE/EAC, this study uncovers differential risk associations for CDKN2B variation by BLK genotype, suggesting novel biological dependency between two risk loci encoding key mediators of tumor suppression and inflammation.},
}

@article {pmid39755595,
year = {2025},
author = {Omollo, V and Roche, SD and Zhang, S and Asewe, M and Rono, BK and Kwach, B and Rota, G and Ong'wen, P and Harkey, K and Odoyo, J and Were, D and Ngure, K and Bukusi, EA and Ortblad, KF},
title = {Measuring the uptake of clinic-based HIV treatment and prevention services following HIV testing and referral at private pharmacies in Kenya.},
journal = {BMC health services research},
volume = {25},
number = {1},
pages = {23},
pmid = {39755595},
issn = {1472-6963},
support = {INV-033052/GATES/Bill & Melinda Gates Foundation/United States ; INV-033052/GATES/Bill & Melinda Gates Foundation/United States ; INV-033052/GATES/Bill & Melinda Gates Foundation/United States ; INV-033052/GATES/Bill & Melinda Gates Foundation/United States ; INV-033052/GATES/Bill & Melinda Gates Foundation/United States ; INV-033052/GATES/Bill & Melinda Gates Foundation/United States ; INV-033052/GATES/Bill & Melinda Gates Foundation/United States ; INV-033052/GATES/Bill & Melinda Gates Foundation/United States ; INV-033052/GATES/Bill & Melinda Gates Foundation/United States ; INV-033052/GATES/Bill & Melinda Gates Foundation/United States ; INV-033052/GATES/Bill & Melinda Gates Foundation/United States ; INV-033052/GATES/Bill & Melinda Gates Foundation/United States ; INV-033052/GATES/Bill & Melinda Gates Foundation/United States ; INV-033052/GATES/Bill & Melinda Gates Foundation/United States ; R00 MH121166/MH/NIMH NIH HHS/United States ; },
mesh = {Humans ; Kenya/epidemiology ; *HIV Infections/diagnosis/prevention & control/drug therapy/epidemiology ; Female ; Male ; Adult ; *Referral and Consultation/statistics & numerical data ; Pilot Projects ; *Pharmacies/statistics & numerical data ; *HIV Testing/statistics & numerical data ; Pre-Exposure Prophylaxis/statistics & numerical data ; Adolescent ; Young Adult ; Middle Aged ; Patient Acceptance of Health Care/statistics & numerical data ; },
abstract = {BACKGROUND: Despite their ubiquity across sub-Saharan Africa, private pharmacies are underutilized for HIV service delivery beyond the sale of HIV self-test kits. To understand what uptake of HIV prevention and treatment services might look like if private pharmacies offered clients free HIV self-testing and referral to clinic-based HIV services, we conducted a pilot study in Kenya.

METHODS: At 20 private pharmacies in Kisumu County, Kenya, pharmacy clients (≥ 18 years) purchasing sexual health-related products (e.g., contraception) were offered free HIV testing. Based on their test result and recent self-reported behaviors associated with HIV risk, clients were encouraged to consider pre-exposure prophylaxis (PrEP), post-exposure prophylaxis (PEP), or antiretroviral therapy (ART) initiation, informed where they could access free services, and issued a referral. We called clients three months after study completion to see if they had initiated the recommended service. Among clients who reported PrEP referral, we used Poisson regression models to examine characteristics associated with PrEP initiation and calculated adjusted prevalence ratios (aPRs).

RESULTS: From March to June 2022, 1500 pharmacy clients completed HIV testing and were referred to clinic-based HIV services; in October 2022, 1178 (79%) were reached and meet our criteria for follow-up. Among those reached, the majority (63%, 742/1178) were women, the median age was 26 years (IQR 22-31), and few (4%, 51/1178) reported any prior PrEP use. At the pharmacy, most clients (96%, 1136/1178) tested HIV-negative and reported PrEP (95%, 1122/1178) or PEP (1%, 14/1178) referral; the remainder (4%, 42/1178) tested HIV-positive and reported ART referral. The uptake of ART (90%, 38/42) and PEP (86%, 12/14) among clients referred was high. The uptake of PrEP was only 9% (101/1122) among those referred and prior PrEP use was the only characteristic significantly associated with initiation (aPR 2.45, 95% confidence interval 1.19 to 5.07).

CONCLUSIONS: Although offering free HIV testing at private pharmacies led to the identification and referral of clients who could benefit from HIV services, additional interventions (e.g., incentives, patient navigators) may be needed to support PrEP referral follow-through. Alternatively, new delivery models that circumvent the need for referrals, such as same-day PrEP initiation at pharmacies, should be considered.},
}

Humans
Kenya/epidemiology
*HIV Infections/diagnosis/prevention & control/drug therapy/epidemiology
Female
Male
Adult
*Referral and Consultation/statistics & numerical data
Pilot Projects
*Pharmacies/statistics & numerical data
*HIV Testing/statistics & numerical data
Pre-Exposure Prophylaxis/statistics & numerical data
Adolescent
Young Adult
Middle Aged
Patient Acceptance of Health Care/statistics & numerical data

@article {pmid39755256,
year = {2025},
author = {Hickey, CL and Zhang, MJ and Allbee-Johnson, M and Romee, R and Majhail, NS and Malki, MMA and Antin, JH and Benjamin, CL and Bredeson, C and Chhabra, S and Grunwald, MR and Inamoto, Y and Kanakry, CG and Milano, F and Soiffer, RJ and Solomon, SR and Spellman, SR and Brunstein, CG and Cutler, C},
title = {Donor Type Does Not Impact Late Graft Failure Following Reduced Intensity Allogeneic Hematopoietic Cell Transplantation with Post-Transplant Cyclophosphamide Based Graft-Versus-Host Disease Prophylaxis.},
journal = {Transplantation and cellular therapy},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jtct.2024.12.021},
pmid = {39755256},
issn = {2666-6367},
abstract = {BACKGROUND: Post-transplant cyclophosphamide (PTCy) is a commonly used graft-vs-host disease (GVHD) prophylaxis, particularly in the setting of haploidentical (haplo) hematopoietic cell transplantation (HCT). The rate of graft failure has been reported to be as high as 12-20% in haplo-HCT recipients using PTCy. The objective of this study was to determine if donor type influenced the risk of late graft failure following RIC HCT using PTCy-based GVHD prophylaxis.

STUDY DESIGN: A retrospective cohort analysis using the CIBMTR research database among adult patients who underwent first reduced intensity conditioning (RIC) haplo or 8/8 MUD HCT between 2011 and 2018 for AML, ALL or MDS with PTCy GVHD prophylaxis. The primary outcome was incidence of late graft failure, defined as secondary graft loss in the absence of relapse, or poor graft function requiring a cellular therapy intervention.

RESULTS: A total of 1336 patients met the eligibility criteria (1151 haplo, 185 MUD). Patients in the MUD group were older (65 vs 61), less ethnically diverse (95% vs 72% Caucasian), received fewer bone marrow grafts (45% vs 16%), and had younger donors (median age 28 vs 37 years old). Conditioning regimens were predominately fludarabine, cyclophosphamide and total body irradiation (87% haplo and 38% MUD). At 2 years, the adjusted probabilities of late graft failure for the haplo group was 6.5% ((95% confidence interval (CI) 5.2-8.0)) vs 5.9% (95% CI 2.7-10.9) for the MUD group (p=0.79). Multivariate analysis for risk factors associated with late graft failure found associations with a diagnosis of MDS (HR 1.98; 95% CI 1.22-3.20; p=0.005), and earlier year of HCT (2015-2018 vs. 2011-2014; HR 0.39; 95% CI 0.24-0.64; p=0.0002). A post-hoc sensitivity analysis was performed to evaluate the effect of donor age and use of PBSC grafts. Graft failure did not differ between haplo and MUD HCT (HR 1.19; p=0.67) when adjusted for donor age nor when restricted to PBSC grafts only (HR 0.85; p=0.70).

CONCLUSION: In this registry-based analysis of patients undergoing RIC HCT for AML, ALL or MDS using GVHD prophylaxis with PTCy, there was no significant difference in late graft failure rates between haplo and MUD donors. Overall rates of late graft failure were high.},
}

@article {pmid39755170,
year = {2025},
author = {Besse, B and Goto, K and Wang, Y and Lee, SH and Marmarelis, ME and Ohe, Y and Caro, RB and Kim, DW and Lee, JS and Cousin, S and Ichihara, E and Li, Y and Paz-Ares, L and Ono, A and Sanborn, RE and Watanabe, N and Jose de Miguel, M and Helissey, C and Shu, CA and Spira, AI and Tomasini, P and Chih-Hsin Yang, J and Zhang, Y and Felip, E and Griesinger, F and Waqar, SN and Calles, A and Neal, JW and Baik, CS and Jänne, PA and Shreeve, SM and Curtin, JC and Patel, B and Gormley, M and Lyu, X and Chen, J and Chu, PL and Mahoney, J and Trani, L and Bauml, JM and Thayu, M and Knoblauch, RE and Cho, BC},
title = {Amivantamab Plus Lazertinib in Patients With EGFR-mutant Non-small Cell Lung Cancer (NSCLC) After Progression on Osimertinib and Platinum-based Chemotherapy: Results From CHRYSALIS-2 Cohort A.},
journal = {Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jtho.2024.12.029},
pmid = {39755170},
issn = {1556-1380},
abstract = {INTRODUCTION: Treatment options for patients with epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC) with disease progression on/after osimertinib and platinum-based chemotherapy are limited.

METHODS: CHRYSALIS-2 Cohort A evaluated amivantamab+lazertinib in patients with EGFR exon 19 deletion- or L858R-mutated NSCLC with disease progression on/after osimertinib and platinum-based chemotherapy. Primary endpoint was investigator-assessed objective response rate (ORR). Patients received intravenous amivantamab 1050 mg (1400 mg if ≥80 kg) plus oral lazertinib 240 mg.

RESULTS: In Cohort A (n=162), investigator-assessed ORR was 28% (95% CI, 22-36). Blinded independent central review (BICR)-assessed ORR was 35% (95% CI, 27-42), with median duration of response (DoR) of 8.3 months (95% CI, 6.7-10.9) and clinical benefit rate of 58% (95% CI, 50-66). At a median follow-up of 12 months, 32/56 responders (57%) achieved a DoR ≥6 months. Median progression-free survival by BICR was 4.5 months (95% CI, 4.1-5.8); median overall survival was 14.8 months (95% CI, 12.2-18.0). Preliminary evidence of central nervous system-anti-tumor activity was reported among 7 patients with baseline brain lesions and no prior brain radiation/surgery. Exploratory biomarker analyses using circulating tumor DNA next-generation sequencing showed responses in patients with and without identified EGFR/MET-dependent resistance. Most frequent adverse events were rash (grouped term; 81%), infusion-related reaction (68%), and paronychia (52%). Most common grade ≥3 treatment-related adverse events were rash (grouped term; 10%), infusion-related reaction (9%), and hypoalbuminemia (6%).

CONCLUSIONS: For patients with limited treatment options, amivantamab+lazertinib demonstrated anti-tumor activity with a safety profile characterized by EGFR/MET-realated adverse events, which were generally manageable.},
}

@article {pmid39754855,
year = {2024},
author = {Hill, M and Garcia, LR and Nguyen, E and Korolkova, A and Cohn, L and Rodriguez, A and Hoh, R and Deeks, SG and Peluso, MJ and Sauceda, JA and Dubé, K},
title = {Evaluating the psychosocial experiences of participants in HIV cure research before, during, and after analytical treatment interruptions: A longitudinal qualitative study in the United States.},
journal = {Social science & medicine (1982)},
volume = {366},
number = {},
pages = {117644},
doi = {10.1016/j.socscimed.2024.117644},
pmid = {39754855},
issn = {1873-5347},
abstract = {The lack of socio-behavioral research on stress and psychosocial experiences among research participants who undergo analytical treatment interruption (ATI) in HIV cure studies underscores a critical gap in cure science. Existing literature acknowledges mixed and potentially adverse mental health impacts of ATIs among trial participants, but empirical insights before, during, and after clinical studies are scarce. We used longitudinal in-depth interviews with 11 participants in HIV cure-related research to explore their experiences with stress, coping, and psychological well-being before, during, and after an ATI. Our framework analyses of participant interviews suggest an evolving interplay between person- and environment-oriented factors that shape psychosocial well-being through multiple pathways. Key emergent themes surrounding stress, coping, and psychological adaptation before the ATI encompass the stress-protective effects of pill (in)significance, curiosity in natural immunological control, and perceived support, and trust with professional help networks comprised of providers and research staff. Themes that promoted positive secondary appraisals of stressors during ATIs involved generativity and meaning-based coping, and the stress-adaptive benefits of support-seeking and actualization. Finally, a theme exposing post-ATI stress revolved around the disappointment that participants noted feeling from needing to restart their HIV medications after the ATI and accepting the permanency of HIV and medications in their lives. Our findings emphasize the importance of building supportive and trusting relationships with research teams, and specify the stress-buffering mechanisms between emotional, informational, and appraisal support on ATI-related stress. Additionally, we outline multiple implications that advocate for the adoption of several precautionary measures in HIV cure research to mitigate psychosocial risks. By documenting the evolution of psychosocial experiences, we offer valuable insights to inform the design of future studies, ensuring their ethicality, acceptability, and inclusivity.},
}

@article {pmid39753771,
year = {2025},
author = {Jia, G and Chen, Z and Ping, J and Cai, Q and Tao, R and Li, C and Bauer, JA and Xie, Y and Ambs, S and Barnard, ME and Chen, Y and Choi, JY and Gao, YT and Garcia-Closas, M and Gu, J and Hu, JJ and Iwasaki, M and John, EM and Kweon, SS and Li, CI and Matsuda, K and Matsuo, K and Nathanson, KL and Nemesure, B and Olopade, OI and Pal, T and Park, SK and Park, B and Press, MF and Sanderson, M and Sandler, DP and Shen, CY and Troester, MA and Yao, S and Zheng, Y and Ahearn, T and Brewster, AM and Falusi, A and Hennis, AJM and Ito, H and Kubo, M and Lee, ES and Makumbi, T and Ndom, P and Noh, DY and O'Brien, KM and Ojengbede, O and Olshan, AF and Park, MH and Reid, S and Yamaji, T and Zirpoli, G and Butler, EN and Huang, M and Low, SK and Obafunwa, J and Weinberg, CR and Zhang, H and Zhao, H and Cote, ML and Ambrosone, CB and Huo, D and Li, B and Kang, D and Palmer, JR and Shu, XO and Haiman, CA and Guo, X and Long, J and Zheng, W},
title = {Refining breast cancer genetic risk and biology through multi-ancestry fine-mapping analyses of 192 risk regions.},
journal = {Nature genetics},
volume = {},
number = {},
pages = {},
pmid = {39753771},
issn = {1546-1718},
support = {R01CA202981//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; R01CA235553//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; R01CA148667//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; R01CA148667//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; },
abstract = {Genome-wide association studies have identified approximately 200 genetic risk loci for breast cancer, but the causal variants and target genes are mostly unknown. We sought to fine-map all known breast cancer risk loci using genome-wide association study data from 172,737 female breast cancer cases and 242,009 controls of African, Asian and European ancestry. We identified 332 independent association signals for breast cancer risk, including 131 signals not reported previously, and for 50 of them, we narrowed the credible causal variants down to a single variant. Analyses integrating functional genomics data identified 195 putative susceptibility genes, enriched in PI3K/AKT, TNF/NF-κB, p53 and Wnt/β-catenin pathways. Single-cell RNA sequencing or in vitro experiment data provided additional functional evidence for 105 genes. Our study uncovered large numbers of association signals and candidate susceptibility genes for breast cancer, uncovered breast cancer genetics and biology, and supported the value of including multi-ancestry data in fine-mapping analyses.},
}