@article {pmid30901049,
year = {2019},
author = {Caterino, JM and Adler, D and Durham, DD and Yeung, SJ and Hudson, MF and Bastani, A and Bernstein, SL and Baugh, CW and Coyne, CJ and Grudzen, CR and Henning, DJ and Klotz, A and Madsen, TE and Pallin, DJ and Reyes-Gibby, CC and Rico, JF and Ryan, RJ and Shapiro, NI and Swor, R and Venkat, A and Wilson, J and Thomas, CR and Bischof, JJ and Lyman, GH},
title = {Analysis of Diagnoses, Symptoms, Medications, and Admissions Among Patients With Cancer Presenting to Emergency Departments.},
journal = {JAMA network open},
volume = {2},
number = {3},
pages = {e190979},
doi = {10.1001/jamanetworkopen.2019.0979},
pmid = {30901049},
issn = {2574-3805},
abstract = {Importance: Better understanding of the emergency care needs of patients with cancer will inform outpatient and emergency department (ED) management.

Objective: To provide a benchmark description of patients who present to the ED with active cancer.

This multicenter prospective cohort study included 18 EDs affiliated with the Comprehensive Oncologic Emergencies Research Network (CONCERN). Of 1564 eligible patients, 1075 adults with active cancer were included from February 1, 2016, through January 30, 2017. Data were analyzed from February 1 through August 1, 2018.

Main Outcomes and Measures: The proportion of patients reporting symptoms (eg, pain, nausea) before and during the ED visit, ED and outpatient medications, most common diagnoses, and suspected infection as indicated by ED antibiotic administration. The proportions observed, admitted, and with a hospital length of stay (LOS) of no more than 2 days were identified.

Results: Of 1075 participants, mean (SD) age was 62 (14) years, and 51.8% were female. Seven hundred ninety-four participants (73.9%; 95% CI, 71.1%-76.5%) had undergone cancer treatment in the preceding 30 days; 674 (62.7%; 95% CI, 59.7%-65.6%) had advanced or metastatic cancer; and 505 (47.0%; 95% CI, 43.9%-50.0%) were 65 years or older. The 5 most common ED diagnoses were symptom related. Of all participants, 82 (7.6%; 95% CI, 6.1%-9.4%) were placed in observation and 615 (57.2%; 95% CI, 54.2%-60.2%) were admitted; 154 of 615 admissions (25.0%; 95% CI, 21.7%-28.7%) had an LOS of 2 days or less (median, 3 days; interquartile range, 2-6 days). Pain during the ED visit was present in 668 patients (62.1%; 95% CI, 59.2%-65.0%; mean [SD] pain score, 6.4 [2.6] of 10.0) and in 776 (72.2%) during the prior week. Opioids were administered in the ED to 228 of 386 patients (59.1%; 95% CI, 18.8%-23.8%) with moderate to severe ED pain. Outpatient opioids were prescribed to 368 patients (47.4%; 95% CI, 3.14%-37.2%) of those with pre-ED pain, including 244 of 428 (57.0%; 95% CI, 52.2%-61.8%) who reported quite a bit or very much pain. Nausea in the ED was present in 336 (31.3%; 95% CI, 28.5%-34.1%); of these, 160 (47.6%; 95% CI, 12.8%-17.1%) received antiemetics in the ED. Antibiotics were administered in the ED to 285 patients (26.5%; 95% CI, 23.9%-29.2%). Of these, 209 patients (73.3%; 95% CI, 17.1%-21.9%) were admitted compared with 427 of 790 (54.1%; 95% CI, 50.5%-57.6%) not receiving antibiotics.

Conclusions and Relevance: This initial prospective, multicenter study profiling patients with cancer who were treated in the ED identifies common characteristics in this patient population and suggests opportunities to optimize care before, during, and after the ED visit. Improvement requires collaboration between specialists and emergency physicians optimizing ED use, improving symptom control, avoiding unnecessary hospitalizations, and appropriately stratifying risk to ensure safe ED treatment and disposition of patients with cancer.},
}

@article {pmid30899120,
year = {2019},
author = {Fong, Y and Huang, Y},
title = {Modified Wilcoxon-Mann-Whitney Test and Power against Strong Null.},
journal = {The American statistician},
volume = {73},
number = {1},
pages = {43-49},
doi = {10.1080/00031305.2017.1328375},
pmid = {30899120},
issn = {0003-1305},
abstract = {The Wilcoxon-Mann-Whitney (WMW) test is a popular rank-based two-sample testing procedure for the strong null hypothesis that the two samples come from the same distribution. A modified WMW test, the Fligner-Policello (FP) test, has been proposed for comparing the medians of two populations. A fact that may be underappreciated among some practitioners is that the FP test can also be used to test the strong null like the WMW. In this paper we compare the power of the WMW and FP tests for testing the strong null. Our results show that neither test is uniformly better than the other and that there can be substantial differences in power between the two choices. We propose a new, modified WMW test that combines the WMW and FP tests. Monte Carlo studies show that the combined test has good power compared to either the WMW and FP test. We provide a fast implementation of the proposed test in an open-source software. Supplementary materials are available online.},
}

@article {pmid30898893,
year = {2019},
author = {Shin, YJ and Sa, JK and Lee, Y and Kim, D and Chang, N and Cho, HJ and Son, M and Oh, MYT and Shin, K and Lee, JK and Park, J and Jo, YK and Kim, M and Paddison, PJ and Tergaonkar, V and Lee, J and Nam, DH},
title = {PIP4K2A as a negative regulator of PI3K in PTEN-deficient glioblastoma.},
journal = {The Journal of experimental medicine},
volume = {},
number = {},
pages = {},
doi = {10.1084/jem.20172170},
pmid = {30898893},
issn = {1540-9538},
abstract = {Glioblastoma (GBM) is the most malignant brain tumor with profound genomic alterations. Tumor suppressor genes regulate multiple signaling networks that restrict cellular proliferation and present barriers to malignant transformation. While bona fide tumor suppressors such as PTEN and TP53 often undergo inactivation due to mutations, there are several genes for which genomic deletion is the primary route for tumor progression. To functionally identify putative tumor suppressors in GBM, we employed in vivo RNAi screening using patient-derived xenograft models. Here, we identified PIP4K2A, whose functional role and clinical relevance remain unexplored in GBM. We discovered that PIP4K2A negatively regulates phosphoinositide 3-kinase (PI3K) signaling via p85/p110 component degradation in PTEN-deficient GBMs and specifically targets p85 for proteasome-mediated degradation. Overexpression of PIP4K2A suppressed cellular and clonogenic growth in vitro and impeded tumor growth in vivo. Our results unravel a novel tumor-suppressive role of PIP4K2A for the first time and support the feasibility of combining oncogenomics with in vivo RNAi screen.},
}

@article {pmid30898265,
year = {2019},
author = {Sarthy, JF and Henikoff, S and Ahmad, K},
title = {Chromatin Bottlenecks in Cancer.},
journal = {Trends in cancer},
volume = {5},
number = {3},
pages = {183-194},
doi = {10.1016/j.trecan.2019.01.003},
pmid = {30898265},
issn = {2405-8025},
abstract = {Cancer accounts for ∼9 million deaths per year worldwide, predominantly affecting adults. Adult malignancies are usually examined after extensive clonal evolution and carry many mutations, obscuring the individual contributions of these alterations to oncogenesis. By contrast, pediatric cancers often contain few mutations, many of which cause defects in chromatin-associated proteins. We explore here the roles that chromatin plays in oncogenesis. We highlight how the developmental regulation of cell proliferation genes and the degradation of chromosome ends are two major bottlenecks in the evolution of malignant cells, and point to a third bottleneck where epigenomic dysfunction triggers expression of tumor-suppressor genes, limiting the development of aggressive and metastatic features in tumors. We also identify opportunities for chromatin-based therapies.},
}

@article {pmid30898164,
year = {2019},
author = {Ishengoma, DS and Mandara, CI and Francis, F and Talundzic, E and Lucchi, NW and Ngasala, B and Kabanywanyi, AM and Mahende, MK and Kamugisha, E and Kavishe, RA and Muro, F and Mohamed, A and Mandike, R and Mkude, S and Chacky, F and Paxton, L and Greer, G and Kitojo, CA and Njau, R and Martin, T and Venkatesan, M and Warsame, M and Halsey, ES and Udhayakumar, V},
title = {Efficacy and safety of artemether-lumefantrine for the treatment of uncomplicated malaria and prevalence of Pfk13 and Pfmdr1 polymorphisms after a decade of using artemisinin-based combination therapy in mainland Tanzania.},
journal = {Malaria journal},
volume = {18},
number = {1},
pages = {88},
doi = {10.1186/s12936-019-2730-1},
pmid = {30898164},
issn = {1475-2875},
abstract = {BACKGROUND: The World Health Organization recommends regular therapeutic efficacy studies (TES) to monitor the performance of first and second-line anti-malarials. In 2016, efficacy and safety of artemether-lumefantrine (AL) for the treatment of uncomplicated falciparum malaria were assessed through a TES conducted between April and October 2016 at four sentinel sites of Kibaha, Mkuzi, Mlimba, and Ujiji in Tanzania. The study also assessed molecular markers of artemisinin and lumefantrine (partner drug) resistance.

METHODS: Eligible patients were enrolled at the four sites, treated with standard doses of AL, and monitored for 28 days with clinical and laboratory assessments. The main outcomes were PCR corrected cure rates, day 3 positivity rates, safety of AL, and prevalence of single nucleotide polymorphisms in Plasmodium falciparum kelch 13 (Pfk13) (codon positions: 440-600) and P. falciparum multi-drug resistance 1 (Pfmdr1) genes (codons: N86Y, Y184F and D1246Y), markers of artemisinin and lumefantrine resistance, respectively.

RESULTS: Of 344 patients enrolled, three withdrew, six were lost to follow-up; and results were analysed for 335 (97.4%) patients. Two patients had treatment failure (one early treatment failure and one recrudescent infection) after PCR correction, yielding an adequate clinical and parasitological response of > 98%. Day 3 positivity rates ranged from 0 to 5.7%. Common adverse events included cough, abdominal pain, vomiting, and diarrhoea. Two patients had serious adverse events; one died after the first dose of AL and another required hospitalization after the second dose of AL (on day 0) but recovered completely. Of 344 samples collected at enrolment (day 0), 92.7% and 100% were successfully sequenced for Pfk13 and Pfmdr1 genes, respectively. Six (1.9%) had non-synonymous mutations in Pfk13, none of which had been previously associated with artemisinin resistance. For Pfmdr1, the NFD haplotype (codons N86, 184F and D1246) was detected in 134 (39.0%) samples; ranging from 33.0% in Mlimba to 45.5% at Mkuzi. The difference among the four sites was not significant (p = 0.578). All samples had a single copy of the Pfmdr1 gene.

CONCLUSION: The study indicated high efficacy of AL and the safety profile was consistent with previous reports. There were no known artemisinin-resistance Pfk13 mutations, but there was a high prevalence of a Pfmdr1 haplotype associated with reduced sensitivity to lumefantrine (but no reduced efficacy was observed in the subjects). Continued TES and monitoring of markers of resistance to artemisinin and partner drugs is critical for early detection of resistant parasites and to inform evidence-based malaria treatment policies. Trial Registration ClinicalTrials.gov NCT03387631.},
}

@article {pmid30896747,
year = {2019},
author = {Disis, MLN},
title = {JAMA Oncology-The Year in Review, 2018.},
journal = {JAMA oncology},
volume = {},
number = {},
pages = {},
doi = {10.1001/jamaoncol.2019.0231},
pmid = {30896747},
issn = {2374-2445},
}

@article {pmid30892988,
year = {2019},
author = {Wei, AH and Strickland, SA and Hou, JZ and Fiedler, W and Lin, TL and Walter, RB and Enjeti, A and Tiong, IS and Savona, M and Lee, S and Chyla, B and Popovic, R and Salem, AH and Agarwal, S and Xu, T and Fakouhi, KM and Humerickhouse, R and Hong, WJ and Hayslip, J and Roboz, GJ},
title = {Venetoclax Combined With Low-Dose Cytarabine for Previously Untreated Patients With Acute Myeloid Leukemia: Results From a Phase Ib/II Study.},
journal = {Journal of clinical oncology : official journal of the American Society of Clinical Oncology},
volume = {},
number = {},
pages = {JCO1801600},
doi = {10.1200/JCO.18.01600},
pmid = {30892988},
issn = {1527-7755},
abstract = {PURPOSE: Effective treatment options are limited for patients with acute myeloid leukemia (AML) who cannot tolerate intensive chemotherapy. An international phase Ib/II study evaluated the safety and preliminary efficacy of venetoclax, a selective B-cell leukemia/lymphoma-2 inhibitor, together with low-dose cytarabine (LDAC) in older adults with AML.

PATIENTS AND METHODS: Adults 60 years or older with previously untreated AML ineligible for intensive chemotherapy were enrolled. Prior treatment of myelodysplastic syndrome, including hypomethylating agents (HMA), was permitted. Eighty-two patients were treated at the recommended phase II dose: venetoclax 600 mg per day orally in 28-day cycles, with LDAC (20 mg/m2 per day) administered subcutaneously on days 1 to 10. Key end points were tolerability, safety, response rates, duration of response (DOR), and overall survival (OS).

RESULTS: Median age was 74 years (range, 63 to 90 years), 49% had secondary AML, 29% had prior HMA treatment, and 32% had poor-risk cytogenetic features. Common grade 3 or greater adverse events were febrile neutropenia (42%), thrombocytopenia (38%), and WBC count decreased (34%). Early (30-day) mortality was 6%. Fifty-four percent achieved complete remission (CR)/CR with incomplete blood count recovery (median time to first response, 1.4 months). The median OS was 10.1 months (95% CI, 5.7 to 14.2), and median DOR was 8.1 months (95% CI, 5.3 to 14.9 months). Among patients without prior HMA exposure, CR/CR with incomplete blood count recovery was achieved in 62%, median DOR was 14.8 months (95% CI, 5.5 months to not reached), and median OS was 13.5 months (95% CI, 7.0 to 18.4 months).

CONCLUSION: Venetoclax plus LDAC has a manageable safety profile, producing rapid and durable remissions in older adults with AML ineligible for intensive chemotherapy. High remission rate and low early mortality combined with rapid and durable remission make venetoclax and LDAC an attractive and novel treatment for older adults not suitable for intensive chemotherapy.},
}

@article {pmid30892118,
year = {2019},
author = {Sridharan, V and Shoda, Y and Heffner, JL and Bricker, J},
title = {Addiction Mindsets and Psychological Processes of Quitting Smoking.},
journal = {Substance use & misuse},
volume = {},
number = {},
pages = {1-10},
doi = {10.1080/10826084.2018.1555259},
pmid = {30892118},
issn = {1532-2491},
abstract = {BACKGROUND: Lay belief systems about the malleability of human attributes have been shown to impact behavior change in multiple domains. Addiction mindset-i.e., beliefs about the permanence (vs. malleability) of addiction - may affect cigarette smokers' ability to quit, but this has never been examined.

OBJECTIVES: The aims of the present research were to develop a measure of addiction mindset (study 1) and examine its associations with various psychological aspects of quitting smoking (study 2).

METHODS: In Study 1, using factor analysis of current smokers' and nonsmokers' (n = 600) responses to 22 items designed to measure addiction mindset, we developed a reliable six-item Addiction Mindset Scale (AMS). In Study 2, adult smokers (n = 200) completed the AMS, and measures of a number of psychological processes related to smoking.

RESULTS: Higher scores on the AMS, indicative of the belief that addiction is malleable (referred to as a growth mindset), were positively and significantly associated with greater motivation to quit, greater commitment to quitting, greater self-efficacy to abstain, less attribution of failure to lack of ability to change addiction, and fewer self-reported barriers to cessation (all p's < .05).

CONCLUSIONS: The results of this study show a relationship between the beliefs about the permanence of addiction and psychological processes relevant to quitting smoking. The findings underscore the potential of future research exploring how addiction mindsets relate to successful smoking cessation as well as other types of addictive behavior and how they can be applied to change people's behavior.},
}

@article {pmid30892059,
year = {2019},
author = {Brusniak, MY and Christianson, C and Witthuhn, E and Needham, S and Olson, JM},
title = {Simultaneous extraction and analysis of multiple cystine-dense peptides by μSPE and microflow-MS/MS from plasma.},
journal = {Bioanalysis},
volume = {},
number = {},
pages = {},
doi = {10.4155/bio-2018-0276},
pmid = {30892059},
issn = {1757-6199},
abstract = {AIM: Develop a universal extraction and liquid chromatography-mass spectrometer method to simultaneously analyze cystine-dense peptide (CDP) miniproteins from rat and human plasma. The results of the analysis will be used to assist selection of therapeutic drug candidates from the vast CDP library.

METHODS & RESULTS: A micro-elution solid-phase extraction method was developed for the sample preparation of the CDP peptides in rat and human plasma followed by analysis by microflow liquid chromatography MS/MS. The methods developed for drug discovery were found to be accurate (±≤15.2% from nominal concentrations) and precise (≤13.4% CV), with a dynamic range of 1.00-500 ng/ml and extraction recoveries of 47.2-99.0%.

CONCLUSION: This bioanalytical method can be utilized to screen CDP proteins and other miniproteins for drug discovery, candidate selection and further drug development.},
}

@article {pmid30892052,
year = {2019},
author = {Bull, M and McKernan, J and Styrchak, S and Kraft, K and Hitti, J and Cohn, SE and Tapia, K and Deng, W and Holte, S and Mullins, JI and Coombs, RW and Frenkel, L},
title = {Phylogenetic analyses comparing HIV sequences from plasma at virologic failure to cervix vs. blood sequences from antecedent antiretroviral therapy suppression.},
journal = {AIDS research and human retroviruses},
volume = {},
number = {},
pages = {},
doi = {10.1089/AID.2018.0211},
pmid = {30892052},
issn = {1931-8405},
abstract = {INTRODUCTION: Identifying tissue sources of HIV that rebound following "failure" of antiretroviral therapy (ART) is critical to evaluating cure strategies. To assess the role of the uterine cervix and peripheral blood mononuclear cells (PBMC) as viral reservoirs, nearest-neighbor phylogenetic analyses compared genetic relatedness of tissue sequences during ART-suppression to those detected in plasma at viral rebound.

METHODS: Blood and genital tract specimens from a natural history cohort of HIV-infected women were collected over five years. HIV DNA sequences extracted from PBMC and cervical biopsies during ART-suppression and plasma RNA from rebound (defined as HIV RNA >3 log10 copies/mL) were derived by single-genome-amplification. Phylogenetic and nearest-neighbor analyses of HIV env sequences and drug resistance in pol sequences were compared between tissues.

RESULTS: Nine instances of plasma viral rebound (median HIV RNA 3.6 log10 c/mL; IQR: 3.1-3.8) were detected in 7 of 57 women. Nearest-neighbor analyses found rebound plasma sequences were closer to uterine cervical sequences in 4/9 (44%), closer to PBMC in 3/9 (33%), and ambiguous in 2/9 (22%) cases. Rebound plasma clades (n=27) shared identical sequences in 7 instances with the cervix vs. 2 with PBMC. Novel drug resistance mutations were detected in 4/9 (44%) rebounds.

CONCLUSIONS: The observed tendency for greater sharing of identical HIV variants and greater nearest-neighbor association between rebounding plasma and uterine cervical vs. PBMC sequences suggests that the uterine cervix may be a relevant HIV reservoir. The cervix, a readily accessible tissue in women, that can be repeatedly sampled, could help assess the HIV reservoir when evaluating cure strategies.},
}

@article {pmid30890759,
year = {2019},
author = {Alsinnawi, M and Zhang, A and Bianchi-Frias, D and Burns, J and Cho, E and Zhang, X and Sowalsky, A and Ye, H and Slee, AE and True, L and Porter, C and Taplin, ME and Balk, S and Nelson, PS and Montgomery, RB and Mostaghel, EA},
title = {Association of prostate cancer SLCO gene expression with Gleason grade and alterations following androgen deprivation therapy.},
journal = {Prostate cancer and prostatic diseases},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41391-019-0141-6},
pmid = {30890759},
issn = {1476-5608},
support = {W81XWH-11-2-0154//U.S. Department of Defense (United States Department of Defense)/ ; W81XWH-13-1-0267//U.S. Department of Defense (United States Department of Defense)/ ; W81XWH-16-1-0432//U.S. Department of Defense (United States Department of Defense)/ ; W81XWH-16-1-0431//U.S. Department of Defense (United States Department of Defense)/ ; Challenge Award//Prostate Cancer Foundation (PCF)/ ; YIA//Prostate Cancer Foundation (PCF)/ ; YIA//Prostate Cancer Foundation (PCF)/ ; Challenge Award//Prostate Cancer Foundation (PCF)/ ; Challenge Award//Prostate Cancer Foundation (PCF)/ ; Challenge Award//Prostate Cancer Foundation (PCF)/ ; Challenge Award//Prostate Cancer Foundation (PCF)/ ; P50 CA097186//U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)/ ; 5P30 CA015704-40//U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)/ ; P50 CA090381//U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)/ ; P50 CA090381//U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)/ ; P50 CA097186//U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)/ ; P50 CA090381//U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)/ ; P50 CA097186//U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)/ ; 5P30 CA015704-40//U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)/ ; P01 CA163227//U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)/ ; P50 CA097186//U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)/ ; P50 CA090381//U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)/ ; },
abstract = {BACKGROUND: SLCO-encoded transporters have been associated with progression to castration-resistant prostate cancer (CRPC) after initiation of androgen deprivation therapy (ADT). Although expressed at lower levels than in CRPC tissues, SLCO-encoded transporters may also play a role in response of primary prostate cancer (PCa) to ADT and biochemical recurrence.

METHODS: We systematically explored expression of the 11 human SLCO genes in a large sample of untreated and ADT-treated normal prostate (NP) and primary PCa tissues, including tumors treated with neoadjuvant abiraterone.

RESULTS: Transporters with the most recognized role in steroid uptake in PCa, including SLCO2B1 (DHEAS) and 1B3 (testosterone), were consistently detected in primary PCa. SLCO1B3 was nearly 5-fold higher in PCa vs NP with no difference in Gleason 3 vs 4 and no change with ADT. SLCO2B1 was detected at 3-fold lower levels in PCa than NP but was nearly 7-fold higher in Gleason 4 vs Gleason 3 and increased 3-fold following ADT (p < 0.05 for all).

CONCLUSIONS: We observed clear differences in SLCO expression in PCa vs NP samples, in Gleason 4 vs Gleason 3 tumors, and in ADT-treated vs untreated tissues. These findings are hypothesis generating due to small sample size, but suggest that baseline and ADT-induced changes in PCa OATP expression may influence steroid uptake and response to ADT, as well as uptake and response to drugs such as abiraterone and docetaxel which are also subject to OATP-mediated transport and are now being routinely combined with ADT in the metastatic castration sensitive setting.},
}

@article {pmid30890385,
year = {2019},
author = {Selinger, C and Bershteyn, A and Dimitrov, DT and Adamson, BJS and Revill, P and Hallett, TB and Phillips, AN and Bekker, LG and Rees, H and Gray, G},
title = {Targeting and vaccine durability are key for population-level impact and cost-effectiveness of a pox-protein HIV vaccine regimen in South Africa.},
journal = {Vaccine},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.vaccine.2019.02.073},
pmid = {30890385},
issn = {1873-2518},
abstract = {BACKGROUND: RV144 is to date the only HIV vaccine trial to demonstrate efficacy, albeit rapidly waning over time. The HVTN 702 trial is currently evaluating in South Africa a similar vaccine formulation to that of RV144 for subtype C HIV with additional boosters (pox-protein regimen). Using a detailed stochastic individual-based network model of disease transmission calibrated to the HIV epidemic, we investigate population-level impact and maximum cost of an HIV vaccine to remain cost-effective.

METHODS: Consistent with the original pox-protein regimen, we model a primary series of five vaccinations meeting the goal of 50% cumulative efficacy 24 months after the first dose and include two-yearly boosters that maintain durable efficacy over 10 years. We simulate vaccination programs in South Africa starting in 2027 under various vaccine targeting and HIV treatment and prevention assumptions.

RESULTS: Our analysis shows that this partially effective vaccine could prevent, at catch-up vaccination with 60% coverage, up to 941,000 (15.6%) new infections between 2027 and 2047 assuming current trends of antiretroviral treatment. An impact of up to 697,000 (11.5%) infections prevented could be achieved by targeting age cohorts of highest incidence. Economic evaluation indicates that, if treatment scale-up was achieved, vaccination could be cost-effective at a total cost of less than $385 and $62 per 10-year series (cost-effectiveness thresholds of $5,691 and $750).

CONCLUSIONS: While a partially effective, rapidly waning vaccine could help to prevent HIV infections, it will not eliminate HIV as a public health priority in sub-Saharan Africa. Vaccination is expected to be most effective under targeted delivery to age groups of highest HIV incidence. Awaiting results of trial, the introduction of vaccination should go in parallel with continued innovation in HIV prevention, including studies to determine the costs of delivery and feasibility and further research into products with greater efficacy and durability.},
}

@article {pmid30889382,
year = {2019},
author = {Srivastava, S and Salter, AI and Liggitt, D and Yechan-Gunja, S and Sarvothama, M and Cooper, K and Smythe, KS and Dudakov, JA and Pierce, RH and Rader, C and Riddell, SR},
title = {Logic-Gated ROR1 Chimeric Antigen Receptor Expression Rescues T Cell-Mediated Toxicity to Normal Tissues and Enables Selective Tumor Targeting.},
journal = {Cancer cell},
volume = {35},
number = {3},
pages = {489-503.e8},
doi = {10.1016/j.ccell.2019.02.003},
pmid = {30889382},
issn = {1878-3686},
abstract = {Many potential targets for CAR-T cells in solid tumors are expressed in some normal tissues, raising concern for off-tumor toxicity. Following lymphodepletion, CAR-T cells targeting the tumor-associated antigen ROR1 lysed tumors in mice but induced lethal bone marrow failure due to recognition of ROR1+ stromal cells. To improve selectivity, we engineered T cells with synthetic Notch (synNotch) receptors specific for EpCAM or B7-H3, which are expressed on ROR1+ tumor cells but not ROR1+ stromal cells. SynNotch receptors induced ROR1 CAR expression selectively within the tumor, resulting in tumor regression without toxicity when tumor cells were segregated from, but not when co-localized with, normal ROR1+ cells. This strategy, thus, permits safe targeting of tumors that are sufficiently separated from normal cells.},
}

@article {pmid30887029,
year = {2019},
author = {Ma, J and Karnovsky, A and Afshinnia, F and Wigginton, J and Rader, DJ and Natarajan, L and Sharma, K and Porter, AC and Rahman, M and He, J and Hamm, L and Shafi, T and Gipson, D and Gadegbeku, C and Feldman, H and Michailidis, G and Pennathur, S},
title = {Differential network enrichment analysis reveals novel lipid pathways in chronic kidney disease.},
journal = {Bioinformatics (Oxford, England)},
volume = {},
number = {},
pages = {},
doi = {10.1093/bioinformatics/btz114},
pmid = {30887029},
issn = {1367-4811},
abstract = {MOTIVATION: Functional enrichment testing methods can reduce data comprising hundreds of altered biomolecules to smaller sets of altered biological 'concepts' that help generate testable hypotheses. This study leveraged differential network enrichment analysis methodology to identify and validate lipid subnetworks that potentially differentiate chronic kidney disease (CKD) by severity or progression.

RESULTS: We built a partial correlation interaction network, identified highly connected network components, applied network-based gene-set analysis to identify differentially enriched subnetworks, and compared the subnetworks in patients with early-stage versus late-stage CKD. We identified two subnetworks 'triacylglycerols' and 'cardiolipins-phosphatidylethanolamines (CL-PE)' characterized by lower connectivity, and a higher abundance of longer polyunsaturated triacylglycerols in patients with severe CKD (stage ≥4) from the Clinical Phenotyping Resource and Biobank Core. These finding were replicated in an independent cohort, the Chronic Renal Insufficiency Cohort. Using an innovative method for elucidating biological alterations in lipid networks, we demonstrated alterations in triacylglycerols and cardiolipins-phosphatidylethanolamines that precede the clinical outcome of end-stage kidney disease by several years.

A complete list of NetGSA results in HTML format can be found at http://metscape.ncibi.org/netgsa/12345-022118/cric_cprobe/022118/results_cric_cprobe/main.html. The DNEA is freely available at https://github.com/wiggie/DNEA. Java wrapper leveraging the cytoscape.js framework is available at http://js.cytoscape.org.

SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.},
}

@article {pmid30886357,
year = {2019},
author = {Setoh, YX and Amarilla, AA and Peng, NYG and Griffiths, RE and Carrera, J and Freney, ME and Nakayama, E and Ogawa, S and Watterson, D and Modhiran, N and Nanyonga, FE and Torres, FJ and Slonchak, A and Periasamy, P and Prow, NA and Tang, B and Harrison, J and Hobson-Peters, J and Cuddihy, T and Cooper-White, J and Hall, RA and Young, PR and Mackenzie, JM and Wolvetang, E and Bloom, JD and Suhrbier, A and Khromykh, AA},
title = {Determinants of Zika virus host tropism uncovered by deep mutational scanning.},
journal = {Nature microbiology},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41564-019-0399-4},
pmid = {30886357},
issn = {2058-5276},
abstract = {Arboviruses cycle between, and replicate in, both invertebrate and vertebrate hosts, which for Zika virus (ZIKV) involves Aedes mosquitoes and primates1. The viral determinants required for replication in such obligate hosts are under strong purifying selection during natural virus evolution, making it challenging to resolve which determinants are optimal for viral fitness in each host. Herein we describe a deep mutational scanning (DMS) strategy2-5 whereby a viral cDNA library was constructed containing all codon substitutions in the C-terminal 204 amino acids of ZIKV envelope protein (E). The cDNA library was transfected into C6/36 (Aedes) and Vero (primate) cells, with subsequent deep sequencing and computational analyses of recovered viruses showing that substitutions K316Q and S461G, or Q350L and T397S, conferred substantial replicative advantages in mosquito and primate cells, respectively. A 316Q/461G virus was constructed and shown to be replication-defective in mammalian cells due to severely compromised virus particle formation and secretion. The 316Q/461G virus was also highly attenuated in human brain organoids, and illustrated utility as a vaccine in mice. This approach can thus imitate evolutionary selection in a matter of days and identify amino acids key to the regulation of virus replication in specific host environments.},
}

@article {pmid30886348,
year = {2019},
author = {Talbert, PB and Meers, MP and Henikoff, S},
title = {Old cogs, new tricks: the evolution of gene expression in a chromatin context.},
journal = {Nature reviews. Genetics},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41576-019-0105-7},
pmid = {30886348},
issn = {1471-0064},
abstract = {Sophisticated gene-regulatory mechanisms probably evolved in prokaryotes billions of years before the emergence of modern eukaryotes, which inherited the same basic enzymatic machineries. However, the epigenomic landscapes of eukaryotes are dominated by nucleosomes, which have acquired roles in genome packaging, mitotic condensation and silencing parasitic genomic elements. Although the molecular mechanisms by which nucleosomes are displaced and modified have been described, just how transcription factors, histone variants and modifications and chromatin regulators act on nucleosomes to regulate transcription is the subject of considerable ongoing study. We explore the extent to which these transcriptional regulatory components function in the context of the evolutionarily ancient role of chromatin as a barrier to processes acting on DNA and how chromatin proteins have diversified to carry out evolutionarily recent functions that accompanied the emergence of differentiation and development in multicellular eukaryotes.},
}

@article {pmid30886145,
year = {2019},
author = {Tsang, TK and Ghebremariam, SL and Gresh, L and Gordon, A and Halloran, ME and Katzelnick, LC and Rojas, DP and Kuan, G and Balmaseda, A and Sugimoto, J and Harris, E and Longini, IM and Yang, Y},
title = {Effects of infection history on dengue virus infection and pathogenicity.},
journal = {Nature communications},
volume = {10},
number = {1},
pages = {1246},
doi = {10.1038/s41467-019-09193-y},
pmid = {30886145},
issn = {2041-1723},
abstract = {The understanding of immunological interactions among the four dengue virus (DENV) serotypes and their epidemiological implications is often hampered by the lack of individual-level infection history. Using a statistical framework that infers full infection history, we analyze a prospective pediatric cohort in Nicaragua to characterize how infection history modulates the risks of DENV infection and subsequent clinical disease. After controlling for age, one prior infection is associated with 54% lower, while two or more are associated with 91% higher, risk of a new infection, compared to DENV-naive children. Children >8 years old have 55% and 120% higher risks of infection and subsequent disease, respectively, than their younger peers. Among children with ≥1 prior infection, intermediate antibody titers increase, whereas high titers lower, the risk of subsequent infection, compared with undetectable titers. Such complex dependency needs to be considered in the design of dengue vaccines and vaccination strategies.},
}

@article {pmid30884788,
year = {2019},
author = {Schübel, R and Sookthai, D and Greimel, J and Johnson, TS and Grafetstätter, ME and Kirsten, R and Kratz, M and Ulrich, CM and Kaaks, R and Kühn, T},
title = {Key Genes of Lipid Metabolism and WNT-Signaling Are Downregulated in Subcutaneous Adipose Tissue with Moderate Weight Loss.},
journal = {Nutrients},
volume = {11},
number = {3},
pages = {},
doi = {10.3390/nu11030639},
pmid = {30884788},
issn = {2072-6643},
support = {Metabolic Dysfunction//Helmholtz Association/ ; },
abstract = {Smaller cross-sectional studies and bariatric surgery trials suggest that weight loss may change the expression of genes in adipose tissue that have been implicated in the development of metabolic diseases, but well-powered intervention trials are lacking. In post hoc analyses of data from a 12-week dietary intervention trial initially designed to compare metabolic effects of intermittent vs. continuous calorie restriction, we analyzed the effects of overall weight loss on the subcutaneous adipose tissue (SAT) transcriptome. Changes in the transcriptome were measured by microarray using SAT samples of 138 overweight or obese individuals (age range: 35⁻65 years, BMI range: 25⁻40, non-smokers, non-diabetics). Participants were grouped post hoc according to the degree of their weight loss by quartiles (average weight loss in quartiles 1 to 4: 0%, -3.2%, -5.9%, and -10.7%). Candidate genes showing differential expression with weight loss according to microarray analyses were validated by reverse transcription quantitative polymerase chain reaction (RT-qPCR), and fold changes (FCs) were calculated to quantify differences in gene expression. A comparison of individuals in the highest vs. the lowest weight loss quartile revealed 681 genes to be differentially expressed (corrected p < 0.05), with 40 showing FCs of at least 0.4. Out of these, expression changes in secreted frizzled-related protein 2 (SFRP2, FC = 0.65, p = 0.006), stearoyl-CoA desaturase (SCD, FC = -1.00, p < 0.001), and hypoxia inducible lipid droplet-associated (HILPDA, FC = -0.45, p = 0.001) with weight loss were confirmed by RT-qPCR. Dietary weight loss induces significant changes in the expression of genes implicated in lipid metabolism (SCD and HILPDA) and WNT-signaling (SFRP2) in SAT.},
}

@article {pmid30883261,
year = {2019},
author = {Singhvi, A and Shaham, S},
title = {Glia-Neuron Interactions in Caenorhabditis elegans.},
journal = {Annual review of neuroscience},
volume = {},
number = {},
pages = {},
doi = {10.1146/annurev-neuro-070918-050314},
pmid = {30883261},
issn = {1545-4126},
abstract = {Glia are abundant components of animal nervous systems. Recognized 170 years ago, concerted attempts to understand these cells began only recently. From these investigations glia, once considered passive filler material in the brain, have emerged as active players in neuron development and activity. Glia are essential for nervous system function, and their disruption leads to disease. The nematode Caenorhabditis elegans possesses glial types similar to vertebrate glia, based on molecular, morphological, and functional criteria, and has become a powerful model in which to study glia and their neuronal interactions. Facile genetic and transgenic methods in this animal allow the discovery of genes required for glial functions, and effects of glia at single synapses can be monitored by tracking neuron shape, physiology, or animal behavior. Here, we review recent progress in understanding glia-neuron interactions in C. elegans. We highlight similarities with glia in other animals, and suggest conserved emerging principles of glial function. Expected final online publication date for the Annual Review of Neuroscience Volume 42 is July 8, 2019. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.},
}

@article {pmid30879508,
year = {2019},
author = {Yuan, T and Fitzpatrick, T and Ko, NY and Cai, Y and Chen, Y and Zhao, J and Li, L and Xu, J and Gu, J and Li, J and Hao, C and Yang, Z and Cai, W and Cheng, CY and Luo, Z and Zhang, K and Wu, G and Meng, X and Grulich, AE and Hao, Y and Zou, H},
title = {Circumcision to prevent HIV and other sexually transmitted infections in men who have sex with men: a systematic review and meta-analysis of global data.},
journal = {The Lancet. Global health},
volume = {7},
number = {4},
pages = {e436-e447},
doi = {10.1016/S2214-109X(18)30567-9},
pmid = {30879508},
issn = {2214-109X},
abstract = {BACKGROUND: Men who have sex with men (MSM) are disproportionately affected by HIV and other sexually transmitted infections (STIs) worldwide. Previous reviews investigating the role of circumcision in preventing HIV and other STIs among MSM were inconclusive. Many new studies have emerged in the past decade. To inform global prevention strategies for HIV and other STIs among MSM, we reviewed all available evidence on the associations between circumcision and HIV and other STIs among MSM.

METHODS: In this systematic review and meta-analysis, we searched PubMed, Web of Science, BioMed Central, Scopus, ResearchGate, Cochrane Library, Embase, PsycINFO, Google Scholar, and websites of international HIV and STI conferences for studies published before March 8, 2018. Interventional or observational studies containing original quantitative data describing associations between circumcision and incident or prevalent infection of HIV and other STIs among MSM were included. Studies were excluded if MSM could not be distinguished from men who have sex with women only. We calculated pooled odds ratios (ORs) and their 95% CIs using random-effect models. We assessed risk of bias using the Newcastle-Ottawa scale.

FINDINGS: We identified 62 observational studies including 119 248 MSM. Circumcision was associated with 23% reduced odds of HIV infection among MSM overall (OR 0·77, 95% CI 0·67-0·89; number of estimates [k]=45; heterogeneity I2=77%). Circumcision was protective against HIV infection among MSM in countries of low and middle income (0·58, 0·41-0·83; k=23; I2=77%) but not among MSM in high-income countries (0·99, 0·90-1·09; k=20; I2=40%). Circumcision was associated with reduced odds of herpes simplex virus (HSV) infection among MSM overall (0·84, 0·75-0·95; k=5; I2=0%) and penile human papillomavirus (HPV) infection among HIV-infected MSM (0·71, 0·51-0·99; k=3; I2=0%).

INTERPRETATION: We found evidence that circumcision is likely to protect MSM from HIV infection, particularly in countries of low and middle income. Circumcision might also protect MSM from HSV and penile HPV infection. MSM should be included in campaigns promoting circumcision among men in countries of low and middle income. In view of the substantial proportion of MSM in countries of low and middle income who also have sex with women, well designed longitudinal studies differentiating MSM only and bisexual men are needed to clarify the effect of circumcision on male-to-male transmission of HIV and other STIs.

FUNDING: National Natural Science Foundation of China, National Science and Technology Major Project of China, Australian National Health and Medical Research Council Early Career Fellowship, Sanming Project of Medicine in Shenzhen, National Institutes of Health, Mega Projects of National Science Research for the 13th Five-Year Plan, Doris Duke Charitable Foundation.},
}

@article {pmid30877760,
year = {2019},
author = {Kaluza, J and Harris, HR and Linden, A and Wolk, A},
title = {Alcohol Consumption and Risk of Chronic Obstructive Pulmonary Disease: A Prospective Cohort Study of Men.},
journal = {American journal of epidemiology},
volume = {},
number = {},
pages = {},
doi = {10.1093/aje/kwz020},
pmid = {30877760},
issn = {1476-6256},
abstract = {Studies indicate an inverse association between moderate alcohol consumption and chronic inflammatory diseases; however, the association between alcohol consumption and chronic obstructive pulmonary disease (COPD) incidence has not been widely studied. We investigated the associations of total alcohol consumption and intake of specific alcoholic beverages with risk of COPD in a population-based prospective cohort study, the Cohort of Swedish Men (n = 44,254). Alcohol consumption was assessed with a self-administered questionnaire in 1997. During follow-up (1998-2014), 2,177 COPD cases were ascertained. Moderate alcohol consumption was associated with the lowest risk of COPD. A J-shaped association was observed for ethanol consumption (P for nonlinearity = 0.003) and beer consumption (P for nonlinearity < 0.001); for wine consumption, a U-shaped association was observed (P for nonlinearity < 0.001). Defining a "standard drink" as 12 g of ethanol, the multivariable-adjusted hazard ratios were 0.77 (95% confidence interval (CI): 0.66, 0.90) and 0.92 (95% CI: 0.81, 1.05) for beer consumption of 4.1-6.0 and >6.0 standard drinks/week (SDW) versus <1.0 SDW, respectively; 0.80 (95% CI: 0.69, 0.93) and 1.00 (95% CI: 0.83, 1.21) for wine consumption of 2.0-4.0 and >4.0 SDW versus <1.0 SDW, respectively; and 1.10 (95% CI: 0.98, 1.24) and 1.20 (95% CI: 0.99, 1.44) for liquor consumption of 2.0-4.0 and >4.0 SDW versus <1.0 SDW, respectively. In conclusion, our findings suggest that moderate beer and wine consumption, but not liquor consumption, may decrease risk of COPD. Additional studies are needed to confirm these associations.},
}

@article {pmid30877580,
year = {2019},
author = {Bauermeister, JA and Golinkoff, JM and Carballo-Diéguez, A and Giguere, R and López, D and Hoesley, CJ and Chen, BA and Anderson, P and Dezzutti, CS and Strizki, J and Sprinkle, C and Heard, F and Hall, W and Jacobson, C and Berthiaume, J and Mayo, A and Richardson, BA and Piper, J and , },
title = {A Mixed-Methods Study Examining Adherence to and Acceptability of Intravaginal Rings for HIV Prevention: Behavioral Results of MTN-027.},
journal = {AIDS and behavior},
volume = {},
number = {},
pages = {},
doi = {10.1007/s10461-019-02457-0},
pmid = {30877580},
issn = {1573-3254},
support = {UM1AI068633//National Institute of Allergy and Infectious Diseases/ ; UM1AI068615//National Institute of Allergy and Infectious Diseases/ ; UM1AI106707//National Institute of Allergy and Infectious Diseases/ ; },
abstract = {Intravaginal rings (IVR) containing antiretroviral drugs are a promising method for HIV prevention. We triangulated quantitative and qualitative assessments to evaluate the acceptability of four IVRs used continuously for 28 days as part of a Phase I trial (N = 48 HIV-negative women; ages 18-45). Adherence was high throughout the trial, yet 30% of participants reported involuntary IVR expulsions followed by re-insertion. Most participants (93.6%) felt comfortable with the IVR being inside their body. Participants reported liking the IVR more (36.2%) or the same amount (55.3%) since starting the study. When given the option of choosing between the IVR and/or a male condom for HIV-prevention, most reported preferring the IVR (n = 29, 63.0%), and over a quarter of the sample reported liking them equally (n = 12, 26.1%). We observed no differences in IVR acceptability across the study arms. High adherence and acceptability underscores the promise of an IVR as a female-controlled, sustained mechanism for HIV prevention.},
}

@article {pmid30875235,
year = {2019},
author = {Roy, R and Chatterjee, A and Das, D and Ray, A and Singh, R and Chattopadhyay, E and Sarkar, N and Eccles, M and Pal, M and Maitra, A and Roy, B},
title = {Genome-wide miRNA methylome analysis in oral cancer: possible biomarkers associated with patient survival.},
journal = {Epigenomics},
volume = {},
number = {},
pages = {},
doi = {10.2217/epi-2018-0078},
pmid = {30875235},
issn = {1750-192X},
abstract = {AIM: The methylome associated with miRNA loci was investigated in oral cancer to explore tobacco specific methylation and potential biomarkers for patient survival.

METHODS: Methylome data was generated from 16 pairs of cancer-normal tissues by reduced representation bisulfite sequencing method. Differentially methylated regions were identified using the DMAP pipeline. In silico validation and Kaplan-Meier survival analyses were performed on The Cancer Genome Atlas data based on our miRNA methylome data.

RESULTS: A total of 4310 unique differentially methylated regions, mapping to 144 miRNA loci, were identified. Three distinct groups of miRNAs were differentially methylated in cancer tissues from smokers, chewers and mixed habitués. Hypermethylation of miR-503, miR-200a/b, miR-320b and miR-489 was associated with worse 5-year survival.

CONCLUSION: Differential methylation patterns in miRNA loci are associated with poor survival underscoring their potential as predictive and prognostic biomarkers in oral cancer.},
}

@article {pmid30874775,
year = {2019},
author = {LaCroix, AZ and Bellettiere, J and Rillamas-Sun, E and Di, C and Evenson, KR and Lewis, CE and Buchner, DM and Stefanick, ML and Lee, IM and Rosenberg, DE and LaMonte, MJ and , },
title = {Association of Light Physical Activity Measured by Accelerometry and Incidence of Coronary Heart Disease and Cardiovascular Disease in Older Women.},
journal = {JAMA network open},
volume = {2},
number = {3},
pages = {e190419},
doi = {10.1001/jamanetworkopen.2019.0419},
pmid = {30874775},
issn = {2574-3805},
abstract = {Importance: To our knowledge, no studies have examined light physical activity (PA) measured by accelerometry and heart disease in older women.

Objective: To investigate whether higher levels of light PA were associated with reduced risks of coronary heart disease (CHD) or cardiovascular disease (CVD) in older women.

Prospective cohort study of older women from baseline (March 2012 to April 2014) through February 28, 2017, for up to 4.91 years. The setting was community-dwelling participants from the Women's Health Initiative. Participants were ambulatory women with no history of myocardial infarction or stroke.

Exposures: Data from accelerometers worn for a requested 7 days were used to measure light PA.

Main Outcomes and Measures: Cox proportional hazards regression models estimated hazard ratios (HRs) and 95% CIs for physician-adjudicated CHD and CVD events across light PA quartiles adjusting for possible confounders. Light PA was also analyzed as a continuous variable with and without adjustment for moderate to vigorous PA (MVPA).

Results: Among 5861 women (mean [SD] age, 78.5 [6.7] years), 143 CHD events and 570 CVD events were observed. The HRs for CHD in the highest vs lowest quartiles of light PA were 0.42 (95% CI, 0.25-0.70; P for trend <.001) adjusted for age and race/ethnicity and 0.58 (95% CI, 0.34-0.99; P for trend = .004) after additional adjustment for education, current smoking, alcohol consumption, physical functioning, comorbidity, and self-rated health. Corresponding HRs for CVD in the highest vs lowest quartiles of light PA were 0.63 (95% CI, 0.49-0.81; P for trend <.001) and 0.78 (95% CI, 0.60-1.00; P for trend = .004). The HRs for a 1-hour/day increment in light PA after additional adjustment for MVPA were 0.86 (95% CI, 0.73-1.00; P for trend = .05) for CHD and 0.92 (95% CI, 0.85-0.99; P for trend = .03) for CVD.

Conclusions and Relevance: The present findings support the conclusion that all movement counts for the prevention of CHD and CVD in older women. Large, pragmatic randomized trials are needed to test whether increasing light PA among older women reduces cardiovascular risk.},
}

@article {pmid30873591,
year = {2019},
author = {Watts, EL and Perez-Cornago, A and Appleby, PN and Albanes, D and Ardanaz, E and Black, A and Bueno-de-Mesquita, HB and Chan, JM and Chen, C and Chubb, SAP and Cook, MB and Deschasaux, M and Donovan, JL and English, DR and Flicker, L and Freedman, ND and Galan, P and Giles, GG and Giovannucci, EL and Gunter, MJ and Habel, LA and Häggström, C and Haiman, C and Hamdy, FC and Hercberg, S and Holly, JM and Huang, J and Huang, WY and Johansson, M and Kaaks, R and Kubo, T and Lane, JA and Layne, TM and Le Marchand, L and Martin, RM and Metter, EJ and Mikami, K and Milne, RL and Morris, HA and Mucci, LA and Neal, DE and Neuhouser, ML and Oliver, SE and Overvad, K and Ozasa, K and Pala, V and Pernar, CH and Pollak, M and Rowlands, MA and Schaefer, CA and Schenk, JM and Stattin, P and Tamakoshi, A and Thysell, E and Touvier, M and Trichopoulou, A and Tsilidis, KK and Van Den Eeden, SK and Weinstein, SJ and Wilkens, L and Yeap, BB and Key, TJ and Allen, NE and Travis, RC},
title = {The associations of anthropometric, behavioural and sociodemographic factors with circulating concentrations of IGF-I, IGF-II, IGFBP-1, IGFBP-2, and IGFBP-3 in a pooled analysis of 16,024 men from 22 studies.},
journal = {International journal of cancer},
volume = {},
number = {},
pages = {},
doi = {10.1002/ijc.32276},
pmid = {30873591},
issn = {1097-0215},
abstract = {Insulin-like growth factors (IGFs) and insulin-like growth factor binding proteins (IGFBPs) have been implicated in the aetiology of several cancers. To better understand whether anthropometric, behavioural, and sociodemographic factors may play a role in cancer risk via IGF signalling, we examined the cross-sectional associations of these exposures with circulating concentrations of IGFs (IGF-I, IGF-II) and IGFBPs (IGFBP-1, IGFBP-2, IGFBP-3). The Endogenous Hormones, Nutritional Biomarkers and Prostate Cancer Collaborative Group dataset includes individual participant data from 16,024 male controls (i.e. without prostate cancer) aged 22-89 years from 22 prospective studies. Geometric means of protein concentrations were estimated using analysis of variance, adjusted for relevant covariates. Older age was associated with higher concentrations of IGFBP-1 and IGFBP-2 and lower concentrations of IGF-I, IGF-II, and IGFBP-3. Higher body mass index was associated with lower concentrations of IGFBP-1 and IGFBP-2. Taller height was associated with higher concentrations of IGF-I and IGFBP-3 and lower concentrations of IGFBP-1. Smokers had higher concentrations of IGFBP-1 and IGFBP-2 and lower concentrations of IGFBP-3 than non-smokers. Higher alcohol consumption was associated with higher concentrations of IGF-II and lower concentrations of IGF-I and IGFBP-2. African Americans had lower concentrations of IGF-II, IGFBP-1, IGFBP-2 and IGFBP-3 and Hispanics had lower IGF-I, IGF-II and IGFBP-3 than non-Hispanic whites. These findings indicate that a range of anthropometric, behavioural, and sociodemographic factors are associated with circulating concentrations of IGFs and IGFBPs in men, which will lead to a greater understanding of the mechanisms through which these factors influence cancer risk. This article is protected by copyright. All rights reserved.},
}

@article {pmid30872361,
year = {2019},
author = {Freitas-Andrade, M and Wang, N and Bechberger, JF and De Bock, M and Lampe, PD and Leybaert, L and Naus, CC},
title = {Targeting MAPK phosphorylation of Connexin43 provides neuroprotection in stroke.},
journal = {The Journal of experimental medicine},
volume = {},
number = {},
pages = {},
doi = {10.1084/jem.20171452},
pmid = {30872361},
issn = {1540-9538},
abstract = {Connexin43 (Cx43) function is influenced by kinases that phosphorylate specific serine sites located near its C-terminus. Stroke is a powerful inducer of kinase activity, but its effect on Cx43 is unknown. We investigated the impact of wild-type (WT) and knock-in Cx43 with serine to alanine mutations at the protein kinase C (PKC) site Cx43S368A, the casein kinase 1 (CK1) sites Cx43S325A/328Y/330A, and the mitogen-activated protein kinase (MAPK) sites Cx43S255/262/279/282A (MK4) on a permanent middle cerebral artery occlusion (pMCAO) stroke model. We demonstrate that MK4 transgenic animals exhibit a significant decrease in infarct volume that was associated with improvement in behavioral performance. An increase in astrocyte reactivity with a concomitant decrease in microglial reactivity was observed in MK4 mice. In contrast to WT, MK4 astrocytes displayed reduced Cx43 hemichannel activity. Pharmacological blockade of Cx43 hemichannels with TAT-Gap19 also significantly decreased infarct volume in WT animals. This study provides novel molecular insights and charts new avenues for therapeutic intervention associated with Cx43 function.},
}

@article {pmid30871976,
year = {2019},
author = {McCune, JS and Wang, T and Bo-Subait, K and Aljurf, M and Beitinjaneh, A and Bubalo, J and Cahn, JY and Cerny, J and Chhabra, S and Cumpston, A and Dupuis, LL and Lazarus, HM and Marks, DI and Maziarz, RT and Norkin, M and Prestidge, T and Mineishi, S and Krem, MM and Pasquini, M and Martin, PJ},
title = {Association of antiepileptic medications with outcomes after allogeneic hematopoietic cell transplantation with busulfan/cyclophosphamide conditioning.},
journal = {Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.bbmt.2019.03.001},
pmid = {30871976},
issn = {1523-6536},
abstract = {High-dose busulfan (BU) followed by high-dose cyclophosphamide (CY) (BU/CY) before allogeneic hematopoietic cell transplantation (HCT) has long been used as treatment for hematologic malignancies. Administration of phenytoin or newer alternative anti-epileptic medications (AEMs) prevents seizures caused by BU. Phenytoin induces enzymes that increase exposure to active CY metabolites in vivo, whereas alternative AEMs do not have this effect. Lower exposure to active CY metabolites with the use of alternative AEMs could decrease the risk of toxicity but might increase the risk of recurrent malignancy after HCT. Previous studies have not determined whether outcomes with alternative AEMs differ from those with phenytoin in patients treated with BU/CY before allogeneic HCT. We studied a cohort of 2155 patients, 1460 treated with phenytoin and 695 treated with alternative AEMs, who received BU/CY before allogeneic HCT from 2004 through 2014. We found no differences suggesting decreased overall or relapse-free survival or increased risks of relapse, non-relapse mortality, acute or chronic GVHD, or regimen-related toxicity associated with the use of alternative AEMs as compared to phenytoin. The risk of dialysis was lower in the alternative AEM group than in the phenytoin group. Alternative AEMs are safe for prevention of seizures after BU administration and can avoid the undesirable toxicities and drug interactions caused by phenytoin.},
}

@article {pmid30871856,
year = {2019},
author = {Minot, SS},
title = {De novo Assembly Vastly Expands the Known Microbial Universe.},
journal = {Trends in microbiology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.tim.2019.02.007},
pmid = {30871856},
issn = {1878-4380},
abstract = {The study of the human microbiome relies heavily on the genomes of bacterial isolates that can be grown in culture. A recent study (Pasolli et al. Cell 2019;176:649-662) of stool microbiome samples generated over 150 000 microbial genomes without any culture, vastly expanding our knowledge of the biases in existing reference databases.},
}

@article {pmid30863552,
year = {2019},
author = {Jariani, A and Warth, C and Deforche, K and Libin, P and Drummond, AJ and Rambaut, A and Matsen Iv, FA and Theys, K},
title = {SANTA-SIM: simulating viral sequence evolution dynamics under selection and recombination.},
journal = {Virus evolution},
volume = {5},
number = {1},
pages = {vez003},
doi = {10.1093/ve/vez003},
pmid = {30863552},
issn = {2057-1577},
abstract = {Simulations are widely used to provide expectations and predictive distributions under known conditions against which to compare empirical data. Such simulations are also invaluable for testing and comparing the behaviour and power of inference methods. We describe SANTA-SIM, a software package to simulate the evolution of a population of gene sequences forwards through time. It models the underlying biological processes as discrete components: replication, recombination, point mutations, insertion-deletions, and selection under various fitness models and population size dynamics. The software is designed to be intuitive to work with for a wide range of users and executable in a cross-platform manner.},
}

@article {pmid30870493,
year = {2019},
author = {Rytlewski, J and Deng, S and Xie, T and Davis, C and Robins, H and Yusko, E and Bienkowska, J},
title = {Model to improve specificity for identification of clinically-relevant expanded T cells in peripheral blood.},
journal = {PloS one},
volume = {14},
number = {3},
pages = {e0213684},
doi = {10.1371/journal.pone.0213684},
pmid = {30870493},
issn = {1932-6203},
abstract = {Current methods to quantify T-cell clonal expansion only account for variance due to random sampling from a highly diverse repertoire space. We propose a beta-binomial model to incorporate time-dependent variance into the assessment of differentially abundant T-cell clones, identified by unique T Cell Receptor (TCR) β-chain rearrangements, and show that this model improves specificity for detecting clinically relevant clonal expansion. Using blood samples from ten healthy donors, we modeled the variance of T-cell clones within each subject over time and calibrated the dispersion parameters of the beta distribution to fit this variance. As a validation, we compared pre- versus post-treatment blood samples from urothelial cancer patients treated with atezolizumab, where clonal expansion (quantified by the earlier binomial model) was previously reported to correlate with benefit. The beta-binomial model significantly reduced the false-positive rate for detecting differentially abundant clones over time compared to the earlier binomial method. In the urothelial cancer cohort, the beta-binomial model enriched for tumor infiltrating lymphocytes among the clones detected as expanding in the peripheral blood in response to therapy compared to the binomial model and improved the overall correlation with clinical benefit. Incorporating time-dependent variance into the statistical framework for measuring differentially abundant T-cell clones improves the model's specificity for T-cells that correlate more strongly with the disease and treatment setting of-interest. Reducing background-level clonal expansion, therefore, improves the quality of clonal expansion as a biomarker for assessing the T cell immune response and correlations with clinical measures.},
}

@article {pmid30869200,
year = {2019},
author = {Amico, KR and Ramirez, C and Caplan, MR and Montgomery, BE and Stewart, J and Hodder, S and Swaminathan, S and Wang, J and Darden-Tabb, NY and McCauley, M and Mayer, KH and Wilkin, T and Landovitz, RJ and Gulick, R and Adimora, AA and , },
title = {Perspectives of US women participating in a candidate PrEP study: adherence, acceptability and future use intentions.},
journal = {Journal of the International AIDS Society},
volume = {22},
number = {3},
pages = {e25247},
doi = {10.1002/jia2.25247},
pmid = {30869200},
issn = {1758-2652},
support = {//Division of AIDS/ ; //Division of AIDS, National Institute of Allergy and Infectious Diseases/ ; UM1-AI068619//National Institutes of Health/ ; UM1-AI068613//National Institutes of Health/ ; UM1-AI068617//National Institutes of Health/ ; UM1-AI-068636//AIDS Clinical Trials Group/ ; //Gilead Sciences/ ; },
abstract = {INTRODUCTION: Limited data exist on acceptability of candidate pre-exposure prophylaxis (PrEP) regimens among US women. We evaluated PrEP experiences, attitudes and future use intentions among sexually active women who completed the US-based HIV Prevention Trials Network 069/AIDS Clinical Trials Group 5305 study.

METHODS: Women participated in the study between March 2013 and November 2015. We analysed computer-assisted self-interview (CASI) surveys among 130 women and conducted in-depth interviews among a subset of 26 women from three sites. Interviews were conducted in mid/late-2015.

RESULTS: Most women (57%) reported very good/excellent PrEP adherence on CASI, although 21% acknowledged over-reporting adherence at least some of the time. Commitment to preventing HIV infection, a sense of ownership of the study, and keeping pills stored in a visible location facilitated adherence. Adherence barriers included "simply forgetting" and being away from home. Most women interviewed did not intend to use PrEP in the future because of lack of perceived need due to their own (as opposed to their partners') low-risk behaviour and concerns about affordability - but not because of side effects or other characteristics of the regimens.

DISCUSSION: Improving HIV prevention options for US women will require access to affordable PrEP as well as expanding women's understanding of relationship- and community-level factors that increase their risk of acquiring HIV.},
}

@article {pmid30868739,
year = {2019},
author = {Mitchell, KM and Hoots, B and Dimitrov, D and German, D and Flynn, C and Farley, JE and Gelman, M and Hughes, JP and Donnell, D and Adeyeye, A and Remien, RH and Beyrer, C and Paz-Bailey, G and Boily, MC},
title = {Improvements in the HIV care continuum needed to meaningfully reduce HIV incidence among men who have sex with men in Baltimore, US: a modelling study for HPTN 078.},
journal = {Journal of the International AIDS Society},
volume = {22},
number = {3},
pages = {e25246},
doi = {10.1002/jia2.25246},
pmid = {30868739},
issn = {1758-2652},
support = {UM1AI1068617//US National Institutes of Health/ ; UM1AI068619//US National Institutes of Health/ ; P30AI094189//US National Institutes of Health/ ; K01DA041259//US National Institutes of Health/ ; //Maryland Department of Health and the Centers for Disease Control and Prevention, and the infrastructure, resources, and services of the Johns Hopkins University Center for AIDS Research/ ; //HPTN Statistical and Data Management Center/ ; //National Institute of Allergy and Infectious Diseases/ ; //National Institute of Mental Health/ ; //National Institute on Drug Abuse/ ; },
abstract = {INTRODUCTION: HIV prevalence is high among men who have sex with men (MSM) in Baltimore, Maryland, United States, and the levels of viral suppression among HIV-positive MSM are relatively low. The HIV Prevention Trials Network 078 trial seeks to increase the levels of viral suppression among US MSM by increasing the rates of diagnosis and linkage to care and treatment. We estimated the increases in viral suppression needed to reach different HIV incidence reduction targets, and the impact of meeting diagnosis and treatment targets.

METHODS: We used a mathematical model of HIV transmission among MSM from Baltimore, US, parameterised with behavioural data and fitted to HIV prevalence and care continuum data for Baltimore wherever possible, to project increases in viral suppression needed to reduce the HIV incidence rate among Baltimore MSM by 10, 20, 30 or 50% after 2, 5 and 10 years. We also projected HIV incidence reductions achieved if US national targets - 90% of people living with HIV (PLHIV) know their HIV serostatus, 90% of those diagnosed are retained in HIV medical care and 80% of those diagnosed are virally suppressed - or UNAIDS 90-90-90 targets (90% of PLHIV know their status, 90% of those diagnosed receive antiretroviral therapy (ART), 90% of those receiving ART are virally suppressed) are each met by 2020.

RESULTS: To reduce the HIV incidence rate by 20% and 50% after five years (compared with the base-case at the same time point), the proportion of all HIV-positive MSM who are virally suppressed must increase above 2015 levels by a median 13 percentage points (95% uncertainty interval 9 to 16 percentage points) from median 49% to 60%, and 27 percentage points (22 to 35) from 49% to 75% respectively. Meeting all three US or 90-90-90 UNAIDS targets results in a 48% (31% to 63%) and 51% (38% to 65%) HIV incidence rate reduction in 2020 respectively.

CONCLUSIONS: Substantial improvements in levels of viral suppression will be needed to achieve significant incidence reductions among MSM in Baltimore, and to meet 2020 US and UNAIDS targets. Future modelling studies should additionally consider the impact of pre-exposure prophylaxis for MSM.},
}

@article {pmid30867038,
year = {2019},
author = {Galipeau, PC and Oman, KM and Paulson, TG and Sanchez, CA and Zhang, Q and Marty, JA and Delrow, JJ and Kuhner, MK and Vaughan, TL and Reid, BJ and Li, X},
title = {Correction to: NSAID use and somatic exomic mutations in Barrett's esophagus.},
journal = {Genome medicine},
volume = {11},
number = {1},
pages = {14},
doi = {10.1186/s13073-019-0625-y},
pmid = {30867038},
issn = {1756-994X},
abstract = {It was highlighted that in the original article [1] the Availability of data and materials section was incorrect.},
}

@article {pmid30866962,
year = {2019},
author = {Díaz Santana, MV and Hankinson, SE and Bigelow, C and Sturgeon, SR and Zoeller, RT and Tinker, L and Manson, JAE and Calafat, AM and Meliker, JR and Reeves, KW},
title = {Urinary concentrations of phthalate biomarkers and weight change among postmenopausal women: a prospective cohort study.},
journal = {Environmental health : a global access science source},
volume = {18},
number = {1},
pages = {20},
doi = {10.1186/s12940-019-0458-6},
pmid = {30866962},
issn = {1476-069X},
support = {R01ES024731//National Institute of Environmental Health Sciences/ ; R01ES024731S1//National Institute of Environmental Health Sciences/ ; HHSN268201600018C//National Heart, Lung, and Blood Institute/ ; HHSN268201600001C//National Heart, Lung, and Blood Institute/ ; HHSN268201600002C//National Heart, Lung, and Blood Institute/ ; HHSN268201600003C//National Heart, Lung, and Blood Institute/ ; HHSN268201600004C//National Heart, Lung, and Blood Institute/ ; },
abstract = {BACKGROUND: Some phthalates are endocrine disrupting chemicals used as plasticizers in consumer products, and have been associated with obesity in cross-sectional studies, yet prospective evaluations of weight change are lacking. Our objective was to evaluate associations between phthalate biomarker concentrations and weight and weight change among postmenopausal women.

METHODS: We performed cross-sectional (N = 997) and longitudinal analyses (N = 660) among postmenopausal Women's Health Initiative participants. We measured 13 phthalate metabolites and creatinine in spot urine samples provided at baseline. Participants' weight and height measured at in-person clinic visits at baseline, year 3, and year 6 were used to calculate body mass index (BMI). We fit multivariable multinomial logistic regression models to explore cross-sectional associations between each phthalate biomarker and baseline BMI category. We evaluated longitudinal associations between each biomarker and weight change using mixed effects linear regression models.

RESULTS: In cross-sectional analyses, urinary concentrations of some biomarkers were positively associated with obesity prevalence (e.g. sum of di (2-ethylhexyl) phthalate metabolites [ΣDEHP] 4th vs 1st quartile OR = 3.29, 95% CI 1.80-6.03 [p trend< 0.001] vs normal). In longitudinal analyses, positive trends with weight gain between baseline and year 3 were observed for mono-(2-ethyl-5-oxohexyl) phthalate, monoethyl phthalate (MEP), mono-hydroxybutyl phthalate, and mono-hydroxyisobutyl phthalate (e.g. + 2.32 kg [95% CI 0.93-3.72] for 4th vs 1st quartile of MEP; p trend < 0.001). No statistically significant associations were observed between biomarkers and weight gain over 6 years.

CONCLUSIONS: Certain phthalates may contribute to short-term weight gain among postmenopausal women.},
}

@article {pmid30865311,
year = {2019},
author = {Schweizer, MT and Gulati, R and Beightol, M and Konnick, EQ and Cheng, HH and Klemfuss, N and De Sarkar, N and Yu, EY and Montgomery, RB and Nelson, PS and Pritchard, CC},
title = {Clinical determinants for successful circulating tumor DNA analysis in prostate cancer.},
journal = {The Prostate},
volume = {},
number = {},
pages = {},
doi = {10.1002/pros.23778},
pmid = {30865311},
issn = {1097-0045},
support = {//UW/FHCRC Institute for Prostate Cancer Research (IPCR)/ ; //FHCRC Solid Tumor Translational Research Program/ ; P30 CA015704//National Cancer Institute grants/ ; R50 CA221836//National Cancer Institute grants/ ; R01 CA181605//National Cancer Institute grants/ ; CA097186//Pacific Northwest Prostate Cancer SPORE/ ; //Prostate Cancer Foundation Young Investigator Awards/ ; W81XWH-16-1-0484//CDMRP Awards/ ; PC170510//CDMRP Awards/ ; PC170503P2//CDMRP Awards/ ; W81XWH-17-1-0380//CDMRP Awards/ ; W81XWH-15-1-0430//CDMRP Awards/ ; },
abstract = {BACKGROUND: Plasma-based cell-free DNA is an attractive biospecimen for assessing somatic mutations due to minimally-invasive real-time sampling. However, next generation sequencing (NGS) of cell-free DNA (cfDNA) may not be appropriate for all patients with advanced prostate cancer (PC).

METHODS: Blood was obtained from advanced PC patients for plasma-based sequencing. UW-OncoPlex, a ∼2 Mb multi-gene NGS panel performed in the CLIA/CAP environment, was optimized for detecting cfDNA mutations. Tumor tissue and germline samples were sequenced for comparative analyses. Multivariate logistic regression was performed to determine the clinical characteristic associated with the successful detection of somatic cfDNA alterations (ie detection of at least one clearly somatic PC mutation).

RESULTS: Plasma for cfDNA sequencing was obtained from 93 PC patients along with tumor tissue (N = 67) and germline (N = 93) controls. We included data from 76 patients (72 prostate adenocarcinoma; 4 variant histology PC) in the analysis. Somatic DNA aberrations were detected in 34 cfDNA samples from patients with prostate adenocarcinoma. High PSA level, high tumor volume, and castration-resistance were significantly associated with successful detection of somatic cfDNA alterations. Among samples with somatic mutations detected, the cfDNA assay detected 93/102 (91%) alterations found in tumor tissue, yielding a clustering-corrected sensitivity of 92% (95% confidence interval 88-97%). All germline pathogenic variants present in lymphocyte DNA were also detected in cfDNA (N = 12). Somatic mutations from cfDNA were detected in 30/33 (93%) instances when PSA was >10 ng/mL.

CONCLUSIONS: Disease burden, including a PSA >10 ng/mL, is strongly associated with detecting somatic mutations from cfDNA specimens.},
}

@article {pmid30865051,
year = {2019},
author = {Mannheimer, S and Hirsch-Moverman, Y and Franks, J and Loquere, A and Hughes, JP and Li, M and Amico, KR and Grant, RM},
title = {Factors Associated With Sex-Related Pre-exposure Prophylaxis Adherence Among Men Who Have Sex With Men in New York City in HPTN 067.},
journal = {Journal of acquired immune deficiency syndromes (1999)},
volume = {80},
number = {5},
pages = {551-558},
doi = {10.1097/QAI.0000000000001965},
pmid = {30865051},
issn = {1944-7884},
abstract = {BACKGROUND: HPTN 067 assessed the feasibility of daily and non-daily dosing of open-label emtricitabine/tenofovir disoproxil fumarate (FTC/TDF)-based pre-exposure prophylaxis (PrEP).

METHODS: Factors associated with sex-related PrEP adherence were assessed among men who have sex with men (MSM) randomized to one of 3 PrEP dosing arms in HPTN 067 in New York City. Sex-related PrEP adherence was defined per protocol as at least 1 PrEP tablet taken within 4 days pre-sex and at least 1 additional PrEP tablet taken within 24 hours post-sex, assessed via electronic drug monitoring and weekly interviews. Demographic data and behavioral measures were evaluated for association with sex-related PrEP adherence. Logistic regression for clustered data was used to estimate the unadjusted and adjusted odds ratios.

RESULTS: Of 176 randomized MSM participants, 59% were Black, 10% White, 25% Hispanic, and 6% other; median age was 31 years. In the multivariable analyses, higher sex-related PrEP adherence was significantly associated with daily dosing arm, older age, employment, and higher PrEP adherence behavioral skills. Lower sex-related PrEP adherence was significantly associated with identifying as Black or Hispanic (compared with White), opiate use, and reporting "I forgot" as an adherence barrier.

CONCLUSIONS: This analysis identified populations of MSM who might benefit from additional support to optimize PrEP adherence, including those who are younger, unemployed, or opiate users. MSM with lower PrEP behavioral skills may benefit from targeted interventions. Further study is needed to assess racial and ethnic disparities in PrEP adherence, which may reflect broader social and economic inequalities not captured in this study.},
}

@article {pmid30863868,
year = {2019},
author = {Plantinga, AM and Chen, J and Jenq, RR and Wu, MC},
title = {pldist: ecological dissimilarities for paired and longitudinal microbiome association analysis.},
journal = {Bioinformatics (Oxford, England)},
volume = {},
number = {},
pages = {},
doi = {10.1093/bioinformatics/btz120},
pmid = {30863868},
issn = {1367-4811},
abstract = {MOTIVATION: The human microbiome is notoriously variable across individuals, with a wide range of 'healthy' microbiomes. Paired and longitudinal studies of the microbiome have become increasingly popular as a way to reduce unmeasured confounding and to increase statistical power by reducing large inter-subject variability. Statistical methods for analyzing such datasets are scarce.

RESULTS: We introduce a paired UniFrac dissimilarity that summarizes within-individual (or within-pair) shifts in microbiome composition and then compares these compositional shifts across individuals (or pairs). This dissimilarity depends on a novel transformation of relative abundances, which we then extend to more than two time points and incorporate into several phylogenetic and non-phylogenetic dissimilarities. The data transformation and resulting dissimilarities may be used in a wide variety of downstream analyses, including ordination analysis and distance-based hypothesis testing. Simulations demonstrate that tests based on these dissimilarities retain appropriate type 1 error and high power. We apply the method in two real datasets.

The R package pldist is available on GitHub at https://github.com/aplantin/pldist.

SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.},
}

@article {pmid30861098,
year = {2019},
author = {Henry, NL and Unger, JM and Till, C and Schott, AF and Crew, KD and Lew, DL and Fisch, MJ and Moinpour, CM and Wade, JL and Hershman, DL},
title = {Association between body mass index and response to duloxetine for aromatase inhibitor-associated musculoskeletal symptoms in SWOG S1202.},
journal = {Cancer},
volume = {},
number = {},
pages = {},
doi = {10.1002/cncr.32024},
pmid = {30861098},
issn = {1097-0142},
support = {5UG1CA189974//National Cancer Institute of the National Institutes of Health/ ; CI-53-10//Lilly USA LLC/ ; //The Hope Foundation/ ; },
abstract = {BACKGROUND: Aromatase inhibitor (AI)-associated musculoskeletal symptoms (AIMSS) negatively impact adherence to and persistence with therapy. In SWOG S1202, patients with AIMSS who were treated with duloxetine, a serotonin norepinephrine reuptake inhibitor, reported improvement in pain by 12 weeks compared with placebo. Based on the authors' prior observation that responses to pain interventions differ between obese and nonobese patients, the current study examined whether response to duloxetine therapy differed by obesity status.

METHODS: In SWOG S1202, a total of 299 AI-treated postmenopausal women with stage I to III (AJCC 7th Edition) breast cancer who developed new or worsening average pain were enrolled, randomized to duloxetine or placebo, and treated for 12 weeks. Patient-reported outcomes were obtained at baseline and through 12 weeks. Patients were categorized into nonobese (body mass index [BMI] <30 kg/m2) or obese (BMI ≥30 kg/m2). The authors tested the interaction between intervention and obesity with respect to average pain at 12 weeks in the 289 eligible patients, using a P value of .05 to indicate statistical significance.

RESULTS: In approximately 54% of evaluable patients with a BMI ≥30 kg/m2 , the reduction in the mean average pain score between baseline and 12 weeks was statistically significantly greater for patients treated with duloxetine compared with those receiving placebo (-2.73 vs -1.64 points; P = .003). Conversely, in the nonobese patients, the reduction in the mean average pain score was similar in the 2 cohorts (-2.46 vs -2.34 points; P = .75). The P value for interaction was .02, thereby meeting the threshold criteria of the current study. Similar findings were evident for other pain-related patient-reported outcomes.

CONCLUSIONS: In this trial, obese patients with AIMSS obtained more analgesic benefit from duloxetine compared with nonobese patients. Additional studies are warranted to determine the biologic basis for these findings.},
}

@article {pmid30860946,
year = {2019},
author = {Bates, JE and Howell, RM and Liu, Q and Yasui, Y and Mulrooney, DA and Dhakal, S and Smith, SA and Leisenring, WM and Indelicato, DJ and Gibson, TM and Armstrong, GT and Oeffinger, KC and Constine, LS},
title = {Therapy-Related Cardiac Risk in Childhood Cancer Survivors: An Analysis of the Childhood Cancer Survivor Study.},
journal = {Journal of clinical oncology : official journal of the American Society of Clinical Oncology},
volume = {},
number = {},
pages = {JCO1801764},
doi = {10.1200/JCO.18.01764},
pmid = {30860946},
issn = {1527-7755},
abstract = {PURPOSE: The impacts of radiotherapy dose and exposed cardiac volume, select chemotherapeutic agents, and age at exposure on risk for late-onset cardiac disease in survivors of childhood cancer remain unresolved.

PATIENTS AND METHODS: We determined the rates of severe to fatal cardiac disease in 24,214 5-year survivors in the Childhood Cancer Survivor Study diagnosed between 1970 and 1999 at a median age of 7.0 years (range, 0 to 20.9 years), with a median attained age of 27.5 years (range, 5.6 to 58.9 years). Using piecewise exponential models, we evaluated the association between cardiac disease rates and demographic and treatment characteristics.

RESULTS: The cumulative incidence of cardiac disease 30 years from diagnosis was 4.8% (95% CI, 4.3 to 5.2). Low to moderate radiotherapy doses (5.0 to 19.9 Gy) to large cardiac volumes (≥ 50% of heart) were associated with an increased rate of cardiac disease (relative rate, 1.6; 95% CI, 1.1 to 2.3) compared with survivors without cardiac radiotherapy exposure. Similarly, high doses (≥ 20 Gy) to small cardiac volumes (0.1% to 29.9%) were associated with an elevated rate (relative rate, 2.4; 95% CI, 1.4 to 4.2). A dose-response relationship was observed between anthracycline chemotherapy and heart failure with younger children (age ≤ 13 years) at the greatest risk for heart failure after comparable dosing.

CONCLUSION: These observations support advances in radiation field design and delivery technology to reduce cardiac dose/volume and should guide future treatment protocols. They also inform clinical practice guidelines for post-therapy surveillance and risk-reducing strategies.},
}

@article {pmid30857553,
year = {2019},
author = {Shenoy, MK and Fadrosh, DW and Lin, DL and Worodria, W and Byanyima, P and Musisi, E and Kaswabuli, S and Zawedde, J and Sanyu, I and Chang, E and Fong, S and McCauley, K and Davis, JL and Huang, L and Lynch, SV},
title = {Gut microbiota in HIV-pneumonia patients is related to peripheral CD4 counts, lung microbiota, and in vitro macrophage dysfunction.},
journal = {Microbiome},
volume = {7},
number = {1},
pages = {37},
doi = {10.1186/s40168-019-0651-4},
pmid = {30857553},
issn = {2049-2618},
support = {U01 HL098964//National Heart, Lung, and Blood Institute/ ; K24 HL087713//National Heart, Lung, and Blood Institute/ ; R01 HL090335//National Heart, Lung, and Blood Institute/ ; },
abstract = {Pneumonia is common and frequently fatal in HIV-infected patients, due to rampant, systemic inflammation and failure to control microbial infection. While airway microbiota composition is related to local inflammatory response, gut microbiota has been shown to correlate with the degree of peripheral immune activation (IL6 and IP10 expression) in HIV-infected patients. We thus hypothesized that both airway and gut microbiota are perturbed in HIV-infected pneumonia patients, that the gut microbiota is related to peripheral CD4+ cell counts, and that its associated products differentially program immune cell populations necessary for controlling microbial infection in CD4-high and CD4-low patients. To assess these relationships, paired bronchoalveolar lavage and stool microbiota (bacterial and fungal) from a large cohort of Ugandan, HIV-infected patients with pneumonia were examined, and in vitro tests of the effect of gut microbiome products on macrophage effector phenotypes performed. While lower airway microbiota stratified into three compositionally distinct microbiota as previously described, these were not related to peripheral CD4 cell count. In contrast, variation in gut microbiota composition significantly related to CD4 cell count, lung microbiota composition, and patient mortality. Compared with patients with high CD4+ cell counts, those with low counts possessed more compositionally similar airway and gut microbiota, evidence of microbial translocation, and their associated gut microbiome products reduced macrophage activation and IL-10 expression and increased IL-1β expression in vitro. These findings suggest that the gut microbiome is related to CD4 status and plays a key role in modulating macrophage function, critical to microbial control in HIV-infected patients with pneumonia.},
}

@article {pmid30854504,
year = {2018},
author = {Donahu, TF and Bagrodia, A and Audenet, F and Donoghue, MTA and Cha, EK and Sfakianos, JP and Sperling, D and Al-Ahmadie, H and Clendenning, M and Rosty, C and Buchanan, DD and Jenkins, M and Hopper, J and Winship, I and Templeton, AS and Walsh, MF and Stadler, ZK and Iyer, G and Taylor, B and Coleman, J and Lindor, NM and Solit, DB and Bochner, BH},
title = {Genomic Characterization of Upper-Tract Urothelial Carcinoma in Patients With Lynch Syndrome.},
journal = {JCO precision oncology},
volume = {2018},
number = {},
pages = {},
doi = {10.1200/PO.17.00143},
pmid = {30854504},
issn = {2473-4284},
abstract = {Purpose: Patients with Lynch syndrome (LS) have a significantly increased risk of developing upper-tract urothelial carcinoma (UTUC). Here, we sought to identify differences in the patterns of mutational changes in LS-associated versus sporadic UTUCs.

Patients and Methods: We performed targeted sequencing of 17 UTUCs from patients with documented LS-associated germline mutations (LS-UTUCs) using the Memorial Sloan Kettering Integrated Molecular Profiling of Actionable Cancer Targets targeted exon capture assay and compared the results with those from a recently characterized cohort of 82 patients with sporadic UTUC.

Results: Patients with LS-UTUC were significantly younger, had had less exposure to tobacco, and more often presented with a ureteral primary site compared with patients with sporadic UTUC. The median number of mutations per tumor was significantly greater in LS-UTUC tumors than in tumors from the sporadic cohort (58; interquartile range [IQR], 47-101 v 6; IQR, 4-10; P < .001), as was the MSIsensor score (median, 25.1; IQR, 17.9-31.2 v 0.03; IQR, 0-0.44; P < .001). Differences in the genetic landscape were observed between sporadic and LS-associated tumors. Alterations in KMT2D, CREBBP, or ARID1A or in DNA damage response and repair genes were present at a significantly higher frequency in LS-UTUC. CIC, NOTCH1, NOTCH3, RB1, and CDKN1B alterations were almost exclusive to LS-UTUC. Although FGFR3 mutations were identified in both cohorts, the R248C hotspot mutation was highly enriched in LS-UTUC.

Conclusion: LSand sporadic UTUCs have overlapping but distinct genetic signatures. LS-UTUC is associated with hypermutation and a significantly higher prevalence of FGFR3 R248C mutation. Prospective molecular characterization of patients to identify those with LS-UTUC may help guide treatment.},
}

@article {pmid30856272,
year = {2019},
author = {Unger, JM and Vaidya, R and Hershman, DL and Minasian, LM and Fleury, ME},
title = {Systematic Review and Meta-Analysis of the Magnitude of Structural, Clinical, and Physician and Patient Barriers to Cancer Clinical Trial Participation.},
journal = {Journal of the National Cancer Institute},
volume = {111},
number = {3},
pages = {245-255},
doi = {10.1093/jnci/djy221},
pmid = {30856272},
issn = {1460-2105},
abstract = {BACKGROUND: Barriers to cancer clinical trial participation have been the subject of frequent study, but the rate of trial participation has not changed substantially over time. Studies often emphasize patient-related barriers, but other types of barriers may have greater impact on trial participation. Our goal was to examine the magnitude of different domains of trial barriers by synthesizing prior research.

METHODS: We conducted a systematic review and meta-analysis of studies that examined the trial decision-making pathway using a uniform framework to characterize and quantify structural (trial availability), clinical (eligibility), and patient/physician barrier domains. The systematic review utilized the PubMed, Google Scholar, Web of Science, and Ovid Medline search engines. We used random effects to estimate rates of different domains across studies, adjusting for academic vs community care settings.

RESULTS: We identified 13 studies (nine in academic and four in community settings) with 8883 patients. A trial was unavailable for patients at their institution 55.6% of the time (95% confidence interval [CI] = 43.7% to 67.3%). Further, 21.5% (95% CI = 10.9% to 34.6%) of patients were ineligible for an available trial, 14.8% (95% CI = 9.0% to 21.7%) did not enroll, and 8.1% (95% CI = 6.3% to 10.0%) enrolled. Rates of trial enrollment in academic (15.9% [95% CI = 13.8% to 18.2%]) vs community (7.0% [95% CI = 5.1% to 9.1%]) settings differed, but not rates of trial unavailability, ineligibility, or non-enrollment.

CONCLUSIONS: These findings emphasize the enormous need to address structural and clinical barriers to trial participation, which combined make trial participation unachievable for more than three of four cancer patients.},
}

@article {pmid30856024,
year = {2019},
author = {Buckley, SA and Mark, NM and Othus, M and Estey, EH and Patel, K and Walter, RB},
title = {Diagnostic utility of bronchoscopy in adults with acute myeloid leukemia and other high-grade myeloid neoplasms.},
journal = {Leukemia & lymphoma},
volume = {},
number = {},
pages = {1-4},
doi = {10.1080/10428194.2019.1581933},
pmid = {30856024},
issn = {1029-2403},
}

@article {pmid30801179,
year = {2019},
author = {Fei, Q and Wang, D and Jasbi, P and Zhang, P and Nagana Gowda, GA and Raftery, D and Gu, H},
title = {Combining NMR and MS with Chemical Derivatization for Absolute Quantification with Reduced Matrix Effects.},
journal = {Analytical chemistry},
volume = {},
number = {},
pages = {},
doi = {10.1021/acs.analchem.8b05611},
pmid = {30801179},
issn = {1520-6882},
abstract = {Absolute quantitation is a major challenge in metabolomics. Previously, we [ Nagana Gowda et al. Anal. Chem. 2018 , 90 , 2001 - 2009 ] showed that nuclear magnetic resonance (NMR) spectroscopy can guide absolute quantitation using mass spectrometry (MS); however, this method does not account for the matrix effect in MS measurements. To surmount this challenge, we have developed a novel method, qNMR-MS, for the absolute quantitation of metabolites using MS by combining it with NMR and chemical derivatization. Metabolite concentrations are first obtained using NMR for a reference sample. Subsequently, both reference and study samples are chemically derivatized with isotope-labeled and unlabeled reagents, respectively. The derivatized reference sample is then mixed with study samples and measured using MS. Comparison of paired isotope unlabeled and labeled MS peaks enables absolute quantitation with virtually no matrix effects. As a proof of concept, we applied the qNMR-MS method for absolute quantitation of amino acids using propyl-chloroformate (PCF) derivatization. For standards, the observed coefficients of determination (R2) of most amino acids were greater than 0.99 across concentrations of 0.2 to 20 uM. For human serum, the results of the qNMR-MS method are comparable to the conventional isotope-labeled internal standard (iSTD) method (R2 ≥ 0.99), with an average median coefficient of variation (CV) of 5.45%. The qNMR-MS method is relatively simple, highly quantitative, has high cost-efficiency (no iSTD required), and offers new avenues for the routine quantitation of amino acids in blood samples; it can, in principle, be extended to a wide variety of metabolites in different biological samples.},
}

@article {pmid30849373,
year = {2019},
author = {Marcandalli, J and Fiala, B and Ols, S and Perotti, M and de van der Schueren, W and Snijder, J and Hodge, E and Benhaim, M and Ravichandran, R and Carter, L and Sheffler, W and Brunner, L and Lawrenz, M and Dubois, P and Lanzavecchia, A and Sallusto, F and Lee, KK and Veesler, D and Correnti, CE and Stewart, LJ and Baker, D and Loré, K and Perez, L and King, NP},
title = {Induction of Potent Neutralizing Antibody Responses by a Designed Protein Nanoparticle Vaccine for Respiratory Syncytial Virus.},
journal = {Cell},
volume = {176},
number = {6},
pages = {1420-1431.e17},
doi = {10.1016/j.cell.2019.01.046},
pmid = {30849373},
issn = {1097-4172},
abstract = {Respiratory syncytial virus (RSV) is a worldwide public health concern for which no vaccine is available. Elucidation of the prefusion structure of the RSV F glycoprotein and its identification as the main target of neutralizing antibodies have provided new opportunities for development of an effective vaccine. Here, we describe the structure-based design of a self-assembling protein nanoparticle presenting a prefusion-stabilized variant of the F glycoprotein trimer (DS-Cav1) in a repetitive array on the nanoparticle exterior. The two-component nature of the nanoparticle scaffold enabled the production of highly ordered, monodisperse immunogens that display DS-Cav1 at controllable density. In mice and nonhuman primates, the full-valency nanoparticle immunogen displaying 20 DS-Cav1 trimers induced neutralizing antibody responses ∼10-fold higher than trimeric DS-Cav1. These results motivate continued development of this promising nanoparticle RSV vaccine candidate and establish computationally designed two-component nanoparticles as a robust and customizable platform for structure-based vaccine design.},
}

@article {pmid30844995,
year = {2019},
author = {van der Straten, A and Browne, EN and Shapley-Quinn, MK and Brown, ER and Reddy, K and Scheckter, R and Soto-Torres, L and Palanee-Phillips, T and Baeten, JM and Mensch, B and , },
title = {First Impressions Matter: How Initial Worries Influence Adherence to the Dapivirine Vaginal Ring.},
journal = {Journal of acquired immune deficiency syndromes (1999)},
volume = {},
number = {},
pages = {},
doi = {10.1097/QAI.0000000000002028},
pmid = {30844995},
issn = {1944-7884},
abstract = {BACKGROUND: In MTN-020/ASPIRE, a dapivirine vaginal ring effectiveness trial in sub-Saharan Africa, we assessed whether worries about ring use changed over time and were associated with adherence.

METHODS: Participants (N=2585) were surveyed at baseline and follow-up about worries regarding daily ring use. First, they answered a question about general worries and then responded to 15 items covering specific worries. From a nested qualitative component (N=214), we extracted themes related to ring worries and adherence. Seven months into the trial, aggregate adherence data were shared with study sites as part of an intervention that included counseling and social support. Nonadherence was defined as dapivirine plasma levels of ≤95 pg/ml. Mixed-effect logistic regression models were used to assess changes in ring worries and nonadherence from baseline to month 3 and later.

RESULTS: Worry about wearing the ring decreased from 29% at baseline to 4% at month 3 (p<0.001), while having a specific worry decreased from 47% to 16% (p<0.001). Among those enrolled preintervention, 29% with baseline worries were nonadherent at month 3 (95% CI: 19%, 39%) compared to 14% without worries (95% CI: 9%, 19%; p=0.005); the difference persisted through month 6. There was no difference in nonadherence by baseline worry for those enrolled postintervention (p=0.40). In the qualitative subset, initial ring anxieties reportedly subsided with self-experimentation and practice and the beneficial influence of the intervention.

CONCLUSIONS: Although worries may be an initial deterrent to correct ring use, intervening early by leveraging social influences from peers and clinicians should facilitate successful adoption and correct ring use.},
}

@article {pmid30844424,
year = {2019},
author = {Creary, LE and Guerra, SG and Chong, W and Brown, CJ and Turner, TR and Robinson, J and Bultitude, WP and Mayor, NP and Marsh, SGE and Saito, K and Lam, K and Duke, JL and Mosbruger, TL and Ferriola, D and Monos, D and Willis, A and Askar, M and Fischer, G and Loong Saw, C and Ragoussis, I and Petrek, M and Serra-Pagés, C and Juan Otero, M and Stavropoulos-Giokas, C and Dinou, A and Ameen, R and Al Shemmari, S and Spierings, E and Gendzekhadze, K and Morris, GP and Zhang, Q and Kashi, Z and Hsu, S and Gangavarapu, S and Mallempati, KC and Yamamoto, F and Osoegawa, K and Vayntrub, T and Chang, CJ and Hansen, JA and Fernández-Viňa, MA},
title = {Next-generation HLA typing of 382 International Histocompatibility Working Group reference B-Lymphoblastoid cell lines: report from the 17th International HLA and Immunogenetics Workshop.},
journal = {Human immunology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.humimm.2019.03.001},
pmid = {30844424},
issn = {1879-1166},
abstract = {Extended molecular characterization of HLA genes in the IHWG reference B-lymphoblastoid cell lines (B-LCLs) was one of the major goals for the 17th International HLA and Immunogenetics Workshop (IHIW). Although reference B-LCLs have been examined extensively in previous workshops complete high-resolution typing was not completed for all the classical class I and class II HLA genes. To address this, we conducted a single-blind study where select panels of B-LCL genomic DNA samples were distributed to multiple laboratories for HLA genotyping by next-generation sequencing methods. Identical cell panels comprised of 24 and 346 samples were distributed and typed by at least four laboratories in order to derive accurate consensus HLA genotypes. Overall concordance rates calculated at both 2- and 4-field allele-level resolutions ranged from 90.4% to 100%. Concordance for the class I genes ranged from 91.7 to 100%, whereas concordance for class II genes was variable; the lowest observed at HLA-DRB3 (84.2%). At the maximum allele-resolution 78 B-LCLs were defined as homozygous for all 11 loci. We identified 11 novel exon polymorphisms in the entire cell panel. A comparison of the B-LCLs NGS HLA genotypes with the HLA genotypes catalogued in the IPD-IMGT/HLA Database Cell Repository, revealed an overall allele match at 68.4%. Typing discrepancies between the two datasets were mostly due to the lower-resolution historical typing methods resulting in incomplete HLA genotypes for some samples listed in the IPD-IMGT/HLA Database Cell Repository. Our approach of multiple-laboratory NGS HLA typing of the B-LCLs has provided accurate genotyping data. The data generated by the tremendous collaborative efforts of the 17th IHIW participants is useful for updating the current cell and sequence databases and will be a valuable resource for future studies.},
}

@article {pmid30840360,
year = {2019},
author = {Markey, KA and Gartlan, KH},
title = {Imaging Flow Cytometry to Assess Antigen-Presenting-Cell Function.},
journal = {Current protocols in immunology},
volume = {},
number = {},
pages = {e72},
doi = {10.1002/cpim.72},
pmid = {30840360},
issn = {1934-368X},
abstract = {This unit describes methods for quantifying phagocytosis and imaging the immunological synapse between T cells and antigen-presenting cells (APCs), with both techniques delivering valuable information about APC function. These aspects of APC biology have traditionally been challenging to quantify, and imaging flow cytometry, which harnesses the high-throughput nature of flow cytometry combined with the capacity of microscopy to deliver spatial localization, facilitates analysis of these APC functions in a fashion that was previously not possible. Imaging flow cytometry allows large numbers of events to be captured and large amounts of fluorescence data to be quantified at the physical location of markers of interest, both on the cell surface and in intracellular compartments, combining key features of traditional flow cytometry and fluorescence microscopy. © 2019 by John Wiley & Sons, Inc.},
}

@article {pmid30840336,
year = {2019},
author = {Baglia, ML and Lin, IH and Cartmel, B and Sanft, T and Ligibel, J and Hershman, DL and Harrigan, M and Ferrucci, LM and Li, FY and Irwin, ML},
title = {Endocrine-related quality of life in a randomized trial of exercise on aromatase inhibitor-induced arthralgias in breast cancer survivors.},
journal = {Cancer},
volume = {},
number = {},
pages = {},
doi = {10.1002/cncr.32051},
pmid = {30840336},
issn = {1097-0142},
support = {P30 CA016359//Breast Cancer Research Fund/ ; R01 CA132931//National Cancer Institute/ ; UL1 TR000142//Clinical and Translational Science Award/ ; },
abstract = {BACKGROUND: The objective of this study was to evaluate the role of a 12-month exercise intervention on endocrine-related quality of life (QOL) and overall QOL among breast cancer survivors with aromatase inhibitor (AI)-induced arthralgia in the Hormones and Physical Exercise (HOPE) Study.

METHODS: This was a randomized controlled trial of 121 breast cancer survivors who were currently receiving AIs and experiencing at least mild arthralgia. QOL was assessed using the Functional Assessment of Cancer Therapy (FACT) questionnaires and the 36-Item Short Form Survey (SF-36) at baseline, 6 months, and 12 months. Participants were randomized to either a 1-year gym-based, supervised exercise intervention group (150 minutes of aerobic exercise and 2 strength-training sessions each week) or a usual care group. Effects of the intervention on QOL were assessed using mixed-model, repeated-measures analysis.

RESULTS: At 12 months, the exercise group had greater improvement in the overall QOL measures as well as the breast cancer-specific (scores, 2.2 vs 0.7; P = .02), endocrine-specific (scores, 5.6 vs 1.6; P < .001), and fatigue-specific (score, 5.8 vs 0.5; P < .001) subscales compared with the usual care group. The results indicated a stronger effect at 12 months versus 6 months after the intervention.

CONCLUSIONS: Combined aerobic and resistance exercise, such as treadmill walking and strength training, improved endocrine-related and overall QOL among breast cancer survivors who were experiencing adverse side effects from AIs. Because adverse side effects associated with AI use are quite common and this is the main reason for treatment discontinuation, this nonpharmacologic intervention could benefit many breast cancer survivors and increase successful adherence to AIs in breast cancer treatment.},
}

@article {pmid30840335,
year = {2019},
author = {Chu, AT and Holt, SK and Wright, JL and Ramos, JD and Grivas, P and Yu, EY and Gore, JL},
title = {Delays in radical cystectomy for muscle-invasive bladder cancer.},
journal = {Cancer},
volume = {},
number = {},
pages = {},
doi = {10.1002/cncr.32048},
pmid = {30840335},
issn = {1097-0142},
abstract = {BACKGROUND: Delays from the diagnosis of muscle-invasive bladder cancer (MIBC) to radical cystectomy (RC) longer than 12 weeks result in higher mortality and shorter progression-free survival. This study sought to identify factors associated with RC delays and to determine whether delays in care in the current treatment paradigm, which includes neoadjuvant chemotherapy (NAC), affect survival.

METHODS: Subjects with American Joint Committee on Cancer stage II urothelial carcinoma of the bladder who underwent RC from 2004 to 2012 were identified from the linked Surveillance, Epidemiology, and End Results national cancer registry and the Medicare claims database and were stratified into RC groups with or without NAC. Cox multivariable proportional hazard models and multivariable logistic regression models assessed the significance of delays in RC for survival and identified independent characteristics associated with RC delays, respectively.

RESULTS: This study identified 1509 patients with MIBC who underwent RC during the study period. In comparison with timely surgery, delays in RC increased overall mortality, regardless of the use of NAC (hazard ratio [HR] without NAC, 1.34; 95% confidence interval [CI], 1.03-1.76; HR after NAC, 1.63; 95% CI, 1.06-2.52). Patients proceeding to RC without NAC had higher odds of delayed care if they lived in a high-poverty neighborhood (odds ratio [OR], 1.37; 95% CI, 1.01-2.08) or nonmetropolitan area (OR, 1.61; 95% CI, 1.01-2.55), were men (OR, 2.22; 95% CI, 1.25-4.00), or required a provider transfer for bladder cancer care (OR, 1.82; 95% CI, 1.10-3.03).

CONCLUSIONS: Delays in care from the time of either the initial diagnosis or the completion of NAC to RC are associated with worse overall survival among patients with MIBC. Timely surgery is fundamental in the treatment of MIBC, and this necessitates attention to disparities in access to complex surgical care and care coordination.},
}

@article {pmid30840316,
year = {2019},
author = {Denburg, AE and Laher, N and Mutyaba, I and McGoldrick, S and Kambugu, J and Sessle, E and Orem, J and Casper, C},
title = {The cost effectiveness of treating Burkitt lymphoma in Uganda.},
journal = {Cancer},
volume = {},
number = {},
pages = {},
doi = {10.1002/cncr.32006},
pmid = {30840316},
issn = {1097-0142},
support = {//Burkitt Lymphoma Fund of Africa/ ; //Martin Fabert Foundation/ ; },
abstract = {BACKGROUND: Perceptions of high cost and resource intensity remain political barriers to the prioritization of childhood cancer treatment programs in many low- and middle-income countries (LMICs). Little knowledge exists of the actual cost and cost-effectiveness of such programs. To improve outcomes for children with Burkitt lymphoma (BL), the most common childhood cancer in Africa, the Uganda Cancer Institute implemented a comprehensive BL treatment program in 2012. We undertook an economic evaluation of the program to ascertain the cost-effectiveness of BL therapy in a specific LIC setting.

METHODS: We compared the treatment of BL to usual care in a cohort of 122 patients treated between 2012 and 2014. Costs included variable, fixed, and family costs. Our primary measure of effectiveness was overall survival (OS). Patient outcomes were determined through prospective capture and retrospective chart abstraction. The cost per disability-adjusted life-year (DALY) averted was calculated using the World Health Organization's Choosing Interventions That Are Cost-Effective (WHO-CHOICE) methodology.

RESULTS: The 2-year OS with treatment was 55% (95% CI, 45% to 64%). The cost per DALY averted in the treatment group was US$97 (Int$301). Cumulative estimate of national DALYs averted through treatment was 8607 years, and the total national annual cost of treatment was US$834,879 (Int$2,590,845). The cost of BL treatment fell well within WHO-CHOICE cost-effectiveness thresholds. The ratio of cost per DALY averted to per capita gross domestic product was 0.14, reflecting a very cost-effective intervention.

CONCLUSION: This study demonstrates that treating BL with locally tailored protocols is very cost-effective by international standards. Studies of this kind will furnish crucial evidence to help policymakers prioritize the allocation of LMIC health system resources among noncommunicable diseases, including childhood cancer.},
}

@article {pmid30839944,
year = {2018},
author = {de Montigny, S and Boily, MC and Mâsse, BR and Mitchell, KM and Dimitrov, DT},
title = {Assessing the utility of the tipping point ratio to monitor HIV treatment programmes in the era of universal access to ART.},
journal = {Infectious Disease Modelling},
volume = {3},
number = {},
pages = {85-96},
doi = {10.1016/j.idm.2018.03.005},
pmid = {30839944},
issn = {2468-0427},
support = {UM1 AI068617/AI/NIAID NIH HHS/United States ; },
abstract = {Background: The epidemiological tipping point ratio (TPR) has been suggested as a useful indicator to monitor the scale-up of antiretroviral treatment (ART) programmes and determine when scale-up is sufficient to control the epidemic. TPR has been defined as the ratio of yearly number of new HIV infections to the yearly number of new ART initiations or to the yearly net increase in the number of people on ART. It has been used to rank the progress of treatment programmes across countries, with the objective of reaching a TPR value under 1. Our study aims to assess if TPR alone can be used as an indicator of ART success across settings by comparing the expected changes in HIV incidence and ART coverage when TPR is maintained constant over time. In particular, we focus on the effect of ART initiation timing (emphasis on ART being initiated early or late during HIV progression) on the interpretation of the TPR.

Methods: We used a dynamic model of HIV transmission in South Africa representing ART rollout leading to universal treatment in 2017. The model is calibrated to HIV incidence, HIV prevalence and ART coverage in 2012 in South Africa, and 1000 simulations are selected for the base-case scenario. To measure the effect of TPR, we simulate TPR-preserving interventions, maintaining TPR (yearly number of new ART initiations denominator) at the value observed in 2019 (between 0.65 and 1.25) for 15 years. We compare ART coverage and HIV incidence across TPR values and across strategies in which ART access is prioritized differently. In a secondary analysis, we illustrate the sensitivity of new ART initiations to ART retention, and we compare both definitions of the TPR.

Results: Our analysis shows that HIV incidence reduction is weakly correlated to TPR: the same reduction in HIV incidence (15%) can be achieved by implementing the same strategy with a wide range of TPR maintained (0.65-1.12). Assuming high retention in ART, TPR-preserving strategies prioritizing early ART initiation yield greater reduction in HIV incidence than strategies where most individuals initiate ART late. High ART coverage is associated with low HIV incidence and it can be reached with a TPR below or equal to one with strategies favoring early ART initiation. Low ART retention over time results in higher HIV incidence even if TPR is maintained low. If ART retention is low, strategies prioritizing late ART initiation are associated with lower HIV incidence than strategies where ART is initiated early. Maintaining a fixed TPR value based on the net increase in people on ART gives higher HIV incidence reduction and requires fast ART scale-up.

Conclusion: Our analysis suggests that the TPR is not an adequate indicator of ART programme impact, without information on ART coverage and retention. Achieving early initiation and adherence to treatment to improve ART coverage might be as important as attaining a specific TPR target. Comparisons of TPR in different settings should account for differences in epidemic conditions.},
}

@article {pmid30835630,
year = {2019},
author = {Winters, BR and Wen, L and Holt, SK and Dash, A and Gore, JL and Schade, GR and Wright, JL},
title = {Does the diagnosis of bladder cancer lead to higher rates of smoking cessation? Findings from the Medicare Health Outcomes Survey.},
journal = {The Journal of urology},
volume = {},
number = {},
pages = {101097JU0000000000000206},
doi = {10.1097/JU.0000000000000206},
pmid = {30835630},
issn = {1527-3792},
abstract = {PURPOSE: Smoking is the most common risk factor for bladder cancer (BC) and is associated with adverse clinical outcomes. The diagnosis of BC represents a 'teachable moment' for smoking cessation. We investigate the likelihood of smoking cessation after BC diagnosis in a population database.

MATERIALS AND METHODS: We evaluated SEER-MHOS (1998-2013) for all patients diagnosed with incident BC who had pre- and post-diagnosis survey data available. We compared these patients to propensity matched non-cancer controls (NCCs) and to a cohort of incident renal cell carcinoma (RCC) patients. Differences in smoking cessation were compared between groups and multivariate logistic regression performed to assess the likelihood of smoking cessation.

RESULTS: 394 newly diagnosed bladder cancer patients were propensity matched to 1,970 NCCs and compared with 169 incident RCC patients. Baseline smoking prevalence was more common in patients diagnosed with BC (16%) compared with RCC (11%) (NS). The smoking cessation rates in BC patients was 27% compared with 21% in NCCs (p=0.30) and 26% in RCC patients (p=0.90). There were no significant differences in the adjusted odds ratios of quitting smoking in BC and RCC patients compared with NCCs (1.3, 95%CI: 0.7 - 2.5; 1.2, 95%CI: 0.5 - 3.6). Independent predictors of smoking cessation in BC patients included age (p=0.03), African American race (p=0.03), and college education (p=0.01).

CONCLUSIONS: Smoking cessation was not significantly different following the diagnosis of BC compared to propensity-matched NCCs. The proportion of individuals quitting was low overall, suggesting improved efforts are needed to utilize this teachable moment in BC patients.},
}

@article {pmid30834353,
year = {2019},
author = {Neuhouser, ML and Clowry, C and Beatty, SJ and Wang, CY and Drewnowski, A and Perrigue, MM},
title = {Rationale and design of the frequency of eating and Satiety Hormones (FRESH) study: A randomized cross-over clinical trial.},
journal = {Contemporary clinical trials communications},
volume = {14},
number = {},
pages = {100334},
doi = {10.1016/j.conctc.2019.100334},
pmid = {30834353},
issn = {2451-8654},
abstract = {Background: The goal of the Frequency of Eating and Satiety Hormones (FRESH) Study is to understand the relationship between eating frequency (EF) and biomarkers of appetite and disease risk. This report gives the study rationale and design.

Methods: The FRESH study was conducted in n = 50 overweight and obese, but otherwise healthy, male and female adults aged 18-50 years. The protocol included four in-person clinic visits for protocol instruction, blood draws, anthropometry, and meal testing; all other activities were done at home. Participants completed two 21-day phases in random order with a two-week washout between phases. One phase was high EF (6 eating occasions/day) and the other was low EF (3 eating occasions/day). Each phase specified time of day for each eating occasion. Participants prepared their own meals throughout the study using study-provided individualized, structured meal plans ensuring that calories, macronutrients and micronutrients were identical during both study phases. Fasting blood was collected before and after each phase to test intervention effects on the biomarkers. At the end of each phase participants also completed extended appetite testing with meals prepared by the study clinic.

Results: Participants were recruited using print, radio, and digital ads. 60 participants consented to enroll; 10 dropped out due to work or school scheduling conflicts and 50 (target sample size) completed the study. Compliance was assessed by completion of daily on-line meal plan checklists.

Conclusions: The FRESH study will provide data on whether higher vs. lower daily EF in the context of constant energy and nutrient intake may be harmful or beneficial based on intervention effects on biomarkers of health and disease risk.},
}

@article {pmid30830494,
year = {2019},
author = {Thompson, B and Barrington, WE and Briant, KJ and Kupay, E and Carosso, E and Gonzalez, NE and Gonzalez, VJ},
title = {Educating Latinas about cervical cancer and HPV: a pilot randomized study.},
journal = {Cancer causes & control : CCC},
volume = {},
number = {},
pages = {},
doi = {10.1007/s10552-019-01150-w},
pmid = {30830494},
issn = {1573-7225},
support = {U54CA153502//National Cancer Institute/ ; U53CA153502-05S1//National Cancer Institute/ ; U54CA132381//National Cancer Institute/ ; UL1RR025014//National Center for Research Resources/ ; },
abstract = {INTRODUCTION: The purpose of this study was to assess effects of three different educational intervention arms on knowledge of and intention to receive Pap testing and HPV co-testing.

METHODS: Three active educational intervention arms were developed: a fotonovela, a radionovela, and a digital story. A pilot randomized controlled trial of 160 Latinas was conducted to assess the effectiveness of the intervention arms in increasing knowledge of cervical cancer and HPV and intention to be screened for cervical cancer compared to an attention control group (flu vaccination).

RESULTS: Women in all three treatment arms significantly increased knowledge about cervical cancer compared to control arm (p = 0.02). Knowledge about cervical cancer screening also increased in the active arms compared to control (p = 0.0003). Knowledge of HPV risk also increased relative to the control (p = 0.0001). There were no significant differences between the intervention arms in increased knowledge of cervical cancer or cervical cancer screening (p = 0.57 and 0.16, respectively).

DISCUSSION: This study supported the use of small media interventions in narrative education form as effective in increasing knowledge and intention to be screened for cervical cancer. The three culturally relevant interventions, built on qualitative data, were all successful in increasing knowledge.},
}

@article {pmid30829324,
year = {2019},
author = {Radtke, S and Perez, AM and Venkataraman, R and Reddy, S and Haworth, KG and Humbert, O and Kiem, HP and Peterson, CW},
title = {Preparation and Gene Modification of Nonhuman Primate Hematopoietic Stem and Progenitor Cells.},
journal = {Journal of visualized experiments : JoVE},
volume = {},
number = {144},
pages = {},
doi = {10.3791/58933},
pmid = {30829324},
issn = {1940-087X},
abstract = {Hematopoietic stem and progenitor cell (HSPC) transplantation has been a cornerstone therapy for leukemia and other cancers for nearly half a century, underlies the only known cure of human immunodeficiency virus (HIV-1) infection, and shows immense promise in the treatment of genetic diseases such as beta thalassemia. Our group has developed a protocol to model HSPC gene therapy in nonhuman primates (NHPs), allowing scientists to optimize many of the same reagents and techniques that are applied in the clinic. Here, we describe methods for purifying CD34+ HSPCs and long-term persisting hematopoietic stem cell (HSC) subsets from primed bone marrow (BM). Identical techniques can be employed for the purification of other HSPC sources (e.g., mobilized peripheral blood stem cells [PBSCs]). Outlined is a 2 day protocol in which cells are purified, cultured, modified with lentivirus (LV), and prepared for infusion back into the autologous host. Key readouts of success include the purity of the CD34+ HSPC population, the ability of purified HSPCs to form morphologically distinct colonies in semisolid media, and, most importantly, gene modification efficiency. The key advantage to HSPC gene therapy is the ability to provide a source of long-lived cells that give rise to all hematopoietic cell types. As such, these methods have been used to model therapies for cancer, genetic diseases, and infectious diseases. In each case, therapeutic efficacy is established by enhancing the function of distinct HSPC progeny, including red blood cells, T cells, B cells, and/or myeloid subsets. The methods to isolate, modify, and prepare HSPC products are directly applicable and translatable to multiple diseases in human patients.},
}

@article {pmid30828695,
year = {2018},
author = {Zheng, Y},
title = {Study Design Considerations for Cancer Biomarker Discoveries.},
journal = {The journal of applied laboratory medicine},
volume = {3},
number = {2},
pages = {282-289},
doi = {10.1373/jalm.2017.025809},
pmid = {30828695},
issn = {2475-7241},
support = {P30 CA015704/CA/NCI NIH HHS/United States ; R01 GM085047/GM/NIGMS NIH HHS/United States ; U01 CA086368/CA/NCI NIH HHS/United States ; U24 CA086368/CA/NCI NIH HHS/United States ; },
abstract = {Background: Biomarker discovery studies have generated an array of omic data, however few novel biomarkers have reached clinical use. Guidelines for rigorous study designs are needed.

Content: Biases frequently occur in sample selection, outcome ascertainment, or unblinded sample handling and assaying process. The principles of a prospective-specimen collection and retrospective-blinded-evaluation (PRoBE) design can be adapted to mitigate various sources of biases in discovery. We recommend establishing quality biospecimen repositories using matched two-phase designs to minimize biases and maximize efficiency. We also highlight the importance of taking the clinical context into consideration in both sample selection and power calculation for discovery studies.

Summary: Biomarker discovery research should follow rigorous design principles in sample se- lection to avoid biases. Consideration of clinical application and the corresponding biomarker performance characteristics in study designs will lead to a more fruitful discovery study.

Impact: Appropriate study designs will improve the quality and clinical rigor of biomarker discovery studies.},
}

@article {pmid30828438,
year = {2019},
author = {Gopaulakrishnan, S and Pollack, S and Stubbs, BJ and Pagès, H and Readey, J and Davis, S and Waldron, L and Morgan, M and Carey, V},
title = {restfulSE: A semantically rich interface for cloud-scale genomics with Bioconductor.},
journal = {F1000Research},
volume = {8},
number = {},
pages = {21},
doi = {10.12688/f1000research.17518.1},
pmid = {30828438},
issn = {2046-1402},
abstract = {Bioconductor's SummarizedExperiment class unites numerical assay quantifications with sample- and experiment-level metadata. SummarizedExperiment is the standard Bioconductor class for assays that produce matrix-like data, used by over 200 packages. We describe the restfulSE package, a deployment of this data model that supports remote storage. We illustrate use of SummarizedExperiment with remote HDF5 and Google BigQuery back ends, with two applications in cancer genomics. Our intent is to allow the use of familiar and semantically meaningful programmatic idioms to query genomic data, while abstracting the remote interface from end users and developers.},
}

@article {pmid30824040,
year = {2019},
author = {Bolaños-Meade, J and Reshef, R and Fraser, R and Fei, M and Abhyankar, S and Al-Kadhimi, Z and Alousi, AM and Antin, JH and Arai, S and Bickett, K and Chen, YB and Damon, LE and Efebera, YA and Geller, NL and Giralt, SA and Hari, P and Holtan, SG and Horowitz, MM and Jacobsohn, DA and Jones, RJ and Liesveld, JL and Logan, BR and MacMillan, ML and Mielcarek, M and Noel, P and Pidala, J and Porter, DL and Pusic, I and Sobecks, R and Solomon, SR and Weisdorf, DJ and Wu, J and Pasquini, MC and Koreth, J},
title = {Three prophylaxis regimens (tacrolimus, mycophenolate mofetil, and cyclophosphamide; tacrolimus, methotrexate, and bortezomib; or tacrolimus, methotrexate, and maraviroc) versus tacrolimus and methotrexate for prevention of graft-versus-host disease with haemopoietic cell transplantation with reduced-intensity conditioning: a randomised phase 2 trial with a non-randomised contemporaneous control group (BMT CTN 1203).},
journal = {The Lancet. Haematology},
volume = {6},
number = {3},
pages = {e132-e143},
doi = {10.1016/S2352-3026(18)30221-7},
pmid = {30824040},
issn = {2352-3026},
abstract = {BACKGROUND: Prevention of graft-versus-host disease (GvHD) without malignant relapse is the overall goal of allogeneic haemopoietic cell transplantation (HCT). We aimed to evaluate regimens using either maraviroc, bortezomib, or post-transplantation cyclophosphamide for GvHD prophylaxis compared with controls receiving the combination of tacrolimus and methotrexate using a novel composite primary endpoint to identify the most promising intervention to be further tested in a phase 3 trial.

METHODS: In this prospective multicentre phase 2 trial, adult patients aged 18-75 years who received reduced-intensity conditioning HCT were randomly assigned (1:1:1) by random block sizes to tacrolimus, mycophenolate mofetil, and post-transplantation cyclophosphamide (cyclophosphamide 50 mg/kg on days 3 and 4, followed by tacrolimus starting on day 5 and mycophenolate mofetil starting on day 5 at 15 mg/kg three times daily not to exceed 1 g from day 5 to day 35); tacrolimus, methotrexate, and bortezomib (bortezomib 1·3 mg/m2 intravenously on days 1, 4, and 7 after HCT); or tacrolimus, methotrexate, and maraviroc (maraviroc 300 mg orally twice daily from day -3 to day 30 after HCT). Methotrexate was administered as a 15 mg/m2 intravenous bolus on day 1 and 10 mg/m2 intravenous bolus on days 3, 6, and 11 after HCT; tacrolimus was given intravenously at a dose of 0·05 mg/kg twice daily (or oral equivalent) starting on day -3 (except the post-transplantation cyclophosphamide, as indicated), with a target level of 5-15 ng/mL. Tacrolimus was continued at least until day 90 and was tapered off by day 180. Each study group was compared separately to a contemporary non-randomised prospective cohort of patients (control group) who fulfilled the same eligibility criteria as the trial, but who were treated with tacrolimus and methotrexate at centres not participating in the trial. The primary endpoint (GvHD-free, relapse-free survival [GRFS]) was defined as the time from HCT to onset of grade 3-4 acute GvHD, chronic GvHD requiring systemic immunosuppression, disease relapse, or death. The study was analysed by modified intention to treat. The study is closed to accrual and this is the planned analysis. This trial is registered with ClinicalTrials.gov, number NCT02208037.

FINDINGS: Between Nov 17, 2014, and May 18, 2016, 273 patients from 31 US centres were randomly assigned to the three study arms: 89 to tacrolimus, methotrexate, and bortezomib; 92 to tacrolimus, methotrexate, and maraviroc; 92 to tacrolimus, mycophenolate mofetil, and post-transplantation cyclophosphamide; and six were excluded. Between Aug 1, 2014, and Sept 14, 2016, 224 controls received tacrolimus and methotrexate. Controls were generally well matched except for more frequent comorbidities than the intervention groups and a different distribution of types of conditioning regimens used. Compared with controls, the hazard ratio for GRFS was 0·72 (90% CI 0·54-0·94; p=0·044) for tacrolimus, mycophenolate mofetil, and post-transplantation cyclophosphamide, 0·98 (0·76-1·27; p=0·92) for tacrolimus, methotrexate, and bortezomib, and 1·10 (0·86-1·41; p=0·49) for tacrolimus, methotrexate, and maraviroc. 238 patients experienced grade 3 or 4 toxicities: 12 (13%) had grade 3 and 67 (73%) grade 4 events with tacrolimus, mycophenolate mofetil, and post-transplantation cyclophosphamide; ten (11%) had grade 3 and 68 (76%) had grade 4 events with tacrolimus, methotrexate, and bortezomib; and 18 (20%) had grade 3 and 63 (68%) had grade 4 events with tacrolimus, methotrexate, and maraviroc. The most common toxicities were haematological (77 [84%] for tacrolimus, mycophenolate mofetil, and post-transplantation cyclophosphamide; 73 [82%] for tacrolimus, methotrexate, and bortezomib; and 78 [85%] for tacrolimus, methotrexate, and maraviroc) and cardiac (43 [47%], 44 [49%], and 43 [47%], respectively).

INTERPRETATION: Tacrolimus, mycophenolate mofetil, and post-transplantation cyclophosphamide was the most promising intervention, yielding the best GRFS; this regimen is thus being prospectively compared with tacrolimus and methotrexate in a phase 3 randomised trial.

FUNDING: US National Health, Lung, and Blood Institute; National Cancer Institute; National Institute of Allergy and Infectious Disease; and Millennium Pharmaceuticals.},
}

@article {pmid30820706,
year = {2019},
author = {Bien, SA and Su, YR and Conti, DV and Harrison, TA and Qu, C and Guo, X and Lu, Y and Albanes, D and Auer, PL and Banbury, BL and Berndt, SI and Bézieau, S and Brenner, H and Buchanan, DD and Caan, BJ and Campbell, PT and Carlson, CS and Chan, AT and Chang-Claude, J and Chen, S and Connolly, CM and Easton, DF and Feskens, EJM and Gallinger, S and Giles, GG and Gunter, MJ and Hampe, J and Huyghe, JR and Hoffmeister, M and Hudson, TJ and Jacobs, EJ and Jenkins, MA and Kampman, E and Kang, HM and Kühn, T and Küry, S and Lejbkowicz, F and Le Marchand, L and Milne, RL and Li, L and Li, CI and Lindblom, A and Lindor, NM and Martín, V and McNeil, CE and Melas, M and Moreno, V and Newcomb, PA and Offit, K and Pharaoh, PDP and Potter, JD and Qu, C and Riboli, E and Rennert, G and Sala, N and Schafmayer, C and Scacheri, PC and Schmit, SL and Severi, G and Slattery, ML and Smith, JD and Trichopoulou, A and Tumino, R and Ulrich, CM and van Duijnhoven, FJB and Van Guelpen, B and Weinstein, SJ and White, E and Wolk, A and Woods, MO and Wu, AH and Abecasis, GR and Casey, G and Nickerson, DA and Gruber, SB and Hsu, L and Zheng, W and Peters, U},
title = {Genetic variant predictors of gene expression provide new insight into risk of colorectal cancer.},
journal = {Human genetics},
volume = {},
number = {},
pages = {},
doi = {10.1007/s00439-019-01989-8},
pmid = {30820706},
issn = {1432-1203},
support = {U01 CA164930//National Cancer Institute/ ; R01 CA201407//National Cancer Institute/ ; },
abstract = {Genome-wide association studies have reported 56 independently associated colorectal cancer (CRC) risk variants, most of which are non-coding and believed to exert their effects by modulating gene expression. The computational method PrediXcan uses cis-regulatory variant predictors to impute expression and perform gene-level association tests in GWAS without directly measured transcriptomes. In this study, we used reference datasets from colon (n = 169) and whole blood (n = 922) transcriptomes to test CRC association with genetically determined expression levels in a genome-wide analysis of 12,186 cases and 14,718 controls. Three novel associations were discovered from colon transverse models at FDR ≤ 0.2 and further evaluated in an independent replication including 32,825 cases and 39,933 controls. After adjusting for multiple comparisons, we found statistically significant associations using colon transcriptome models with TRIM4 (discovery P = 2.2 × 10- 4, replication P = 0.01), and PYGL (discovery P = 2.3 × 10- 4, replication P = 6.7 × 10- 4). Interestingly, both genes encode proteins that influence redox homeostasis and are related to cellular metabolic reprogramming in tumors, implicating a novel CRC pathway linked to cell growth and proliferation. Defining CRC risk regions as one megabase up- and downstream of one of the 56 independent risk variants, we defined 44 non-overlapping CRC-risk regions. Among these risk regions, we identified genes associated with CRC (P < 0.05) in 34/44 CRC-risk regions. Importantly, CRC association was found for two genes in the previously reported 2q25 locus, CXCR1 and CXCR2, which are potential cancer therapeutic targets. These findings provide strong candidate genes to prioritize for subsequent laboratory follow-up of GWAS loci. This study is the first to implement PrediXcan in a large colorectal cancer study and findings highlight the utility of integrating transcriptome data in GWAS for discovery of, and biological insight into, risk loci.},
}

@article {pmid30820047,
year = {2019},
author = {Kunkle, BW and Grenier-Boley, B and Sims, R and Bis, JC and Damotte, V and Naj, AC and Boland, A and Vronskaya, M and van der Lee, SJ and Amlie-Wolf, A and Bellenguez, C and Frizatti, A and Chouraki, V and Martin, ER and Sleegers, K and Badarinarayan, N and Jakobsdottir, J and Hamilton-Nelson, KL and Moreno-Grau, S and Olaso, R and Raybould, R and Chen, Y and Kuzma, AB and Hiltunen, M and Morgan, T and Ahmad, S and Vardarajan, BN and Epelbaum, J and Hoffmann, P and Boada, M and Beecham, GW and Garnier, JG and Harold, D and Fitzpatrick, AL and Valladares, O and Moutet, ML and Gerrish, A and Smith, AV and Qu, L and Bacq, D and Denning, N and Jian, X and Zhao, Y and Del Zompo, M and Fox, NC and Choi, SH and Mateo, I and Hughes, JT and Adams, HH and Malamon, J and Sanchez-Garcia, F and Patel, Y and Brody, JA and Dombroski, BA and Naranjo, MCD and Daniilidou, M and Eiriksdottir, G and Mukherjee, S and Wallon, D and Uphill, J and Aspelund, T and Cantwell, LB and Garzia, F and Galimberti, D and Hofer, E and Butkiewicz, M and Fin, B and Scarpini, E and Sarnowski, C and Bush, WS and Meslage, S and Kornhuber, J and White, CC and Song, Y and Barber, RC and Engelborghs, S and Sordon, S and Voijnovic, D and Adams, PM and Vandenberghe, R and Mayhaus, M and Cupples, LA and Albert, MS and De Deyn, PP and Gu, W and Himali, JJ and Beekly, D and Squassina, A and Hartmann, AM and Orellana, A and Blacker, D and Rodriguez-Rodriguez, E and Lovestone, S and Garcia, ME and Doody, RS and Munoz-Fernadez, C and Sussams, R and Lin, H and Fairchild, TJ and Benito, YA and Holmes, C and Karamujić-Čomić, H and Frosch, MP and Thonberg, H and Maier, W and Roschupkin, G and Ghetti, B and Giedraitis, V and Kawalia, A and Li, S and Huebinger, RM and Kilander, L and Moebus, S and Hernández, I and Kamboh, MI and Brundin, R and Turton, J and Yang, Q and Katz, MJ and Concari, L and Lord, J and Beiser, AS and Keene, CD and Helisalmi, S and Kloszewska, I and Kukull, WA and Koivisto, AM and Lynch, A and Tarraga, L and Larson, EB and Haapasalo, A and Lawlor, B and Mosley, TH and Lipton, RB and Solfrizzi, V and Gill, M and Longstreth, WT and Montine, TJ and Frisardi, V and Diez-Fairen, M and Rivadeneira, F and Petersen, RC and Deramecourt, V and Alvarez, I and Salani, F and Ciaramella, A and Boerwinkle, E and Reiman, EM and Fievet, N and Rotter, JI and Reisch, JS and Hanon, O and Cupidi, C and Andre Uitterlinden, AG and Royall, DR and Dufouil, C and Maletta, RG and de Rojas, I and Sano, M and Brice, A and Cecchetti, R and George-Hyslop, PS and Ritchie, K and Tsolaki, M and Tsuang, DW and Dubois, B and Craig, D and Wu, CK and Soininen, H and Avramidou, D and Albin, RL and Fratiglioni, L and Germanou, A and Apostolova, LG and Keller, L and Koutroumani, M and Arnold, SE and Panza, F and Gkatzima, O and Asthana, S and Hannequin, D and Whitehead, P and Atwood, CS and Caffarra, P and Hampel, H and Quintela, I and Carracedo, Á and Lannfelt, L and Rubinsztein, DC and Barnes, LL and Pasquier, F and Frölich, L and Barral, S and McGuinness, B and Beach, TG and Johnston, JA and Becker, JT and Passmore, P and Bigio, EH and Schott, JM and Bird, TD and Warren, JD and Boeve, BF and Lupton, MK and Bowen, JD and Proitsi, P and Boxer, A and Powell, JF and Burke, JR and Kauwe, JSK and Burns, JM and Mancuso, M and Buxbaum, JD and Bonuccelli, U and Cairns, NJ and McQuillin, A and Cao, C and Livingston, G and Carlson, CS and Bass, NJ and Carlsson, CM and Hardy, J and Carney, RM and Bras, J and Carrasquillo, MM and Guerreiro, R and Allen, M and Chui, HC and Fisher, E and Masullo, C and Crocco, EA and DeCarli, C and Bisceglio, G and Dick, M and Ma, L and Duara, R and Graff-Radford, NR and Evans, DA and Hodges, A and Faber, KM and Scherer, M and Fallon, KB and Riemenschneider, M and Fardo, DW and Heun, R and Farlow, MR and Kölsch, H and Ferris, S and Leber, M and Foroud, TM and Heuser, I and Galasko, DR and Giegling, I and Gearing, M and Hüll, M and Geschwind, DH and Gilbert, JR and Morris, J and Green, RC and Mayo, K and Growdon, JH and Feulner, T and Hamilton, RL and Harrell, LE and Drichel, D and Honig, LS and Cushion, TD and Huentelman, MJ and Hollingworth, P and Hulette, CM and Hyman, BT and Marshall, R and Jarvik, GP and Meggy, A and Abner, E and Menzies, GE and Jin, LW and Leonenko, G and Real, LM and Jun, GR and Baldwin, CT and Grozeva, D and Karydas, A and Russo, G and Kaye, JA and Kim, R and Jessen, F and Kowall, NW and Vellas, B and Kramer, JH and Vardy, E and LaFerla, FM and Jöckel, KH and Lah, JJ and Dichgans, M and Leverenz, JB and Mann, D and Levey, AI and Pickering-Brown, S and Lieberman, AP and Klopp, N and Lunetta, KL and Wichmann, HE and Lyketsos, CG and Morgan, K and Marson, DC and Brown, K and Martiniuk, F and Medway, C and Mash, DC and Nöthen, MM and Masliah, E and Hooper, NM and McCormick, WC and Daniele, A and McCurry, SM and Bayer, A and McDavid, AN and Gallacher, J and McKee, AC and van den Bussche, H and Mesulam, M and Brayne, C and Miller, BL and Riedel-Heller, S and Miller, CA and Miller, JW and Al-Chalabi, A and Morris, JC and Shaw, CE and Myers, AJ and Wiltfang, J and O'Bryant, S and Olichney, JM and Alvarez, V and Parisi, JE and Singleton, AB and Paulson, HL and Collinge, J and Perry, WR and Mead, S and Peskind, E and Cribbs, DH and Rossor, M and Pierce, A and Ryan, NS and Poon, WW and Nacmias, B and Potter, H and Sorbi, S and Quinn, JF and Sacchinelli, E and Raj, A and Spalletta, G and Raskind, M and Caltagirone, C and Bossù, P and Orfei, MD and Reisberg, B and Clarke, R and Reitz, C and Smith, AD and Ringman, JM and Warden, D and Roberson, ED and Wilcock, G and Rogaeva, E and Bruni, AC and Rosen, HJ and Gallo, M and Rosenberg, RN and Ben-Shlomo, Y and Sager, MA and Mecocci, P and Saykin, AJ and Pastor, P and Cuccaro, ML and Vance, JM and Schneider, JA and Schneider, LS and Slifer, S and Seeley, WW and Smith, AG and Sonnen, JA and Spina, S and Stern, RA and Swerdlow, RH and Tang, M and Tanzi, RE and Trojanowski, JQ and Troncoso, JC and Van Deerlin, VM and Van Eldik, LJ and Vinters, HV and Vonsattel, JP and Weintraub, S and Welsh-Bohmer, KA and Wilhelmsen, KC and Williamson, J and Wingo, TS and Woltjer, RL and Wright, CB and Yu, CE and Yu, L and Saba, Y and , and , and , and , and Pilotto, A and Bullido, MJ and Peters, O and Crane, PK and Bennett, D and Bosco, P and Coto, E and Boccardi, V and De Jager, PL and Lleo, A and Warner, N and Lopez, OL and Ingelsson, M and Deloukas, P and Cruchaga, C and Graff, C and Gwilliam, R and Fornage, M and Goate, AM and Sanchez-Juan, P and Kehoe, PG and Amin, N and Ertekin-Taner, N and Berr, C and Debette, S and Love, S and Launer, LJ and Younkin, SG and Dartigues, JF and Corcoran, C and Ikram, MA and Dickson, DW and Nicolas, G and Campion, D and Tschanz, J and Schmidt, H and Hakonarson, H and Clarimon, J and Munger, R and Schmidt, R and Farrer, LA and Van Broeckhoven, C and C O'Donovan, M and DeStefano, AL and Jones, L and Haines, JL and Deleuze, JF and Owen, MJ and Gudnason, V and Mayeux, R and Escott-Price, V and Psaty, BM and Ramirez, A and Wang, LS and Ruiz, A and van Duijn, CM and Holmans, PA and Seshadri, S and Williams, J and Amouyel, P and Schellenberg, GD and Lambert, JC and Pericak-Vance, MA},
title = {Genetic meta-analysis of diagnosed Alzheimer's disease identifies new risk loci and implicates Aβ, tau, immunity and lipid processing.},
journal = {Nature genetics},
volume = {51},
number = {3},
pages = {414-430},
doi = {10.1038/s41588-019-0358-2},
pmid = {30820047},
issn = {1546-1718},
abstract = {Risk for late-onset Alzheimer's disease (LOAD), the most prevalent dementia, is partially driven by genetics. To identify LOAD risk loci, we performed a large genome-wide association meta-analysis of clinically diagnosed LOAD (94,437 individuals). We confirm 20 previous LOAD risk loci and identify five new genome-wide loci (IQCK, ACE, ADAM10, ADAMTS1, and WWOX), two of which (ADAM10, ACE) were identified in a recent genome-wide association (GWAS)-by-familial-proxy of Alzheimer's or dementia. Fine-mapping of the human leukocyte antigen (HLA) region confirms the neurological and immune-mediated disease haplotype HLA-DR15 as a risk factor for LOAD. Pathway analysis implicates immunity, lipid metabolism, tau binding proteins, and amyloid precursor protein (APP) metabolism, showing that genetic variants affecting APP and Aβ processing are associated not only with early-onset autosomal dominant Alzheimer's disease but also with LOAD. Analyses of risk genes and pathways show enrichment for rare variants (P = 1.32 × 10-7), indicating that additional rare variants remain to be identified. We also identify important genetic correlations between LOAD and traits such as family history of dementia and education.},
}

@article {pmid30819455,
year = {2019},
author = {Carlos, RC and Sicks, JD and Chiles, C and Gansauer, L and Kamen, CS and Kazak, AE and Neuman, HB and Unger, JM and Weaver, KE},
title = {Lung Cancer Screening in the National Cancer Institute Community Oncology Research Program: Availability and Service Organization.},
journal = {Journal of the American College of Radiology : JACR},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jacr.2018.12.016},
pmid = {30819455},
issn = {1558-349X},
abstract = {PURPOSE: Annual low-dose CT (LDCT) for lung screening in high-risk individuals decreases both lung cancer-specific mortality and all-cause mortality. Community oncology practice networks constituting the National Cancer Institute Community Oncology Research Program (NCORP) conduct clinical trials across the cancer spectrum. The authors report access to and characteristics of LDCT screening for lung cancer in these community oncology practices.

METHODS: A landscape capacity assessment was conducted in 2017 across the NCORP network. The primary outcome was the proportion of adult oncology practice groups offering LDCT lung screening on site. The secondary outcomes were the proportion of those screening services (1) with radiologist participation in service management and (2) offered at ACR Designated Lung Cancer Screening Centers.

RESULTS: Fifty-two percent of components and subcomponents responded to at least some portion of the assessment, representing 217 practice groups. Analyzing the 211 adult oncology practice groups responding to the primary question, 73% offered lung screening services on site. Radiologists participated in managing 69% of these services. Forty-seven percent were offered in ACR Designated Lung Cancer Screening Centers. Minority and underserved practice groups were less likely to offer lung screening; however, this association dissipated when analyses focused on practices within the United States. Safety net and Critical Access Hospital designation increased the likelihood of screening availability.

CONCLUSIONS: The majority of community oncology practice groups within the NCORP offered lung screening on site, although radiologist participation in service management and ACR Lung Cancer Screening Center designation, markers of service quality, were more variable.},
}

@article {pmid30819038,
year = {2019},
author = {Bansal, A and Sullivan, SD and Lin, VW and Purdum, AG and Navale, L and Cheng, P and Ramsey, SD},
title = {Estimating Long-Term Survival for Patients with Relapsed or Refractory Large B-cell Lymphoma Treated with Chimeric Antigen Receptor Therapy: A Comparison of Standard and Mixture Cure Models.},
journal = {Medical decision making : an international journal of the Society for Medical Decision Making},
volume = {},
number = {},
pages = {272989X18820535},
doi = {10.1177/0272989X18820535},
pmid = {30819038},
issn = {1552-681X},
abstract = {Patients treated with anti-CD19 chimeric antigen receptor (CAR) T-cell therapies have shown either sustained remission or rapid progression. Traditional survival modeling may underestimate outcomes in these situations, by assuming the same mortality rate for all patients. To illustrate this issue, we compare standard parametric models to mixture cure models for estimating long-term overall survival in patients with relapsed or refractory large B-cell lymphoma treated with axicabtagene ciloleucel (axi-cel). Compared to standard models without cure proportions, mixture cure models have similar fit, but substantially different extrapolated survival. Standard models (Weibull and generalized gamma) estimate mean survival of 2.0 years (95% CI (1.5, 3.0)) and 3.0 years (95% CI (1.7, 5.6)), respectively, compared to 15.7 years (95% CI (9.3, 21.1)) and 17.5 yrs (12.0, 22.8) from mixture cure models (using Weibull and generalized gamme distributions). For cancer therapies where substantial fractions achieve long term remission, our results suggest that assumptions of the modeling approach should be considered. Given sufficient follow-up, mixture cure models may provide a more accurate estimate of long-term overall survival compared with standard models.},
}

@article {pmid30819011,
year = {2019},
author = {Stoner, MCD and Rucinski, KB and Edwards, JK and Selin, A and Hughes, JP and Wang, J and Agyei, Y and Gomez-Olive, FX and MacPhail, C and Kahn, K and Pettifor, A},
title = {The Relationship Between School Dropout and Pregnancy Among Adolescent Girls and Young Women in South Africa: A HPTN 068 Analysis.},
journal = {Health education & behavior : the official publication of the Society for Public Health Education},
volume = {},
number = {},
pages = {1090198119831755},
doi = {10.1177/1090198119831755},
pmid = {30819011},
issn = {1552-6127},
abstract = {BACKGROUND: Prevention of both school dropout and teen pregnancy represent clear public health priorities for South Africa, yet their complex and potentially cyclical relationship has not been fully explored.

OBJECTIVE: To further understand how this relationship operates, we analyzed data from a randomized trial of young women aged 13 to 20 years enrolled in school in rural South Africa to estimate the association between pregnancy and subsequent dropout and between dropout and subsequent pregnancy.

METHOD: We examined inverse probability (IP) of exposure-weighted survival curves for school dropout by pregnancy and for pregnancy by school dropout. We used weighted curves to calculate 1-, 2-, and 3-year risk differences and risk ratios. Additionally, we used an IP-weighted marginal structural cox model to estimate a hazard ratio (HR) for each relationship.

RESULTS: Dropout from school was associated with subsequent pregnancy (HR 3.58; 95% confidence interval [CI] [2.04, 6.28]) and pregnancy was associated with subsequent school dropout (HR 2.36; 95% CI [1.29, 4.31]). Young women who attended school but attended fewer days had a higher hazard of pregnancy than those who attended more school (HR 3.64; 95% CI [2.27, 5.84]).

CONCLUSION: Pregnancy is both a cause and a consequence of school dropout. Consideration of school attendance and academic performance could ultimately enhance pregnancy prevention efforts in this population. Programs should be tailored differently for (1) girls who have dropped out of school, (2) those who are in school and at risk for pregnancy, and (3) those who are in school and become pregnant.},
}

@article {pmid30818369,
year = {2019},
author = {Khanal, S and Galloway, DA},
title = {High-risk human papillomavirus oncogenes disrupt the Fanconi anemia DNA repair pathway by impairing localization and de-ubiquitination of FancD2.},
journal = {PLoS pathogens},
volume = {15},
number = {2},
pages = {e1007442},
doi = {10.1371/journal.ppat.1007442},
pmid = {30818369},
issn = {1553-7374},
abstract = {Persistent expression of high-risk HPV oncogenes is necessary for the development of anogenital and oropharyngeal cancers. Here, we show that E6/E7 expressing cells are hypersensitive to DNA crosslinking agent cisplatin and have defects in repairing DNA interstrand crosslinks (ICL). Importantly, we elucidate how E6/E7 attenuate the Fanconi anemia (FA) DNA crosslink repair pathway. Though E6/E7 activated the pathway by increasing FancD2 monoubiquitination and foci formation, they inhibited the completion of the repair by multiple mechanisms. E6/E7 impaired FancD2 colocalization with double-strand breaks (DSB), which subsequently hindered the recruitment of the downstream protein Rad51 to DSB in E6 cells. Further, E6 expression caused delayed FancD2 de-ubiquitination, an important process for effective ICL repair. Delayed FancD2 de-ubiquitination was associated with the increased chromatin retention of FancD2 hindering USP1 de-ubiquitinating activity, and persistently activated ATR/CHK-1/pS565 FancI signaling. E6 mediated p53 degradation did not hamper the cell cycle specific process of FancD2 modifications but abrogated repair by disrupting FancD2 de-ubiquitination. Further, E6 reduced the expression and foci formation of Palb2, which is a repair protein downstream of FancD2. These findings uncover unique mechanisms by which HPV oncogenes contribute to genomic instability and the response to cisplatin therapies.},
}

@article {pmid30817250,
year = {2019},
author = {Ramanathan, RK and McDonough, SL and Philip, PA and Hingorani, SR and Lacy, J and Kortmansky, JS and Thumar, J and Chiorean, EG and Shields, AF and Behl, D and Mehan, PT and Gaur, R and Seery, T and Guthrie, KA and Hochster, HS},
title = {Phase IB/II Randomized Study of FOLFIRINOX Plus Pegylated Recombinant Human Hyaluronidase Versus FOLFIRINOX Alone in Patients With Metastatic Pancreatic Adenocarcinoma: SWOG S1313.},
journal = {Journal of clinical oncology : official journal of the American Society of Clinical Oncology},
volume = {},
number = {},
pages = {JCO1801295},
doi = {10.1200/JCO.18.01295},
pmid = {30817250},
issn = {1527-7755},
abstract = {PURPOSE: Pegylated recombinant human hyaluronidase (PEGPH20) degrades hyaluronan (HA) and, in combination with chemotherapy, prolongs survival in preclinical models. The activity of PEGPH20 with modified fluorouracil, leucovorin, irinotecan, and oxaliplatin (mFOLFIRINOX) was evaluated in patients with metastatic pancreatic cancer (mPC).

MATERIALS AND METHODS: Patients had untreated mPC, a performance status of 0 to 1, and adequate organ function. Tumor HA status was not required for eligibility. After a phase Ib dose-finding study of mFOLFIRINOX plus PEGPH20, the phase II open-label study randomly assigned patients (1:1) to the combination arm or to mFOLFIRINOX alone (n = 138). The primary end point was overall survival (OS).

RESULTS: PEGPH20 dosages of 3 µg/kg every 2 weeks were more tolerable than twice-weekly dosages used in the phase I study, so 3 µg/kg every 2 weeks was the phase II dosage. An amendment instituted enoxaparin prophylaxis in the PEGPH20 combination arm as a result of increased thromboembolic (TE) events. The planned interim futility analysis when 35 deaths (of 103 analyzable patients) occurred resulted in an OS hazard ratio (HR) of 2.07 that favored the control arm, and the study was closed to accrual. The treatment-related grade 3 to 4 toxicity was significantly increased in the PEGPH20 combination arm relative to control (odds ratio, 2.7; 95% CI, 1.1 to 7.1). The median OS in the mFOLFIRINOX arm was 14.4 months (95% CI, 10.1 to 15.7 months) versus 7.7 months (95% CI, 4.6 to 9.3 months) in the PEGPH20 combination arm.

CONCLUSION: Addition of PEGPH20 to mFOLFIRINOX seems to be detrimental in patients unselected for tumor HA status. This combination caused increased toxicity (mostly GI and TE events) and resulted in decreased treatment duration compared with mFOLFIRINOX alone. The median OS in the mFOLFIRINOX control arm (14.4 months) is, to our knowledge, the longest yet reported and can be considered for patients with good PS.},
}

@article {pmid30817058,
year = {2019},
author = {Daniel, LC and Wang, M and Mulrooney, DA and Srivastava, D and Schwartz, LA and Edelstein, K and Brinkman, TM and Zhou, ES and Howell, RM and Gibson, TM and Leisenring, W and Oeffinger, KC and Neglia, J and Robison, LL and Armstrong, GT and Krull, KR},
title = {Sleep, emotional distress, and physical health in survivors of childhood cancer: A report from the Childhood Cancer Survivor Study.},
journal = {Psycho-oncology},
volume = {},
number = {},
pages = {},
doi = {10.1002/pon.5040},
pmid = {30817058},
issn = {1099-1611},
abstract = {OBJECTIVE: Sleep disorders are associated with psychological and physical health, though reports in long-term survivors of childhood cancer are limited. We characterized the prevalence and risk factors for behaviors consistent with sleep disorders in survivors and examined longitudinal associations with emotional distress and physical health outcomes.

METHODS: Survivors (n=1933; median [IQR] age=35 [30, 41]) and siblings (n=380; age=33 [27, 40]) from the Childhood Cancer Survivor Study completed measures of sleep quality, fatigue, and sleepiness. Emotional distress and physical health outcomes were assessed approximately five years before and after the sleep survey. Multivariable logistic or modified Poisson regression models examined associations with cancer diagnosis, treatment exposures, and emotional and physical health outcomes.

RESULTS: Survivors were more likely to report poor sleep efficiency (30.8% vs. 24.7%; prevalence ratio [PR]=1.26, 95% confidence interval [1.04-1.53]), daytime sleepiness (18.7% vs. 14.2%; PR=1.31[1.01-1.71]), and sleep supplement use (13.5% vs. 8.3%; PR=1.56[1.09-2.22]) than siblings. Survivors who developed emotional distress were more likely to report poor sleep efficiency (PR=1.70[1.40-2.07]), restricted sleep time (PR=1.35[1.12-1.62]), fatigue (PR=2.11[1.92-2.32]), daytime sleepiness (PR=2.19[1.71-2.82]), snoring (PR=1.85[1.08-3.16]), and more sleep medication (PR=2.86[2.00-4.09]) and supplement use (PR=1.89[1.33-2.69]). Survivors reporting symptoms of insomnia (PR=1.46[1.02-2.08]), fatigue (PR=1.31[1.01-1.72]), and using sleep medications (PR=2.16[1.13-4.12]) were more likely to develop migraines/headaches.

CONCLUSIONS: Survivors report more sleep difficulties and efforts to manage sleep than siblings. These sleep behaviors are related to worsening or persistently elevated emotional distress and may result in increased risk for migraines. Behavioral interventions targeting sleep may be important for improving health outcomes.},
}

@article {pmid30816957,
year = {2019},
author = {Kanate, AS and Kumar, A and Dreger, P and Dreyling, M and Le Gouill, S and Corradini, P and Bredeson, C and Fenske, TS and Smith, SM and Sureda, A and Moskowitz, A and Friedberg, JW and Inwards, DJ and Herrera, AF and Kharfan-Dabaja, MA and Reddy, N and Montoto, S and Robinson, SP and Abutalib, SA and Gisselbre, C and Vose, J and Gopal, A and Shadman, M and Perales, MA and Carpenter, P and Savani, BN and Hamadani, M},
title = {Maintenance Therapies for Hodgkin and Non-Hodgkin Lymphomas After Autologous Transplantation: A Consensus Project of ASBMT, CIBMTR, and the Lymphoma Working Party of EBMT.},
journal = {JAMA oncology},
volume = {},
number = {},
pages = {},
doi = {10.1001/jamaoncol.2018.6278},
pmid = {30816957},
issn = {2374-2445},
abstract = {Importance: Maintenance therapies are often considered as a therapeutic strategy in patients with lymphoma following autologous hematopoietic cell transplantation (auto-HCT) to mitigate the risk of disease relapse. With an evolving therapeutic landscape, where novel drugs are moving earlier in therapy lines, evidence relevant to contemporary practice is increasingly limited. The American Society for Blood and Marrow Transplantation (ASBMT), Center for International Blood and Marrow Transplant Research (CIBMTR), and European Society for Blood and Marrow Transplantation (EBMT) jointly convened an expert panel with diverse expertise and geographical representation to formulate consensus recommendations regarding the use of maintenance and/or consolidation therapies after auto-HCT in patients with lymphoma.

Observations: The RAND-modified Delphi method was used to generate consensus statements where at least 75% vote in favor of a recommendation was considered as consensus. The process included 3 online surveys moderated by an independent methodological expert to ensure anonymity and an in-person meeting. The panel recommended restricting the histologic categories covered in this project to Hodgkin lymphoma (HL), mantle cell lymphoma (MCL), diffuse large B-cell lymphoma (DLBCL), and follicular lymphoma. On completion of the voting process, the panel generated 22 consensus statements regarding post auto-HCT maintenance and/or consolidation therapies. The grade A recommendations included endorsement of: (1) brentuximab vedotin (BV) maintenance and/or consolidation in BV-naïve high-risk HL, (2) rituximab maintenance in MCL undergoing auto-HCT after first-line therapy, (3) rituximab maintenance in rituximab-naïve FL, and (4) No post auto-HCT maintenance was recommended in DLBCL. The panel also developed consensus statements for important real-world clinical scenarios, where randomized data are lacking to guide clinical practice.

Conclusions and Relevance: In the absence of contemporary evidence-based data, the panel found RAND-modified Delphi methodology effective in providing a rigorous framework for developing consensus recommendations for post auto-HCT maintenance and/or consolidation therapies in lymphoma.},
}

@article {pmid30816931,
year = {2019},
author = {Conant, EF and Barlow, WE and Herschorn, SD and Weaver, DL and Beaber, EF and Tosteson, ANA and Haas, JS and Lowry, KP and Stout, NK and Trentham-Dietz, A and diFlorio-Alexander, RM and Li, CI and Schnall, MD and Onega, T and Sprague, BL and , },
title = {Association of Digital Breast Tomosynthesis vs Digital Mammography With Cancer Detection and Recall Rates by Age and Breast Density.},
journal = {JAMA oncology},
volume = {},
number = {},
pages = {},
doi = {10.1001/jamaoncol.2018.7078},
pmid = {30816931},
issn = {2374-2445},
abstract = {Importance: Breast cancer screening examinations using digital breast tomosynthesis (DBT) has been shown to be associated with decreased false-positive test results and increased breast cancer detection compared with digital mammography (DM). Little is known regarding the size and stage of breast cancer types detected and their association with age and breast density.

Objective: To determine whether screening examinations using DBT detect breast cancers that are associated with an improved prognosis and to compare the detection rates by patient age and breast density.

This retrospective analysis of prospective cohort data from 3 research centers in the Population-based Research Optimizing Screening Through Personalized Regimens (PROSPR) consortium included data of women aged 40 to 74 years who underwent screening examinations using DM and DBT from January 1, 2011, through September 30, 2014. Statistical analysis was performed from November 8, 2017, to August 14, 2018.

Exposures: Use of DBT as a supplement to DM at breast cancer screening examination.

Main Outcomes and Measures: Recall rate, cancer detection rate, positive predictive value, biopsy rate, and distribution of invasive cancer subtypes.

Results: Among 96 269 women (mean [SD] patient age for all examinations, 55.9 [9.0] years), patient age was 56.4 (9.0) years for DM and 54.6 (8.9) years for DBT. Of 180 340 breast cancer screening examinations, 129 369 examinations (71.7%) used DM and 50 971 examinations (28.3%) used DBT. Screening examination with DBT (73 of 99 women [73.7%]) was associated with the detection of smaller, more often node-negative, HER2-negative, invasive cancers compared with DM (276 of 422 women [65.4%]). Screening examination with DBT was also associated with lower recall (odds ratio, 0.64; 95% CI, 0.57-0.72; P < .001) and higher cancer detection (odds ratio, 1.41; 95% CI, 1.05-1.89; P = .02) compared with DM for all age groups even when stratified by breast density. The largest increase in cancer detection rate and the greatest shift toward smaller, node-negative invasive cancers detected with DBT was for women aged 40 to 49 years. For women aged 40 to 49 years with nondense breasts, the cancer detection rate for examinations using DBT was 1.70 per 1000 women higher compared with the rate using DM; for women with dense breasts, the cancer detection rate was 2.27 per 1000 women higher for DBT. For these younger women, screening with DBT was associated with only 7 of 28 breast cancers (25.0%) categorized as poor prognosis compared with 19 of 47 breast cancers (40.4%) when screening with DM.

Conclusions and Relevance: The findings suggest that screening with DBT is associated with increased specificity and an increased proportion of breast cancers detected with better prognosis compared with DM. In the subgroup of women aged 40 to 49 years, routine DBT screening may have a favorable risk-benefit ratio.},
}

@article {pmid30816632,
year = {2019},
author = {Kiweewa, FM and Brown, E and Mishra, A and Nair, G and Palanee-Phillips, T and Mgodi, N and Nakabiito, C and Chakhtoura, N and Hillier, SL and Baeten, JM and , },
title = {Acquisition of Sexually Transmitted Infections among Women Using a Variety of Contraceptive Options: A prospective Study among High-risk African Women.},
journal = {Journal of the International AIDS Society},
volume = {22},
number = {2},
pages = {e25257},
doi = {10.1002/jia2.25257},
pmid = {30816632},
issn = {1758-2652},
support = {UM1AI068633//National Institute of Allergy and Infectious Diseases/ ; UM1AI068615//National Institute of Allergy and Infectious Diseases/ ; UM1AI106707//National Institute of Allergy and Infectious Diseases/ ; //Eunice Kennedy Shriver National Institute of Child Health and Human Development/ ; //National Institute of Mental Health/ ; NCT01617096//National Institutes of Health/ ; },
abstract = {INTRODUCTION: In many African settings, women concurrently face substantial risk of human immunodeficiency virus type 1 (HIV-1) infection, sexually transmitted infections (STIs) and unintended pregnancies. Few studies have evaluated STI risk among users of hormonal implants and copper intrauterine devices (IUDs) although these long-acting reversible contraceptive methods are being promoted widely because of their benefits. Within a prospective study of women at risk for HIV-1, we compared the risk of acquisition of Chlamydia trachomatis, Neisseria gonorrhoeae and Trichomonas vaginalis among women using different contraceptive methods.

METHODS: MTN-020/ASPIRE was a randomized trial of the dapivirine vaginal ring for HIV-1 prevention among 2629 women aged 18 to 45 years from Malawi, South Africa, Uganda and Zimbabwe, of whom 2264 used copper IUDs or progestin-based injectables or implants during follow-up. Screening for the above STIs occurred semi-annually.

RESULTS: Over 3440 person-years of follow-up, 408 cases of C. trachomatis (incidence 11.86/100 person-years), 196 of N. gonorrhoeae (5.70/100 person-years) and 213 cases of T. vaginalis (6.19/100 person-years) were detected. C. trachomatis and N. gonorrhoeae incidence were not significantly different across contraceptive methods. T. vaginalis incidence was significantly higher for copper IUD users compared to depot medroxyprogesterone acetate (DMPA), implant and norethisterone enanthate users.

CONCLUSION: Among African women at high HIV-1 risk, STIs were common. Risk of cervical infections did not differ across contraceptive methods. Significantly higher rates of T. vaginalis were observed among progestin-based methods compared to copper IUD users. Overall, these findings call for more intensive routine screening for STIs, and they support current World Health Organization guidance that women should have a wide range of contraceptive options.},
}

@article {pmid30814672,
year = {2019},
author = {Maloney, DG},
title = {Anti-CD19 CAR T cell therapy for lymphoma - off to the races!.},
journal = {Nature reviews. Clinical oncology},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41571-019-0183-7},
pmid = {30814672},
issn = {1759-4782},
}

@article {pmid30814668,
year = {2019},
author = {Li, AZ and Corey, L and Zhu, J},
title = {Random-Reaction-Seed Method for Automated Identification of Neurite Elongation and Branching.},
journal = {Scientific reports},
volume = {9},
number = {1},
pages = {2908},
doi = {10.1038/s41598-019-39962-0},
pmid = {30814668},
issn = {2045-2322},
support = {R01 AI042528//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; R01 AI111780//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; PO1 AI030731//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; },
abstract = {Conventional deterministic algorithms (i.e., skeletonization and edge-detection) lack robustness and sensitivity to reliably detect the neurite elongation and branching of low signal-to-noise-ratio microscopy images. Neurite outgrowth experiments produce an enormous number of images that require automated measurement; however, the tracking of neurites is easily lost in the automated process due to the intrinsic variability of neurites (either axon or dendrite) under stimuli. We have developed a stochastic random-reaction-seed (RRS) method to identify neurite elongation and branching accurately and automatically. The random-seeding algorithm of RRS is based on the hidden-Markov-model (HMM) to offer a robust enough way for tracing arbitrary neurite structures, while the reaction-seeding algorithm of RRS secures the efficiency of random seeding. It is noteworthy that RRS is capable of tracing a whole neurite branch by only one initial seed, so that RRS is proficient at quantifying extensive amounts of neurite outgrowth images with noisy background in microfluidic devices of biomedical engineering fields. The method also showed notable performance for reconstructing of net-like structures, and thus is expected to be proficient for biomedical feature extractions in a wide range of applications, such as retinal vessel segmentation and cell membrane profiling in spurious-edge-tissues.},
}

@article {pmid30814056,
year = {2019},
author = {Varelias, A and Gartlan, KH and Wilkinson, AN and Olver, SD and Samson, LD and Tey, SK and MacDonald, KPA and Hill, GR},
title = {Expansion of IL-17A-secreting CD8+ mucosa-associated invariant T cells in peripheral blood following stem cell mobilization.},
journal = {Blood advances},
volume = {3},
number = {5},
pages = {718-723},
doi = {10.1182/bloodadvances.2018025601},
pmid = {30814056},
issn = {2473-9537},
}

@article {pmid30811478,
year = {2019},
author = {Richardson, LA and Schmid, SL and Bhandoola, A and Harly, C and Hedenström, A and Laub, MT and Mace, GM and Sengupta, P and Stock, AM and Read, AF and Malik, HS and Estelle, M and Lowell, S and Kimmelman, J},
title = {The PLOS Biology XV Collection: 15 Years of Exceptional Science Highlighted across 12 Months.},
journal = {PLoS biology},
volume = {17},
number = {2},
pages = {e3000180},
doi = {10.1371/journal.pbio.3000180},
pmid = {30811478},
issn = {1545-7885},
}

@article {pmid30809032,
year = {2019},
author = {Inamoto, Y and Petriček, I and Burns, L and Chhabra, S and DeFilipp, Z and Hematti, P and Rovó, A and Schears, R and Shah, A and Agrawal, V and Al-Khinji, A and Ahmed, I and Ali, A and Aljurf, M and Alkhateeb, H and Beitinjaneh, A and Bhatt, N and Buchbinder, D and Byrne, M and Callander, N and Fahnehjelm, K and Farhadfar, N and Gale, RP and Ganguly, S and Hildebrandt, GC and Horn, E and Jakubowski, A and Kamble, RT and Law, J and Lee, C and Nathan, S and Penack, O and Pingali, R and Prasad, P and Pulanic, D and Rotz, S and Shreenivas, A and Steinberg, A and Tabbara, K and Tichelli, A and Wirk, B and Yared, J and Basak, GW and Battiwalla, M and Duarte, R and Savani, BN and Flowers, MED and Shaw, BE and Valdés-Sanz, N},
title = {Correction: Non-GVHD ocular complications after hematopoietic cell transplantation: expert review from the Late Effects and Quality of Life Working Committee of the CIBMTR and Transplant Complications Working Party of the EBMT.},
journal = {Bone marrow transplantation},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41409-019-0472-x},
pmid = {30809032},
issn = {1476-5365},
abstract = {In the original version of this article, author 'Aisha Al-Khinji' was incorrectly listed as 'Aisha Ahmed'. This has now been corrected in both the PDF and HTML versions of the article to 'Aisha Al-Khinji'.},
}

@article {pmid30808685,
year = {2019},
author = {Yeshurun, M and Weisdorf, D and Rowe, JM and Tallman, MS and Zhang, MJ and Wang, HL and Saber, W and de Lima, M and Sandmaier, BM and Uy, G and Kamble, RT and Cairo, MS and Cooper, BW and Cahn, JY and Ganguly, S and Camitta, B and Verdonck, LF and Dandoy, C and Diaz, MA and Savani, BN and George, B and Liesveld, J and McGuirk, J and Byrne, M and Grunwald, MR and Drobyski, WR and Pulsipher, MA and Abdel-Azim, H and Prestidge, T and Wieduwilt, MJ and Martino, R and Norkin, M and Beitinjaneh, A and Seo, S and Nishihori, T and Wirk, B and Frangoul, H and Bashey, A and Mori, S and Marks, DI and Bachanova, V},
title = {The impact of the graft-versus-leukemia effect on survival in acute lymphoblastic leukemia.},
journal = {Blood advances},
volume = {3},
number = {4},
pages = {670-680},
doi = {10.1182/bloodadvances.2018027003},
pmid = {30808685},
issn = {2473-9537},
abstract = {Allogeneic hematopoietic cell transplant is a potential curative therapy for acute lymphoblastic leukemia (ALL). Delineating the graft-versus-leukemia (GVL) effect as a function of graft-versus-host disease (GVHD) offers the potential to improve survival. We examined 5215 transplant recipients with ALL reported to the Center for International Blood and Marrow Transplant Research registry. Overall survival (OS) was compared according to the presence and severity of GVHD and evaluated in 3 cohorts: 2593 adults in first or second complete remission (CR1/CR2), 1619 pediatric patients in CR1/CR2, and 1003 patients with advanced (CR ≥3 or active disease) ALL. For patients in CR1/CR2, development of acute GVHD (aGVHD) or chronic GVHD (cGVHD) was associated with lower risk of relapse than no GVHD (hazard ratio [HR], 0.49-0.69). Patients with advanced ALL developing grades III and IV aGVHD or cGVHD were also at lower risk of relapse (HRs varied from 0.52 to 0.67). Importantly, adult and children in CR1/CR2 with grades I and II aGVHD without cGVHD experienced the best OS compared with no GVHD (reduction of mortality with HR, 0.83-0.76). Increased nonrelapse mortality accompanied grades III and IV aGVHD (HRs varied from 2.69 to 3.91) in all 3 cohorts and abrogated any protection from relapse, resulting in inferior OS. Patients with advanced ALL had better OS (reduction in mortality; HR, 0.69-0.73) when they developed cGVHD with or without grades I and II aGVHD. In conclusion, GVHD was associated with an increased GVL effect in ALL. GVL exerted a net beneficial effect on OS only if associated with low-grade aGVHD in CR1/CR2 or with cGVHD in advanced ALL.},
}

@article {pmid30808470,
year = {2019},
author = {Marcum, ZA and Hohl, SD and Gray, SL and Barthold, D and Crane, PK and Larson, EB},
title = {Brain Health and Dementia Prevention: A Mixed-method Analysis.},
journal = {American journal of health behavior},
volume = {43},
number = {2},
pages = {300-310},
doi = {10.5993/AJHB.43.2.7},
pmid = {30808470},
issn = {1945-7359},
abstract = {Objective: In this study, we assessed patient knowledge, beliefs, and attitudes about brain health and strategies for Alzheimer's disease and related dementias (ADRD) prevention. Methods: We administered a Web-based survey consisting of 17 questions about brain health and strategies for ADRD prevention in a convenience sample of 1661 patients in an integrated healthcare delivery system in Washington state between February and March 2018. We calculated frequency distributions of the quantitative data and conducted inductive content analysis of qualitative data. Results: Most respondents were female (77%), 51-70 years of age (64%), and white (89%). Although most agreed it is possible to improve brain health and reduce personal ADRD risk, one- third lacked confidence that they could take action to reduce personal ADRD risk. Participants' responses to open-ended questions revealed 10 themes grouped into 3 organizing categories regarding their perceptions about how to prevent ADRD onset: (1) understand ADRD; (2) stay engaged; and (3) manage one's own health and healthcare. Conclusions: Survey respondents were engaged and aware of dementia prevention, but they lacked access to personally action- able evidence..},
}

@article {pmid30804564,
year = {2019},
author = {Xue, KS and Bloom, JD},
title = {Reconciling disparate estimates of viral genetic diversity during human influenza infections.},
journal = {Nature genetics},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41588-019-0349-3},
pmid = {30804564},
issn = {1546-1718},
support = {R01 AI127893/AI/NIAID NIH HHS/United States ; },
}

@article {pmid30804488,
year = {2019},
author = {Godwin, CD and Fromm, JR and Othus, M and Sandmaier, BM and Mielcarek, MB and Wood, BL and Appelbaum, FR and Storb, R and Walter, RB},
title = {Pre-transplant bone marrow monocytic myeloid-derived suppressor cell frequency is not associated with outcome after allogeneic hematopoietic cell transplantation for acute myeloid leukemia in remission.},
journal = {Bone marrow transplantation},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41409-019-0481-9},
pmid = {30804488},
issn = {1476-5365},
support = {T32-HL007093//U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)/ ; T32 HL007093/HL/NHLBI NIH HHS/United States ; P01 CA018029/CA/NCI NIH HHS/United States ; P30 CA015704/CA/NCI NIH HHS/United States ; P30-CA015704//U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)/ ; P01-CA018029//U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)/ ; P01-CA078902//U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)/ ; P01 CA078902/CA/NCI NIH HHS/United States ; },
}

@article {pmid30802187,
year = {2019},
author = {Mossavar-Rahmani, Y and Kamensky, V and Manson, JE and Silver, B and Rapp, SR and Haring, B and Beresford, SAA and Snetselaar, L and Wassertheil-Smoller, S},
title = {Artificially Sweetened Beverages and Stroke, Coronary Heart Disease, and All-Cause Mortality in the Women's Health Initiative.},
journal = {Stroke},
volume = {50},
number = {3},
pages = {555-562},
doi = {10.1161/STROKEAHA.118.023100},
pmid = {30802187},
issn = {1524-4628},
abstract = {Background and Purpose- We examine the association between self-reported consumption of artificially sweetened beverages (ASB) and stroke and its subtypes, coronary heart disease, and all-cause mortality in a cohort of postmenopausal US women. Methods- The analytic cohort included 81 714 women from the Women's Health Initiative Observational Study, a multicenter longitudinal study of the health of 93 676 postmenopausal women of ages 50 to 79 years at baseline who enrolled in 1993 to 1998. This prospective study had a mean follow-up time of 11.9 years (SD of 5.3 years.) Participants who completed a follow-up visit 3 years after baseline were included in the study. Results- Most participants (64.1%) were infrequent consumers (never or <1/week) of ASB, with only 5.1% consuming ≥2 ASBs/day. In multivariate analyses, those consuming the highest level of ASB compared to never or rarely (<1/wk) had significantly greater likelihood of all end points (except hemorrhagic stroke), after controlling for multiple covariates. Adjusted models indicated that hazard ratios and 95% confidence intervals were 1.23 (1.02-1.47) for all stroke; 1.31 (1.06-1.63) for ischemic stroke; 1.29 (1.11-1.51) for coronary heart disease; and 1.16 (1.07-1.26) for all-cause mortality. In women with no prior history of cardiovascular disease or diabetes mellitus, high consumption of ASB was associated with more than a 2-fold increased risk of small artery occlusion ischemic stroke hazard ratio =2.44 (95% confidence interval, 1.47-4.04.) High consumption of ASBs was associated with significantly increased risk of ischemic stroke in women with body mass index ≥30; hazard ratio =2.03 (95% confidence interval, 1.38-2.98). Conclusions- Higher intake of ASB was associated with increased risk of stroke, particularly small artery occlusion subtype, coronary heart disease, and all-cause mortality. Although requiring replication, these new findings add to the potentially harmful association of consuming high quantities of ASB with these health outcomes.},
}

@article {pmid30799773,
year = {2019},
author = {Zhao, W and Zheng, J and Chen, YQ and Hsu, L},
title = {Adjusted time-varying population attributable hazard in case-control studies.},
journal = {Statistical methods in medical research},
volume = {},
number = {},
pages = {962280219831725},
doi = {10.1177/0962280219831725},
pmid = {30799773},
issn = {1477-0334},
abstract = {Population attributable fraction is a widely used measure for quantifying the disease burden associated with a modifiable exposure of interest at the population level. It has been extended to a time-varying measure, population attributable hazard function, to provide additional information on when and how the exposure's impact varies over time. However, like the classic population attributable fraction, the population attributable hazard is generally biased if confounders are present. In this article, we provide a natural definition of adjusted population attributable hazard to take into account the effects of confounders, and its alternative that is identifiable from case-control studies under the rare disease assumption. We propose a novel estimator, which combines the odds ratio estimator from logistic regression model, and the conditional density function estimator of the exposure and confounding variables distribution given the failure times of cases or the current times of controls from a kernel smoother. We show that the proposed estimators are consistent and asymptotically normal with variance that can be estimated empirically from the data. Simulation studies demonstrate that the proposed estimators perform well in finite sample sizes. Finally, we illustrate the method by an analysis of a case-control study of colorectal cancer. Supplementary materials for this article are available online.},
}

@article {pmid30798855,
year = {2019},
author = {McKean, M and Oba, J and Ma, J and Roth, KG and Wang, WL and Macedo, MP and Carapeto, FCL and Haydu, LE and Siroy, AE and Vo, P and Hong, DS and Eterovic, AK and Patel, KP and Bassett, RL and Grimm, EA and Lazar, AJ and Woodman, SE},
title = {Tyrosine Kinase Inhibitor and Immune Checkpoint Inhibitor Responses in KIT-Mutant Metastatic Melanoma.},
journal = {The Journal of investigative dermatology},
volume = {139},
number = {3},
pages = {728-731},
doi = {10.1016/j.jid.2018.10.009},
pmid = {30798855},
issn = {1523-1747},
}

@article {pmid30797618,
year = {2019},
author = {Marshall, CH and Sokolova, AO and McNatty, AL and Cheng, HH and Eisenberger, MA and Bryce, AH and Schweizer, MT and Antonarakis, ES},
title = {Differential Response to Olaparib Treatment Among Men with Metastatic Castration-resistant Prostate Cancer Harboring BRCA1 or BRCA2 Versus ATM Mutations.},
journal = {European urology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.eururo.2019.02.002},
pmid = {30797618},
issn = {1873-7560},
abstract = {BACKGROUND: Poly ADP-ribose polymerase (PARP) inhibitors, such as olaparib, are being explored as a treatment option for metastatic castration-resistant prostate cancer (mCRPC) in men harboring mutations in homologous recombination DNA-repair genes. Whether responses to PARP inhibitors differ according to the affected gene is currently unknown.

OBJECTIVE: To determine whether responses to PARP inhibitors differ between men with BRCA1/2 and those with ATM mutations.

This was a multicenter retrospective review of 23 consecutive men with mCRPC and pathogenic germline and/or somatic BRCA1/2 or ATM mutations treated with olaparib at three academic sites in the USA.

The proportion of patients achieving a ≥50% decline in prostate-specific antigen (PSA50 response) was compared using Fisher's exact test. Clinical and radiographic progression-free survival (PFS) and overall survival were estimated using Kaplan-Meier analyses and compared using the log-rank test.

RESULTS AND LIMITATIONS: The study included two men with BRCA1 mutations, 15 with BRCA2 mutations, and six with ATM mutations. PSA50 responses to olaparib were achieved in 76% (13/17) of men with BRCA1/2 versus 0% (0/6) of men with ATM mutations (Fisher's exact test; p=0.002). Patients with BRCA1/2 mutations had median PFS of 12.3mo versus 2.4mo for those with ATM mutations (hazard ratio 0.17, 95% confidence interval 0.05-0.57; p=0.004). Limitations include the retrospective design and relatively small sample size.

CONCLUSIONS: Men with mCRPC harboring ATM mutations experienced inferior outcomes to PARP inhibitor therapy compared to those harboring BRCA1/2 mutations. Alternative therapies should be explored for patients with ATM mutations.

PATIENT SUMMARY: Mutations in BRCA1/2 and ATM genes are common in metastatic prostate cancer. In this study we compared outcomes for men with BRCA1/2 mutations to those for men with ATM mutations being treated with olaparib. We found that men with ATM mutations do not respond as well as men with BRCA1/2 mutations.},
}

@article {pmid30794931,
year = {2019},
author = {Kilari, D and D'Souza, A and Fraser, R and Qayed, M and Davila, O and Agrawal, V and Diaz, MA and Chhabra, S and Cerny, J and Copelan, E and Farhadfar, N and Freytes, CO and Gale, RP and Ganguly, S and Hildebrandt, GC and Holmberg, L and Kamble, RT and Kapoor, P and Lazarus, H and Lee, C and Murthy, HS and Naik, S and Nishihori, T and Saad, A and Savani, BN and Seo, S and Warwick, A and Wirk, B and Yared, JA and Nieto, Y and Hari, P},
title = {Autologous Transplantation for Male Germ Cell Tumors: Improved Outcomes over 3 decades.},
journal = {Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.bbmt.2019.02.015},
pmid = {30794931},
issn = {1523-6536},
abstract = {PURPOSE: The curative potential of autologous hematopoietic cell transplantation (autoHCT) for male germ cell tumors (GCT) is well established. Optimal timing and number (single, ST vs. tandem, TT vs. three) of autoHCT are controversial with wide practice variation.

PATIENTS AND METHODS: We examined survival trends among 2,395 recipients of autoHCT for male GCT between 1990-2015 reported to the Center for International Blood and Marrow Transplant Research. Trends and outcomes were analyzed by year of transplant for intervals 1990-94 (N = 288), 1995-99 (N = 351), 2000-04 (N = 376), 2005-09 (N = 509) and 2010-15 (N = 871). Multivariate analysis was restricted to the subset from 2000-2015 (n = 267) with research level data.

RESULTS: Median follow up was 51 months. Median age at autoHCT was 31 years; 633(26%) had primary extragonadal GCT and 1,167 (49%) underwent TT. The 3-year progression-free (PFS) and overall survival (OS) improved from 24 (18-31)% and 35 (29-40)% in 1990-94 to 47 (43-50)% and 54 (50-57)% in 2010-15 (p < 0.0001), respectively. TT recipients were more likely to undergo autoHCT as first salvage treatment than ST recipients. The proportion of TT increased from 38% of all autoHCT in 2000-04 to 77% in 2010-15. Non-seminoma histology, residual disease at autoHCT, > 1 line of pre-transplant chemotherapy and ST versus TT were associated with inferior PFS and OS.

CONCLUSIONS: Post-transplant survival has improved significantly over time for relapsed/refractory male GCT and was associated with the increased use of TT (compared with ST) and earlier autoHCT in the disease course.},
}

@article {pmid30794930,
year = {2019},
author = {Cohen, JA and Baldassari, LE and Atkins, HL and Bowen, JD and Bredeson, C and Carpenter, PA and Corboy, JR and Freedman, MS and Griffith, LM and Lowsky, R and Majhail, NS and Muraro, PA and Nash, RA and Pasquini, MC and Sarantopoulos, S and Savani, BN and Storek, J and Sullivan, KM and Georges, GE},
title = {AUTOLOGOUS HEMATOPOIETIC CELL TRANSPLANTATION FOR TREATMENT-REFRACTORY RELAPSING MULTIPLE SCLEROSIS: POSITION STATEMENT FROM THE AMERICAN SOCIETY FOR BLOOD AND MARROW TRANSPLANTATION.},
journal = {Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.bbmt.2019.02.014},
pmid = {30794930},
issn = {1523-6536},
abstract = {Multiple sclerosis (MS) is a chronic, disabling, immune-mediated, central nervous system demyelinating and degenerative disease. Approved disease modifying therapies may be incompletely effective in some patients with highly active relapsing disease and high risk of disability. Immunoablative or myeloablative therapy followed by autologous hematopoietic cell transplantation (AHCT) has been investigated in retrospective studies, clinical trials, and meta-analyses/systematic reviews as an approach to address this unmet clinical need. On behalf of the American Society for Blood and Bone Marrow Transplantation (ASBMT), a panel of experts in AHCT and MS convened to review available evidence and make recommendations on MS as an indication for AHCT. Review of recent literature identified eight retrospective studies, eight clinical trials, and three meta-analyses/systematic reviews. In aggregate, these studies indicate that AHCT is an efficacious and safe treatment for active relapsing forms of MS to prevent clinical relapses, MRI lesion activity, and disability worsening, and to reverse disability, without unexpected adverse events. Based on the available evidence, the ASBMT recommends that treatment-refractory relapsing MS with high risk of future disability be considered a "standard of care, clinical evidence available" indication for AHCT. Collaboration of neurologists with expertise in treating MS and transplant physicians with experience performing AHCT for autoimmune disease is crucial for appropriate patient selection and optimizing transplant procedures to improve patient outcomes. Transplant centers in the United States and Canada are strongly encouraged to report baseline and outcomes data on patients receiving AHCT for multiple sclerosis to the Center for International Blood and Marrow Transplant Research.},
}

@article {pmid30794764,
year = {2019},
author = {Moon, AM and Weiss, NS and Beste, LA and Su, F and Ho, SB and Jin, GY and Lowy, E and Berry, K and Ioannou, GN},
title = {Reply.},
journal = {Gastroenterology},
volume = {},
number = {},
pages = {},
doi = {10.1053/j.gastro.2019.02.024},
pmid = {30794764},
issn = {1528-0012},
}

@article {pmid30794725,
year = {2019},
author = {Leeman, J and Askelson, N and Ko, LK and Rohweder, CL and Avelis, J and Best, A and Friedman, D and Glanz, K and Seegmiller, L and Stradtman, L and Vanderpool, RC},
title = {Understanding the processes that Federally Qualified Health Centers use to select and implement colorectal cancer screening interventions: a qualitative study.},
journal = {Translational behavioral medicine},
volume = {},
number = {},
pages = {},
doi = {10.1093/tbm/ibz023},
pmid = {30794725},
issn = {1613-9860},
abstract = {Colorectal cancer (CRC) screening is highly effective at reducing cancer-related morbidity and mortality, yet screening rates remain suboptimal. Evidence-based interventions can increase screening rates, particularly when they target multiple levels (e.g., patients, providers, health care systems). However, effective interventions remain underutilized. Thus, there is a pressing need to build capacity to select and implement multilevel CRC screening interventions. We report on formative research aimed at understanding how Federally Qualified Health Center (FQHC) staff select and implement CRC screening interventions, which will inform development of capacity-building strategies. We report the qualitative findings from a study that used a mixed methods design, starting with a quantitative survey followed by a qualitative study. In-depth interviews were conducted with 28 staff from 14 FQHCs in 8 states. The Consolidated Framework for Implementation Research (CFIR) guided interview questions and data analysis. Related to the CFIR process domain, few respondents described conducting formal assessments of factors contributing to low screening rates prior to planning their interventions. Many described engaging champions, implementation leaders, and external change agents. Few described a systematic approach to executing implementation plans beyond conducting plan-do-study-act cycles. Reflection and evaluation consisted primarily of reviewing Uniform Data System performance measures. Findings also include themes related to factors influencing these implementation processes. Although FQHCs are implementing CRC screening interventions, they are not actively targeting the multilevel factors influencing their CRC screening rates. Our findings on gaps in FQHCs' implementation processes will inform development of strategies to build capacity to select and implement multilevel CRC screening interventions.},
}

@article {pmid30794534,
year = {2019},
author = {Hart, SFM and Mi, H and Green, R and Xie, L and Pineda, JMB and Momeni, B and Shou, W},
title = {Uncovering and resolving challenges of quantitative modeling in a simplified community of interacting cells.},
journal = {PLoS biology},
volume = {17},
number = {2},
pages = {e3000135},
doi = {10.1371/journal.pbio.3000135},
pmid = {30794534},
issn = {1545-7885},
abstract = {Quantitative modeling is useful for predicting behaviors of a system and for rationally constructing or modifying the system. The predictive power of a model relies on accurate quantification of model parameters. Here, we illustrate challenges in parameter quantification and offer means to overcome these challenges, using a case example in which we quantitatively predict the growth rate of a cooperative community. Specifically, the community consists of two Saccharomyces cerevisiae strains, each engineered to release a metabolite required and consumed by its partner. The initial model, employing parameters measured in batch monocultures with zero or excess metabolite, failed to quantitatively predict experimental results. To resolve the model-experiment discrepancy, we chemically identified the correct exchanged metabolites, but this did not improve model performance. We then remeasured strain phenotypes in chemostats mimicking the metabolite-limited community environments, while mitigating or incorporating effects of rapid evolution. Almost all phenotypes we measured, including death rate, metabolite release rate, and the amount of metabolite consumed per cell birth, varied significantly with the metabolite environment. Once we used parameters measured in a range of community-like chemostat environments, prediction quantitatively agreed with experimental results. In summary, using a simplified community, we uncovered and devised means to resolve modeling challenges that are likely general to living systems.},
}

@article {pmid30793950,
year = {2019},
author = {Thill, M and Thatcher, N and Hanes, V and Lyman, GH},
title = {Biosimilars: what the oncologist should know.},
journal = {Future oncology (London, England)},
volume = {},
number = {},
pages = {},
doi = {10.2217/fon-2018-0728},
pmid = {30793950},
issn = {1744-8301},
abstract = {As originator biologic medicines lose patent protection, some biopharmaceutical companies are focusing on developing similar versions of these costly and complex therapies with a goal of providing more affordable treatment options. Many of these molecules, known as biosimilars, are now approved worldwide and several more are expected to be introduced in the near future. As more biosimilars become available, it is important for clinicians to become familiar with this new category of products and understand how biosimilars are developed, how their development differs from that of originator biologics and how they differ from generics. This review aims to provide the practicing clinician with the knowledge needed to understand biosimilars, along with some guidance on their use in treating oncologic diseases.},
}

@article {pmid30793644,
year = {2019},
author = {Acharya, UH and Dhawale, T and Yun, S and Jacobson, CA and Chavez, JC and Ramos, JD and Appelbaum, J and Maloney, DG},
title = {Management of cytokine release syndrome and neurotoxicity in chimeric antigen receptor T-cell therapy.},
journal = {Expert review of hematology},
volume = {},
number = {},
pages = {},
doi = {10.1080/17474086.2019.1585238},
pmid = {30793644},
issn = {1747-4094},
abstract = {INTRODUCTION: Chimeric antigen receptor (CAR) T cell immunotherapy has demonstrated remarkable anti-tumor activity in B-cell malignancies and is under investigation in other hematologic malignancies and solid tumors. While highly efficacious, post-infusion T cell activity often results in massive cytokine release precipitating cytokine release syndrome (CRS), the signature toxicity of CAR T cells. This toxicity is characterized by systemic immune activation resulting in fever, hypotension, respiratory insufficiency and capillary leak. Either in conjunction with or in the absence of CRS, a subset of patients may also develop mild to severe neurotoxicity. Although the precise pathogenesis of CRS and neurotoxicity aren't fully elucidated, risk factors and mitigation strategies have been reported. Areas covered: This manuscript provides an in-depth overview of the pathogenesis, clinical characteristics, current toxicity management strategies, and future perspectives pertaining to CRS and neurotoxicity. Expert Opinion: As CAR T cell based therapies gain popularity in the management of various malignancies, the complimentary toxicities of CRS and neurotoxicity pose a clinical challenge in practice. Risk adaptive modeling incorporating disease profile, patient demographics, lymphodepletion, cell dosing, CAR T construct, and potentially cytokine gene polymorphisms may be instructive to asses individualized risk and optimal CRS/neurotoxicity management.},
}

@article {pmid30793095,
year = {2019},
author = {Hemming, ML and Klega, KS and Rhoades, J and Ha, G and Acker, KE and Andersen, JL and Thai, E and Nag, A and Thorner, AR and Raut, CP and George, S and Crompton, BD},
title = {Detection of Circulating Tumor DNA in Patients With Leiomyosarcoma With Progressive Disease.},
journal = {JCO precision oncology},
volume = {2019},
number = {},
pages = {},
doi = {10.1200/PO.18.00235},
pmid = {30793095},
issn = {2473-4284},
support = {K08 CA188073/CA/NCI NIH HHS/United States ; },
abstract = {Purpose: Leiomyosarcoma (LMS) is a soft tissue sarcoma characterized by multiple copy number alterations (CNAs) and without common recurrent single nucleotide variants. We evaluated the feasibility of detecting circulating tumor DNA (ctDNA) with next-generation sequencing in a cohort of patients with LMS whose tumor burden ranged from no evidence of disease to metastatic progressive disease.

Patients and Methods: Cell-free DNA in plasma samples and paired genomic DNA from resected tumors were evaluated from patients with LMS by ultra-low passage whole genome sequencing (ULP-WGS). Sequencing reads were aligned to the human genome and CNAs identified in cell-free DNA and tumor DNA by ichorCNA software to determine the presence of ctDNA. Clinical data were reviewed to assess disease burden and clinicopathologic features.

Results: We identified LMS ctDNA in eleven of sixteen patients (69%) with disease progression and total tumor burden over 5 cm. Sixteen patients with stable disease or low disease burden at the time of blood draw were found to have no detectable ctDNA. Higher ctDNA fraction of total cell-free DNA was associated with increasing tumor size and disease progression. Conserved CNAs were found between primary tumors and ctDNA in each case, and recurrent CNAs were found across LMS samples. ctDNA levels declined following resection of progressive disease in one case and became detectable upon disease relapse in another individual patient.

Conclusion: These results suggest that ctDNA, assayed by a widely available sequencing approach, may be useful as a biomarker for a subset of uterine and extrauterine LMS. Higher levels of ctDNA correlate with tumor size and disease progression. Liquid biopsies may assist in guiding treatment decisions, monitoring response to systemic therapy, surveying for disease recurrence and differentiating benign and malignant smooth muscle tumors.},
}

@article {pmid30789451,
year = {2019},
author = {Lin, J and Xue, X and Anastos, K and Cohen, MH and Gange, SJ and Lazar, JM and Liu, C and Mack, WJ and Tien, PC and Tilley, C and Hodis, HN and Landay, AL and Tracy, RP and Kaplan, RC and Hanna, DB},
title = {Elevated Microparticle Tissue Factor Activity is Associated with Carotid Artery Plaque in HIV Infected Women.},
journal = {Journal of acquired immune deficiency syndromes (1999)},
volume = {},
number = {},
pages = {},
doi = {10.1097/QAI.0000000000001988},
pmid = {30789451},
issn = {1944-7884},
support = {L30 AI107910/AI/NIAID NIH HHS/United States ; U01 AI103397/AI/NIAID NIH HHS/United States ; U01 AI031834/AI/NIAID NIH HHS/United States ; U01 AI035004/AI/NIAID NIH HHS/United States ; R01 HL095140/HL/NHLBI NIH HHS/United States ; R21 HL120394/HL/NHLBI NIH HHS/United States ; U01 AI034989/AI/NIAID NIH HHS/United States ; R01 HL126543/HL/NHLBI NIH HHS/United States ; R01 HL083760/HL/NHLBI NIH HHS/United States ; R01 HL132794/HL/NHLBI NIH HHS/United States ; U01 AI034994/AI/NIAID NIH HHS/United States ; UL1 TR000454/TR/NCATS NIH HHS/United States ; R01 HL140976/HL/NHLBI NIH HHS/United States ; U01 AI103401/AI/NIAID NIH HHS/United States ; UL1 TR000040/TR/NCATS NIH HHS/United States ; U01 AI103390/AI/NIAID NIH HHS/United States ; U01 AI034993/AI/NIAID NIH HHS/United States ; U01 AI103408/AI/NIAID NIH HHS/United States ; P30 AI050410/AI/NIAID NIH HHS/United States ; K01 HL137557/HL/NHLBI NIH HHS/United States ; U01 HD032632/HD/NICHD NIH HHS/United States ; U01 AI042590/AI/NIAID NIH HHS/United States ; },
abstract = {BACKGROUND: Expression of tissue factor (TF) on the surface of activated monocytes may trigger thrombosis, leading to clotting risk, inflammation, and atherosclerosis. TF-positive microparticles (MP-TF) represent a functionally active form of TF that may be promulgated by long-term HIV infection. We hypothesized that greater MP-TF activity is associated with carotid artery plaque in HIV+ women.

SETTING: In a case-control study nested within the Women's Interagency HIV Study (WIHS), eligible HIV+ participants underwent B-mode carotid artery ultrasound at 2 study visits occurring 7 years apart. Cases were defined by presence of at least 1 carotid artery plaque assessed at either visit. Cases were matched 1:2 to controls who were found not to have carotid artery plaques.

METHODS: Conditional logistic regression estimated the association of MP-TF activity with presence of carotid artery plaque, adjusting for demographic and behavioral characteristics, HIV-related factors, cardiometabolic risk factors, and serum inflammation biomarkers (hsCRP, IL-6, sCD14, sCD163, Gal-3, Gal-3BP).

RESULTS: Elevated MP-TF activity (>0.537 pg/mL) was found to be significantly associated with greater odds of plaque (adjusted odds ratio 3.86, 95% CI 1.06-14.07, p=0.04). The association was attenuated after further adjustment for IL-6, but was unaffected by adjustment for other biomarkers including those denoting monocyte activation.

CONCLUSIONS: Our findings suggest a link among HIV infection, innate immune system perturbation, coagulation, and atherosclerosis.},
}

@article {pmid30789436,
year = {2019},
author = {Sangaramoorthy, M and Hines, LM and Torres-Mejía, G and Phipps, AI and Baumgartner, KB and Wu, AH and Koo, J and Ingles, SA and Slattery, ML and John, EM},
title = {A pooled analysis of breast-feeding and breast cancer risk by hormone receptor status in parous Hispanic women.},
journal = {Epidemiology (Cambridge, Mass.)},
volume = {},
number = {},
pages = {},
doi = {10.1097/EDE.0000000000000981},
pmid = {30789436},
issn = {1531-5487},
support = {R03 CA199343/CA/NCI NIH HHS/United States ; R01 CA078682/CA/NCI NIH HHS/United States ; R01 CA140002/CA/NCI NIH HHS/United States ; R01 CA063446/CA/NCI NIH HHS/United States ; U01 CA164920/CA/NCI NIH HHS/United States ; },
abstract = {BACKGROUND: Data on breast-feeding and breast cancer risk are sparse and inconsistent for Hispanic women.

METHODS: Pooling data for nearly 6,000 parous Hispanic women from four population-based studies conducted between 1995 and 2007 in the U.S. and Mexico, we examined the association of breast-feeding with risk of breast cancer overall and subtypes defined by estrogen receptor (ER) and progesterone receptor (PR) status, as well as the joint effects of breast-feeding, parity, and age at first birth. We calculated odds ratios (ORs) and 95% confidence intervals (CIs) using logistic regression.

RESULTS: Among parous Hispanic women, older age at first birth was associated with increased breast cancer risk, whereas parity was associated with reduced risk. These associations were found for hormone receptor positive (HR+) breast cancer only and limited to premenopausal women. Age at first birth and parity were not associated with risk of ER-PR- breast cancer. Increasing duration of breast-feeding was associated with decreasing breast cancer risk (≥25 vs. 0 months: OR=0.73, 95% CI=0.60-0.89, Ptrend =0.03), with no heterogeneity by menopausal status or subtype. At each parity level, breast-feeding further reduced HR+ breast cancer risk. Additionally, breast-feeding attenuated the increase in risk of HR+ breast cancer associated with older age at first birth.

CONCLUSIONS: Our findings suggest that breast-feeding is associated with reduced risk of both HR+ and ER-PR- breast cancer among Hispanic women, as reported for other populations, and may attenuate the increased risk in women with a first pregnancy at older ages.},
}

@article {pmid30789432,
year = {2019},
author = {VanderWeele, TJ and Luedtke, AR and van der Laan, MJ and Kessler, RC},
title = {Selecting optimal subgroups for treatment using many covariates.},
journal = {Epidemiology (Cambridge, Mass.)},
volume = {},
number = {},
pages = {},
doi = {10.1097/EDE.0000000000000991},
pmid = {30789432},
issn = {1531-5487},
support = {R01 CA222147/CA/NCI NIH HHS/United States ; },
abstract = {We consider the problem of selecting the optimal subgroup to treat when data on covariates is available from a randomized trial or observational study. We distinguish between four different settings including (i) treatment selection when resources are constrained, (ii) treatment selection when resources are not constrained, (iii) treatment selection in the presence of side effects and costs, and (iv) treatment selection to maximize effect heterogeneity. We show that, in each of these cases, the optimal treatment selection rule involves treating those for whom the predicted mean difference in outcomes comparing those with versus without treatment, conditional on covariates, exceeds a certain threshold. The threshold varies across these four scenarios but the form of the optimal treatment selection rule does not. The results suggest a move away from traditional subgroup analysis for personalized medicine. New randomized trial designs are proposed so as to implement and make use of optimal treatment selection rules in health care practice.},
}

@article {pmid30787463,
year = {2019},
author = {Escala-Garcia, M and Guo, Q and Dörk, T and Canisius, S and Keeman, R and Dennis, J and Beesley, J and Lecarpentier, J and Bolla, MK and Wang, Q and Abraham, J and Andrulis, IL and Anton-Culver, H and Arndt, V and Auer, PL and Beckmann, MW and Behrens, S and Benitez, J and Bermisheva, M and Bernstein, L and Blomqvist, C and Boeckx, B and Bojesen, SE and Bonanni, B and Børresen-Dale, AL and Brauch, H and Brenner, H and Brentnall, A and Brinton, L and Broberg, P and Brock, IW and Brucker, SY and Burwinkel, B and Caldas, C and Caldés, T and Campa, D and Canzian, F and Carracedo, A and Carter, BD and Castelao, JE and Chang-Claude, J and Chanock, SJ and Chenevix-Trench, G and Cheng, TD and Chin, SF and Clarke, CL and , and Cordina-Duverger, E and Couch, FJ and Cox, DG and Cox, A and Cross, SS and Czene, K and Daly, MB and Devilee, P and Dunn, JA and Dunning, AM and Durcan, L and Dwek, M and Earl, HM and Ekici, AB and Eliassen, AH and Ellberg, C and Engel, C and Eriksson, M and Evans, DG and Figueroa, J and Flesch-Janys, D and Flyger, H and Gabrielson, M and Gago-Dominguez, M and Galle, E and Gapstur, SM and García-Closas, M and García-Sáenz, JA and Gaudet, MM and George, A and Georgoulias, V and Giles, GG and Glendon, G and Goldgar, DE and González-Neira, A and Alnæs, GIG and Grip, M and Guénel, P and Haeberle, L and Hahnen, E and Haiman, CA and Håkansson, N and Hall, P and Hamann, U and Hankinson, S and Harkness, EF and Harrington, PA and Hart, SN and Hartikainen, JM and Hein, A and Hillemanns, P and Hiller, L and Holleczek, B and Hollestelle, A and Hooning, MJ and Hoover, RN and Hopper, JL and Howell, A and Huang, G and Humphreys, K and Hunter, DJ and Janni, W and John, EM and Jones, ME and Jukkola-Vuorinen, A and Jung, A and Kaaks, R and Kabisch, M and Kaczmarek, K and Kerin, MJ and Khan, S and Khusnutdinova, E and Kiiski, JI and Kitahara, CM and Knight, JA and Ko, YD and Koppert, LB and Kosma, VM and Kraft, P and Kristensen, VN and Krüger, U and Kühl, T and Lambrechts, D and Le Marchand, L and Lee, E and Lejbkowicz, F and Li, L and Lindblom, A and Lindström, S and Linet, M and Lissowska, J and Lo, WY and Loibl, S and Lubiński, J and Lux, MP and MacInnis, RJ and Maierthaler, M and Maishman, T and Makalic, E and Mannermaa, A and Manoochehri, M and Manoukian, S and Margolin, S and Martinez, ME and Mavroudis, D and McLean, C and Meindl, A and Middha, P and Miller, N and Milne, RL and Moreno, F and Mulligan, AM and Mulot, C and Nassir, R and Neuhausen, SL and Newman, WT and Nielsen, SF and Nordestgaard, BG and Norman, A and Olsson, H and Orr, N and Pankratz, VS and Park-Simon, TW and Perez, JIA and Pérez-Barrios, C and Peterlongo, P and Petridis, C and Pinchev, M and Prajzendanc, K and Prentice, R and Presneau, N and Prokofieva, D and Pylkäs, K and Rack, B and Radice, P and Ramachandran, D and Rennert, G and Rennert, HS and Rhenius, V and Romero, A and Roylance, R and Saloustros, E and Sawyer, EJ and Schmidt, DF and Schmutzler, RK and Schneeweiss, A and Schoemaker, MJ and Schumacher, F and Schwentner, L and Scott, RJ and Scott, C and Seynaeve, C and Shah, M and Simard, J and Smeets, A and Sohn, C and Southey, MC and Swerdlow, AJ and Talhouk, A and Tamimi, RM and Tapper, WJ and Teixeira, MR and Tengström, M and Terry, MB and Thöne, K and Tollenaar, RAEM and Tomlinson, I and Torres, D and Truong, T and Turman, C and Turnbull, C and Ulmer, HU and Untch, M and Vachon, C and van Asperen, CJ and van den Ouweland, AMW and van Veen, EM and Wendt, C and Whittemore, AS and Willett, W and Winqvist, R and Wolk, A and Yang, XR and Zhang, Y and Easton, DF and Fasching, PA and Nevanlinna, H and Eccles, DM and Pharoah, PDP and Schmidt, MK},
title = {Genome-wide association study of germline variants and breast cancer-specific mortality.},
journal = {British journal of cancer},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41416-019-0393-x},
pmid = {30787463},
issn = {1532-1827},
support = {0000//Cancer Research UK (CRUK)/ ; 14-04-97088, 17-29-06014 and 17-44-020498//Russian Foundation for Basic Research (RFBR)/ ; C1275/A11699, C1275/C22524, C1275/A19187, C1275/A15956//Cancer Research UK (CRUK)/ ; 2007-3839, 2009 4363//KWF Kankerbestrijding (Dutch Cancer Society)/ ; C490/A10124, C490/A16561//Cancer Research UK (CRUK)/ ; DAMD17-01-1-0729//United States Department of Defense | United States Air Force | Air Force Materiel Command (AFMC)/ ; G0700491//Medical Research Council/United Kingdom ; C1287/A16563, C1287/A10118//Cancer Research UK (CRUK)/ ; 0000//Breast Cancer Now (BCN)/ ; 2010PR62, 2013PR044//Breast Cancer Campaign/United Kingdom ; 266528//Suomen Akatemia | Biotieteiden ja Ympäristön Tutkimuksen Toimikunta (Research Council for Biosciences and Environment)/ ; },
abstract = {BACKGROUND: We examined the associations between germline variants and breast cancer mortality using a large meta-analysis of women of European ancestry.

METHODS: Meta-analyses included summary estimates based on Cox models of twelve datasets using ~10.4 million variants for 96,661 women with breast cancer and 7697 events (breast cancer-specific deaths). Oestrogen receptor (ER)-specific analyses were based on 64,171 ER-positive (4116) and 16,172 ER-negative (2125) patients. We evaluated the probability of a signal to be a true positive using the Bayesian false discovery probability (BFDP).

RESULTS: We did not find any variant associated with breast cancer-specific mortality at P < 5 × 10-8. For ER-positive disease, the most significantly associated variant was chr7:rs4717568 (BFDP = 7%, P = 1.28 × 10-7, hazard ratio [HR] = 0.88, 95% confidence interval [CI] = 0.84-0.92); the closest gene is AUTS2. For ER-negative disease, the most significant variant was chr7:rs67918676 (BFDP = 11%, P = 1.38 × 10-7, HR = 1.27, 95% CI = 1.16-1.39); located within a long intergenic non-coding RNA gene (AC004009.3), close to the HOXA gene cluster.

CONCLUSIONS: We uncovered germline variants on chromosome 7 at BFDP < 15% close to genes for which there is biological evidence related to breast cancer outcome. However, the paucity of variants associated with mortality at genome-wide significance underpins the challenge in providing genetic-based individualised prognostic information for breast cancer patients.},
}

@article {pmid30787294,
year = {2019},
author = {Fourati, S and Ribeiro, SP and Blasco Tavares Pereira Lopes, F and Talla, A and Lefebvre, F and Cameron, M and Kaewkungwal, J and Pitisuttithum, P and Nitayaphan, S and Rerks-Ngarm, S and Kim, JH and Thomas, R and Gilbert, PB and Tomaras, GD and Koup, RA and Michael, NL and McElrath, MJ and Gottardo, R and Sékaly, RP},
title = {Integrated systems approach defines the antiviral pathways conferring protection by the RV144 HIV vaccine.},
journal = {Nature communications},
volume = {10},
number = {1},
pages = {863},
doi = {10.1038/s41467-019-08854-2},
pmid = {30787294},
issn = {2041-1723},
abstract = {The RV144 vaccine trial showed reduced risk of HIV-1 acquisition by 31.2%, although mechanisms that led to protection remain poorly understood. Here we identify transcriptional correlates for reduced HIV-1 acquisition after vaccination. We assess the transcriptomic profile of blood collected from 223 participants and 40 placebo recipients. Pathway-level analysis of HIV-1 negative vaccinees reveals that type I interferons that activate the IRF7 antiviral program and type II interferon-stimulated genes implicated in antigen-presentation are both associated with a reduced risk of HIV-1 acquisition. In contrast, genes upstream and downstream of NF-κB, mTORC1 and host genes required for viral infection are associated with an increased risk of HIV-1 acquisition among vaccinees and placebo recipients, defining a vaccine independent association with HIV-1 acquisition. Our transcriptomic analysis of RV144 trial samples identifies IRF7 as a mediator of protection and the activation of mTORC1 as a correlate of the risk of HIV-1 acquisition.},
}

@article {pmid30786186,
year = {2019},
author = {Khorana, AA and Soff, GA and Kakkar, AK and Vadhan-Raj, S and Riess, H and Wun, T and Streiff, MB and Garcia, DA and Liebman, HA and Belani, CP and O'Reilly, EM and Patel, JN and Yimer, HA and Wildgoose, P and Burton, P and Vijapurkar, U and Kaul, S and Eikelboom, J and McBane, R and Bauer, KA and Kuderer, NM and Lyman, GH and , },
title = {Rivaroxaban for Thromboprophylaxis in High-Risk Ambulatory Patients with Cancer.},
journal = {The New England journal of medicine},
volume = {380},
number = {8},
pages = {720-728},
doi = {10.1056/NEJMoa1814630},
pmid = {30786186},
issn = {1533-4406},
support = {U01 HL143402/HL/NHLBI NIH HHS/United States ; R34 HL127156/HL/NHLBI NIH HHS/United States ; },
mesh = {Administration, Oral ; Adult ; Aged ; Aged, 80 and over ; Antineoplastic Agents/therapeutic use ; Double-Blind Method ; Factor Xa Inhibitors/adverse effects/*therapeutic use ; Female ; Hemorrhage/chemically induced ; Humans ; Incidence ; Intention to Treat Analysis ; Kaplan-Meier Estimate ; Male ; Middle Aged ; Neoplasms/complications/*drug therapy ; Risk Factors ; Rivaroxaban/adverse effects/*therapeutic use ; Treatment Outcome ; Venous Thromboembolism/etiology/*prevention & control ; },
abstract = {BACKGROUND: Ambulatory patients receiving systemic cancer therapy are at varying risk for venous thromboembolism. However, the benefit of thromboprophylaxis in these patients is uncertain.

METHODS: In this double-blind, randomized trial involving high-risk ambulatory patients with cancer (Khorana score of ≥2, on a scale from 0 to 6, with higher scores indicating a higher risk of venous thromboembolism), we randomly assigned patients without deep-vein thrombosis at screening to receive rivaroxaban (at a dose of 10 mg) or placebo daily for up to 180 days, with screening every 8 weeks. The primary efficacy end point was a composite of objectively confirmed proximal deep-vein thrombosis in a lower limb, pulmonary embolism, symptomatic deep-vein thrombosis in an upper limb or distal deep-vein thrombosis in a lower limb, and death from venous thromboembolism and was assessed up to day 180. In a prespecified supportive analysis involving the same population, the same end point was assessed during the intervention period (first receipt of trial agent to last dose plus 2 days). The primary safety end point was major bleeding.

RESULTS: Of 1080 enrolled patients, 49 (4.5%) had thrombosis at screening and did not undergo randomization. Of the 841 patients who underwent randomization, the primary end point occurred in 25 of 420 patients (6.0%) in the rivaroxaban group and in 37 of 421 (8.8%) in the placebo group (hazard ratio, 0.66; 95% confidence interval [CI], 0.40 to 1.09; P = 0.10) in the period up to day 180. In the prespecified intervention-period analysis, the primary end point occurred in 11 patients (2.6%) in the rivaroxaban group and in 27 (6.4%) in the placebo group (hazard ratio, 0.40; 95% CI, 0.20 to 0.80). Major bleeding occurred in 8 of 405 patients (2.0%) in the rivaroxaban group and in 4 of 404 (1.0%) in the placebo group (hazard ratio, 1.96; 95% CI, 0.59 to 6.49).

CONCLUSIONS: In high-risk ambulatory patients with cancer, treatment with rivaroxaban did not result in a significantly lower incidence of venous thromboembolism or death due to venous thromboembolism in the 180-day trial period. During the intervention period, rivaroxaban led to a substantially lower incidence of such events, with a low incidence of major bleeding. (Funded by Janssen and others; CASSINI ClinicalTrials.gov number, NCT02555878.).},
}

Administration, Oral
Adult
Aged
Aged, 80 and over
Antineoplastic Agents/therapeutic use
Double-Blind Method
Factor Xa Inhibitors/adverse effects/*therapeutic use
Female
Hemorrhage/chemically induced
Humans
Incidence
Intention to Treat Analysis
Kaplan-Meier Estimate
Male
Middle Aged
Neoplasms/complications/*drug therapy
Risk Factors
Rivaroxaban/adverse effects/*therapeutic use
Treatment Outcome
Venous Thromboembolism/etiology/*prevention & control

@article {pmid30785776,
year = {2019},
author = {Todd, JL and Hill, JA and Cheng, GS},
title = {Herpesviruses: Silent Instigators of Lung Injury after Hematopoietic Cell Transplant.},
journal = {American journal of respiratory and critical care medicine},
volume = {},
number = {},
pages = {},
doi = {10.1164/rccm.201901-0185ED},
pmid = {30785776},
issn = {1535-4970},
}

@article {pmid30785418,
year = {2019},
author = {Beieler, A and Magaret, A and Zhou, Y and Schleyer, A and Wald, A and Dhanireddy, S},
title = {Outpatient Parenteral Antimicrobial Therapy in Vulnerable Populations-- People Who Inject Drugs and the Homeless.},
journal = {Journal of hospital medicine},
volume = {14},
number = {2},
pages = {105-109},
doi = {10.12788/jhm.3138},
pmid = {30785418},
issn = {1553-5606},
abstract = {Outpatient parenteral antimicrobial therapy (OPAT) programs can provide high-value care but may be challenging in people who inject drugs (PWID) and homeless individuals. We conducted a single-center, retrospective, cohort study of adults who received OPAT at an urban, public health hospital from January 1, 2015 to April 30, 2016, grouped by PWID and housing status. Outcomes included clinical cure, length of stay, secondary bacteremia, line-tampering, and readmission. A total of 596 patients (homeless PWID (9%), housed PWID (8%), homeless non-PWID (8%), and housed non-PWID (75%), received OPAT. Assuming that patients lost to follow-up failed therapy, homeless PWID were least likely to achieve cure compared with housed non-PWID, (odds ratio [OR] = 0.33, 95% CI 0.18-0.59; P < .001). Housed PWID were also less likely to achieve cure (OR = 0.37, 95% CI 0.20-0.67; P = .001). Cure rates did not differ in patients not lost to follow-up. OPAT can be effective in PWID and the homeless, but loss to follow-up is a significant barrier.},
}

@article {pmid30785094,
year = {2019},
author = {Deng, N and Li, M and Shen, D and He, Q and Sun, W and Liu, M and Liu, Y and Zhou, Y and Zheng, J and Shen, F},
title = {LRP1 receptor-mediated immunosuppression of α-MMC on monocytes.},
journal = {International immunopharmacology},
volume = {70},
number = {},
pages = {80-87},
doi = {10.1016/j.intimp.2019.01.036},
pmid = {30785094},
issn = {1878-1705},
abstract = {Alpha-MMC is a type I ribosome-inactivating protein purified from bitter gourd that has strong anti-tumour and antiviral activity. Alpha-MMC also has immunosuppressive effects, but the mechanism of these immunosuppressive effects remains unclear. It is reported that the binding of α-MMC to its specific cell membrane LRP1 receptor is key to its biological effects. In this study, we investigated the effect of α-MMC on cytotoxicity and cytokine release regulation in three immune cells, human monocyte THP-1 cells, B-lymphocyte WIL2 cells and T-lymphocyte H9 cells, and explored the correlation between this effect and LRP1 receptor distribution on these three cell types. We demonstrate that α-MMC has a significant effect of apoptosis induction and cytokine release in THP-1 cells but has no effect on WIL2-S and H9 cells. Specifically, at a non-cytotoxic dose (80 μg/ml), α-MMC regulates THP-1 cells by inhibiting IL-1β, IL-2, IL-8, IL-9, IL-12, MIP-1α/β, MCP-1 and TNF-α expression and enhancing IL-1ra and RANTES expression, resulting in the inhibition of cellular immune function. Subsequent experiments showed that the cytokine expression regulated by α-MMC can be blocked by silencing the LRP1 receptor of α-MMC. Further research indicated that phosphorylation of 9 signalling proteins of the MAPK pathway was significantly regulated by α-MMC and was blocked by LRP1 silencing. We conclude that the regulation of cytokine expression induced by α-MMC in monocyte THP-1 cells is mediated by the LRP1 receptor, likely via the MAPK signalling pathway. Our results suggest that the inhibition effect on monocytes/macrophages mediates the immunosuppressive function of α-MMC. Due to the selective cytotoxicity and cytokine release regulation of α-MMC in monocytes/macrophages, α-MMC may be used for killing Tumour-Associated Macrophages (M2 subtypes) or inhibiting their cytokine release in the tumour microenvironment.},
}