@article {pmid41934618,
year = {2026},
author = {Singh Mahla, R},
title = {Comment on: Fcgamma-receptor-activation by circulating immune complexes in systemic autoimmune diseases and its reduction by CD19-CAR T-cell therapy.},
journal = {Rheumatology (Oxford, England)},
volume = {},
number = {},
pages = {},
doi = {10.1093/rheumatology/keag174},
pmid = {41934618},
issn = {1462-0332},
}

@article {pmid41936367,
year = {2026},
author = {, },
title = {Global burden of cancer in children and adolescents aged 0-19 years, 1990-2023: a systematic analysis for the Global Burden of Disease Study 2023.},
journal = {Lancet (London, England)},
volume = {407},
number = {10536},
pages = {1360-1373},
doi = {10.1016/S0140-6736(26)00200-X},
pmid = {41936367},
issn = {1474-547X},
mesh = {Humans ; Adolescent ; Child ; *Neoplasms/epidemiology/mortality ; Child, Preschool ; Infant ; *Global Burden of Disease/trends ; Young Adult ; Infant, Newborn ; Male ; Disability-Adjusted Life Years ; Female ; Incidence ; Global Health/statistics & numerical data ; Life Expectancy ; Prevalence ; Risk Factors ; },
abstract = {BACKGROUND: Information on childhood cancer burden is crucial for effective cancer policy planning. Unfortunately, observed paediatric cancer data are not available in every country, and previous global burden estimates have not discretely reported several common cancers of childhood. We aimed to inform efforts to address childhood cancer burden globally by analysing results from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2023, which now include nine additional cancer causes compared with previous GBD analyses.

METHODS: GBD 2023 data sources for cancer estimation included population-based cancer registries, vital registration systems, and verbal autopsies. For childhood cancers (defined as those occurring at ages 0-19 years), mortality was estimated using cancer-specific ensemble models and incidence was estimated using mortality estimates and modelled mortality-to-incidence ratios (MIRs). Years of life lost (YLLs) were estimated by multiplying age-specific cancer deaths by the standard life expectancy at the age of death. Prevalence was estimated using survival estimates modelled from MIRs and multiplied by sequelae-specific disability weights to estimate years lived with disability (YLDs). Disability-adjusted life-years (DALYs) were estimated as the sum of YLLs and YLDs. Estimates are presented globally and by geographical and resource groupings, and all estimates are presented with 95% uncertainty intervals (UIs).

FINDINGS: Globally, in 2023, there were an estimated 377 000 incident childhood cancer cases (95% UI 288 000-489 000), 144 000 deaths (131 000-162 000), and 11·7 million (10·7-13·2) DALYs due to childhood cancer. Deaths due to childhood cancer decreased by 27·0% (15·5-36·1) globally, from 197 000 (173 000-218 000) in 1990, but increased in the WHO African region by 55·6% (25·5-92·4), from 31 500 (24 900-38 500) to 49 000 (42 600-58 200) between 1990 and 2023. In 2023, age-standardised YLLs due to childhood cancer were inversely correlated with country-level Socio-demographic Index. Childhood cancer was the eighth-leading cause of childhood deaths and the ninth-leading cause of DALYs among all cancers in 2023. The percentage of DALYs due to uncategorised childhood cancers was reduced from 26·5% (26·5-26·5) in GBD 2017 to 10·5% (8·1-13·1) with the addition of the nine new cancer causes. Target cancers for the WHO Global Initiative for Childhood Cancer (GICC) comprised 47·3% (42·2-52·0) of global childhood cancer deaths in 2023.

INTERPRETATION: Global childhood cancer burden remains a substantial contributor to global childhood disease and cancer burden and is disproportionately weighted towards resource-limited settings. The estimation of additional cancer types relevant in childhood provides a step towards alignment with WHO GICC targets. Efforts to decrease global childhood cancer burden should focus on addressing the inequities in burden worldwide and support comprehensive improvements along the childhood cancer diagnosis and care continuum.

FUNDING: St Jude Children's Research Hospital, Gates Foundation, and St Baldrick's Foundation.},
}

Humans
Adolescent
Child
*Neoplasms/epidemiology/mortality
Child, Preschool
Infant
*Global Burden of Disease/trends
Young Adult
Infant, Newborn
Male
Disability-Adjusted Life Years
Female
Incidence
Global Health/statistics & numerical data
Life Expectancy
Prevalence
Risk Factors

@article {pmid41933184,
year = {2026},
author = {Li, S and Ghajar, CM},
title = {A tumor-derived metabolite primes the leptomeningeal pre-metastatic niche.},
journal = {Nature cancer},
volume = {},
number = {},
pages = {},
pmid = {41933184},
issn = {2662-1347},
}

@article {pmid41934616,
year = {2026},
author = {Núñez, ER and Triplette, M},
title = {Care Coordination as the Bridge: Closing the Gaps in Lung Cancer Screening.},
journal = {Annals of the American Thoracic Society},
volume = {},
number = {},
pages = {},
doi = {10.1093/annalsats/aaoag081},
pmid = {41934616},
issn = {2325-6621},
}

@article {pmid41867730,
year = {2026},
author = {Hollis, JA and Stonick, JA and Topalidou, I and Young, JM and Moens, CB and Lehrbach, NJ and Campbell, MG and Malik, HS},
title = {Remote homology and functional genetics unmask deeply preserved Scm3/HJURP orthologs in metazoans.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {41867730},
issn = {2692-8205},
abstract = {In most animals and fungi, centromere identity and function depend on the Scm3/HJURP chaperone, which deposits CENPA at centromeres. However, Scm3/HJURP orthologs appeared to be missing in insects, nematodes, many vertebrates, and other metazoans, suggesting radical chaperone replacement in these lineages. Here, we combine remote homology detection, AlphaFold-based structural modeling, and functional genetics in zebrafish and Caenorhabditis elegans to identify previously unknown Scm3/HJURP orthologs that localize to centromeres and whose loss causes catastrophic mitotic failure. We further show that Drosophila CAL1, long considered a functional analog, is instead a highly diverged Scm3/HJURP ortholog. Despite rapid primary-sequence divergence, predicted and known structures reveal a broadly conserved CENPA-H4-binding scm3 fold across fungi, vertebrates, nematodes, insects, and basally-branching metazoans. Our work demonstrates how rapid divergence can obscure the broad conservation of essential centromere machinery and provides a broadly applicable strategy to unmasking missing orthologs.},
}

@article {pmid41925941,
year = {2026},
author = {Owens, GC and Contreras, EM and Kienzler, JC and Treger, J and Soto, H and Orpilla, JR and Qiao, C and Chang, JW and Lee, A and Kim, WJ and Sun, MZ and Peeters, SF and Bethel, JA and Kondajji, AM and Holland, EC and Becher, OJ and Liau, LM and Prins, RM and Wang, AC},
title = {Therapeutic efficacy of dendritic cell vaccination in a novel syngeneic mouse model of diffuse hemispheric glioma, H3 G34-mutant.},
journal = {Journal of neuro-oncology},
volume = {177},
number = {2},
pages = {},
pmid = {41925941},
issn = {1573-7373},
}

@article {pmid41930736,
year = {2026},
author = {Zou, R and D Williamson, B and M Shortreed, S and Coley, RY},
title = {Validation of a Risk-Prediction Model in the Presence of Outcome Misclassification.},
journal = {Statistics in medicine},
volume = {45},
number = {8-9},
pages = {e70377},
doi = {10.1002/sim.70377},
pmid = {41930736},
issn = {1097-0258},
support = {R01-MH125821/MH/NIMH NIH HHS/United States ; U19-MH099201/MH/NIMH NIH HHS/United States ; U19-MH121738/MH/NIMH NIH HHS/United States ; },
mesh = {Humans ; Electronic Health Records/statistics & numerical data ; *Models, Statistical ; Risk Assessment/methods/statistics & numerical data ; Computer Simulation ; ROC Curve ; Bias ; Area Under Curve ; },
abstract = {Electronic health records (EHRs) provide a rich data source for building prediction models to improve the quality of care. However, EHR data are prone to measurement error, and outcomes used to evaluate prediction model performance may be misclassified. Comparing risk predictions to misclassified outcomes will result in unreliable estimates of a prediction model's performance. We propose a method that leverages a smaller chart review sample with gold-standard outcome measurements to adjust validation for outcome misclassification and provide more accurate prediction model evaluation. We derive formulae to estimate true positive rate (TPR), false positive rate (FPR), positive predictive value (PPV), negative predictive value (NPV), and area under the receiver operating characteristic curve (AUC) in the presence of outcome misclassification. Different scenarios of misclassification are explored, including when the misclassification is independent or dependent on features, and when misclassification is unidirectional (e.g., only missed diagnoses) or bidirectional. In simulation studies, we compare the bias and 95% confidence interval coverage of performance estimates obtained using our proposed method to those estimated with misclassified outcomes (without accounting for misclassification) or in the smaller chart review sample. Simulation results indicate that, across all misclassification scenarios examined, our proposed estimates have good accuracy and improved precision. Outcome misclassification should be considered when evaluating a prediction model's performance in order to accurately inform decision-making about whether and how to use a clinical prediction model.},
}

Humans
Electronic Health Records/statistics & numerical data
*Models, Statistical
Risk Assessment/methods/statistics & numerical data
Computer Simulation
ROC Curve
Bias
Area Under Curve

@article {pmid41932032,
year = {2026},
author = {Geidel, G and Fekade, N and Raabe, K and Smit, DJ and Adam, L and Heidrich, I and Rünger, A and Kött, J and Zell, T and Amaral, T and Ascierto, PA and Corrie, P and Dummer, R and Eggermont, A and Guo, J and Hassel, JC and Jalving, M and Johnson, DB and Kandolf, L and Kirkwood, JM and Lebbé, C and Lee, R and Long, GV and Lorigan, P and Malvehy, J and Mangana, J and Mohr, P and Patel, SP and Rizos, H and Robert, C and Schadendorf, D and Sondak, VK and Svane, IM and Wainstein, A and Zager, JS and Pantel, K and Hauschild, A and Gebhardt, C and , },
title = {Translating ctDNA into cutaneous melanoma care: An international expert survey.},
journal = {European journal of cancer (Oxford, England : 1990)},
volume = {239},
number = {},
pages = {116676},
doi = {10.1016/j.ejca.2026.116676},
pmid = {41932032},
issn = {1879-0852},
abstract = {BACKGROUND: Circulating tumor DNA (ctDNA) is a promising biomarker in melanoma, with higher sensitivity for tumor burden detection than conventional diagnostics. While well established in research, clinical routine implementation remains pending. Key global questions concern optimal clinical applications and barriers to adoption.

METHODS: A web-based survey of 116 members of the Melanoma World Society Study Group assessed international expert opinions on ctDNA utility across predefined clinical scenarios. The questionnaire included 18 general questions on ctDNA use and 5 clinical vignettes with de-identified patient data and retrospectively obtained ctDNA results.

RESULTS: ctDNA was rated most valuable for detecting minimal residual disease (mean score 3.63), surveillance of recurrent disease (3.85), and stage IV melanoma (3.82), with limited utility in early stages. Experts considered ctDNA superior to S100 and LDH for early relapse detection and identifying progressive disease. Most participants (80%) agreed that ctDNA correlates with radiographic response, and 82% favored its integration into routine follow-ups. In urgent high-tumor-burden settings, 82.8% would initiate BRAFi/MEKi therapy based on ctDNA if tissue analysis was pending, and 93.9% if unavailable. For central nervous system lesions, 62% did not support blood ctDNA, while 66% considered cerebrospinal fluid valuable. Pragmatic approaches with small to mid-size targeted panels and short turnaround times were preferred. Major barriers included the need for prospective trials (85%), standardized guidelines (83%), and reimbursement policies (82%).

CONCLUSION: Key opinion leaders regarded ctDNA as a valuable adjunct selected melanoma scenarios. Validation through prospective studies, guideline development, and reimbursement frameworks are essential for broader clinical implementation.},
}

@article {pmid41932899,
year = {2026},
author = {Williamson, C and Moodley, C and Magaret, CA and Giorgi, EE and Rolland, M and Westfall, DH and Yssel, A and Deng, W and Rossenkhan, R and Mkhize, NN and Chen, L and Zhao, H and Bhattacharya, T and Pankow, A and Murrell, B and York, T and Gwashu-Nyangiwe, A and Ndabambi, N and Thebus, R and Cohen, P and Lambson, B and Kaldine, H and Bhebhe, S and Juraska, M and Bai, H and deCamp, AC and Miner, MD and Ludwig, J and Molitor, C and Beaume, N and Matten, D and Huang, Y and Zhang, L and Reeves, DB and Mayer, B and Karuna, ST and Hural, JA and Morris, L and Montefiori, D and Bumgarner, RE and Moore, PL and Edlefsen, PT and Edupuganti, S and Mgodi, N and McElrath, MJ and Cohen, MS and Corey, L and Gilbert, PB and Mullins, JI},
title = {Influence of the broadly neutralizing antibody VRC01 on HIV breakthrough virus populations in antibody-mediated prevention trials.},
journal = {Nature communications},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41467-026-70888-0},
pmid = {41932899},
issn = {2041-1723},
support = {UM1 AI068614/AI/NIAID NIH HHS/United States ; UM1 AI068635/AI/NIAID NIH HHS/United States ; UM1 AI068618/AI/NIAID NIH HHS/United States ; UM1 AI068619/AI/NIAID NIH HHS/United States ; UM1 AI068613/AI/NIAID NIH HHS/United States ; UM1 AI068617/AI/NIAID NIH HHS/United States ; R01 AI152115/AI/NIAID NIH HHS/United States ; K25 AI155224, R01 AI186721-01//U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (NIAID)/ ; R01 AI157854/AI/NIAID NIH HHS/United States ; 1032144, INV-016189//Bill and Melinda Gates Foundation (Bill & Melinda Gates Foundation)/ ; 2018-02381//Vetenskapsrådet (Swedish Research Council)/ ; },
abstract = {In the antibody mediated prevention (AMP) trials, the broadly neutralizing antibody (bNAb) VRC01 demonstrated protective efficacy against susceptible HIV strains. To understand how VRC01 shaped breakthrough infections, deep sequencing was performed on 172 participants (>100,000 gag-Δpol and rev-env-Δnef sequences), at diagnosis and over time, in the placebo and treatment arms of the African (HVTN703/HPTN081; NCT02568215) and Americas/Europe (HVTN704/HPTN085; NCT02716675) cohorts. A high frequency of multilineage infections was detected (38%), including co-infection with both VRC01 sensitive and resistant viruses. This high frequency is largely accounted for by low-abundance lineages. Although VRC01 does not significantly affect the genetic transmission bottleneck compared to placebo, higher VRC01 doses trend towards greater VRC01 neutralization differences among co-infecting lineages. Two-thirds of multilineage infections showed evidence of recombination at the diagnostic timepoint. In the treatment group there is evidence of recombinant viruses preferentially inheriting resistance-associated mutations. This study provides critical insights into viral genetic and antigenic diversity that needs to be targeted to achieve protection, and highlights the role of recombination in facilitating escape.},
}

@article {pmid41933174,
year = {2026},
author = {Cummings, JL and Agadjanyan, MG and Barry, M and Corey, L and Doody, R and Hendrix, S and Mattke, S and Mattsson-Carlgren, N and McDade, E and Menetski, JP and Mohs, RC and Partrick, KA and Petrovsky, N and Selkoe, DJ and Silva, D and Sperling, RA and Tiede, B and Vradenburg, G},
title = {Target product profiles for treatments to delay or prevent symptomatic Alzheimer's disease.},
journal = {Nature medicine},
volume = {},
number = {},
pages = {},
pmid = {41933174},
issn = {1546-170X},
abstract = {Despite advances in understanding the mechanisms, risk factors and treatment strategies for Alzheimer's disease (AD), no approved therapies exist to prevent or delay onset in at-risk individuals or those with elevated biomarkers who do not yet show symptoms. Multiple candidate interventions are now being evaluated in clinical trials in these settings, raising key questions around which populations are most appropriate and what criteria should guide regulatory and clinical decision-making. Data are expected within 1-2 years, underscoring the need for stakeholder alignment on clinically meaningful and acceptable characteristics of preventative therapies or other products. To address this need, the Global CEO Initiative on Alzheimer's Disease convened an international group of experts to develop target product profiles for therapies designed to delay or prevent the onset of clinical symptoms in AD. These target product profiles outline minimum and preferred characteristics, including intended use, target populations, safety expectations and efficacy benchmarks. This effort provides a foundational framework to accelerate therapeutic development and guide researchers, regulators and patients in the evaluation of emerging therapies for preventing symptomatic AD.},
}

@article {pmid41846968,
year = {2026},
author = {Santos, JJS and Souza, CK and Zanella, GC and Goulart, DB and Arruda, B and Boggiatto, P and Palmer, MV and Snyder, CA and Kristula, MA and Dickens, C and Webb, TL and Atkinson, RK and Dadonaite, B and Dwivedi, G and Alameh, MG and Bloom, JD and Weissman, D and Althouse, GC and Baker, AL and Hensley, SE},
title = {Evaluation of an H5 influenza virus mRNA-lipid nanoparticle (LNP) vaccine in lactating dairy cows.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {41846968},
issn = {2692-8205},
abstract = {Highly pathogenic avian influenza (HPAI) clade 2.3.4.4b H5N1 virus has recently emerged in dairy cattle in the United States. The virus replicates primarily in the mammary gland of infected cattle, leading to dramatic reductions in milk production. It is thought that the virus transmits from animal to animal through viral shedding in milk, and therefore, vaccines that decrease the amount of virus in milk can potentially limit the current outbreak and reduce the risk of H5N1 spillover into humans. Here, we assess the immunogenicity and efficacy of a clade 2.3.4.4b H5 mRNA-LNP vaccine in lactating dairy cows. We found that the H5 mRNA-LNP vaccine elicited robust antibody responses in sera and milk and significantly reduced viral replication and disease caused by clade 2.3.4.4b H5N1 intramammary infection.},
}

@article {pmid41922791,
year = {2026},
author = {Contieri, R and Gontero, P and Hurle, R and Afferi, L and Albisinni, S and Babjuk, M and Birtle, A and Black, P and Brausi, M and Bruins, M and Čapoun, O and Carrion, A and Catto, J and Choudhury, A and Cimadamore, A and Comperat, E and Daneshmand, S and D'andrea, D and Del Giudice, F and Escrig, JLD and Hensley, P and Krajewski, W and Laukhtina, E and Li, R and Liedberg, F and Lotan, Y and Marcq, G and Mariappan, P and Mari, A and Martini, A and Lecomte, AM and Meijer, R and Mir, MC and Mori, K and Moschini, M and Mostafid, H and O'Donnell, M and Palou, J and Panebianco, V and Perdonà, S and Porten, S and Psutka, S and Rink, M and Roupret, M and Seisen, T and Soloway, M and Soukup, V and Steinberg, G and Stenzl, A and Teoh, JY and Tully, K and van der Heijden, T and van Rhijn, BWG and Witjes, A and Xylinas, E and Kamat, AM and Pradere, B and Mertens, LS},
title = {Active surveillance in low-grade NMIBC - results of an international two-round modified Delphi consensus.},
journal = {Nature reviews. Urology},
volume = {},
number = {},
pages = {},
pmid = {41922791},
issn = {1759-4820},
abstract = {Standard management for recurrent low-grade non-muscle-invasive bladder cancer (LG-NMIBC) often involves a substantial treatment burden, which is not justified by the relatively indolent course of the disease, prompting a need for de-intensification strategies. Active surveillance (AS) is an alternative approach aimed at reducing overtreatment in selected patients. However, the broader adoption of AS is hindered by a lack of standardized protocols for patient selection, monitoring and intervention. To address this gap, we conducted an international, two-round Delphi consensus among 51 bladder cancer experts to establish foundational statements for the use of AS. Consensus was achieved on 20 statements, providing clear recommendations for terminology; inclusion and exclusion criteria; follow-up monitoring; and exit criteria. This Delphi consensus provides the first expert-driven framework to standardize the clinical application of AS for LG-NMIBC. These statements could guide current clinical practice and unify the design of future trials.},
}

@article {pmid41923460,
year = {2026},
author = {Jin, Y and Luedtke, A and Moodie, Z and Janes, H and Benkeser, D},
title = {Comparing HIV Vaccine Immunogenicity Across Trials With Different Populations and Study Designs.},
journal = {Statistics in medicine},
volume = {45},
number = {8-9},
pages = {e70495},
doi = {10.1002/sim.70495},
pmid = {41923460},
issn = {1097-0258},
support = {5UM1AI068635/NH/NIH HHS/United States ; },
mesh = {*AIDS Vaccines/immunology ; Humans ; *HIV Infections/prevention & control/immunology ; *Immunogenicity, Vaccine ; *Randomized Controlled Trials as Topic/methods ; *Research Design ; Computer Simulation ; Vaccine Efficacy ; Models, Statistical ; },
abstract = {Safe and effective preventive vaccines have the potential to help stem the HIV epidemic. The efficacy of such vaccines is typically measured in randomized, double-blind phase IIb/III trials and described as a reduction in newly acquired HIV infections. However, such trials are often expensive, time-consuming, and/or logistically challenging. These challenges lead to a great interest in immune responses induced by vaccination, and in identifying which immune responses predict vaccine efficacy. These responses are termed vaccine correlates of protection. Studies of vaccine-induced immunogenicity vary in size and design, ranging from small, early-phase trials to case-control studies nested in a broader late-phase randomized trial. Moreover, trials can be conducted in geographically diverse study populations across the world. Such diversity presents a challenge for objectively comparing vaccine-induced immunogenicity. To address these practical challenges, we propose a framework that is capable of identifying appropriate causal estimands and estimators, which can be used to provide standardized comparisons of vaccine-induced immunogenicity across trials. We evaluate the performance of the proposed estimands via extensive simulation studies. Our estimators are well-behaved and enjoy robustness properties. The proposed technique is applied to compare vaccine immunogenicity using data from three recent HIV vaccine trials.},
}

*AIDS Vaccines/immunology
Humans
*HIV Infections/prevention & control/immunology
*Immunogenicity, Vaccine
*Randomized Controlled Trials as Topic/methods
*Research Design
Computer Simulation
Vaccine Efficacy
Models, Statistical

@article {pmid41923535,
year = {2026},
author = {Zhu, K and Chuen Gary Chan, K and Zhao, YQ and Zheng, Y},
title = {Two-Step Error-Controlling Classifiers With Application to Cost-Effective Disease Diagnosis.},
journal = {Statistics in medicine},
volume = {45},
number = {8-9},
pages = {e70498},
doi = {10.1002/sim.70498},
pmid = {41923535},
issn = {1097-0258},
support = {R01 CA236558/NH/NIH HHS/United States ; U24 CA288285/NH/NIH HHS/United States ; U24 CA086368/NH/NIH HHS/United States ; },
mesh = {Humans ; *Prostatic Neoplasms/diagnosis/classification ; Male ; *Cost-Benefit Analysis ; Biomarkers, Tumor ; },
abstract = {Accurate classifiers that use novel biomarkers and readily available predictors significantly enhance decision-making in various clinical scenarios, such as assessing the need for biopsies in cancer diagnosis. When classification performance is limited, a decision framework can be applied to rule in or rule out invasive diagnostic procedures while incorporating a neutral zone for indeterminate classifications. Building on this framework, we propose a new family of two-step classifiers that selectively use costly biomarker testing for a targeted subset of individuals undergoing multiple evaluations. The optimal solution expands upon the Neyman-Pearson Lemma, highlighting a vital trade-off between the costs of expensive biomarker measurements and improving classification performance while minimizing uncertainty in the decision process. We demonstrate the practical utility of our approach through a biomarker study focused on prostate cancer diagnosis.},
}

Humans
*Prostatic Neoplasms/diagnosis/classification
Male
*Cost-Benefit Analysis
Biomarkers, Tumor

@article {pmid41924784,
year = {2026},
author = {Khan, A and Schwartz, JY and Patel, D and Njoku, C and Bosse, K and Heidaran, M and Atkins, JW},
title = {Two decades of advancing safe and effective cell-based therapies: a review of the impact, promise, and current limitations of USA regulation 21 CFR Part 1271.},
journal = {Cytotherapy},
volume = {28},
number = {6},
pages = {102119},
doi = {10.1016/j.jcyt.2026.102119},
pmid = {41924784},
issn = {1477-2566},
abstract = {BACKGROUND AIMS: Over the past 20 years, USA regulation 21 CFR Part 1271 has served as the cornerstone regulation for human cells, tissues, and cellular and tissue-based products (HCT/Ps) in the United States. Designed to ensure public health safety while fostering innovation, the framework has significantly shaped the development and oversight of regenerative medicine.

METHODS: This paper examines the evolution of 21 CFR Part 1271 since its inception, highlighting key amendments, milestones, and regulatory challenges. It explores its impact on the industry, focusing on case studies that underscore its influence on clinical translation and commercialization.

RESULTS: The analysis shows that 21 CFR Part 1271 addresses ongoing controversies, such as compliance and enforcement challenges, and discusses how emerging technologies like exosomes, gene editing, and bioprinting may reshape its future.

CONCLUSION: By reflecting on two decades of regulatory experience, this paper provides insights into the successes and limitations of 21 CFR Part 1271 and proposes pathways for its modernization to address the growing complexity of regenerative medicine.},
}

@article {pmid41925553,
year = {2026},
author = {Urujeni, C and Epplein, M and Li, CI and Pete, D},
title = {Racial and ethnic differences in gastric cancer by stage of diagnosis in the United States (2009-2019).},
journal = {Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology},
volume = {},
number = {},
pages = {},
doi = {10.1158/1055-9965.EPI-25-1356},
pmid = {41925553},
issn = {1538-7755},
abstract = {BACKGROUND: Despite the United States having a low overall gastric cancer (GC) incidence rate, there remain disparities by race/ethnicity. We examined the incidence of GC by stage at diagnosis among Hispanic, Asian/Pacific Islander (A/PI), American Indian/Alaska Native (AI/AN), and non-Hispanic Black (NHB) populations, compared to non-Hispanic White (NHW) population, during 2009-2019.

METHODS: Using Surveillance, Epidemiology, and End Results data, age-adjusted GC incidence rates, rate ratios (RRs) and 95% confidence intervals (CIs) were calculated by stage and race/ethnicity. Stratified analyses were performed by sex, age and anatomical site.

RESULTS: Compared to NHW individuals, incidence rates of regional and distant stage GC diagnosis were nearly two times higher in Hispanic (RRRegional, 1.87; 95% CI, 1.78-1.97; RRDistant, 1.92; 95% CI, 1.84-2.00), A/PI (RRregional, 2.17; 95% CI, 2.04-2.30; RRDistant, 1.58; 95% CI, 1.49-1.68), and NHB (RRregional, 1.78; 95% CI, 1.67-1.88; RRDistant, 1.80; 95% CI, 1.71-1.89) individuals. In stratified analyses, the increased rate of advanced-stage diagnosis for Hispanic, A/PI, and NHB individuals remained generally consistent by sex and age, although young AI/AN individuals also had a significantly higher rate of distant GC (RR, 2.38; 95% CI, 1.36-3.83). By site, the increased rates of advanced-stage diagnosis were limited to non-cardia and overlapping/unspecified GC, whereas these populations had lower rates of cardia GC than NHW individuals.

CONCLUSIONS: Hispanic, A/PI, and NHB individuals have disproportionately high advanced-stage non-cardia GC rates compared to NHW individuals.

IMPACT: This study has identified significant disparities in advanced-stage non-cardia GC, suggesting the need to identify strategies to improve early detection in these populations.},
}

@article {pmid41925563,
year = {2026},
author = {Schaefer, DA and Guo, M and Keane, EP and Song, MT and Larizza, IS and Adri, F and Wolfe, ED and Saadeh, N and Boardman, AC and Acharya, NB and Waldman, LP and Monahan, JA and Ramirez-Gamero, AF and Diaz Gonzalez-Colmenero, F and Watson, J and Cronin, AE and Celano, CM and Brown, L and Lee, SJ and Stoto, MA and Gudenkauf, LM and Amonoo, HL},
title = {Supportive Care Interventions in Hematopoietic Stem Cell Transplantation: Systematic Review and Meta-Analysis.},
journal = {Blood advances},
volume = {},
number = {},
pages = {},
doi = {10.1182/bloodadvances.2026019724},
pmid = {41925563},
issn = {2473-9537},
abstract = {There is no comprehensive synthesis of supportive care interventions for patients with hematologic malignancies receiving transplantation and cellular therapies (TCTs). This systematic review and meta-analysis aimed to characterize randomized controlled trials (RCTs) of TCT supportive care interventions and examine effects on patient-reported outcomes (PROs). We systematically searched MEDLINE, Embase, CINAHL, PsycInfo, Web of Science, and CENTRAL databases. We used the Cochrane Risk of Bias 2.0 protocol, grouped findings by intervention and PRO types, and synthesized results narratively. We conducted exploratory random-effects meta-analyses to estimate pooled intervention effects on anxiety, depression, and quality of life (QOL). Fifty-three RCTs published from 1992 to 2025 met criteria. All RCTs included hematopoietic stem cell transplantation (HSCT) recipients; none were tested in patients receiving cellular therapies. Included studies reported a range of sample sizes (11-711), participant demographics (mean age 33-63 years; 22-64% female), and PROs. There were nine intervention categories: cognitive behavioral (n=5), exercise only (n=17), expressive helping (n=2), mind-body/stress management (n=7), multimodal (exercise plus another modality; n=6), music/art (n=12), palliative care (n=2), positive psychology (n=1), and self-management/self-efficacy (n=5). Interventions were mostly feasible and acceptable, with promising improvements in psychological distress, QOL, and physical outcomes. Meta-analysis showed non-significant trends toward exercise interventions improving QOL (SMD=0.09; 95% CI: -0.07 to 0.25) and music/art interventions reducing acute depressive symptoms (SMD=-0.26; 95% CI: -0.52 to 0.00). Among patients undergoing HSCT for hematologic malignancies, supportive care interventions show feasibility, acceptability, and promise for improving PROs. However, larger, rigorously designed trials using standardized PRO measures are needed to establish efficacy.},
}

@article {pmid41918519,
year = {2026},
author = {Mngadi, K and Broder, GB},
title = {Editorial: Community-centric strategies for HIV and STI prevention in key populations.},
journal = {Frontiers in reproductive health},
volume = {8},
number = {},
pages = {1798107},
pmid = {41918519},
issn = {2673-3153},
}

@article {pmid41918932,
year = {2026},
author = {Hecht, JR and Molina, JR and Liechty, K and Welling, TH and Grierson, PM and Patel, SP and Kirtane, K and Morelli, MP and Locke, FL and Maloney, DG and Punekar, SR and Nikiforow, S and Lin, Y and Ulrickson, M and Specht, JM and Lozac'hmeur, A and Osterman, CK and Garde, RJ and Rangel, GA and Ng, EW and Welch, JS and Tebbets, JC and Go, WY and Simeone, DM},
title = {BASECAMP-1 screening study: a model for efficient enrolment in precision oncology clinical trials.},
journal = {BMJ oncology},
volume = {5},
number = {1},
pages = {e001033},
pmid = {41918932},
issn = {2752-7948},
abstract = {OBJECTIVE: Identifying eligible patients for precision oncology clinical trials is challenging, particularly for rare molecular subpopulations. To address this challenge, A2 Biotherapeutics developed BASECAMP-1 (NCT04981119), a non-interventional master screening study to identify patients eligible for interventional studies of logic-gated Tmod chimeric antigen receptor T-cell therapies. Eligible patients for these interventional trials have an advanced solid malignancy and are germline human leucocyte antigen (HLA)-A*02 heterozygous, with tumour-associated HLA-A loss of heterozygosity (LOH). HLA-A LOH occurs in ~16% of advanced solid malignancies; therefore, an efficient screening strategy is required. This report describes BASECAMP-1; compares the efficiency of two screening methods; and discusses the broader advantages of BASECAMP-1 beyond efficient enrolment.

METHODS AND ANALYSIS: Patients are identified for BASECAMP-1 using two approaches. In the traditional approach, common for clinical trials, investigators consent and screen all patients who might be good candidates for cell therapy trials, with no prior knowledge of patient HLA-A type or LOH status. To further optimise our approach, we co-developed with Tempus AI (Tempus) the bioinformatic programme Aware, which identifies potentially eligible patients with tumour-associated HLA-A*02 LOH within a clinico-genomic database that includes linked genomic and transcriptomic sequencing and clinical data collected during routine care.

RESULTS: Over 42 months of using a traditional approach to identify eligible patients, 1918 patients at 13 study sites were consented and screened for BASECAMP-1; of these, 30 patients with tumour-associated HLA-A*02 LOH were enrolled (~0.7 participants per month). Over the last 30 months of that same period, Tempus Aware screening was implemented and 55 patients with tumour-associated HLA-A*02 LOH were enrolled (~1.8 participants per month). The bioinformatic approach identified more patients than the traditional approach and used sequencing results produced as part of the standard clinical tumour sequencing workflow, reducing resource use and study staff burden. Additional advantages of using a screening study, such as BASECAMP-1, include manufacturing efficiencies and collection of a large dataset of molecular and clinical parameters that can be used to supplement trial analyses.

CONCLUSIONS: The BASECAMP-1 study demonstrates a clinico-genomic screening approach can more efficiently identify patients for precision oncology trials. Furthermore, precision oncology can be enhanced through collaborative data-sharing.

TRIAL REGISTRATION NUMBER: NCT04981119.},
}

@article {pmid41919503,
year = {2026},
author = {Paschalis, A and Figueiredo, I and Bogdan, D and Lundberg, A and Santos, R and Gurel, B and Taha, T and Longoria, O and Ferreira, A and Bertan, C and Brittain, N and Nelson, R and Walker, L and Neeb, A and Welti, J and Yuan, W and Mitsopoulos, C and Plymate, SR and Haffner, MC and Sowalsky, AG and Carreira, S and Sharp, A and Gaughan, L and de Bono, J},
title = {Androgen receptor splice variant 7 expression levels distinguish AR-mutated from nonmutated metastatic castration-resistant prostate cancers.},
journal = {The Journal of clinical investigation},
volume = {136},
number = {7},
pages = {},
doi = {10.1172/JCI198193},
pmid = {41919503},
issn = {1558-8238},
mesh = {Humans ; Male ; *Receptors, Androgen/genetics/biosynthesis ; *Prostatic Neoplasms, Castration-Resistant/genetics/metabolism/pathology/drug therapy ; *Mutation ; *Alternative Splicing ; Neoplasm Metastasis ; *Gene Expression Regulation, Neoplastic ; Protein Isoforms/genetics/biosynthesis ; *Neoplasm Proteins/genetics/biosynthesis ; Cell Line, Tumor ; Aged ; },
abstract = {New androgen receptor (AR) pathway inhibitors (ARPIs) in clinical development, including AR degraders and CYP11A inhibitors, largely target ligand-dependent AR activation and have reported antitumor activity in metastatic castration-resistant prostate cancer (mCRPC) resistant to established ARPIs, predominately against tumors with AR mutations. We hypothesized that AR-mutated mCRPC exhibits lower AR splice variant 7 (AR-V7) expression and remains full-length-AR (FL-AR) driven, explaining, in part, the antitumor activity of these AR ligand-binding domain (LBD) targeting drugs. The data herein demonstrate that mCRPC tissue biopsies with detectable AR mutations express significantly lower levels of AR-V7 protein and associate with better overall survival and enhanced sensitivity to ARPIs. This is independent of differences in the total number of global splicing events but may be related to differences in splicing factor expression between AR-mutated and nonmutated mCRPC. In conclusion, AR-mutated mCRPC frequently exhibits low AR-V7 expression, arguably explaining the enhanced sensitivity to ARPIs observed in these cancers. Consequently, AR mutation status may serve as a biomarker to predict response to AR-directed therapies.},
}

Humans
Male
*Receptors, Androgen/genetics/biosynthesis
*Prostatic Neoplasms, Castration-Resistant/genetics/metabolism/pathology/drug therapy
*Mutation
*Alternative Splicing
Neoplasm Metastasis
*Gene Expression Regulation, Neoplastic
Protein Isoforms/genetics/biosynthesis
*Neoplasm Proteins/genetics/biosynthesis
Cell Line, Tumor
Aged

@article {pmid41920173,
year = {2026},
author = {Sanchez Mendez, J and Queme, B and Fu, Y and Morrison, JL and Lewinger, JP and Kawaguchi, ES and Mi, H and Obón-Santacana, M and Moratalla-Navarro, F and Martín, V and Moreno, V and Qu, C and Huyghe, JR and Newcomb, PA and Phipps, AI and Thomas, CE and Conti, DV and Wang, J and Platz, EA and Visvanathan, K and Keku, TO and Newton, CC and Um, CY and Kundaje, A and Gunter, MJ and Dimou, N and Papadimitriou, N and van Duijnhoven, FJB and Männistö, S and Rennert, G and Wolk, A and Hoffmeister, M and Brenner, H and Tian, Y and Le Marchand, L and Bouras, E and Tsilidis, KK and Bishop, DT and Maclnnis, RJ and Buchanan, DD and Ulrich, CM and Peoples, AR and Pellatt, A and Li, L and Devall, MA and Albanes, D and Berndt, SI and Gruber, SB and Ruiz-Narvaez, E and Song, M and Drew, DA and Chan, AT and Giannakis, M and Hsu, L and Peters, U and Stern, MC and Gauderman, WJ},
title = {TGF-β-pathway-based polygenic risk score modifies the association between red meat intake and colorectal cancer risk: Application of a novel pathway-based PRS method.},
journal = {Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology},
volume = {},
number = {},
pages = {},
doi = {10.1158/1055-9965.EPI-25-1754},
pmid = {41920173},
issn = {1538-7755},
abstract = {BACKGROUND: Red and/or processed meat are established colorectal cancer (CRC) risk factors. Genome-wide association studies (GWAS) have reported over 200 variants associated with CRC risk. We used functional annotation data to identify subsets of variants within known pathways to construct pathway-based Polygenic Risk Scores (pPRS) to assess interactions with meat intake.

METHODS: A pooled sample of 30,812 cases and 40,504 CRC controls from 27 studies were analyzed. Quantiles for red and processed meat intake were constructed. 204 GWAS variants were annotated to genes with AnnoQ and assessed for overrepresentation in PANTHER-reported pathways. pPRS's were constructed from significantly overrepresented pathways. Covariate-adjusted logistic regression models evaluated interactions between pPRS and red or processed meat intake in relation to CRC risk.

RESULTS: A total of 30 variants were overrepresented in four pathways: Presenilin-Alzheimer disease, Cadherin/WNT-signaling, Gonadotropin-releasing hormone receptor, and TGF-β signaling. We found a significant interaction between TGF-β-pPRS and red meat intake (ORint = 0.95; 95% CI = 0.92-0.98; p = 0.003). When variants in the TGF-β pathway were assessed, we observed significant interactions of red meat with rs2337113 (intron SMAD7 gene, Chr18), and rs2208603 (intergenic region BMP5, Chr6) (p = 0.0005 & 0.036, respectively). There was no evidence of pPRS x red meat interactions for other pathways or with processed meat Conclusions:This pathway-based interaction analysis revealed a statistically significant interaction between variants in the TGF-β pathway and red meat consumption that impacts CRC risk.

IMPACT: These findings shed light into the possible mechanistic link between red meat consumption and CRC risk.},
}

@article {pmid41920180,
year = {2026},
author = {Thomas, CE and Loroña, NC and LaBrie, SD and Curtis, KR and Yin, H and Ma, N and Randolph, TW and Qu, C and Huyghe, JR and Thomas, S and Hsu, L and Koehne, AL and Nayemi, S and Ammar, H and Kahsai, OJ and Redwood, D and Li, CI and Li, L and Peters, U and Figueiredo, JC and Thomas, TK and Phipps, AI and Hullar, MAJ},
title = {The phylum Fusobacteriota is associated with CRC-specific mortality: Results from the Translational Research Program in Cancer Differences across Populations.},
journal = {Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology},
volume = {},
number = {},
pages = {},
doi = {10.1158/1055-9965.EPI-25-1580},
pmid = {41920180},
issn = {1538-7755},
abstract = {BACKGROUND: The microbiome is an important component of the tumor microenvironment implicated in colorectal cancer (CRC). However, its relationship with CRC-specific mortality remains unclear.

METHODS: We included 581 participants with CRC (167 African American, 176 Alaska Native, 118 Hispanic, 120 non-Hispanic White) from the Translational Research Program in Cancer Differences across Populations (TRPCDP). We sequenced the V4 region of the 16S rRNA bacterial gene using DNA extracted from formalin-fixed paraffin embedded tumors. 204 participants died of CRC and 377 did not die of CRC. Participants who died of CRC were matched to participants who did not die of CRC during follow-up by age, sex, tumor site, tumor stage, year of diagnosis, and population group. Logistic regression estimated odds ratios (ORs) and 95% confidence intervals (CIs) for associations between bacterial presence with CRC-specific mortality, adjusting for matching factors and tissue macrodissection status.

RESULTS: Individuals who died from CRC were 1.71 times as likely to have bacteria from the Fusobacteriota phylum present in their tumors (OR=1.71, 95% CI: 1.19-2.47). Associations with Fusobacteriota were strongest among African American participants (OR=2.36, 95% CI: 1.14-4.99) compared to other populations, however this different was not statistically significant (OR range = 1.05-1.38, Pinteraction = 0.697). Candidate pathways of pyruvate fermentation to acetate and lactate II and peptidoglycan biosynthesis I were associated with higher odds of CRC death.

CONCLUSIONS: Fusobacteriota was significantly associated with CRC-specific mortality with noted differences across populations.

IMPACT: This finding highlights the tumor microbiome as a candidate for further investigation into CRC outcome disparities.},
}

@article {pmid41921118,
year = {2026},
author = {Gupta, A and Till, C and LeBlanc, ML and Hershman, DL and Unger, JM},
title = {Composition of Health Care Contact Days and Mortality Prediction Among Older Adult Clinical Trial Participants.},
journal = {JCO oncology practice},
volume = {},
number = {},
pages = {OP2501182},
doi = {10.1200/OP-25-01182},
pmid = {41921118},
issn = {2688-1535},
abstract = {PURPOSE: Contact days exceeding trial protocol-mandated care may represent adverse clinical events and portend worse outcomes. Identifying patients at risk of poor outcomes could enable clinical teams to intervene early and support patients' needs.

MATERIALS AND METHODS: We linked data from 6 SWOG trials to Medicare claims. We calculated contact days (days with ambulatory, emergency department, inpatient, or facility-based care) and their composition using protocol calendars. Total contact days were delineated as protocol-mandated (planned) ambulatory or unplanned (including unplanned ambulatory v unplanned inpatient). Cox frailty landmark regression analysis was used in a random 60% training set to identify the optimal threshold (percentile) and landmark (months) for contact-day measures as the predictor based on the chi-square statistic. Candidate predictors were tested in the remaining 40% sample.

RESULTS: We included 1,429 patients (median age, 71 years, 7.6% Black, 21.4% female). In the first 3 months, among 15,301 contact days in the training set (6.4 contact days per person per month; 21.2% of total days), 4,102 (26.8%) were protocol-mandated ambulatory, and 11,199 (73.2%) were unplanned (including 7,328 [47.9%] ambulatory and 3,871 [25.3%] inpatient). The 2-month follow-up time at the 75th percentile threshold was the optimal model in the training set. In the test set, unplanned contact days, especially unplanned inpatient contact days, were associated with subsequent survival (≥1 unplanned inpatient contact days, adjusted hazard ratio, 1.25 [1.02-1.52], P = .014).

CONCLUSION: One in five trial follow-up days was a health care contact day, of which the majority were unplanned ambulatory contact days. Meaningfully decreasing contact-day burdens will require addressing uncoordinated unplanned ambulatory contact days. The low threshold (≥1 in the first 2 months) of unplanned inpatient days in predicting mortality highlights the adverse impact of any acute care use on survival.},
}

@article {pmid41921232,
year = {2026},
author = {Do, OA and Huang, LC and Tam, LT and Raub, S and Ermoian, RP and Leary, SES and Werny, DM and Ellenbogen, RG and Emerson, S and Ferreira, M and Lee, A and Ruzevick, JJ and Ronsley, RJ},
title = {Postoperative Visual Outcomes in Pediatric Craniopharyngioma: A Comparison of Endoscopic Endonasal and Transcranial Approaches.},
journal = {Journal of pediatric hematology/oncology},
volume = {},
number = {},
pages = {},
doi = {10.1097/MPH.0000000000003195},
pmid = {41921232},
issn = {1536-3678},
support = {N/A//N/A/ ; },
abstract = {OBJECTIVE: To compare postoperative visual outcomes in pediatric patients undergoing resection of craniopharyngioma via endoscopic endonasal versus transcranial craniotomy approaches.

METHODS: We retrospectively reviewed 37 pediatric patients (74 eyes) who underwent resection of histologically confirmed craniopharyngioma at a tertiary center between 1995 and 2023. Ophthalmologic evaluations included best-corrected visual acuity (VA), optic nerve findings, and visual fields. Outcomes were assessed at early, intermediate, and long-term follow-up and compared by surgical approach.

RESULTS: Twenty-five patients (68%) underwent craniotomy and 12 (32%) endoscopic resection. Preoperatively, 51% had normal vision in both eyes, while 6 were legally blind. Postoperatively, no significant differences in VA or visual fields were observed between approaches at any interval. Optic nerve pallor was somewhat more frequent in the endoscopic group, though not statistically significant. Gross total resection was achieved in 66% of endoscopic versus 34% of craniotomy cases. Most craniotomies (88%) occurred before 2015, compared with 16% of endoscopic cases.

CONCLUSIONS: Both endoscopic and transcranial approaches yielded comparable visual outcomes in pediatric craniopharyngioma surgery. Rates of gross total resection were higher in the endoscopic cohort, suggesting that surgical approach should remain anatomy-driven, with either technique capable of preserving visual function in appropriately selected patients.},
}

@article {pmid41921603,
year = {2026},
author = {Murphy, AJ and Chen, Y and Cameron, DB and Geiger, EJ and Ramsey, D and Green, DM and Howell, RM and Kieran, K and Krull, KR and Meacham, LR and Ness, KK and Oeffinger, KC and Yasui, Y and Armstrong, GT and Chow, EJ and Weldon, CB and Weil, BR},
title = {Late complications of treatment for childhood pelvic sarcoma: A report from the Childhood Cancer Survivor Study (CCSS).},
journal = {Journal of pediatric surgery},
volume = {},
number = {},
pages = {163117},
doi = {10.1016/j.jpedsurg.2026.163117},
pmid = {41921603},
issn = {1531-5037},
abstract = {OBJECTIVE: Evaluate late effects in survivors of childhood pelvic sarcoma by disease origin (bony vs. soft-tissue) and local control modality (bone surgery, pelvic organ resection, radiotherapy).

METHODS: Among 5-year pediatric pelvic sarcoma survivors, we assessed long-term outcomes including late (>5 years) mortality, graded chronic health conditions (CHCs), subsequent malignant neoplasms (SMNs), physical function/activity, cancer-related pain, and pregnancy/siring a pregnancy. Associations with disease origin and local control modality were analyzed using cumulative incidence and Cox or multivariable logistic regression.

RESULTS: Among 745 eligible survivors, the 35-year cumulative incidence of late all-cause and health-related mortality was 25.7% (95%CI=22.1%-29.3%) and 12.2% (95%CI=9.4%-15.1%), vs. 2.5% (95%CI=1.3%-3.7%) and 1.4% (95%CI=0.5%-2.4%) in matched US population. Cumulative incidence of severe/life-threatening CHCs was 47.6% (95%CI=43.0%-52.1%) for survivors vs. 12.2% (95%CI=11.3%-13.2%) for siblings. Cumulative incidence of SMNs was 7.6% (95%CI=5.0%-10.2%). Bone sarcomas were associated with increased all-cause mortality (HR=1.92, 95%CI=1.16-3.17), health-related mortality (HR=2.12, 95%CI=1.03-4.38), and CHCs (HR=2.55, 95%CI=1.65-3.95) vs. soft-tissue sarcomas. Analyzing all survivors, radiotherapy was associated with increased CHCs (HR=2.42, 95%CI=1.53-3.81), multiple CHCs (HR=2.27, 95%CI=1.03-4.97), functional impairment (OR=2.21, 95%CI=1.30-3.74), and pain (OR=2.29, 95%CI=1.33-3.93). Bone surgery was associated with functional impairment (OR=2.64, 95%CI=1.30-5.37), performance limitations (OR=2.12, 95%CI=1.19-3.79), and pain (OR=2.59, 95%CI=1.37-4.89). Pelvic organ resection was associated with decreased pregnancy (OR=0.25, 95%CI=0.10-0.63).

CONCLUSIONS: Late effects differed by pelvic sarcoma origin (bone vs. soft-tissue) and local control modality. The associations between local control choices and late effects in this study can guide counseling of patients and families at the time of diagnosis, treatment, local control, or after completion of therapy.

CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT01120353.},
}

@article {pmid41921744,
year = {2026},
author = {Hoobler, R and Tabung, FK and Lin, T and Gigic, B and Smith, KS and Woodruff, K and Crowder, SL and Hardikar, S and Byrd, DA and Coletta, AM and Sanchez, A and Chaix, A and Greathouse, KL and Ilozumba, MN and Ose, J and Damerell, V and Strehli, I and McLaws, M and Florou, V and Huang, LC and Shibata, D and Figueiredo, JC and Toriola, AT and Li, CI and Ulrich, CM and Playdon, MC},
title = {Dietary patterns associated with weight loss among patients with colorectal cancer during the first six months post-diagnosis: A cross-sectional analysis from the ColoCare Study.},
journal = {Journal of the Academy of Nutrition and Dietetics},
volume = {},
number = {},
pages = {156351},
doi = {10.1016/j.jand.2026.156351},
pmid = {41921744},
issn = {2212-2672},
abstract = {BACKGROUND: Unintentional weight loss following a cancer diagnosis is associated with increased risk of adverse clinical outcomes. Nutritional guidance for the prevention of weight loss post-cancer diagnosis is limited, particularly regarding optimal dietary patterns.

OBJECTIVE: To identify common dietary patterns among a cohort of patients with colorectal cancer (CRC) and evaluate their associations with weight loss in the six-months following CRC diagnosis.

DESIGN: A cross-sectional analysis of data from CRC patients enrolled in the ColoCare Study between 2010 to 2021.

PARTICIPANTS: /setting: 405 patients newly diagnosed with CRC from four study sites located in Washington, Utah, Missouri, and Los Angeles. Included participants completed a six-month Food Frequency Questionnaire and had self-reported weight data from study enrollment to six months.

MAIN OUTCOME MEASURES: The primary outcome was weight loss ≥5% from study enrollment to six-month follow-up visit.

Principal Component Analysis was leveraged to identify common dietary patterns and Healthy Eating Index (HEI)-2020 scores were calculated as a reference dietary pattern. Associations between adherence to dietary patterns (scaled to compare the 90th versus 10th percentile) and six-month weight loss were evaluated using multivariable logistic regression. All tests were two-sided.

RESULTS: Four dietary patterns were identified: "Western," "Prudent," "Refined Grain, Sugar, and Dairy," and "High-Fat, High-Protein Foods." High compared to low adherence to the "Refined Grain, Sugar, and Dairy" dietary pattern was associated with greater odds of weight loss in the first six-months following CRC diagnosis (OR = 2.04, 95% CI 1.10-3.81, p = 0.02). There was evidence for effect modification by cancer type and history of unintentional weight loss at study enrollment.

CONCLUSION: These results highlight the potential for dietary patterns to influence weight loss in the first six months following a cancer diagnosis. Further research is needed to refine dietary guidance for CRC patients to improve clinical outcomes.},
}

@article {pmid41922350,
year = {2026},
author = {Zwimpfer, TA and Fereday, S and Pandey, A and Ariyaratne, D and Jayawardana, MW and Twomey, L and Laumont, CM and Kennedy, CJ and Bolithon, A and Meagher, NS and Milne, K and Hamilton, P and Alsop, J and Antoniou, AC and Au-Yeung, G and Beckmann, MW and Berrington de Gonzalez, A and Bisinotto, C and Blome, F and Bodelon, C and Boros, J and Brand, AH and Carney, ME and Cazorla-Jiménez, A and Chiu, DS and Christie, EL and Chudecka-Głaz, A and Coulson, P and Cushing-Haugen, KL and Cybulski, C and Darcy, KM and David, C and Davidson, T and Ekici, AB and Elishaev, E and Emons, J and Engler, T and Farrell, R and Fischer, A and García-Closas, M and Gentry-Maharaj, A and Ghatage, P and Glasspool, R and Harter, P and Hartkopf, AD and Hartmann, A and Heikaus, S and Hernandez, BY and Hettiaratchi, A and Heublein, S and Huntsman, DG and Jimenez-Linan, M and Jones, ME and Kang, E and Kaznowska, E and Kluz, T and Kommoss, FKF and Konecny, G and Kruitwagen, RFPM and Kwon, J and Lambrechts, D and Lee, CH and Lester, J and Leung, SCY and Leung, Y and Linder, A and Lissowska, J and Loverix, L and Lubiński, J and Mateoiu, C and McNeish, IA and Moubarak, M and Nelson, GS and Nevins, N and Olawaiye, AB and Olbrecht, S and Orsulic, S and Osorio, A and Quinn, CM and Mohan, GR and Ray-Coquard, I and Rodríguez-Antona, C and Roxburgh, P and Ruebner, M and Salfinger, SG and Samra, S and Schoemaker, MJ and Sinn, HP and Sonke, GS and Steele, L and Stewart, CJR and Talhouk, A and Tan, A and Tarney, CM and Taylor, SE and Van de Vijver, KK and van der Aa, MA and Van Gorp, T and Van Nieuwenhuysen, E and Van-Wagensveld, L and Wahner-Hendrickson, AE and Walter, C and Wang, C and Welz, J and Wentzensen, N and Wilkens, LR and Winham, SJ and Winterhoff, B and Anglesio, MS and Berchuck, A and Candido Dos Reis, FJ and Cohen, PA and Conrads, TP and Crowe, P and Doherty, JA and Fasching, PA and Fortner, RT and García, MJ and Gayther, SA and Goodman, MT and Gronwald, J and Harris, HR and Heitz, F and Horlings, HM and Karlan, BY and Kelemen, LE and Larry Maxwell, G and Menon, U and Modugno, F and Neuhausen, SL and Schildkraut, JM and Staebler, A and Sundfeldt, K and Swerdlow, AJ and Vergote, I and Wu, AH and Brenton, JD and Pharoah, PDP and Pearce, CL and Pike, MC and Goode, EL and Ramus, SJ and Köbel, M and Nelson, BH and DeFazio, A and Friedlander, ML and Bowtell, DDL and Garsed, DW},
title = {Clinicopathologic and molecular predictors of survival in BRCA-deficient tubo-ovarian high-grade serous carcinoma.},
journal = {Nature communications},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41467-026-71134-3},
pmid = {41922350},
issn = {2041-1723},
support = {GNT1186505, GNT2029088, 2009840, 2033042//Department of Health | National Health and Medical Research Council (NHMRC)/ ; 0297//Gottfried und Julia Bangerter-Rhyner-Stiftung (Bangerter-Stiftung)/ ; MCRF22018//Victorian Cancer Agency (VCA)/ ; 2025/OCRF0071//Ovarian Cancer Research Foundation (OCRF)/ ; },
abstract = {BRCA-associated homologous recombination deficiency (HRD) is present in ~50% of high-grade serous carcinomas (HGSC) and predicts sensitivity to platinum-based therapy. However, there is little understanding of why some patients with BRCA-deficient tumors experience poor outcomes. In a large HGSC cohort (n = 1389) including 282 individuals with pathogenic germline BRCA variants (gBRCApv), residual disease after primary surgery has limited prognostic effect in gBRCApv-carriers compared to non-carriers, and prognostic outcomes differ based on the mutation location within functional domains of the BRCA genes. Multi-omic profiling is performed on 154 tumors, enriched for patients with BRCA-deficient tumors that experienced short overall survival (≤ 3 years, n = 42). Patients with BRCA2-deficient HGSC and loss of NF1 survive twice as long as those without NF1 loss, whereas PIK3CA, RAD21 and MYC amplification define BRCA2-deficient HGSC with exceptionally short survival. Patients with BRCA1-deficient HGSC and a more elevated HRD score survive significantly longer. BRCA1-deficient tumors in short survivors have evidence of immunosuppressive c-kit signaling and EMT. Our findings confirm that outcome is not determined by BRCA status alone, but rather a combination of co-occurring genomic alterations, the extent of DNA repair deficiency, and the tumor-immune microenvironment.},
}

@article {pmid41922703,
year = {2026},
author = {Aczel, B and Szaszi, B and Clelland, HT and Kovacs, M and Holzmeister, F and van Ravenzwaaij, D and Schulz-Kümpel, H and Hoffmann, S and Nilsonne, G and Kosa, L and Torma, ZA and Abdelfatah, Y and Aberson, CL and Acar, OA and Acem, E and Adamkovic, M and Adamovich, T and Adiasto, K and Ahnström, L and Akil, AM and Al-Busaidi, AS and Al-Hoorie, AH and Albers, CJ and Allen, PJ and Alsalti, T and Altman, M and Alzahawi, S and Ambrosini, E and Anafinova, S and Anand, R and Angerer, M and Angulo-Brunet, A and Antonietti, A and Arato, J and Arenas, A and Aviña, MM and Azevedo, F and Bachl, M and Bago, B and Bahník, Š and Baker, BJ and Balayan, E and Baldwin, CL and Banai, B and Banas, K and Bartoš, F and Baskin, E and Bastiaansen, JA and Bault, N and Bauman, CW and Beazer, QH and Behnke, M and Bendixen, T and Berger, S and Bernard, A and Bernardic, U and Bloom, PA and Boldt, A and Bosch-Rosa, C and Botvinik-Nezer, R and Bouyamourn, A and Bozkurt, O and Brehm, L and Breuer, J and Briggs, R and Brohmer, H and Buchanan, E and Buckenmaier, J and Buckley, J and Buczny, J and Burghart, M and Butt, BH and Byrd, N and Cafarelli, V and Callahan, P and Capitán, T and Carriere, K and Cataldo, AM and Cepaluni, G and Chan, E and Chandler, JJ and Chang, CC and Chen, X and Chen, SS and Chen, F and Chen, H and Chirkov, V and Cialfi, D and Clarke, B and Coelho, SG and Cohen, C and Collins, J and Cook, SW and Corlazzoli, G and Cummins, J and Czymara, C and D'hondt, J and Rosa, AD and Davis, AMB and Davis, CP and Day, MV and De Keyzer, F and de Leeuw, JR and de Vries, TR and Debnath, R and Dechterenko, F and Demiral, EE and Desgroseilliers, M and Dianovics, D and Diveica, V and Dochow-Sondershaus, S and Dohle, S and Dong, L and Dora, J and Dorrough, AR and Dreber, A and Du, H and Edlund, JE and Eerland, A and Efendić, E and Elder, J and Elsherif, MM and Ernst, M and Estrada, E and Eudave, L and Evans, TR and Farrera, A and Ferrouhi, EM and Fiala, L and Fialho, FM and Fiechter, JL and Fišar, M and Flores-Kanter, PE and Folwarczny, M and Fossum, JL and Franco, VR and Freichel, R and Freire, D and Frese, J and Furnas, AC and Gaebler, JD and Gajary, LC and Galang, CM and Ganschow, B and Garrison, SM and Gasiorowska, A and Ponne, BG and Gauriot, R and Geminiani, A and Geraldes, D and Gernsbacher, MA and Giani, C and Glerean, E and Gligorić, V and Gnambs, T and Godefroidt, A and González-Bustamante, B and Goreis, A and Graf-Vlachy, L and Grieder, M and Grigoryev, D and Grinschgl, S and Grüning, DJ and Guassi Moreira, JF and Guichet, C and Gurgand, L and Habibnia, H and Hafenbrack, AC and Hafenbrädl, S and Häffner, C and Hagemeister, F and Haigh, M and Hajdu, N and Hajimoladarvish, N and Hall, JD and Hamjediers, M and Hardwick, RM and Harma, M and Harp, NR and Hartvig, ÁD and Heiberger, RH and Heim, A and Hernæs, Ø and Hernaus, D and Heyman, T and Hicks, J and Hogeveen, J and Höpler, J and Houlihan, SD and Huber, C and Hughes, C and Hummler, T and Huth, K and Ingendahl, M and Ishii, T and Isler, O and Izydorczak, K and Jackson, IR and Jahn, A and Jain, M and Jakubow, A and Jang, D and Jang, J and Jekel, M and Jia, F and Jiménez-Leal, W and Johnson, R and Jones, A and Jungkunz, S and Kačmár, P and Kaiser, C and Kalaycı, Y and Kantorowicz, J and Karabulut, A and Karch, JD and Karimi-Rouzbahani, H and Karl, JA and Kažemekaitytė, A and Kazlou, A and Kekecs, Z and Kim, J and Kirchler, MH and Kiss-Dobronyi, B and Klasmeier, KN and Klein, JW and Koba, C and Kołczyńska, M and Kolias, P and Kolouch Grabovský, M and Korbmacher, M and Korda, Ž and Kowal, M and Kretzschmar, A and Krivoshchekov, V and Krypotos, AM and Kubsch, M and Kunisato, Y and Lacko, D and Landwehr, JR and Lange, M and Lee, H and Lee, D and Lee, S and Lemay, EP and Lempert, D and Leo, A and Lesage, E and Levin, JM and Li, P and Lin, J and Lindsay, L and Lisovoj, D and Liu, M and Liu, S and Liu, T and Iacono, SL and Lodder, P and López-Bueno, R and Lopez-Nicolas, R and Loter, K and Lou, NM and Lovakov, A and Lu, JG and Ludwig, J and Luebber, F and Lukavský, J and Luo, CQ and Lyu, X and Maassen, E and Máčel, M and Mack, ML and Madan, CR and Mädebach, A and Maffly-Kipp, J and Mallinson, DJ and Marchetti, I and Marghetis, T and Marini, MM and Fages, DM and Martínez, M and Martinoli, M and Masiliunas, A and Massoni, S and Mathieu, KC and Mayer, S and Mayer, DJ and Mayer, M and McCormick, EM and McDonough, IM and McGowan, AL and McIntyre, MM and McKee, P and Meier, AN and Meier, PF and Melero, H and Merkle, C and Merz, R and Michaelides, MP and Michaelsen, P and Mikolajczak, G and Mill, W and Millroth, P and Miroshnik, KG and Misiak, M and Mora, YL and Moreau, D and Moreh, C and Morvinski, C and Mushtaq, F and Nagy, T and Nater, C and Naumann, E and Navarrete, G and Nebe, S and Nedderhoff, A and Nennstiel, R and Neugebauer, M and Nicolaisen-Sobesky, E and Nielsen, YA and Niso, G and Nowak, B and Okan, M and Ong, K and Onicas, AI and Oswald, C and Otten, K and Pandey, S and Pantazi, M and Papale, P and Pärnamets, P and Pauer, S and Pavlov, YG and Pawel, S and Peelle, JE and Peetz, HK and Peez, A and Pesciarelli, F and Peterson, BD and Petruželka, B and Petter, J and Pfänder, J and Pfuhl, G and Phillips, J and Pietryka, MT and Pirrone, A and Pit, IL and Plachti, A and Plank, IS and Ploner, M and Poldrack, RA and Pollmann, MMH and Porcher, S and Präg, P and Pua, AAY and Pugel, J and Puri, R and Püski, M and Radkani, S and Raes, L and Rafaï, I and Raiber, K and Rathje, S and Rehms, R and Reshetnikov, M and Reynolds, CJ and Reynolds, JP and Rigaud, K and Rioux, C and Rivera, S and Robertson, O and Román-Caballero, R and Ropovik, I and Röseler, L and Ross, RM and Rotella, A and Rüffer, FF and Rusche, F and Rusconi, M and Russo, I and Sahm, AHJ and Salamon, J and Samahita, M and Sanaei, A and Sangchooli, A and Sarafoglou, A and Scandola, M and Schaak, H and Schaerer, M and Schares, E and Schilling, HT and Schmalz, X and Schmidt, K and Schonberg, T and Schreiner, MR and Schröder, JM and Schubert, AL and Schuetze, B and Schultz, DH and Schulze, L and Schwartz, ST and Schwitter, N and Scoggins, B and Seetahul, Y and Seri, R and Shanks, DR and Shaw, ST and Shaw, J and Shen, Q and Siemroth, C and Sladekova, M and Somo, A and Sondhi, A and Sonmez, B and Spantig, L and Speekenbrink, M and Stamos, A and Stasielowicz, L and Steckermeier, LC and Steinkamp, SR and Stoevenbelt, AH and Street, CNH and Suchow, JW and Sunde, HF and Sundquist, J and Suschevskiy, V and Swain, SD and Szecsi, P and Szekely-Copîndean, RD and Szumowska, E and Tacconelli, A and Talbert, E and Tang, JP and Tendeiro, JN and Testori, M and Toffalini, E and Tomašević, A and Topel, S and Torkkeli, L and Tozzi, L and Traczyk, J and Trinidad, A and Trübutschek, D and Turek, K and Uhlich, M and Uhlmann, EL and Urbanska, K and Van Assche, J and van Assen, MALM and van Dongen, NNN and van Lieshout, K and van Veldhuizen, R and Varga, MA and Vaughn, LA and Venczel, F and Vezzoli, M and Vierus, P and Visalli, A and Voldal, E and Votta, F and Wagenmakers, EJ and Waldendorf, A and Walker, MJ and Wall, MB and Wallen, H and Wang, K and Wang, I and Wang, YA and Weinmann, M and Weiß, M and Westheide, C and Wichman, A and Wilcke, JC and Williams, BJ and Wisniewski, D and Woiczyk, TKA and Woźniak, M and Wright, JD and Youyou, W and Wulff, JN and Yang, T and Yeung, SK and Yuen, KSL and Zawistowski, M and Zein, RA and Zhao, X and Zheng, Z and Zhou, S and Ziller, C and Zimmerman, D and Zogmaister, C and Zultan, R and Fox, N and Errington, TM and Nosek, BA},
title = {Investigating the analytical robustness of the social and behavioural sciences.},
journal = {Nature},
volume = {652},
number = {8108},
pages = {135-142},
pmid = {41922703},
issn = {1476-4687},
mesh = {*Social Sciences/standards/statistics & numerical data/methods ; *Behavioral Sciences/standards/statistics & numerical data ; Reproducibility of Results ; Humans ; *Research Design/standards ; *Behavioral Research/standards ; },
abstract = {The same dataset can be analysed in different justifiable ways to answer the same research question, potentially challenging the robustness of empirical science[1-3]. In this crowd initiative, we investigated the degree to which research findings in the social and behavioural sciences are contingent on analysts' choices. We examined a stratified random sample of 100 studies published between 2009 and 2018, in which, for one claim per study, at least five reanalysts independently reanalysed the original data. The statistical appropriateness of the reanalyses was assessed in peer evaluations, and the robustness indicators were inspected along a range of research characteristics and study designs. We found that 34% of the independent reanalyses yielded the same result (within a tolerance region of ±0.05 Cohen's d) as the original report; with a four times broader tolerance region, this indicator increased to 57%. Of the reanalyses conducted, 74% reached the same conclusion as the original investigation, 24% yielded no effects or inconclusive results and 2% reported the opposite effect. This exploratory study indicates that the common single-path analyses in social and behavioural research should not be simply assumed to be robust to alternative analyses[4]. Therefore, we recommend the development and use of practices to explore and communicate this neglected source of uncertainty.},
}

*Social Sciences/standards/statistics & numerical data/methods
*Behavioral Sciences/standards/statistics & numerical data
Reproducibility of Results
Humans
*Research Design/standards
*Behavioral Research/standards

@article {pmid41822160,
year = {2026},
author = {Lu, SZ and Vermani, A and Sanno, K and Lu, J and Matsen, FA and Jagota, M and Song, YS},
title = {Conditionally Site-Independent Neural Evolution of Antibody Sequences.},
journal = {ArXiv},
volume = {},
number = {},
pages = {},
pmid = {41822160},
issn = {2331-8422},
abstract = {Common deep learning approaches for antibody engineering focus on modeling the marginal distribution of sequences. By treating sequences as independent samples, however, these methods overlook affinity maturation as a rich and largely untapped source of information about the evolutionary process by which antibodies explore the underlying fitness landscape. In contrast, classical phylogenetic models explicitly represent evolutionary dynamics but lack the expressivity to capture complex epistatic interactions. We bridge this gap with COSINE, a continuous-time Markov chain parameterized by a deep neural network. Mathematically, we prove that COSINE provides a first-order approximation to the intractable sequential point mutation process, capturing epistatic effects with an error bound that is quadratic in branch length. Empirically, COSINE outperforms state-of-the-art language models in zero-shot variant effect prediction by explicitly disentangling selection from context-dependent somatic hypermutation. Finally, we introduce Guided Gillespie, a classifier-guided sampling scheme that steers COSINE at inference time, enabling efficient optimization of antibody binding affinity toward specific antigens.},
}

@article {pmid41913502,
year = {2026},
author = {Dussault, N and Morphew, J and Nwagwu, V and Gatta, B and Richardson, A and Payne, N and White-Chu, EF and Wilson, L and Dalton, H and Winstead-Derlega, CE and Ramos, K and Jones, CA},
title = {Top Ten Tips Palliative Care Clinicians Should Know About Wound Care.},
journal = {Journal of palliative medicine},
volume = {},
number = {},
pages = {10966218261436630},
doi = {10.1177/10966218261436630},
pmid = {41913502},
issn = {1557-7740},
abstract = {Wounds are a common and burdensome problem for patients with serious illness receiving palliative care and hospice services. Declining mobility, functional impairment, malnutrition, progression of underlying disease, and age-related skin changes all increase risk. Wound management can therefore be challenging for clinicians, patients, and caregivers. Symptoms such as pain, odor, drainage, functional limitations, and psychological distress can substantially worsen suffering. Optimal care requires an interdisciplinary approach that considers the patient's underlying illness, prognosis, and goals of care. Palliative care clinicians are well-positioned to reduce this distress and improve comfort through goal-concordant wound-care strategies. Given the high prevalence of wounds in palliative care populations and the need for skilled, patient-centered management, we convened a panel of palliative care clinicians, geriatricians, geropsychologists, and wound-care specialists to identify core principles and practical strategies for supporting patients with wounds. In this article, we outline key tips for assessing and managing wounds, including understanding prognosis and goals of care, evaluating care settings, tailoring management to the underlying disease process, and addressing symptoms such as pain, odor, and psychosocial distress. A thoughtful, interdisciplinary approach is essential to reduce the physical and emotional burden wounds place on patients and caregivers.},
}

@article {pmid41914866,
year = {2026},
author = {Ghodsi, A and Owens, L and Demirci, RA and Gafita, A and Cheng, HH and Hawley, JE and Raychaudhuri, R and Khan, H and Sunkara, R and Hsieh, AC and Grivas, P and Montgomery, B and Yezefski, TA and Nelson, PS and Yu, EY and Schweizer, MT and Chen, DL and Gulati, R and Iravani, A},
title = {PSMA PET/CT-derived Tumor Volume for Predicting Outcomes in Patients with Metastatic Castration-Resistant Prostate Cancer Receiving [177]Lu-PSMA-617.},
journal = {Radiology},
volume = {318},
number = {3},
pages = {e250649},
doi = {10.1148/radiol.250649},
pmid = {41914866},
issn = {1527-1315},
mesh = {Humans ; Male ; *Prostatic Neoplasms, Castration-Resistant/pathology/diagnostic imaging/radiotherapy ; *Positron Emission Tomography Computed Tomography/methods ; Aged ; *Lutetium/therapeutic use ; *Heterocyclic Compounds, 1-Ring/therapeutic use ; *Dipeptides/therapeutic use ; Tumor Burden ; Middle Aged ; Radiopharmaceuticals/therapeutic use ; Retrospective Studies ; Prostate-Specific Antigen ; Predictive Value of Tests ; Treatment Outcome ; Radioisotopes/therapeutic use ; },
abstract = {Background Accurate prediction of the response of patients with metastatic castration-resistant prostate cancer (mCRPC) to lutetium 177 prostate-specific membrane antigen-617 (Lu-PSMA) therapy would be helpful for treatment selection. Purpose To evaluate the incremental value of total tumor volume (TTV) in prediction models developed for patients receiving Lu-PSMA. Materials and Methods Previously developed prediction models using baseline variables (time since diagnosis, chemotherapy status, hemoglobin, dichotomized number of metastases, tumor mean standardized uptake value, and bone and liver involvement) were externally validated in patients treated with Lu-PSMA between June 2022 and April 2024. The concordance index (ie, C index) for overall survival (OS), prostate-specific antigen (PSA) progression-free survival (PSA-PFS), and 50% or greater decline in PSA from baseline (PSA50) was assessed. The predictive value of prostate-specific membrane antigen PET/CT-derived TTV was evaluated by re-estimating previous models (Cox regression for OS and PSA-PFS; logistic regression for PSA50) and replacing the dichotomized number of metastases with the continuous number of metastases or TTV. Results Data from 168 patients (median age, 73 years [IQR, 68-78 years]) were analyzed. External validation of the original models achieved C indexes of 0.70 (95% CI: 0.64, 0.77) for OS, 0.68 (95% CI: 0.63, 0.73) for PSA-PFS, and 0.72 (95% CI: 0.64, 0.80) for PSA50. Replacing the dichotomized number of metastases with TTV increased the C index for OS by 0.04 (95% CI: 0.01, 0.07; P = .002). A higher TTV was associated with shorter OS (hazard ratio, 1.35 [95% CI: 1.08, 1.68]), whereas there was no evidence of an independent association between dichotomized number of metastases and OS (hazard ratio, 1.23 [95% CI: 0.64, 2.36]; P = .53). A higher TTV was associated with shorter PSA-PFS (hazard ratio, 1.25 [95% CI: 1.10, 1.42]) and lower PSA50 (odds ratio, 0.70 [95% CI: 0.53, 0.91]). Conclusion Previously developed models predicted OS, PSA-PFS, and PSA50 in patients with mCRPC receiving Lu-PSMA. The inclusion of TTV produces prediction models with better discriminatory ability than the dichotomized or continuous number of metastases. © RSNA, 2026 Supplemental material is available for this article. See also the editorial by Vargas and Woo in this issue.},
}

Humans
Male
*Prostatic Neoplasms, Castration-Resistant/pathology/diagnostic imaging/radiotherapy
*Positron Emission Tomography Computed Tomography/methods
Aged
*Lutetium/therapeutic use
*Heterocyclic Compounds, 1-Ring/therapeutic use
*Dipeptides/therapeutic use
Tumor Burden
Middle Aged
Radiopharmaceuticals/therapeutic use
Retrospective Studies
Prostate-Specific Antigen
Predictive Value of Tests
Treatment Outcome
Radioisotopes/therapeutic use

@article {pmid41915825,
year = {2026},
author = {Srinivasan, S and Munch, MM and Soge, OO and Sweeney, YTC and Proll, S and Hoffman, NG and Fredricks, DN and Patton, DL},
title = {The Vaginal Microbiota in Pig-Tailed Macaques and Colonization with Neisseria gonorrhoeae.},
journal = {Sexually transmitted diseases},
volume = {},
number = {},
pages = {},
doi = {10.1097/OLQ.0000000000002314},
pmid = {41915825},
issn = {1537-4521},
abstract = {BACKGROUND: Pig-tailed macaques (Macaca nemestrina) may serve as a useful animal model of Neisseria gonorrhoeae (GC) infection, but no such models are currently available. To aid in the development of a macaque model of gonorrhea, we characterized the macaque vaginal microbiota and evaluated the effect of streptomycin treatment on GC colonization.

METHODS: Six female pig-tailed macaques were observed for 96 days with cervicovaginal samples collected every 2-3 days. Samples were taken for one month prior to streptomycin treatment to characterize the vaginal microbiota using 16S rRNA gene sequencing over a menstrual cycle. The animals were treated intramuscularly with streptomycin for 22 days. They were challenged twice with a two-week interval with endocervical GC and once after cessation of antibiotics. GC colonization was assessed via 16S rRNA gene sequencing, nucleic acid amplification tests, and culture.

RESULTS: The macaque vaginal microbiota was diverse and heterogeneous with several anaerobes typically noted in the human vagina including Fannyhessea vaginae, Amygdalobacter indicium and Parvimonas micra. Streptomycin treatment resulted in changes in the diversity and composition of the microbiota, but prolonged GC colonization was not achieved in any animal. Changes in the microbiota were noted during menses.

CONCLUSIONS: Alternative approaches are needed to facilitate the establishment of GC infection in pig-tailed macaques.},
}

@article {pmid41542557,
year = {2026},
author = {Ahn, JJ and Yu, TC and Dadonaite, B and Radford, CE and Bloom, JD},
title = {Influenza hemagglutinin subtypes have different sequence constraints despite sharing extremely similar structures.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {41542557},
issn = {2692-8205},
support = {P30 CA015704/CA/NCI NIH HHS/United States ; S10 OD028685/OD/NIH HHS/United States ; 75N93021C00015/AI/NIAID NIH HHS/United States ; S10 OD020069/OD/NIH HHS/United States ; R01 AI165821/AI/NIAID NIH HHS/United States ; },
abstract = {Hemagglutinins (HA) from different influenza A virus subtypes share as little as ~40% amino acid identity, yet their protein structure and cell entry function are highly conserved. Here we examine the extent that sequence constraints on HA differ across three subtypes. To do this, we first use pseudovirus deep mutational scanning to measure how all amino-acid mutations to an H7 HA affect its cell entry function. We then compare these new measurements to previously described measurements of how all mutations to H3 and H5 HAs affect cell entry function. We find that ~50% of HA sites display substantially diverged preferences for different amino acids across the HA subtypes. The sites with the most divergent amino-acid preferences tend to be buried and have biochemically distinct wildtype amino acids in the different HA subtypes. We provide an example of how rewiring the interactions among contacting residues has dramatically shifted which amino acids are tolerated at specific sites. Overall, our results show how proteins with the same structure and function can become subject to very different site-specific evolutionary constraints as their sequences diverge.},
}

@article {pmid41867175,
year = {2026},
author = {Hall, M and Probert, W and Abeler-Dörner, L and Wymant, C and Di Lauro, F and Xi, X and Sauter, R and Golubchik, T and Bonsall, D and Pickles, M and Cori, A and Bwalya, J and Floyd, S and Mandla, N and Shanaube, K and Yang, B and Bock, P and Donnell, D and Grabowski, MK and Pillay, D and Ratmann, O and Fidler, S and Ayles, H and Hayes, R and Fraser, C and , },
title = {The age and sex dynamics of heterosexual HIV transmission in Zambia: an HPTN 071 (PopART) phylogenetic and modelling study.},
journal = {medRxiv : the preprint server for health sciences},
volume = {},
number = {},
pages = {},
pmid = {41867175},
abstract = {While much progress has been made in reducing the incidence of HIV-1 infection in sub-Saharan Africa in recent years, bringing the epidemic to an end will require identification of the demographic groups that continue to contribute to transmission. Pathogen phylogenetics and individual-based mathematical models (IBMs) of transmission are approaches that enable researchers to explore such questions. Here, we used both methods to characterise the ages and sexes of the individuals involved in heterosexual transmission in the context of the HPTN 071 (PopART) trial in Zambia. The two methods produced largely concordant results, strengthening confidence in both. A principal finding was that when the age gap in transmission (the difference of ages between the two individuals) was stratified by recipient age, the largest differences were for the youngest female recipients and the smallest for the youngest males. For women under 21 this stood at a male 9.87 years older (95% CI: 8.02 - 11.59) in the phylogenetics, compared to 6.93 (95% HDI: 6.56 - 7.32) in the IBM. As the age of female recipients increased, this gap decreased towards parity. Conversely, the under-21 male recipients saw the smallest gaps with the female older by 0.14 years (95% CI: -2.95 - 3.23) in the phylogenetics and 1.38 years (95% HDI: 0.98 - 1.68) in the IBM. As the age of male recipients decreased, this gap steadily increased. The consequence of this pattern is that transmission to new age cohorts first entering into sexual activity is driven predominantly by male-to-female transmission. We also showed that targeting interventions at younger adults captures most of the benefit of population-wide approaches. We used the IBM to simulate the PopART universal testing and treatment intervention into the future, showing that effective treatment of under-35-year-olds would account for 94.3% (95% HDI: 65.8% - 126.6%) of the reduction in incidence by 2039 that would be achieved by treating the entire population, while effective treatment of under-35 men accounts for 60% (95% HDI: 23.2% - 92.1%). Finally, we simulated a one-year cessation of ART treatment for the whole population, which resulted in an immediate increase in both incidence and the average age at transmission of both sources and recipients. The magnitude of this was 4.6 years (95% HDI: 2.17 - 6.24) for female recipients, 5.3 (95% HDI: 2.74 - 7.09) for male recipients, 5.24 (95% HDI: 2.78 - 6.97) for female sources, and 6.04 (95% HDI: 2.92 - 8.09) for male sources. These changes would be slow to reverse even after ART was restored. These findings indicate that substantial reductions in HIV incidence can be achieved through intensified testing and treatment of individuals aged under 35, and in particular young men, a group that drives the infection of younger women and for whom engagement with care remains disproportionately low.},
}

@article {pmid41908584,
year = {2026},
author = {Kumar, S and Jiang, J and Donald-Paladino, MS and Chen, J and Gutierrez, A and Federation, AJ and Szulzewsky, F and Holland, EC and Ferguson, FM and Nabet, B},
title = {Development of PROTACs for targeted degradation of oncogenic TRK fusions.},
journal = {RSC chemical biology},
volume = {},
number = {},
pages = {},
pmid = {41908584},
issn = {2633-0679},
abstract = {Chromosomal translocations leading to the fusion of tropomyosin receptor kinases (TRKs) with diverse partner proteins have been identified as oncogenic drivers in many adult and pediatric cancers. While first-generation TRK kinase inhibitors, such as entrectinib and larotrectinib, have shown positive responses in TRK fusion-positive cancers, resistance mutations against these inhibitors in the kinase domain limit their efficacy. Second-generation inhibitors are in clinical evaluation, highlighting a need for novel therapeutic modalities to achieve durable suppression of the oncogenic activity of TRK fusions. Here, we developed heterobifunctional small molecule degraders (PROTACs) to achieve targeted degradation of TRK fusions. By conjugating entrectinib to thalidomide, we identified JWJ-01-378 as a potent and selective cereblon (CRBN)-recruiting degrader of the TPM3-TRKA fusion. JWJ-01-378 induced TPM3-TRKA degradation through the ubiquitin-proteasome system and proteomics analysis confirmed the acute selectivity of JWJ-01-378 for achieving TPM3-TRKA degradation with minimal off-target effects. Importantly, JWJ-01-378 did not degrade CRBN neosubstrates that are targeted by existing TRK PROTACs including CG-428. While JWJ-01-378 was also able to degrade wild-type TRK, it was unable to degrade TRK inhibitor resistant mutants and ALK fusions. TPM3-TRKA degradation by JWJ-01-378 suppressed downstream signaling and reduced cancer cell viability, with improved responses compared to a heterobifunctional control compound that cannot degrade TPM3-TRKA. Together, our study expands the toolbox of selective compounds for evaluating targeted degradation of TRK fusions in diseases including cancer.},
}

@article {pmid41909516,
year = {2026},
author = {Chaturvedi, S and Nagalla, S and Kolodny, S and Oladapo, A and Bernheisel, C and Swallow, E and Goldschmidt, D and Greatsinger, A and Ormenaj, L and Sareen, S and Ruiz Lopez, JN and Vredenburg, M and Levy, MY},
title = {Real-world avatrombopag use for immune thrombocytopenia in the United States: the REAL-AVA 2.0 multisite chart review study.},
journal = {Blood vessels, thrombosis & hemostasis},
volume = {3},
number = {2},
pages = {100142},
pmid = {41909516},
issn = {2950-3272},
abstract = {The REAL-AVA 2.0 study was a retrospective multisite chart review evaluating avatrombopag (AVA) effectiveness among patients with primary immune thrombocytopenia (ITP) who underwent routine care in academic- and community-based practices in the United States and initiated AVA between 1 July 2019 and 30 June 2024. Treatment response was defined as achieving platelet counts (PC) ≥30 × 10[3]/μL, ≥50 × 10[3]/μL, or ≥100 × 10[3]/μL. The discontinuation of steroids and/or immunosuppressants after AVA initiation was evaluated. Analyses were performed in the overall population and among 2 stratified subgroups: ITP disease duration (acute, <3 months; persistent, 3-12 months; and chronic, ≥12 months) and prior thrombopoietin receptor agonists exposure status. Among the 177 patients included in the study, 90% achieved or maintained a PC ≥30 × 10[3]/μL response, 86% achieved or maintained a PC ≥50 × 10[3]/μL response, and 76% of patients achieved or maintained a PC ≥100 × 10[3]/μL response, with a median duration of response to AVA of 12.1, 12.4, and 10.0 months, respectively. The median durability of response was 96% at the PC ≥30 × 10[3]/μL threshold, 93% at the PC ≥50 × 10[3]/μL threshold, and 76% at the PC ≥100 × 10[3]/μL threshold. Almost all patients (98%) who used concomitant steroids at AVA initiation subsequently reduced the steroid dose (19%) or discontinued steroid use completely (79%), and 40% of those who used immunosuppressants discontinued them after AVA initiation. Results of the subgroup analyses were consistent with the overall sample. Findings show that AVA is an effective treatment option for patients with ITP, demonstrating durable PC response in a diverse population.},
}

@article {pmid41909709,
year = {2026},
author = {Menezes, F and Chen, S and Grunenberg, N and Malahleha, M and Mngadi, K and Muyoyeta, M and Laher, F and Chirenje, ZM and Bekker, LG and Goepfert, P and Gray, GE and Tomaras, G and McElrath, MJ and Kallas, E and Roxby, AC and Moodie, Z},
title = {AS01B-, MF59-, and alum-based adjuvants and HIV vaccine immunogenicity: a post-hoc cross-protocol comparison of results from HVTN 100, 107, 120, and 702.},
journal = {Frontiers in immunology},
volume = {17},
number = {},
pages = {1768201},
pmid = {41909709},
issn = {1664-3224},
mesh = {Humans ; *AIDS Vaccines/immunology/administration & dosage ; *Alum Compounds/administration & dosage ; Adult ; Female ; Male ; *Adjuvants, Immunologic/administration & dosage ; *HIV Infections/immunology/prevention & control ; *Squalene/administration & dosage ; *Polysorbates/administration & dosage ; *Immunogenicity, Vaccine ; Middle Aged ; HIV Antibodies/immunology/blood ; Cross-Sectional Studies ; Retrospective Studies ; *Saponins/administration & dosage ; Double-Blind Method ; *Adjuvants, Vaccine/administration & dosage ; CD4-Positive T-Lymphocytes/immunology ; *HIV-1/immunology ; Immunoglobulin G/immunology ; Young Adult ; },
abstract = {INTRODUCTION: Vaccine adjuvants are crucial in HIV vaccine development, enhancing immune responses. Immune responses generated by different adjuvanted vaccines are rarely compared directly with the same vaccine antigens.

METHODS: This retrospective cross-protocol, cross-sectional analysis examined four randomized, controlled, double-blinded, multicenter trials (HVTN 100, 107, 120, and 702) of adults without HIV who received the ALVAC-HIV (vCP2438) vaccine and a bivalent gp120 protein booster with either MF59, Alum, or AS01B adjuvant. Participants received ALVAC-HIV at months 0, 1, 3, 6, and 12, and the adjuvanted protein at months 3, 6, and 12. Data from month 6.5 were compared for IgG V1V2 binding antibodies (bAb) and CD4+ T-cell responses, measured as IFN-γ and/or IL-2 expression, using Wilcoxon and Barnard's tests with FDR p-value multiplicity adjustment. Reactogenicity and adverse event profiles were also assessed.

RESULTS: AS01B elicited higher CD4+ T cell magnitudes among positive responders than either MF59 or Alum adjuvant to the 3 antigens considered: 1086, TV1, ZM96. No statistically significant differences were observed between MF59 and Alum in CD4+ T-cell responses. Regarding IgG bAb responses, AS01B induced significantly higher magnitudes among positive responders compared to both MF59 and Alum for the C.1086C V1V2 and Con 6 gp120/B antigens. Additionally, AS01B elicited greater IgG bAb responses than MF59 for gp70-96ZM651.02 V1V2 and gp70_B.CaseA V1V2, although no significant differences were found between AS01B and Alum for these antigens. AS01B also showed a trend toward greater reactogenicity, though this difference did not reach statistical significance. Importantly, no serious adverse events occurred in any of the groups.

CONCLUSION: The AS01B adjuvant demonstrated superior IgG binding antibody and CD4+ T-cell responses compared with MF59 and Alum, when given with gp120 protein boost after ALVAC-HIV prime. These findings support AS01B as a superior adjuvant for HIV vaccine development, relative to MF59 and Alum.},
}

Humans
*AIDS Vaccines/immunology/administration & dosage
*Alum Compounds/administration & dosage
Adult
Female
Male
*Adjuvants, Immunologic/administration & dosage
*HIV Infections/immunology/prevention & control
*Squalene/administration & dosage
*Polysorbates/administration & dosage
*Immunogenicity, Vaccine
Middle Aged
HIV Antibodies/immunology/blood
Cross-Sectional Studies
Retrospective Studies
*Saponins/administration & dosage
Double-Blind Method
*Adjuvants, Vaccine/administration & dosage
CD4-Positive T-Lymphocytes/immunology
*HIV-1/immunology
Immunoglobulin G/immunology
Young Adult

@article {pmid41910996,
year = {2026},
author = {Abrams, HR},
title = {Audiences in the Electronic Medical Record.},
journal = {JAMA internal medicine},
volume = {},
number = {},
pages = {},
doi = {10.1001/jamainternmed.2026.0289},
pmid = {41910996},
issn = {2168-6114},
}

@article {pmid41911315,
year = {2026},
author = {Ortblad, KF and Wairimu, N and Culquichicon, C and Njeru, I and Malen, RC and Reedy, AM and Ekwunife, O and McGowan, M and Mwangi, M and Muthoni, A and Kiboi, D and Njoroge, S and Gao, F and Baeten, JM and Ngure, K},
title = {Effect of enhanced peer PrEP referral with HIV self-testing delivery among young Kenyan women: A randomized controlled trial of peer networks.},
journal = {PLoS medicine},
volume = {23},
number = {3},
pages = {e1005023},
doi = {10.1371/journal.pmed.1005023},
pmid = {41911315},
issn = {1549-1676},
abstract = {BACKGROUND: Adolescent girls and young women (AGYW) in Africa experience high HIV acquisition risk and low engagement in prevention services. Knowledge of HIV-negative status paired with peer support might motivate AGYW-who are highly socially connected-to initiate HIV prevention services, including pre-exposure prophylaxis (PrEP).

METHODS AND FINDINGS: We conducted a randomized controlled trial (ClinicalTrials.gov: NCT04982250) of AGYW peer networks in Central Kenya. Index peers aged 16-24 years who had used oral PrEP in the past 12 months were randomized 1:1 to: (1) enhanced peer referral: group training on PrEP referral strategies and delivery of HIV self-testing (HIVST) kits (n = 8 kits, 2 kits/peer); or (2) standard peer referral: informal PrEP referral strategies. Index peers were encouraged to refer four peers who could benefit from PrEP. Outcomes for referred peers-PrEP initiation (primary), PrEP continuation (i.e., month one refills), and HIV testing (any form following referral)-were reported by index peers three months later. Implementation outcomes and costs were also assessed. Risk differences (RDs) were estimated using generalized linear mixed-effects regression models with study group fixed effects and index peer random effects. From May 3, 2023 to February 16, 2024, 316 index peers were screened and 82 enrolled/randomized (median age 22 years, IQR 20-23): 40 to the enhanced group and 42 to the standard. No index peers were lost to follow-up. Index peers reported outcomes for 241 referred peers (median age 22 years, IQR 21-24): 137 in the enhanced group and 104 in the standard. At follow-up, there were no significant differences in PrEP initiation between the enhanced group (30%, 41/137) and the standard (41%, 41/104; RD -6%, 95% CI [-26%, 11%], p = 0.51). Enhanced peer referral was not associated with PrEP continuation (RD 1%, 95% CI [-10%, 13%], p = 0.82) but was associated with increased recent HIV testing (RD 39%, 95% CI [24%, 54%], p < 0.001). Three referred peers, all in the enhanced group, tested HIV-positive; two social harms (verbal abuse among index peers, one in each group) were reported. Index and referred peers in both study groups found enhanced peer referral acceptable and feasible, but it cost almost eight times more per peer referred to PrEP than standard referral ($23 versus $3 USD). Relying on index peers to report outcomes for referred peers was a study limitation.

CONCLUSIONS: Enhanced peer PrEP referral with training and HIVST delivery did not increase PrEP initiation among Kenyan AGYW but was associated with increased HIV testing, suggesting opportunities to combine peer-delivered HIVST with additional implementation strategies to improve AGYW's PrEP engagement.},
}

@article {pmid41912411,
year = {2026},
author = {Etzioni, R and Gogebakan, K and Gulati, R and Owens, L and Lange, J and Kessler, L and Smith, R and Schrag, D and Robbins, HA},
title = {Measuring and defining screening benefit in a new era of cancer early detection.},
journal = {Journal of the National Cancer Institute},
volume = {},
number = {},
pages = {},
doi = {10.1093/jnci/djag100},
pmid = {41912411},
issn = {1460-2105},
abstract = {We are at a watershed moment in the history of early cancer detection in which many novel tests are poised to become available for population screening. An ongoing debate concerns how to properly evaluate these tests and specifically whether a shorter-term, incidence-based outcome might substitute for cancer mortality as an endpoint in randomized trials of screening test efficacy. An incidence-based endpoint promises to reduce time and resources, but there is no framework for how studies using this endpoint should report results and how they should be interpreted in terms of clinical utility. We consider whether publication of incidence-based results ahead of any mortality results could result in adoption of new screening tests ahead of reliable mortality results becoming available. We argue that guardrails are needed for this scenario, including standards for conduct and reporting of trials with incidence-based endpoints to assure valid interpretation of clinical utility. For example, information regarding the type and timing of tests used for diagnostic workup in screen and control groups will be needed. Clinicians and policy makers will need to determine acceptable measurements and magnitudes of this modified measure of test efficacy. The roles of incidence-based and mortality-based endpoints in determining practice standards will need to be defined, along with specifications for permissible adjunct evidence, such as modeling studies and real-world data. As screening trials for new multi-cancer tests will soon begin to report incidence-based results, resolution of these questions is a matter of urgency.},
}

@article {pmid41912885,
year = {2026},
author = {Ahmad, Z and Carninci, P},
title = {Decoding the regulatory grammar of human gene promoters.},
journal = {Cell research},
volume = {},
number = {},
pages = {},
pmid = {41912885},
issn = {1748-7838},
}

@article {pmid41043723,
year = {2026},
author = {El-Serag, HB and Lopez, C and Luster, M and Reddy, KR and Parikh, N and Singal, AG and Marrero, JA and Thrift, AP and Chhatwal, J and Feng, Z and Page-Lester, S and Jin, Q and Tayob, N and Kanwal, F},
title = {HES V2.0 validation and performance compared to GALAD and ASAP in the HEDS cohort.},
journal = {Journal of hepatology},
volume = {84},
number = {3},
pages = {578-586},
pmid = {41043723},
issn = {1600-0641},
support = {U01 CA230997/CA/NCI NIH HHS/United States ; R01 CA230503/CA/NCI NIH HHS/United States ; U24 CA230144/CA/NCI NIH HHS/United States ; R01 CA190776/CA/NCI NIH HHS/United States ; P01 CA263025/CA/NCI NIH HHS/United States ; U24 CA086368/CA/NCI NIH HHS/United States ; P30 DK056338/DK/NIDDK NIH HHS/United States ; U01 CA271887/CA/NCI NIH HHS/United States ; },
mesh = {Humans ; *Carcinoma, Hepatocellular/diagnosis/blood/etiology ; *Liver Neoplasms/diagnosis/blood/etiology ; Male ; Female ; Middle Aged ; Aged ; *Liver Cirrhosis/complications/blood ; *Early Detection of Cancer/methods ; *Biomarkers, Tumor/blood ; Retrospective Studies ; alpha-Fetoproteins/analysis ; Prospective Studies ; Cohort Studies ; Sensitivity and Specificity ; },
abstract = {BACKGROUND & AIMS: We previously developed HES V2.0, a biomarker panel (age, ALT, platelets, etiology, AFP, AFP-L3, DCP, and their 1-year gradients) for early detection of hepatocellular carcinoma (HCC) among patients with cirrhosis. We externally validated HES V2.0 and compared its performance with HES V1.0, GALAD, and ASAP.

METHODS: We conducted a PRoBE (prospective specimen-collection, retrospective blinded-evaluation) cohort study in the HEDS (Hepatocellular Carcinoma Early Detection Strategy) cohort of 1,485 patients with cirrhosis, of whom 119 developed HCC. Patient- and test-level true positive rates (TPR) for HCC were calculated at 6, 12, and 24 months before diagnosis, using thresholds at a fixed false positive rate (FPR) of 10% and 18.1% (corresponding to the GALAD cut-off of -1.36).

RESULTS: HES V2.0 and GALAD had the same AUROC (0.79) but differed in TPR/FPR profiles. At 10% FPR, HES V2.0 achieved 2.0%, 6.7%, and 6.0% higher sensitivity than GALAD at 6, 12, and 24 months before HCC diagnosis (one-sided p = 0.24, 0.025, and 0.078, respectively). At 18.1% FPR, GALAD showed 6% and 2% higher sensitivity than HES V2.0 at 6 and 12 months, respectively, and similar sensitivity at 24 months (all p >0.05). HES V2.0 demonstrated 11.9% higher sensitivity than HES V1.0 at 12 months (p = 0.007) and 10.9-16.3% higher sensitivity than ASAP. In patients with the necessary laboratory data to calculate temporal gradients, HES V2.0 outperformed GALAD by 3.5-8.7% at all time points (an 8.7-24.0% relative increase; p <0.05 for several comparisons).

CONCLUSIONS: In this phase III biomarker validation study, HES V2.0 showed higher sensitivity than ASAP and comparable or superior sensitivity to GALAD, particularly at 12 months before HCC diagnosis at 10% FPR and when temporal gradients in AFP, AFP-L3, and DCP were available.

IMPACT AND IMPLICATIONS: Hepatocellular carcinoma (HCC) remains a leading cause of cancer-related mortality, with early detection being critical for improving survival outcomes. This study provides a rigorous phase III validation of the HES V2.0 biomarker panel, demonstrating its superior or comparable sensitivity to established models like GALAD and ASAP in a large, diverse cirrhosis cohort from the United States. The findings are particularly impactful for clinicians and researchers focused on liver cancer surveillance, as HES V2.0 offers enhanced detection performance, especially when longitudinal biomarker data are available. These results support the integration of HES V2.0 into clinical workflows and future trials, potentially improving early HCC detection and enabling timely curative interventions for at-risk patients.},
}

Humans
*Carcinoma, Hepatocellular/diagnosis/blood/etiology
*Liver Neoplasms/diagnosis/blood/etiology
Male
Female
Middle Aged
Aged
*Liver Cirrhosis/complications/blood
*Early Detection of Cancer/methods
*Biomarkers, Tumor/blood
Retrospective Studies
alpha-Fetoproteins/analysis
Prospective Studies
Cohort Studies
Sensitivity and Specificity

@article {pmid41043776,
year = {2026},
author = {McCurdy, SR and Solomon, SR and Shaffer, BC and He, M and Bolon, YT and Blouin, AG and Keyzner, A and Socola, FA and Ibrahim, U and Zou, J and Safah, H and Saba, N and Gadalla, S and Perales, MA and Paczesny, S and Marsh, SGE and Petersdorf, EW and Wang, T and Lee, SJ and Fuchs, EJ},
title = {Post-Transplant Cyclophosphamide Improves Survival in HLA-DPB1 Mismatched Unrelated Donor Allogeneic Transplantation.},
journal = {Transplantation and cellular therapy},
volume = {32},
number = {1},
pages = {74.e1-74.e14},
pmid = {41043776},
issn = {2666-6367},
support = {P30 CA008748/CA/NCI NIH HHS/United States ; R03 AG074068/AG/NIA NIH HHS/United States ; U24 CA076518/CA/NCI NIH HHS/United States ; },
mesh = {Humans ; *Cyclophosphamide/therapeutic use/pharmacology ; *Unrelated Donors ; Male ; Female ; *Hematopoietic Stem Cell Transplantation/methods/adverse effects/mortality ; Middle Aged ; *Graft vs Host Disease/prevention & control/etiology ; Adult ; Retrospective Studies ; *HLA-DP beta-Chains/immunology ; Transplantation, Homologous/methods ; *Immunosuppressive Agents/therapeutic use ; Adolescent ; Young Adult ; Aged ; },
abstract = {HLA-DPB1 mismatching is common in unrelated donor (URD) hematopoietic cell transplantation (HCT) and increases graft-versus-host disease (GVHD) when using methotrexate and tacrolimus (MTX/Tac)-based GVHD prophylaxis. Historically, national and international guidelines recommended prioritizing HLA-DPB1 matching in URD selection. The impact of HLA-DPB1 matching in URD HCT when using post-transplantation cyclophosphamide (PTCy) has been understudied. Our primary endpoint was the association of GVHD-prophylaxis strategy with overall survival (OS) after T cell-replete 12/12 HLA-matched or HLA-DPB1 permissive or non-permissive (NP) mismatch (MM) (defined by the T-cell-epitope groups model) URD HCT. GVHD-free, relapse-free survival (GRFS) was our key secondary endpoint. This was a retrospective cohort study using the Center for International Blood and Marrow Transplant Research (CIBMTR) database. Recipients underwent a first HCT from 2015-2020 for acute leukemia or myelodysplastic syndrome using either HLA-DPB1 NP MM (n = 329), permissive MM (n = 992), or 12/12 HLA-matched (n = 300) URD with PTCy ± mycophenolate mofetil and/or a calcineurin inhibitor, or HLA-DPB1 NP MM (n = 709), permissive MM (n = 2,395), or 12/12 HLA-matched (n = 911) URD with MTX/Tac. HLA-DPB1 NP MM HCT with MTX/Tac was associated with higher treatment-related mortality (TRM) (hazard ratio [HR]: 1.64, 1.08-2.49, P = .019), lower relapse (HR: 0.73, 0.59-0.92, P = .0073), inferior OS (HR: 1.27, 1.03 -1.57, P = .023), and worse GRFS (HR: 1.61, 1.34-1.94, P < .0001) when compared with HLA-DPB1 NP MM HCT with PTCy. Adjusted 1-yr estimates for GRFS were 54% (95% confidence interval [CI]: 49-60%) for PTCy and 40% (CI: 37-44%) for MTX/Tac. For permissive MM URD HCT, MTX/Tac was associated with inferior GRFS (HR 1.54, CI: 1.36-1.76, P < .0001) when compared with PTCy. When using PTCy, there were no significant differences in the above outcomes for HLA-DPB1 NP MM, HLA-DPB1 permissive MM, or 12/12 HLA-matched URD HCT. PTCy should be the preferred GVHD prophylaxis strategy for HLA-DPB1 MM URD HCT. Furthermore, within PTCy platforms, survival is comparable across HLA-DPB1 match and thus NP mismatching at HLA-DPB1 should not be avoided in URD selection when using PTCy.},
}

Humans
*Cyclophosphamide/therapeutic use/pharmacology
*Unrelated Donors
Male
Female
*Hematopoietic Stem Cell Transplantation/methods/adverse effects/mortality
Middle Aged
*Graft vs Host Disease/prevention & control/etiology
Adult
Retrospective Studies
*HLA-DP beta-Chains/immunology
Transplantation, Homologous/methods
*Immunosuppressive Agents/therapeutic use
Adolescent
Young Adult
Aged

@article {pmid41045294,
year = {2025},
author = {Fernández-Penny, FE and Mozingo, K and Bhurgri, A and Perez, HA and Samorodnitsky, S and Lehmann, AE and Humphreys, IM and Abuzeid, WM and Jafari, A},
title = {Patient and Procedural Predictors of Early Recovery Quality After Endoscopic Endonasal Surgery.},
journal = {International forum of allergy & rhinology},
volume = {15},
number = {12},
pages = {1412-1415},
doi = {10.1002/alr.70037},
pmid = {41045294},
issn = {2042-6984},
}

@article {pmid41045472,
year = {2025},
author = {Ko, B and Rojanasopondist, P and Grady, WM},
title = {Top advances of the year: Noninvasive colorectal cancer screening tests.},
journal = {Cancer},
volume = {131},
number = {20},
pages = {e70115},
doi = {10.1002/cncr.70115},
pmid = {41045472},
issn = {1097-0142},
support = {//RACE Charities/ ; U2CCA271902//Division of Cancer Prevention, National Cancer Institute/ ; //Cottrell Family Fund/ ; },
mesh = {Humans ; *Colorectal Neoplasms/diagnosis/blood ; *Early Detection of Cancer/methods ; Feces/chemistry ; Occult Blood ; Biomarkers, Tumor/blood ; Sensitivity and Specificity ; Mass Screening/methods ; },
abstract = {Colorectal cancer (CRC) screening has been shown to be more effective in preventing deaths from this common cancer, but current methods are suboptimal. Because of limitations and barriers, interval cancers occur, and many people (25%-40%) are not compliant with colorectal cancer screening. Advances over the past year, which have led to a blood-based screening test and more accurate stool tests, address the limitations of current tests. Three clinical trials published in the past year have led to a novel blood-based test, a multitarget stool eRNA test, and an improved multitarget stool DNA test for colorectal cancer screening. The multitarget eRNA stool-based test and multitarget stool DNA test are 94.4% sensitive (87.9% specificity) and 93.5% sensitive (90.6% specificity) for CRC and 45.9% sensitive and 43.4% sensitive for advanced polyps, respectively. The blood test uses cell free DNA to detect CRC and is 83% sensitive for CRC (89.6% specificity) and 13% sensitive for advanced adenomas. These advances provide a novel effective blood-based test for CRC screening, which promises to increase compliance, and more accurate stool-based tests, which promise to lead to fewer interval CRCs.},
}

Humans
*Colorectal Neoplasms/diagnosis/blood
*Early Detection of Cancer/methods
Feces/chemistry
Occult Blood
Biomarkers, Tumor/blood
Sensitivity and Specificity
Mass Screening/methods

@article {pmid41045509,
year = {2025},
author = {Kim, D and Ding, W and Shaw, AN and Torkel, M and Turtle, CJ and Yang, P and Yang, J},
title = {Multi-view gene panel characterization for spatially resolved omics.},
journal = {Briefings in bioinformatics},
volume = {26},
number = {5},
pages = {},
pmid = {41045509},
issn = {1477-4054},
support = {//AIR@innoHK program of the Innovation and Technology Commission of Hong Kong/ ; DI2-0000000197//Chan Zuckerberg Initiative Single Cell Biology Data Insights/ ; APP2017023//National Health and Medical Research Council (NHMRC) Investigator/ ; 1173469//NHMRC Investigator/ ; //Metcalf Prize from National Stem Cell Foundation of Australia/ ; //CLEARbridge Foundation/ ; //Anthony Rothe Memorial Trust/ ; 2033771//NHMRC/ ; //Australian Commonwealth Government Research Training Program Stipend Scholarship/ ; //Children's Medical Research Institute Top up Award/ ; },
mesh = {Humans ; Algorithms ; *Gene Expression Profiling/methods ; *Transcriptome ; *Genomics/methods ; *Computational Biology/methods ; },
abstract = {Spatially resolved transcriptomics has revolutionized the study of complex tissues by enabling cellular and subcellular resolution. However, targeted spatial technologies depend on pre-selected gene panels, which are typically curated based on prior biological knowledge or specific research hypotheses. While existing methods often focus on optimizing for cell type identification, we argue that effective panel design should also account for transcriptional variation, pathway-level coverage, and minimal gene redundancy. To meet these broader criteria, we developed a two-part framework: (i) panelScope, a gene panel characterization platform that characterizes panels from multiple perspectives, allowing for holistic comparisons of gene panels for custom panel design; and (ii) panelScope-OA, a genetic algorithm that integrates these characterization metrics into a multi-loss function to automate panel optimization. We applied panelScope and panelScope-OA to characterize nine panels across four datasets. Notably, computationally constructed gene panels performed competitively in capturing major cell types when compared to our in-house manually curated panel. However, refined manual curation offered distinct advantages, particularly in capturing minor cell types. Our results demonstrate the utility of panelScope and panelScope-OA by offering quantitative and multi-dimensional insights to support the design of panels tailored to diverse research needs.},
}

Humans
Algorithms
*Gene Expression Profiling/methods
*Transcriptome
*Genomics/methods
*Computational Biology/methods

@article {pmid41046057,
year = {2026},
author = {Arnold, DE and Leiding, JW and Logan, B and Marsh, RA and Griffith, LM and Grunebaum, E and Murguía-Favela, L and Mallhi, K and Chellapandian, D and Deal, CL and Lim, SS and Prasad, V and Heimall, J and Chandrakasan, S and Chen, K and Yu, LC and Seroogy, CM and Gillio, A and Bednarski, JJ and Kapoor, N and Moore, TB and Cuvelier, GDE and Touzot, F and Rayes, A and Ebens, CL and Schaefer, E and Bauchat, A and Chopek, A and Burroughs, L and Cowan, MJ and Dvorak, CC and Haddad, E and Kohn, DB and Notarangelo, LD and Pai, SY and Puck, JM and Pulsipher, MA and Torgerson, T and Malech, HL and Kang, EM and Parikh, S},
title = {Umbilical Cord Blood Transplantation Provides an Alternative for Patients With Chronic Granulomatous Disease Lacking HLA-Matched Donors: A PIDTC Report.},
journal = {Transplantation and cellular therapy},
volume = {32},
number = {1},
pages = {89.e1-89.e10},
pmid = {41046057},
issn = {2666-6367},
support = {U01 TR001263/TR/NCATS NIH HHS/United States ; U10 HL069254/HL/NHLBI NIH HHS/United States ; UL1 TR002494/TR/NCATS NIH HHS/United States ; U24 CA076518/CA/NCI NIH HHS/United States ; U54 AI082973/AI/NIAID NIH HHS/United States ; R24 AI184316/AI/NIAID NIH HHS/United States ; KL2 TR002492/TR/NCATS NIH HHS/United States ; U01 HL069294/HL/NHLBI NIH HHS/United States ; U54 NS064808/NS/NINDS NIH HHS/United States ; ZIA AI001222/ImNIH/Intramural NIH HHS/United States ; Z99 CA999999/ImNIH/Intramural NIH HHS/United States ; },
mesh = {Humans ; *Granulomatous Disease, Chronic/therapy ; Male ; *Cord Blood Stem Cell Transplantation/methods ; Child ; Child, Preschool ; Adolescent ; Infant ; Female ; Transplantation Conditioning/methods ; *HLA Antigens/immunology ; Retrospective Studies ; Graft vs Host Disease/etiology ; },
abstract = {BACKGROUND: Allogeneic hematopoietic cell transplantation corrects the phagocytic defect in patients with chronic granulomatous disease (CGD) and resolves infection risk and immune dysregulation. Umbilical cord blood transplantation (UCBT) is an option for patients lacking suitable HLA-matched bone marrow or peripheral blood stem cell donors. However, information related to UCBT for CGD is limited to a few small case series and limited subsets of larger cohorts where detailed information is lacking.

OBJECTIVES: To describe UCBT procedures and outcomes in patients with CGD.

STUDY DESIGN: Thirty-nine patients with CGD who underwent UCBT at Primary Immune Deficiency Treatment Consortium (PIDTC) centers between 2001 and 2019 were included.

RESULTS: All patients were male, and most (97%) had X-linked CGD due to pathogenic variants in CYBB. High infection burden (1.72/person years) and inflammatory disease (38%) were common in the year pre-UCBT. Median age at receipt of UCBT was 2.1 (range 0.3-14.0) years. Most (87%) patients received UCB from unrelated donors, and most (72%) patients received busulfan and cyclophosphamide-based conditioning. All but two (95%) patients received serotherapy with anti-thymocyte globulin or alemtuzumab. Neutrophil and platelet recovery occurred at a median of 18 (range 12-46) and 38 (range 21-186) days, respectively. Nine patients experienced early graft failure [donor myeloid chimerism <10% or receipt of second hematopoietic cell transplantation (HCT) within 100 days] for a cumulative incidence of 23.1% (95% CI 11.3-37.3). There were no cases of late graft failure (after 100 days), and median whole blood and myeloid donor chimerism of engrafted patients were >95% at all time points. One of the nine patients with early graft failure had autologous reconstitution. The remaining 8 patients underwent repeat HCT; six of the patients survived and achieved durable myeloid engraftment on long-term follow-up. Twenty-eight patients were alive at a median follow-up of 4.28 (IQR 2.66-6.08) years. Estimated 3-year overall and event-free survival were 73.7% (95% CI 56.5-84.9) and 56.2% (95% CI 39.3-70.1), respectively. No identifiable factors, including history of infection or inflammatory disease in the year prior to UCBT, year of UCBT, age at UCBT, conditioning regimen, cell dose, and recipient and donor HLA match, were associated with graft failure or survival. Infections decreased with time post-UCBT and pre-existing inflammatory disease resolved in all surviving patients CONCLUSIONS: UCBT for CGD is associated with high rates of early graft failure. Nevertheless, UCBT can provide an effective alternative for CGD patients when HLA-matched donors are not available with resolution of disease. Strategies to overcome high rates of early graft failure while optimizing conditioning regimens to minimize toxicity are needed.},
}

Humans
*Granulomatous Disease, Chronic/therapy
Male
*Cord Blood Stem Cell Transplantation/methods
Child
Child, Preschool
Adolescent
Infant
Female
Transplantation Conditioning/methods
*HLA Antigens/immunology
Retrospective Studies
Graft vs Host Disease/etiology

@article {pmid41046201,
year = {2025},
author = {Robesti, D and Micheli, F and Rai, SN and Fallara, G and Gallina, A and Montorsi, F and Briganti, A and Fossati, N and Grivas, P and van der Heijden, AG and Ploussard, G and Malavaud, B and Martini, A},
title = {Addressing Uneven Treatment Discontinuation Rate in the Chemotherapy Arm of the EV-302 Phase 3 Randomized Clinical Trial: Implications for Outcome Interpretation.},
journal = {Clinical genitourinary cancer},
volume = {23},
number = {6},
pages = {102423},
doi = {10.1016/j.clgc.2025.102423},
pmid = {41046201},
issn = {1938-0682},
mesh = {Humans ; *Antibodies, Monoclonal, Humanized/administration & dosage/therapeutic use ; *Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; *Urinary Bladder Neoplasms/drug therapy/mortality/pathology ; *Carcinoma, Transitional Cell/drug therapy/mortality ; Male ; Female ; Treatment Outcome ; *Withholding Treatment/statistics & numerical data ; Kaplan-Meier Estimate ; },
abstract = {INTRODUCTION: The EV-302 trial demonstrated a very significant overall survival (OS) benefit for Enfortumab Vedotin plus Pembrolizumab (EVP) relative to standard chemotherapy (CHT) for patients with metastatic urothelial carcinoma. However, questions have been raised regarding the high rate of treatment discontinuation in the CHT arm for reasons unrelated to adverse events or progression (33% vs. 10% with EVP, P < .01), potentially resulting in loss of unaccounted information, or informative censoring, and affecting survival results interpretation.

MATERIALS AND METHODS: We performed a multistep analysis to assess the impact of differential dropout on trial outcomes. First, Kaplan-Meier (KM) curves were reconstructed from published data to estimate time-to-event outcomes. Second, a reverse KM analysis was conducted to evaluate censoring patterns in the overall population and key subgroups (PD-L1 expression; cisplatin eligibility). Third, simulation models were employed to test whether informative censoring could negatively impact survival benefit by EVP. Finally, we compared the CHT arm of EV-302 to those of other contemporary RCTs through reconstructed survival analyses and risk-of-bias assessments.

RESULTS: Overall, no significant imbalance in censoring between the treatment arms of EV-302 was found on reverse KM analysis when assessing OS (P = .73); however, a significant difference was noted for progression-free survival (PFS) (P = .002). Simulation analysis revealed that even under extreme assumptions of informative censoring, the OS benefit of EVP remained statistically significant. Comparison with historical RCTs confirmed that the CHT outcomes in EV-302 were not anomalously poor. Risk of bias was low overall, although deviations from intervention and outcome measurement were flagged for EV-302.

CONCLUSIONS: Despite the high discontinuation rate in the CHT arm, OS benefit with EVP remains robust. These findings support the reliability of EV-302 results and mitigate concerns about informative censoring, thus encouraging the use of EVP in clinical practice.},
}

Humans
*Antibodies, Monoclonal, Humanized/administration & dosage/therapeutic use
*Antineoplastic Combined Chemotherapy Protocols/therapeutic use
*Urinary Bladder Neoplasms/drug therapy/mortality/pathology
*Carcinoma, Transitional Cell/drug therapy/mortality
Male
Female
Treatment Outcome
*Withholding Treatment/statistics & numerical data
Kaplan-Meier Estimate

@article {pmid41047130,
year = {2025},
author = {Johnson, JJ and Ghosh, S and Shaw, PA and Neuhouser, ML and Lampe, JW and Tinker, LF and Prentice, RL and Tasevska, N and Freedman, LS and Boyer, BB and Hopkins, SE and Nash, SH and Votruba, SB and Krakoff, J and O'Brien, DM},
title = {The carbon isotope ratio of alanine is a biomarker of added sugar and sugar-sweetened beverage intakes: a pooled analysis of 4 studies.},
journal = {The American journal of clinical nutrition},
volume = {122},
number = {6},
pages = {1769-1777},
pmid = {41047130},
issn = {1938-3207},
support = {75N92021D00002/HL/NHLBI NIH HHS/United States ; 75N92021D00005/WH/WHI NIH HHS/United States ; 75N92021D00001/HL/NHLBI NIH HHS/United States ; R01 CA119171/CA/NCI NIH HHS/United States ; P30 DK035816/DK/NIDDK NIH HHS/United States ; R01 DK074842/DK/NIDDK NIH HHS/United States ; 75N92021D00004/WH/WHI NIH HHS/United States ; R01 DK109946/DK/NIDDK NIH HHS/United States ; P20 RR016430/RR/NCRR NIH HHS/United States ; P30 CA015704/CA/NCI NIH HHS/United States ; P20 GM103395/GM/NIGMS NIH HHS/United States ; 75N92021D00003/WH/WHI NIH HHS/United States ; U01 CA197902/CA/NCI NIH HHS/United States ; },
mesh = {Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; *Alanine ; Biomarkers/blood ; *Carbon Isotopes/analysis ; Cross-Sectional Studies ; Diet ; *Dietary Sugars/administration & dosage ; *Sugar-Sweetened Beverages/analysis ; Clinical Trials as Topic ; },
abstract = {BACKGROUND: The alanine carbon isotope ratio (CIR) biomarker was positively associated with added sugar (AS) and sugar-sweetened beverage (SSB) intakes in multiple studies from the United States. Association strengths varied, and Ala CIR also correlated with protein source in certain studies.

OBJECTIVES: This study examined Ala CIR associations with AS and SSB intakes and animal protein ratio (APR; animal protein/total protein), and adjustment for APR, by pooling data from 4 previous studies.

METHODS: We pooled diet and biomarker data from 4 studies (n = 346). These included a cross-sectional study of Yup'ik Alaska Native adults (n = 62), a 12-wk randomized controlled feeding study in males (n = 32), a 2-wk habitual intake controlled feeding study in postmenopausal females (n = 153), and a 15-d habitual intake controlled feeding study of adults (n = 99). We estimated correlations between amino acid CIRs and diet and performed multivariable regression of Ala CIR on standardized intake variables to determine simultaneous associations with AS (g/d) or SSBs (servings/d) and APR. We included study by intake interactions to allow for heterogeneity among studies. We then performed models where leucine (Leu) CIR was included to adjust for APR.

RESULTS: There were positive correlations between Ala CIR and AS intake (r = 0.54; 95% CI: 0.46, 0.61), log-SSB intake (r = 0.63; 95% CI: 0.56, 0.69), and APR (r = 0.32; 95% CI: 0.22, 0.41). Study-specific slopes for the relationship between Ala CIR and AS or SSB intake were similar in models with and without adjustment for APR. Across studies, slopes ranged from 0.34 (95% CI: 0.08, 0.61) to 1.75 (95% CI: 1.29, 2.20) for AS intake in models with APR and from 0.35 (95% CI: 0.01, 0.68) to 1.11 (95% CI: 0.81, 1.40) for SSB intake in models with APR. Replacing APR with Leu CIR resulted in similar slopes between Ala CIR and AS/SSB intake.

CONCLUSIONS: The Ala CIR is a robust biomarker of AS/SSB intake. Potential associations with APR can be adjusted for using a simultaneously measured biomarker. The DBD study was registered at clinicaltrials.gov as NCT01237093 and the NPAAS, an ancillary study of the Women's Health Initiative, at clinicaltrials.gov as NCT00000611.},
}

Adult
Aged
Female
Humans
Male
Middle Aged
*Alanine
Biomarkers/blood
*Carbon Isotopes/analysis
Cross-Sectional Studies
Diet
*Dietary Sugars/administration & dosage
*Sugar-Sweetened Beverages/analysis
Clinical Trials as Topic

@article {pmid41047833,
year = {2025},
author = {Bower, JE and Radin, A and Ganz, PA and Irwin, MR and Cole, SW and Petersen, L and Asher, A and Hurvitz, SA and Crespi, CM},
title = {Inflammation and dimensions of fatigue in women with early stage breast cancer: A longitudinal examination.},
journal = {Cancer},
volume = {131},
number = {20},
pages = {e70038},
pmid = {41047833},
issn = {1097-0142},
support = {//Breast Cancer Research Foundation/ ; P30 CA016042/CA/NCI NIH HHS/United States ; R01 CA160427/CA/NCI NIH HHS/United States ; },
mesh = {Humans ; Female ; *Breast Neoplasms/complications/pathology/blood ; *Fatigue/etiology/blood ; Middle Aged ; *Inflammation/blood ; Longitudinal Studies ; C-Reactive Protein/metabolism/analysis ; Adult ; Interleukin-6/blood ; Receptors, Tumor Necrosis Factor, Type II/blood ; Tumor Necrosis Factor-alpha/blood ; Aged ; Neoplasm Staging ; },
abstract = {BACKGROUND: Fatigue is a common and long-lasting side effect of cancer. Although fatigue is a multidimensional symptom, biologic mechanisms of fatigue dimensions have not been identified.

METHODS: Women recently diagnosed with early stage breast cancer (n = 192) completed assessments before and after adjuvant therapy and at 6-month, 12-month, and 18-month posttreatment follow-up visits. At each assessment, women completed the Multidimensional Fatigue Symptom Inventory and provided blood for protein markers of inflammation (tumor necrosis factor [TNF] alpha [TNF-α], soluble tumor necrosis factor receptor type II [sTNF-RII], interleukin 6 [IL-6], and C-reactive protein [CRP]). Mixed-effect linear models examined within-person and between-person associations between inflammatory markers and dimensions of fatigue.

RESULTS: Analyses demonstrated a positive within-person association between general fatigue and TNF-α (b = 1.67; p = .037), sTNF-RII (b = 2.77; p = .002), and IL-6 (b = 0.86; p = .010) when controlling for age, race, education, body mass index, and cancer stage. Similarly, there was a positive within-person association between physical fatigue and TNF-α (b = 1.58; p = .007), sTNF-RII (b = 2.38; p < .001), and CRP (b = 0.43; p = .007). Conversely, there were negative within-person associations between emotional fatigue and TNF-α (b = -1.92; p = .004) and sTNF-RII (b = -2.10; p = .006). General and physical fatigue were positively associated with CRP at the between-person level (b = 0.82, p = .024 for general; b = 0.71; p = .012 for physical). No significant associations between mental fatigue and inflammatory makers were found.

CONCLUSIONS: The current findings identified distinct dimensions of fatigue associated with inflammatory activity in women with breast cancer and highlighted individual variability in inflammatory markers as a key predictor of fatigue symptoms.},
}

Humans
Female
*Breast Neoplasms/complications/pathology/blood
*Fatigue/etiology/blood
Middle Aged
*Inflammation/blood
Longitudinal Studies
C-Reactive Protein/metabolism/analysis
Adult
Interleukin-6/blood
Receptors, Tumor Necrosis Factor, Type II/blood
Tumor Necrosis Factor-alpha/blood
Aged
Neoplasm Staging

@article {pmid41051932,
year = {2025},
author = {Jones, SMW and Aoki, RF and Alexeeff, SE and Carrell, D and Cronkite, D and Kushi, LH and Mosen, D and Strayhorn, S and Tuzzio, L and Mogk, J and Mammini, L and Kroenke, CH},
title = {Evaluation of the Electronic Health Record-Support Social Support Score in Breast Cancer: Comparison of Count and Item Response Theory Scores.},
journal = {Population health management},
volume = {28},
number = {6},
pages = {273-280},
pmid = {41051932},
issn = {1942-7905},
support = {R01 CA253028/CA/NCI NIH HHS/United States ; },
mesh = {Humans ; Female ; *Electronic Health Records ; *Social Support ; *Breast Neoplasms/psychology ; Middle Aged ; Aged ; Surveys and Questionnaires ; California ; Adult ; },
abstract = {In breast cancer, clinicians add data on social support to patient electronic health records (EHRs) often in free text notes, but those data may be challenging to use for population health initiatives or research purposes. We evaluated the EHR-Support score designed to summarize need for social support using data from the EHR. This study included 996 women from the Pathways study, a Kaiser Permanente Northern California cohort of women diagnosed in 2005-2013 with breast cancer. This unique data resource included both EHR data and questionnaire data on patient-reported social support. Using unstructured EHR data and natural language processing, we developed 11 concept groups (items) characterizing social support. We also used structured data to create two additional concept groups. EHR-Support scores reflecting the lack of social support were generated three ways: counting the number of negative concept groups (count score), using item response theory (IRT), and converting counts to the IRT metric (converted count scores). The count scores were only associated with two of six patient-reported measures (r's: -0.004 to -0.073). The IRT score (r's: -0.038 to -0.179) and converted count score (r's: -0.032 to -0.195) were associated with five of six patient-reported measures, indicating more need for support was associated with less patient-reported social support. The EHR-Support score is a valid and feasible measure of social support that can be used for health services research and managing population health. The converted count score may provide the best balance of validity, precision from IRT and feasibility.},
}

Humans
Female
*Electronic Health Records
*Social Support
*Breast Neoplasms/psychology
Middle Aged
Aged
Surveys and Questionnaires
California
Adult

@article {pmid41052219,
year = {2025},
author = {Brokaw, A and Wallen, G and Orvis, A and Kwon, HJ and Seepersaud, R and Nguyen, S and Sharma, K and Coleman, M and Quach, P and Twentyman, J and Vornhagen, J and Jones, LA and Lin, C and Gafken, PR and Rajagopal, L},
title = {The serine protease HtrA regulates Group B Streptococcus virulence and affects the host response to infection.},
journal = {PLoS pathogens},
volume = {21},
number = {10},
pages = {e1013562},
pmid = {41052219},
issn = {1553-7374},
support = {T32 AI007509/AI/NIAID NIH HHS/United States ; R01 AI145890/AI/NIAID NIH HHS/United States ; P30 CA015704/CA/NCI NIH HHS/United States ; R01 AI133976/AI/NIAID NIH HHS/United States ; R01 AI112619/AI/NIAID NIH HHS/United States ; R01 AI152268/AI/NIAID NIH HHS/United States ; R01 AI167421/AI/NIAID NIH HHS/United States ; },
mesh = {*Streptococcus agalactiae/pathogenicity/enzymology/genetics ; *Streptococcal Infections/microbiology/immunology/pathology ; Female ; Pregnancy ; Animals ; Mice ; Virulence ; Humans ; *Bacterial Proteins/metabolism/genetics ; *Pregnancy Complications, Infectious/microbiology ; Virulence Factors/metabolism ; *High-Temperature Requirement A Serine Peptidase 1/metabolism ; },
abstract = {Group B Streptococcus (GBS) rectovaginally colonizes up to 20% of women worldwide and is a leading cause of invasive infections during pregnancy, contributing annually to a significant proportion of preterm births, neonatal infections, and stillbirths. Despite its reputation as a perinatal pathogen, GBS infection rates in non-pregnant adults are also increasing. While much progress has been made to understand transcriptional regulation of virulence by two-component systems, many aspects of GBS virulence regulation remain understudied. Although many bacterial pathogens utilize high temperature response A (HtrA) family serine proteases to regulate virulence and stress responses through varied mechanisms, the function of HtrA in GBS was unknown. Here, we demonstrate that HtrA is localized to the GBS membrane and regulates the abundance of endogenous surface and secreted proteins, including a subset of virulence factors. Although deletion of htrA (ΔhtrA) increased dissemination to placentas and fetuses, this strain caused significantly fewer adverse pregnancy outcomes compared to isogenic wild-type (WT). Placentas from ΔhtrA-infected dams contained more chemokines, pro-inflammatory IL-1β, and neutrophil myeloperoxidase than isogenic WT-infected placentas, suggesting that ΔhtrA GBS induces potent neutrophil chemotaxis. However, immunosuppressive IL-10 was present at increased concentration, which may in part explain the attenuation of adverse pregnancy outcomes during ΔhtrA infection. Finally, we note that recombinant GBS HtrA directly cleaves human fibronectin in vitro, highlighting that this protease may also target host substrates during infection. Together, these findings support a role for HtrA as a post-translational regulator of GBS virulence and suggest that inhibiting HtrA activity may hold therapeutic promise against GBS induced adverse pregnancy outcomes.},
}

*Streptococcus agalactiae/pathogenicity/enzymology/genetics
*Streptococcal Infections/microbiology/immunology/pathology
Female
Pregnancy
Animals
Mice
Virulence
Humans
*Bacterial Proteins/metabolism/genetics
*Pregnancy Complications, Infectious/microbiology
Virulence Factors/metabolism
*High-Temperature Requirement A Serine Peptidase 1/metabolism

@article {pmid41052403,
year = {2026},
author = {Modi, D and Aljawai, YM and DeFor, TE and Bupp, C and Al Malki, MM and Bolaños-Meade, J and Gooptu, M and Jimenez Jimenez, AM and Liu, H and Mensah, FA and Mielcarek, M and Shaffer, BC and Shaw, BE and Spellman, SR and Stefanski, HE and Auletta, JJ and Devine, SM and Khimani, F and Abboud, R},
title = {Matched unrelated vs haploidentical donor hematopoietic cell transplantation using posttransplant cyclophosphamide.},
journal = {Blood advances},
volume = {10},
number = {1},
pages = {233-245},
pmid = {41052403},
issn = {2473-9537},
support = {27307C0011/ES/NIEHS NIH HHS/United States ; 27305C0011/ES/NIEHS NIH HHS/United States ; U24 CA076518/CA/NCI NIH HHS/United States ; P30 CA008748/CA/NCI NIH HHS/United States ; 27398C0011/ES/NIEHS NIH HHS/United States ; },
mesh = {Humans ; *Cyclophosphamide/therapeutic use ; *Hematopoietic Stem Cell Transplantation/methods/adverse effects ; Female ; Male ; Middle Aged ; Adult ; Graft vs Host Disease/prevention & control/etiology ; *Transplantation, Haploidentical/methods/adverse effects ; *Unrelated Donors ; Transplantation Conditioning/methods ; Aged ; Myelodysplastic Syndromes/therapy/mortality ; Young Adult ; Registries ; Treatment Outcome ; Adolescent ; },
abstract = {Posttransplant cyclophosphamide (PTCy)-based graft-versus-host disease (GVHD) prophylaxis is now standard for matched unrelated donor (MUD) hematopoietic cell transplantation (HCT). Previous studies comparing MUD and haploidentical donor HCT using PTCy were limited in size and follow-up. We therefore performed a registry-based analysis examining the impact of donor type on HCT with PTCy. Adult patients (n = 5873) receiving MUD (n = 1973) or haploidentical (n = 3900) HCT with PTCy for acute leukemia (74.2%) or myelodysplastic syndrome (MDS; 25.8%) reported to the Center for International Blood and Marrow Transplant Research between 2017 and 2021 were included. Primary end points were 3-year overall survival (OS) and GVHD-free, relapse-free survival (GRFS). Cox regression and sensitivity analyses were performed through adjustment of propensity scores. Haploidentical HCT had worse OS (hazard ratio [HR], 1.15; 95% confidence interval [CI], 1.04-1.27; P = .005) and GRFS (HR, 1.19; 95% CI, 1.10-1.29; P < .001) versus MUD HCT. Donor age was the only other donor factor associated with survival. Results were confirmed in sensitivity analysis. When restricted to reduced intensity conditioning or donors <30 years, OS did not differ between groups. Haploidentical HCT was associated with higher primary graft failure (HR, 1.67; P = .002), increased grade 3/4 acute GVHD (HR, 1.28; P = .039), higher moderate/severe chronic GVHD (HR, 1.47; P < .001), and nonrelapse mortality (HR, 1.34; P < .001). Grade 2 to 4 acute GVHD and relapse risk did not differ. This large analysis showed that in adults with acute leukemia or MDS, MUD HCT was associated with improved outcomes versus haploidentical HCT with PTCy-based GVHD prophylaxis.},
}

Humans
*Cyclophosphamide/therapeutic use
*Hematopoietic Stem Cell Transplantation/methods/adverse effects
Female
Male
Middle Aged
Adult
Graft vs Host Disease/prevention & control/etiology
*Transplantation, Haploidentical/methods/adverse effects
*Unrelated Donors
Transplantation Conditioning/methods
Aged
Myelodysplastic Syndromes/therapy/mortality
Young Adult
Registries
Treatment Outcome
Adolescent

@article {pmid41052404,
year = {2026},
author = {Valtis, YK and Lin, C and Nemirovsky, D and Devlin, S and Rejeski, K and Curran, KJ and Wang, X and Shah, NN and Jeyakumar, N and Miller, K and Zhang, A and Kota, VK and Al Darobi, AH and Muhsen, I and Sasine, J and Aldoss, I and Advani, AS and Reshef, R and Chen, EC and Kopmar, N and Tsai, SB and Hilal, T and Shah, BD and Faramand, R and Solh, MM and Tan, V and Bezerra, E and Battiwalla, M and Ramakrishnan, A and Mathews, J and Shaughnessy, P and Mountjoy, L and Hoeg, RT and Dykes, KC and Logan, AC and Kumaran, MV and Schwartz, M and Tracy, S and Moore, J and Odstrcil Bobillo, S and Frey, NV and Connor, M and Ladha, A and Dholaria, B and Sutherland, K and Roloff, GW and Muffly, LS and Park, JH},
title = {CAR HEMATOTOX independently predicts outcomes after CD19 CAR-T therapy for acute lymphoblastic leukemia.},
journal = {Blood advances},
volume = {10},
number = {1},
pages = {276-288},
pmid = {41052404},
issn = {2473-9537},
support = {P30 CA008748/CA/NCI NIH HHS/United States ; ZIA BC011823/ImNIH/Intramural NIH HHS/United States ; },
mesh = {Adolescent ; Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Young Adult ; *Antigens, CD19/immunology ; *Immunotherapy, Adoptive/methods/adverse effects ; *Precursor Cell Lymphoblastic Leukemia-Lymphoma/therapy/mortality/diagnosis ; Prognosis ; *Receptors, Chimeric Antigen/immunology ; Treatment Outcome ; },
abstract = {Chimeric antigen receptor (CAR) T-cell (CAR-T) treatment for B-cell acute lymphoblastic leukemia (ALL) induces high initial response rates, but most patients relapse. Low disease burden (often defined as <5% blasts in the bone marrow) is associated with better outcomes. CAR HEMATOTOX (HT) is a score using prelymphodepletion hematologic and inflammatory parameters to predict outcomes in lymphoma. Here, we assess its prognostic utility in a large multicenter adult B-cell ALL cohort. Patients who received brexucabtagene autoleucel across 33 centers in North America were included as part of the Real-World Outcomes Collaborative of CAR-T in Adult ALL (ROCCA) consortium. An independent cohort of 61 patients with ALL treated with an investigational CD19 CAR-T therapy at 1 center was also described. Among 199 ROCCA consortium patients, 43 (22%) patients with HTlow scores had lower rates of delayed neutrophil recovery than those with HThigh scores (26% vs 52%, P = .002) and fewer severe infections (2.5% vs 18.8%, P = .011). They also had higher response rates, overall survival (OS), and event-free survival (EFS), as well as lower nonrelapse mortality and cumulative incidence of relapse. The survival differences remained significant after multivariable adjustment for disease burden and other covariates. In the investigational cohort of 61 patients, patients with HTlow scores had improved OS and EFS, as well as higher peak CAR-T expansion. In summary, CAR HT score is a prognostic factor independent of disease burden in adult ALL. HTlow score is associated with superior outcomes after CD19 CAR-Ts and higher CAR-T expansion in a single-center cohort. These trials were registered at www.clinicaltrials.gov as #NCT01044069 and #NCT01860937.},
}

Adolescent
Adult
Aged
Female
Humans
Male
Middle Aged
Young Adult
*Antigens, CD19/immunology
*Immunotherapy, Adoptive/methods/adverse effects
*Precursor Cell Lymphoblastic Leukemia-Lymphoma/therapy/mortality/diagnosis
Prognosis
*Receptors, Chimeric Antigen/immunology
Treatment Outcome

@article {pmid41052457,
year = {2025},
author = {Balogh, EP and Levit, LA and Unger, JM and Accordino, MK and Chism, DD and Kirkwood, MK and Parsons, HM and Patel, MI and Peppercorn, JM and Polite, BN and Sedrak, MS and Sharma, P and Subbiah, IM and Temel, JS and Yabroff, KR and Osarogiagbon, RU},
title = {ASCO State of Cancer Care in America Special Report 2025: Access to Cancer Clinical Trials in the United States.},
journal = {JCO oncology practice},
volume = {21},
number = {12},
pages = {1746-1758},
doi = {10.1200/OP-25-00233},
pmid = {41052457},
issn = {2688-1535},
mesh = {*Health Services Accessibility/economics/organization & administration/statistics & numerical data ; *Medical Oncology/economics/organization & administration/statistics & numerical data ; Research Design ; Clinical Trials as Topic/economics/organization & administration/statistics & numerical data ; *Neoplasms/epidemiology/therapy ; Patient-Centered Care/economics/organization & administration/statistics & numerical data ; United States/epidemiology ; Cost of Illness ; Humans ; },
abstract = {Improving patient access to cancer clinical trials is a fundamental ASCO priority because clinical cancer research is the essential link transforming biomedical discoveries into meaningful progress in cancer care and patient outcomes. Today's standard of care emerged from yesterday's clinical trials. However, numerous barriers continue to threaten patient access to cancer clinical trials. This Special Report describes the essential role clinical trials play in improving cancer care and patient outcomes, current challenges in the design and conduct of clinical trials, and steps taken by ASCO to make clinical trials more accessible, patient-centered, and embedded within the communities where people live.},
}

*Health Services Accessibility/economics/organization & administration/statistics & numerical data
*Medical Oncology/economics/organization & administration/statistics & numerical data
Research Design
Clinical Trials as Topic/economics/organization & administration/statistics & numerical data
*Neoplasms/epidemiology/therapy
Patient-Centered Care/economics/organization & administration/statistics & numerical data
United States/epidemiology
Cost of Illness
Humans

@article {pmid41053004,
year = {2025},
author = {Foster, L and Anderson, LD and Chung, A and Chaulagain, CP and Pettijohn, E and Cowan, AJ and Costello, C and Larson, S and Sborov, DW and Shain, KH and Silbermann, R and Voorhees, P and Krevvata, M and Pei, H and Patel, S and Khare, V and Cortoos, A and Carson, R and Lin, TS and Badros, A},
title = {Daratumumab plus lenalidomide maintenance in newly diagnosed multiple myeloma after transplant: AURIGA subgroup analyses.},
journal = {Blood cancer journal},
volume = {15},
number = {1},
pages = {154},
pmid = {41053004},
issn = {2044-5385},
mesh = {Humans ; *Multiple Myeloma/therapy/mortality/drug therapy/diagnosis ; *Lenalidomide/administration & dosage/therapeutic use ; Female ; Male ; Middle Aged ; Aged ; *Antineoplastic Combined Chemotherapy Protocols/therapeutic use/adverse effects ; *Antibodies, Monoclonal/administration & dosage/therapeutic use ; Adult ; *Hematopoietic Stem Cell Transplantation ; Maintenance Chemotherapy ; },
abstract = {In the primary analysis (32.3-month median follow-up) of the randomized, phase 3 AURIGA study (NCT03901963), daratumumab-lenalidomide (D-R) maintenance significantly improved MRD-negative conversion rates and reduced the risk of disease progression or death by 47% versus R maintenance in anti-CD38 monoclonal antibody-naïve and post-transplant MRD-positive patients with newly diagnosed MM. Here, we present a post hoc analysis across relevant subgroups, including high-risk cytogenetic abnormalities (HRCAs) per original, revised, and modified International Myeloma Society (IMS) 2024 criteria. MRD-negative (10[-5]) conversion rates by 12 months of maintenance were higher for D-R versus R across cytogenetically high-risk subgroups per original (31.8% vs 6.7%), revised (43.8% vs 13.3%), and modified IMS 2024 (41.2% vs 0%) criteria and cytogenetically ultra-high-risk disease (≥2 revised HRCAs; 54.5% vs 0%). Similar trends in overall MRD-negative conversion rates were observed across subgroups. D-R demonstrated a trend towards improved PFS versus R (HR [95% CI]) in cytogenetically high-risk subgroups per original (0.60 [0.21-1.70]), revised (0.53 [0.21-1.31]), and modified IMS 2024 (0.45 [0.13-1.53]) criteria and cytogenetically ultra-high-risk disease (0.61 [0.17-2.25]). Similar outcomes were observed regardless of age or race, with no additional safety concerns among older (≥65 years) or Black patients. These data support the benefit of D-R maintenance regardless of age, race, and risk status.},
}

Humans
*Multiple Myeloma/therapy/mortality/drug therapy/diagnosis
*Lenalidomide/administration & dosage/therapeutic use
Female
Male
Middle Aged
Aged
*Antineoplastic Combined Chemotherapy Protocols/therapeutic use/adverse effects
*Antibodies, Monoclonal/administration & dosage/therapeutic use
Adult
*Hematopoietic Stem Cell Transplantation
Maintenance Chemotherapy

@article {pmid41053137,
year = {2025},
author = {Mkhize, NN and Zhang, B and Brackett, C and Elyanu, PJ and Tapley, A and Dadabhai, S and Hu, J and Do, BTN and Schuster, DJ and Heptinstall, J and Sawant, S and Seaton, K and Sarzotti-Kelsoe, M and Hudson, A and Jin, Y and Bhebhe, S and Kaldine, H and Kgagudi, P and Modise, T and Mgodi, NM and Andriesen, J and Randhawa, AK and Fisher, LH and Kee, JJ and Magaret, CA and Peng, J and Kenny, A and Carpp, LN and Chen, Z and Heng, S and Villaran, M and Takalani, A and Le Roux, B and Wilkinson, E and Odhiambo, J and Shah, P and Polakowski, L and Yacovone, M and Samandari, T and Chirenje, Z and Makhema, J and Kamuti, E and Njekwa, K and Nuwagaba-Biribonwoha, H and Baguma, A and Badal-Faesen, S and Brumskine, W and Coetzer, S and Dawson, R and Delany-Moretlwe, S and Diacon, AH and Fry, S and Gill, K and Madikida, A and Hoosain, ZAE and Hosseinipour, MC and Inambao, M and Innes, C and Innes, S and Kalonji, D and Mwape, H and Kassim, P and Kamanga, MC and Kilembe, W and Laher, F and Malahleha, M and Maluleke, VL and Mboya, G and Madiega, PA and McHarry, K and Mitha, E and Duki, Y and Mda, P and Moerane, M and Moloantoa, T and Nuwamanya, S and Mahomed, S and Naicker, V and Nana, A and Nanvubya, A and Kawoozo, B and Nchabeleng, M and Otieno, W and Potgieter, EL and Potloane, D and Punt, Z and Said, J and Singh, Y and Kassim, S and van der Vendt, D and Tayob, MS and Vahed, Y and Wabwire, DO and Kublin, JG and Bekker, LG and Corey, L and Gray, GE and Huang, Y and Kotze, P and Garrett, N and Hural, J and Ferrari, G and Andersen-Nissen, E and Montefiori, D and Moore, PL and McElrath, MJ and Tomaras, GD and Gilbert, PB and , },
title = {Neutralizing and binding antibodies are a correlate of risk of COVID-19 in the CoVPN 3008 study in people with HIV.},
journal = {Nature communications},
volume = {16},
number = {1},
pages = {8876},
pmid = {41053137},
issn = {2041-1723},
support = {U01 AI068619/AI/NIAID NIH HHS/United States ; R37AI054165//U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (NIAID)/ ; U01 AI069463/AI/NIAID NIH HHS/United States ; S10 OD028685/OD/NIH HHS/United States ; T32 AI007044/AI/NIAID NIH HHS/United States ; UM1 AI068614-14//U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (NIAID)/ ; T32AI007044-45//U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (NIAID)/ ; UM1 AI068618/AI/NIAID NIH HHS/United States ; UM1 AI069463/AI/NIAID NIH HHS/United States ; UM1 AI068635/AI/NIAID NIH HHS/United States ; UM1 AI068619/AI/NIAID NIH HHS/United States ; UM1 AI068614/AI/NIAID NIH HHS/United States ; UM1 AI069518/AI/NIAID NIH HHS/United States ; 3UM1AI068618-15S1//U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (NIAID)/ ; R37 AI054165/AI/NIAID NIH HHS/United States ; U01 AI068636/AI/NIAID NIH HHS/United States ; },
mesh = {Humans ; *COVID-19/immunology/prevention & control/epidemiology/virology ; *Antibodies, Neutralizing/immunology/blood ; *HIV Infections/immunology/complications/virology ; *SARS-CoV-2/immunology ; *Antibodies, Viral/immunology/blood ; Male ; Female ; Adult ; Middle Aged ; *COVID-19 Vaccines/immunology/administration & dosage ; 2019-nCoV Vaccine mRNA-1273/immunology ; },
abstract = {People with HIV (PWH) are understudied in COVID-19 vaccine trials, leaving knowledge gaps on whether the identified immune correlates of protection also hold in PWH. CoVPN 3008 (NCT05168813) enrolled predominantly PWH and reported lower COVID-19 incidence for a Hybrid vs. Vaccine Group (baseline SARS-CoV-2-positive and one mRNA-1273 dose vs. negative and two doses). Using case-cohort sampling, antibody markers at enrolment (M0) and four weeks post-final vaccination (Peak) are assessed as immune correlates of COVID-19. For the Hybrid Group [n = 287 (195 PWH)], all M0 markers inversely correlate with COVID-19 through 230 days post-Peak, with 50% inhibitory dilution BA.4/5 neutralizing antibody titer (nAb-ID50 BA.4/5) the strongest and only independent correlate (HR per 10-fold increase=0.46, 95% CI 0.28, 0.75; P = 0.002). For the Vaccine Group [n = 115 (86 PWH)], Peak nAb-ID50 BA.4/5 correlates with reduced COVID-19 risk (1.9%, 1.1%, and 0.3% at titers 10, 100, and 1000 AU/ml) through 92, but not 165, days post-Peak. Using multivariable Cox analysis of binding and nAb, nAb titers predict COVID-19 in PWH. Two doses of a 100-µg Ancestral strain mRNA vaccine in baseline-SARS-CoV-2-negative individuals elicit sufficient cross-reacting Omicron antibodies to reduce COVID-19 incidence for 90 days post-Peak, but viral evolution and waning antibodies abrogate this protection thereafter.},
}

Humans
*COVID-19/immunology/prevention & control/epidemiology/virology
*Antibodies, Neutralizing/immunology/blood
*HIV Infections/immunology/complications/virology
*SARS-CoV-2/immunology
*Antibodies, Viral/immunology/blood
Male
Female
Adult
Middle Aged
*COVID-19 Vaccines/immunology/administration & dosage
2019-nCoV Vaccine mRNA-1273/immunology

@article {pmid41053396,
year = {2025},
author = {Gieselmann, L and DeLaitsch, AT and Rohde, M and Gruell, H and Kreer, C and Ercanoglu, MS and Gristick, HB and Schommers, P and Ahmadov, E and Radford, C and Mazzolini, A and Zhang, L and West, AP and Worczinski, J and Momot, A and Reichwein, ML and Knüfer, J and Stumpf, R and Mkhize, NN and Kaldine, H and Bhebhe, S and Deshpande, S and Giovannoni, F and Stefanutti, E and Benigni, F and Havenar-Daughton, C and Corti, D and Kroidl, A and Adhikari, A and Nanfack, AJ and Ambada, GE and Duerr, R and Maganga, L and William, W and Ntinginya, NE and Wolf, T and Geldmacher, C and Hoelscher, M and Lehmann, C and Moore, PL and Mora, T and Walczak, AM and Gilbert, PB and Doria-Rose, NA and Huang, Y and Bloom, JD and Seaman, MS and Bjorkman, PJ and Klein, F},
title = {Profiling of HIV-1 elite neutralizer cohort reveals a CD4bs bnAb for HIV-1 prevention and therapy.},
journal = {Nature immunology},
volume = {26},
number = {11},
pages = {2016-2029},
pmid = {41053396},
issn = {1529-2916},
support = {INV-036842/GATES/Gates Foundation/United States ; ANR-19-CE45-0018//Agence Nationale de la Recherche (French National Research Agency)/ ; 1U54AI170856//U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (NIAID)/ ; INV-002143/GATES/Gates Foundation/United States ; R01AI140891//U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (NIAID)/ ; INV-002143/GATES/Gates Foundation/United States ; P01AI100148//U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (NIAID)/ ; 1032144//Bill and Melinda Gates Foundation (Bill & Melinda Gates Foundation)/ ; U01 AI169385/AI/NIAID NIH HHS/United States ; P01 AI100148/AI/NIAID NIH HHS/United States ; R01 AI140891/AI/NIAID NIH HHS/United States ; U54 AI170856/AI/NIAID NIH HHS/United States ; U01AI169385//U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (NIAID)/ ; },
mesh = {*HIV-1/immunology ; Humans ; *HIV Infections/immunology/prevention & control/virology/therapy ; Animals ; *HIV Antibodies/immunology/therapeutic use ; *CD4 Antigens/immunology/metabolism ; Mice ; *Antibodies, Neutralizing/immunology/therapeutic use ; HIV Envelope Protein gp120/immunology ; Antibodies, Monoclonal/immunology ; B-Lymphocytes/immunology ; },
abstract = {Administration of HIV-1 neutralizing antibodies can suppress viremia and prevent infection in vivo. However, clinical use is challenged by envelope diversity and rapid viral escape. Here, we performed single B cell profiling of 32 top HIV-1 elite neutralizers to identify broadly neutralizing antibodies with highest antiviral activity. From 831 expressed monoclonal antibodies, we identified 04_A06, a VH1-2-encoded broadly neutralizing antibody to the CD4 binding site with remarkable breadth and potency against multiclade pseudovirus panels (geometric mean half-maximal inhibitory concentration = 0.059 µg ml[-1], breadth = 98.5%, 332 strains). Moreover, 04_A06 was not susceptible to classic CD4 binding site escape variants and maintained full viral suppression in HIV-1-infected humanized mice. Structural analyses revealed an unusually long 11-amino-acid heavy chain insertion that facilitates interprotomer contacts with highly conserved residues on the adjacent gp120 protomer. Finally, 04_A06 demonstrated high activity against contemporaneously circulating viruses from the Antibody-Mediated Prevention trials (geometric mean half-maximal inhibitory concentration = 0.082 µg ml[-1], breadth = 98.4%, 191 virus strains), and in silico modeling for 04_A06LS predicted prevention efficacy of >93%. Thus, 04_A06 will provide unique opportunities for effective treatment and prevention of HIV-1 infection.},
}

*HIV-1/immunology
Humans
*HIV Infections/immunology/prevention & control/virology/therapy
Animals
*HIV Antibodies/immunology/therapeutic use
*CD4 Antigens/immunology/metabolism
Mice
*Antibodies, Neutralizing/immunology/therapeutic use
HIV Envelope Protein gp120/immunology
Antibodies, Monoclonal/immunology
B-Lymphocytes/immunology

@article {pmid41053438,
year = {2025},
author = {Zainal, NH and Bossarte, RM and Gildea, SM and Hwang, I and Kennedy, CJ and Liu, H and Leung, LB and Luedtke, A and Marx, BP and Petukhova, MV and Post, EP and Ross, EL and Sampson, NA and Sverdrup, E and Turner, B and Wager, S and Kessler, RC},
title = {Correction: Developing an individualized treatment rule for Veterans with major depressive disorder using electronic health records.},
journal = {Molecular psychiatry},
volume = {30},
number = {12},
pages = {6173},
doi = {10.1038/s41380-025-03299-0},
pmid = {41053438},
issn = {1476-5578},
}

@article {pmid41053791,
year = {2025},
author = {Kim, D and Highland, HM and Smit, RAJ and Hysong, MR and Buchanan, VL and Young, KL and Zhao, C and Spracklen, CN and Kilpeläinen, TO and Guo, B and Darst, BF and Cai, Y and Wang, Z and Lundin, J and Berndt, SI and Manson, JE and Marouli, E and Lange, L and Lange, E and Fornage, M and Gignoux, CR and Haiman, CA and Rich, SS and Buyske, S and Loos, RJF and Kooperberg, C and Peters, U and Avery, CL and Gordon-Larsen, P and Graff, M and Raffield, LM and North, KE},
title = {Genetic underpinnings of the heterogeneous impact of obesity on lipid levels and cardiovascular disease.},
journal = {Genome medicine},
volume = {17},
number = {1},
pages = {113},
pmid = {41053791},
issn = {1756-994X},
support = {R01 HL143885/HL/NHLBI NIH HHS/United States ; Intramural Research Program/CP/NCI NIH HHS/United States ; R01 HL142302/HL/NHLBI NIH HHS/United States ; R01 DK139598/DK/NIDDK NIH HHS/United States ; R01HG010297/HG/NHGRI NIH HHS/United States ; R01 HD057194/HD/NICHD NIH HHS/United States ; R01 HG010297/HG/NHGRI NIH HHS/United States ; R01HD057194//Eunice Kennedy Shriver National Institute of Child Health and Human Development/ ; R01 DK122503/DK/NIDDK NIH HHS/United States ; NNF22OC0074128//Novo Nordisk Foundation Center for Basic Metabolic Research/ ; R01DK122503/DK/NIDDK NIH HHS/United States ; R01HL142302/HL/NHLBI NIH HHS/United States ; 903805//American Heart Association/ ; },
mesh = {Humans ; *Obesity/genetics/complications/blood ; *Cardiovascular Diseases/genetics/etiology/blood ; Genome-Wide Association Study ; Body Mass Index ; Male ; Female ; Middle Aged ; *Lipids/blood ; Mendelian Randomization Analysis ; Genetic Predisposition to Disease ; Multifactorial Inheritance ; Polymorphism, Single Nucleotide ; Triglycerides/blood ; },
abstract = {BACKGROUND: Obesity is thought to increase cardiovascular disease (CVD) risk partly through dyslipidemia. Yet, obesity's effects on dyslipidemia are not uniform. Understanding the shared genetic basis between obesity and lipid traits can provide insight into this heterogeneity and its implications for CVD risk.

METHODS: We examined local genetic correlations between three lipid measures [high-density lipoprotein cholesterol (HDL), low-density lipoprotein cholesterol (LDL), and triglycerides (TG)] and body mass index (BMI) using genome-wide association study summary statistics from European ancestry UK Biobank participants. We identified genomic loci with opposing genetic effects on obesity and dyslipidemia risk (protective BMI-lipid loci) and those with concordant directions for both obesity and dyslipidemia risk (adverse BMI-lipid loci). Gene-based association analyses were used to prioritize potential causal genes. We then constructed polygenic risk scores for BMI (PRSBMI) based on protective and adverse loci and assessed their associations with BMI, lipid levels, CVD, and related traits in the diverse Population Architecture using Genomics and Epidemiology (PAGE) study. PheWAS was performed in the All of Us cohort. Mendelian randomization (MR) was conducted to assess the causal impact of protective/adverse loci on cardiometabolic outcomes. Finally, we investigated the associations with fat distribution traits using MRI-based fat measures in the UK Biobank.

RESULTS: Among 2495 regions, we identified 789 HDL, 26 LDL, and 494 TG loci with significant local genetic correlation with BMI (including overlapping loci). Of these, 3 HDL, 10 LDL, and 8 TG loci showed protective correlations. Gene-based analyses prioritized 18 candidate causal genes. The protective PRSBMI(+)HDL(+) was associated with higher BMI but favorable lipid profiles and reduced CVD risk in PAGE. PheWAS revealed protective associations with hyperlipidemia, atrial fibrillation, and Alzheimer's disease. MR supported the favorable causal effects of these protective loci on several cardiometabolic outcomes. Notably, protective PRSBMI(+)TG(-) was uniquely associated with decreased visceral-to-abdominal subcutaneous adipose tissue ratio.

CONCLUSIONS: Identifying and validating genomic loci with shared genetic signals between BMI and lipid levels further supports the importance of genetics in defining the heterogeneous impact of obesity on dyslipidemia and CVD.},
}

Humans
*Obesity/genetics/complications/blood
*Cardiovascular Diseases/genetics/etiology/blood
Genome-Wide Association Study
Body Mass Index
Male
Female
Middle Aged
*Lipids/blood
Mendelian Randomization Analysis
Genetic Predisposition to Disease
Multifactorial Inheritance
Polymorphism, Single Nucleotide
Triglycerides/blood

@article {pmid41054394,
year = {2025},
author = {Schuurmans, F and Wittner, A and van den Bijgaart, RJE and Tahk, S and Boros, MGM and Looman, MWG and Fenn, NC and Humpe, A and Hopfner, KP and Adema, GJ},
title = {Development of aGD2-SIRPα fusion antibodies targeting neuroblastoma and the innate immune checkpoint receptor CD47.},
journal = {Molecular cancer therapeutics},
volume = {},
number = {},
pages = {},
doi = {10.1158/1535-7163.MCT-24-1090},
pmid = {41054394},
issn = {1538-8514},
abstract = {Neuroblastoma (NB) is a childhood malignancy characterized by overexpression of disialoganglioside GD2. Treatment with anti-GD2 monoclonal antibodies (aGD2 mAbs) has prolonged the survival of NB patients, however, long-term efficacy needs further improvement. NB tumor cells upregulate expression of the innate immune checkpoint and don't eat me signal CD47 to evade immune recognition and phagocytosis by Signal regulatory protein alpha (SIRPα) expressing myeloid cells. Targeting of CD47 remains challenging because ubiquitous CD47 expression on healthy cells causes on-target off-tumor related toxicities and functions as an antigen sink. To locally restrict CD47 blockade to the NB tumor site, we successfully developed aGD2-SIRPα fusion mAbs for the murine and human setting. These fusion mAbs are equipped with a functional Fc-domain and the extracellular SIRPα domain 1 either fused to the N-terminus of the light chain or to the C-terminus of the heavy chain. Both aGD2-SIRPα fusion mAbs selectively bind NB tumor cells and provide GD2-dependent SIRPα domain-mediated CD47 blockade (Fig. 1a). Furthermore, they potently induce innate immune effector mechanisms through the interaction of the mAbs Fc-domain with Fcγ receptors. Functional analysis of the fusion mAbs demonstrated enhanced phagocytosis and NK cell-mediated killing of NB tumor cells compared to the conventional aGD2 mAb. In addition, these novel antibodies modulate the cytokine production by primary macrophages. The aGD2-SIRPα fusion mAbs outperformed aGD2 mAb across a broad range of CD47/GD2 co-expressing tumor cells. This research shows the successful development of aGD2-SIRPα fusion mAbs to provide targeted blockade of CD47 for the treatment of solid NB tumors.},
}

@article {pmid41055541,
year = {2025},
author = {Salerno, S and Roberts, EK and Needham, BL and McCormick, TH and Li, F and Mukherjee, B and Shi, X},
title = {What's the Weight? Estimating Controlled Outcome Differences in Complex Surveys for Health Disparities Research.},
journal = {Statistics in medicine},
volume = {44},
number = {23-24},
pages = {e70289},
pmid = {41055541},
issn = {1097-0258},
support = {//Fred Hutchinson Cancer Center/ ; UG3 CA267907/CA/NCI NIH HHS/United States ; P2C HD042828/HD/NICHD NIH HHS/United States ; 1712933//Division of Mathematical Sciences/ ; R35 GM144128/GM/NIGMS NIH HHS/United States ; R01 HD107015/MH/NIMH NIH HHS/United States ; R01 HD107015/HD/NICHD NIH HHS/United States ; DP2 MH122405/MH/NIMH NIH HHS/United States ; R01 GM139926/GM/NIGMS NIH HHS/United States ; P2C HD042828/MH/NIMH NIH HHS/United States ; },
mesh = {Female ; Humans ; Male ; Middle Aged ; Bias ; Black or African American/statistics & numerical data/genetics ; Computer Simulation ; *Health Status Disparities ; Nutrition Surveys/statistics & numerical data ; Propensity Score ; Socioeconomic Factors ; Telomere/genetics ; United States ; White/genetics/statistics & numerical data ; },
abstract = {In this work, we are motivated by the problem of estimating racial disparities in health outcomes, specifically the average controlled difference (ACD) in telomere length between Black and White individuals, using data from the National Health and Nutrition Examination Survey (NHANES). To do so, we build a propensity for race to properly adjust for other social determinants while characterizing the controlled effect of race on telomere length. Propensity score methods are broadly employed with observational data as a tool to achieve covariate balance, but how to implement them in complex surveys is less studied-in particular, when the survey weights depend on the group variable under comparison (as the NHANES sampling scheme depends on self-reported race). We propose identification formulas to properly estimate the ACD in outcomes between Black and White individuals, with appropriate weighting for both covariate imbalance across the two racial groups and generalizability. Via extensive simulation, we show that our proposed methods outperform traditional analytic approaches in terms of bias, mean squared error, and coverage when estimating the ACD for our setting of interest. In our data, we find that evidence of racial differences in telomere length between Black and White individuals attenuates after accounting for confounding by socioeconomic factors and utilizing appropriate propensity score and survey weighting techniques. Software to implement these methods and code to reproduce our results can be found in the R package svycdiff, available through the Comprehensive R Archive Network (CRAN) at cran.r-project.org/web/packages/svycdiff/, or in a development version on GitHub at github.com/salernos/svycdiff.},
}

Female
Humans
Male
Middle Aged
Bias
Black or African American/statistics & numerical data/genetics
Computer Simulation
*Health Status Disparities
Nutrition Surveys/statistics & numerical data
Propensity Score
Socioeconomic Factors
Telomere/genetics
United States
White/genetics/statistics & numerical data

@article {pmid41055602,
year = {2025},
author = {Song, X and Wang, CY},
title = {A Corrected Score Approach for Proportional Hazards Model With Error-Contaminated Covariates Subject to Detection Limits.},
journal = {Statistics in medicine},
volume = {44},
number = {23-24},
pages = {e70243},
pmid = {41055602},
issn = {1097-0258},
support = {R01AG085616/NH/NIH HHS/United States ; R03CA235122/NH/NIH HHS/United States ; R21 AI176947/AI/NIAID NIH HHS/United States ; R21 CA239168/CA/NCI NIH HHS/United States ; R01 HL130483/HL/NHLBI NIH HHS/United States ; 1916411//National Science Foundation/ ; R01 AG085616/AG/NIA NIH HHS/United States ; R21AI176947/NH/NIH HHS/United States ; UL1TR002378/NH/NIH HHS/United States ; UL1 TR002378/TR/NCATS NIH HHS/United States ; R21CA239168/NH/NIH HHS/United States ; R03 CA235122/CA/NCI NIH HHS/United States ; R01HL130483/NH/NIH HHS/United States ; },
mesh = {Humans ; Acquired Immunodeficiency Syndrome/drug therapy ; Bias ; Clinical Trials as Topic/statistics & numerical data ; Computer Simulation ; Likelihood Functions ; *Proportional Hazards Models ; Survival Analysis ; },
abstract = {In survival analysis under the proportional hazards model, covariates may be subject to both measurement error and detection limits. Most existing approaches only address one of these two complications and can lead to substantial bias and erroneous inference when dealing with both simultaneously. There is very limited research that addresses both these problems at the same time. These approaches are exclusively based on likelihood and require distribution assumptions on the underlying true covariates, as well as restricted independence assumptions on the censoring time. We propose a novel corrected score approach that relieves such stringent assumptions and is simpler in computation. The estimator is shown to be consistent and asymptotically normal. The finite sample performance of the proposed estimator is assessed through simulation studies and illustrated by application to data from an AIDS clinical trial. The approach can be used in the case of replicate data or instrumental data. It can also be extended to more general models and outcomes.},
}

Humans
Acquired Immunodeficiency Syndrome/drug therapy
Bias
Clinical Trials as Topic/statistics & numerical data
Computer Simulation
Likelihood Functions
*Proportional Hazards Models
Survival Analysis

@article {pmid41055680,
year = {2025},
author = {Halm, EA and Del Vecchio, NJ and Rendle, KA and Tiro, JA and Zheng, Y and Winer, RL and Haas, JS and Corley, DA and Skinner, CS and Schottinger, J and Ghai, NR and Chubak, J},
title = {Longitudinal Adherence to Screening for Colorectal, Cervical, and Lung Cancer in a US Consortium.},
journal = {Journal of general internal medicine},
volume = {},
number = {},
pages = {},
pmid = {41055680},
issn = {1525-1497},
support = {U24 CA221936/CA/NCI NIH HHS/United States ; UM1 CA221939/CA/NCI NIH HHS/United States ; },
abstract = {BACKGROUND: Effective screening for colorectal, cervical, and lung cancer requires adherence over time, but little is known about repeat testing in real-world practice.

OBJECTIVE: Describe patterns of longitudinal screening adherence and identify patient and system factors associated with repeat testing.

DESIGN: Retrospective cohort study of colorectal, cervical, or lung cancer screening in 2010-2019.

PARTICIPANTS: Adults eligible for repeat colorectal (stool-based), cervical, or lung cancer screening following a negative index test in ten regional health systems comprising the US PROSPR consortium.

MAIN MEASURES: Repeat screening based on guideline-recommended intervals. For the colorectal and lung cohorts with opportunities for multiple annual screening rounds, the main outcome was repeat screening categorized as none, inconsistent, or consistent.

RESULTS: The sample size was: 1,566,346 for colorectal, 216,344 for cervical, and 6,209 for lung cancer screening. For colorectal, cervical, and lung screeners, mean age at index was 58.2, 39.4, and 64.6 years, respectively, and 49%, 55% and 30% were Hispanic and/or non-white. Completion of the next screening round was 62% for colorectal, 56% for cervical, and 56% for lung cancer. For colorectal, over the next two rounds of testing, 53% were consistent, 33% inconsistent, and 14% no repeat screeners. The comparable percentages over 3 + rounds for colorectal were 40% consistent, 50% inconsistent, and 11% no repeat screeners. For lung, over the next two rounds, 47% were consistent, 31% inconsistent, and 22% no repeat screeners. The proportions over 3 + rounds for lung were 44% consistent, 42% inconsistent, and 14% no repeat screening. The health system was the strongest predictor of repeat and consistent testing with three- to ten-fold variation.

CONCLUSIONS: Adherence to longitudinal screening for colorectal, cervical and lung cancer was suboptimal, particularly as the number of testing rounds increased. System-level strategies are needed to increase screening adherence given the strong relationship between health system and outcomes.},
}

@article {pmid41056200,
year = {2025},
author = {Lee, T and Buchanan, AL and Katenka, N and Forastiere, L and Halloran, ME and Nikolopoulos, G},
title = {Assessing spillover effects: Handling missing outcomes in network-based studies.},
journal = {Statistical methods in medical research},
volume = {34},
number = {12},
pages = {2284-2301},
doi = {10.1177/09622802251382586},
pmid = {41056200},
issn = {1477-0334},
support = {DP2 DA046856/DA/NIDA NIH HHS/United States ; R01 AI085073/AI/NIAID NIH HHS/United States ; P30 DA011041/DA/NIDA NIH HHS/United States ; DP1 DA034989/DA/NIDA NIH HHS/United States ; R01 MH134715/MH/NIMH NIH HHS/United States ; R01 DA058994/DA/NIDA NIH HHS/United States ; },
mesh = {Humans ; Causality ; Computer Simulation ; HIV Infections/transmission/prevention & control ; *Models, Statistical ; *Probability ; Risk-Taking ; Substance Abuse, Intravenous ; },
abstract = {Estimating causal effects in the presence of spillover among individuals within a social network poses challenges due to missing information. Spillover effects refer to the impact of an intervention on individuals not directly exposed themselves but connected to intervention recipients within the network. In network-based studies, outcomes may be missing due to study termination or participant dropout, termed censoring. We introduce an inverse probability censoring weighted estimator which extends the inverse probability weighted estimator for network-based observational studies to handle possible outcome censoring. We prove the consistency and asymptotic normality of the proposed estimator and derive a closed-form estimator for its asymptotic variance. Applying the inverse probability censoring weighted estimator, we assess spillover effects in a network-based study of a nonrandomized intervention with outcome censoring. A simulation study evaluates the finite-sample performance of the inverse probability censoring weighted estimator, demonstrating its effectiveness with sufficiently large sample sizes and number of connected subnetworks. We then employ the method to assess spillover effects of community alerts on self-reported human immunodeficiency virus risk behavior among people who inject drugs and their contacts in the Transmission Reduction Intervention Project (TRIP), from 2013 to 2015, Athens, Greece. Results suggest that community alerts may help reduce human immunodeficiency virus risk behavior for both the individuals who receive them and others in their network, possibly through shared information. In this study, we found that the risk of human immunodeficiency virus behavior was reduced by increasing the proportion of a participant's immediate contacts exposed to community alerts.},
}

Humans
Causality
Computer Simulation
HIV Infections/transmission/prevention & control
*Models, Statistical
*Probability
Risk-Taking
Substance Abuse, Intravenous

@article {pmid41056445,
year = {2025},
author = {Jiang, CY and Hwang, H and Epstein, IY and Bakaloudi, DR and Talukder, R and Taylor, AK and Nizam, A and Jindal, T and Glover, MJ and Khaki, AR and Barata, PC and Nguyen, CB and Oh, E and Davis, NB and Mabey, H and Hoimes, CJ and Evans, ST and Abuqayas, B and Lemke, E and Tsung, I and Qiao, W and Kilari, D and Zakharia, Y and Bilen, MA and Milowsky, MI and Shah, SA and Gupta, S and Emamekhoo, H and Bellmunt, J and Alva, AS and Grivas, P and Msaouel, P and Koshkin, VS and Campbell, MT and Alhalabi, O},
title = {Efficacy of erdafitinib before or after enfortumab vedotin in FGFR3-altered advanced urothelial cancer: analysis of the UNITE collaborative study.},
journal = {The oncologist},
volume = {30},
number = {11},
pages = {},
pmid = {41056445},
issn = {1549-490X},
mesh = {Humans ; *Receptor, Fibroblast Growth Factor, Type 3/genetics ; Female ; Male ; Middle Aged ; Aged ; *Pyrazoles/therapeutic use/pharmacology/administration & dosage ; Retrospective Studies ; *Quinoxalines/therapeutic use/pharmacology/administration & dosage ; *Antibodies, Monoclonal/therapeutic use/pharmacology/administration & dosage ; *Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Aged, 80 and over ; *Urologic Neoplasms/drug therapy/pathology/genetics ; Adult ; },
abstract = {BACKGROUND: Erdafitinib is approved for locally advanced/metastatic urothelial cancer (LA/mUC). As enfortumab vedotin (EV) plus pembrolizumab enters frontline management, outcomes with erdafitinib pre- and post-EV are clinically relevant but not specifically evaluated in clinical trials.

METHODS: UNITE is a multi-institutional retrospective study of patients with LA/mUC treated with novel targeted agents. All patients with FGFR3 alterations treated with EV only, erdafitinib then EV (Erda->EV), and EV then erdafitinib (EV->Erda) were included. Sequential treatment with EV and Erda was not required. Primary endpoints were observed response rates (ORR) and progression-free survival (PFS); secondary endpoint was overall survival (OS).

RESULTS: We identified 83 patients with FGFR3 alterations and separated them into three cohorts: EV only (n = 44), Erda->EV (n = 24), and EV->Erda (n = 15). Most (72%) received ≥2 lines of therapy before erdafitinib (checkpoint inhibitor [87%], platinum-based chemotherapy [64%]). Median PFS with erdafitinib for EV-naïve cohort was 7.5 months and in EV-treated cohort 4.0 months (HR 0.78; 95% CI 0.35-1.7). ORR with erdafitinib for EV-naïve was 33% and EV-treated 31% (OR 1.1; 95% CI 0.29-4.1). Median PFS with EV for patients who were erdafitinib-naïve was 6 months and in erdafitinib-treated 5.3 months (HR 0.61; 95% CI 0.34-1.09). ORR with EV was 54% in erdafitinib-naïve cohort and 32% in erdafitinib-treated cohort (OR 2.5; 95% CI 0.87-6.3).

CONCLUSION: In patients with FGFR3-altered LA/mUC, erdafitinib is active pre- and post-EV. Outcomes with erdafitinib were consistent with clinical trial data generated prior to broader frontline use of EV. Findings are hypothesis-generating and given small sample size should be interpreted with caution.},
}

Humans
*Receptor, Fibroblast Growth Factor, Type 3/genetics
Female
Male
Middle Aged
Aged
*Pyrazoles/therapeutic use/pharmacology/administration & dosage
Retrospective Studies
*Quinoxalines/therapeutic use/pharmacology/administration & dosage
*Antibodies, Monoclonal/therapeutic use/pharmacology/administration & dosage
*Antineoplastic Combined Chemotherapy Protocols/therapeutic use
Aged, 80 and over
*Urologic Neoplasms/drug therapy/pathology/genetics
Adult

@article {pmid41056518,
year = {2025},
author = {Cassaday, RD},
title = {Challenges and opportunities for improvement in the practical management of adults with acute lymphoblastic leukemia.},
journal = {Blood advances},
volume = {9},
number = {24},
pages = {6345-6353},
pmid = {41056518},
issn = {2473-9537},
mesh = {Humans ; *Precursor Cell Lymphoblastic Leukemia-Lymphoma/therapy/diagnosis ; Adult ; Disease Management ; },
abstract = {As our approaches to the management of adults with acute lymphoblastic leukemia (ALL) have become more effective, they have introduced new administrative complexities. These include challenges pertaining to medication administration and financial implications of treatment choices. Because approximately half of these patients are typically treated outside of larger referral centers, these difficulties are being passed on to clinicians in settings that rarely encounter this complex disease. Instead of an evidence-focused review on contemporary management of ALL in adults, this article seeks to highlight how some of these important medical advances may be difficult to operationalize outside of high-volume centers. It will also attempt to identify areas in which clinicians and investigators might consider modifying their respective approaches to mitigate how the realities of modern medical care may affect our ability to optimally manage these patients now and in the future.},
}

Humans
*Precursor Cell Lymphoblastic Leukemia-Lymphoma/therapy/diagnosis
Adult
Disease Management

@article {pmid41056754,
year = {2025},
author = {Laing, KJ and Sholukh, AM and MacPhee, KJ and McClurkan, CL and Pagnon, A and Ruiz, J and Bchir, S and Oualim, A and Hyrien, O and Corey, L and Wald, A and Gurunathan, S and Noriega, F and Coronel, D and Koelle, DM},
title = {Safety and immunogenicity of investigational herpes simplex virus-2 vaccines in adults with recurrent genital infection.},
journal = {Vaccine},
volume = {65},
number = {},
pages = {127821},
doi = {10.1016/j.vaccine.2025.127821},
pmid = {41056754},
issn = {1873-2518},
mesh = {Humans ; *Herpes Genitalis/prevention & control/immunology ; *Herpesvirus 2, Human/immunology ; Female ; Adult ; Male ; Antibodies, Viral/blood ; Antibodies, Neutralizing/blood ; *Herpes Simplex Virus Vaccines/immunology/adverse effects/administration & dosage ; Middle Aged ; Young Adult ; *Immunogenicity, Vaccine ; CD4-Positive T-Lymphocytes/immunology ; Adjuvants, Immunologic/administration & dosage ; Double-Blind Method ; Adolescent ; },
abstract = {HSV529 and G103 are investigational therapeutic vaccines for genital herpes. HSV529 is a replication-defective HSV-2. G103 contains three recombinant HSV-2 proteins: truncated UL19 and gD2 and full-length UL25. A randomized, placebo-controlled clinical trial was conducted over a two-dose schedule to assess various combinations of G103 and HSV529 with GLA-SE adjuvant in 24 participants. No immediate unsolicited adverse reactions were observed. Most injection site reactions (>50 %) were grade 2 with one reported grade 3 swelling. Grade 2 systemic reactions (headache and myalgia) were independent of GLA-SE dose. The vaccine candidates showed adequate safety profiles. All participants had baseline immune responses to HSV-2. gD2, UL19, and UL25-specific CD4 T cells increased in G103 recipients after the first dose and were most robust for gD2. Binding antibody levels increased most markedly for UL25, as did neutralizing antibodies.},
}

Humans
*Herpes Genitalis/prevention & control/immunology
*Herpesvirus 2, Human/immunology
Female
Adult
Male
Antibodies, Viral/blood
Antibodies, Neutralizing/blood
*Herpes Simplex Virus Vaccines/immunology/adverse effects/administration & dosage
Middle Aged
Young Adult
*Immunogenicity, Vaccine
CD4-Positive T-Lymphocytes/immunology
Adjuvants, Immunologic/administration & dosage
Double-Blind Method
Adolescent

@article {pmid41057532,
year = {2025},
author = {Masterson, JM and Zheng, R and Luu, M and Murphy, A and Nyame, YA and Ritch, C and Gale, R and Spiegel, B and Freedland, SJ and Daskivich, TJ},
title = {Racial and ethnic differences in valuation of life expectancy in prostate cancer treatment decision making.},
journal = {Prostate cancer and prostatic diseases},
volume = {},
number = {},
pages = {},
pmid = {41057532},
issn = {1476-5608},
support = {K08 CA230155/CA/NCI NIH HHS/United States ; },
abstract = {BACKGROUND: Life expectancy (LE) is essential for triage between aggressive and conservative management for all prostate cancer risk subtypes. We sought to investigate differences in how Black and Hispanic men interpret LE in treatment decision-making.

METHODS: We used targeted crowdsourcing to sample a cohort reflecting sociodemographics of a US prostate cancer population. Subjects completed a conjoint analysis exercise where they iteratively chose between aggressive treatment versus conservative management across levels of 4 tradeoffs-tumor risk (lives saved by aggressive treatment at 5/10/20 year); erectile dysfunction; urinary incontinence; and irritative urinary symptoms-while considering their LE as calculated by the Prostate Cancer Comorbidity Index. Multinomial conditional logistic regression compared odds of choosing aggressive vs. conservative treatment across LEs ranging from 0 to 20 years overall and across racial/ethnic subgroups.

RESULTS: Of 2046 men, 435 (22%) were Black and 230 (11%) were Hispanic. Across all men, the odds of aggressive treatment choice increased by 17% for every 5 years of additional LE (OR = 1.17, 95%CI = 1.12-1.22, p < 0.001). Men were significantly more likely to choose aggressive treatment at LE > 13 y and non-aggressive treatment at LE ≤ 10 y. Among Black men, LE was not associated with treatment choice, as they consistently preferred aggressive treatment across all LE categories. Among Hispanic men, increased LE was associated with a higher likelihood of choosing aggressive treatment, with significant preference for aggressive treatment observed only when LE > 10 years. These patterns remained consistent when further stratified by tumor risk.

CONCLUSIONS: LE had no impact on treatment decisions in Black men, in contrast to other races and ethnicities. Future research is needed to identify reasons for this phenomenon and to inform culturally relevant approaches to communicating competing mortality risks.},
}

@article {pmid41057655,
year = {2025},
author = {Attard, G and Agarwal, N and Graff, JN and Sandhu, S and Efstathiou, E and Özgüroğlu, M and Pereira de Santana Gomes, AJ and Vianna, K and Luo, H and Gotto, GT and Cheng, HH and Kim, W and Varela, CR and Schaeffer, D and Kramer, K and Li, S and Baron, B and Shen, F and Mundle, SD and McCarthy, SA and Olmos, D and Chi, KN and Rathkopf, DE},
title = {Niraparib and abiraterone acetate plus prednisone for HRR-deficient metastatic castration-sensitive prostate cancer: a randomized phase 3 trial.},
journal = {Nature medicine},
volume = {31},
number = {12},
pages = {4109-4118},
pmid = {41057655},
issn = {1546-170X},
support = {P30 CA008748/CA/NCI NIH HHS/United States ; },
mesh = {Aged ; Aged, 80 and over ; Humans ; Male ; Middle Aged ; *Abiraterone Acetate/administration & dosage/adverse effects/therapeutic use ; *Antineoplastic Combined Chemotherapy Protocols/therapeutic use/adverse effects ; BRCA1 Protein/genetics ; BRCA2 Protein/genetics ; Double-Blind Method ; *Indazoles/administration & dosage/adverse effects/therapeutic use ; Neoplasm Metastasis ; *Piperidines/administration & dosage/adverse effects/therapeutic use ; Poly(ADP-ribose) Polymerase Inhibitors/administration & dosage ; *Prednisone/administration & dosage/adverse effects/therapeutic use ; Progression-Free Survival ; *Prostatic Neoplasms, Castration-Resistant/drug therapy/genetics/pathology ; *Recombinational DNA Repair/genetics/drug effects ; },
abstract = {Inhibition of poly(ADP-ribose) polymerase (PARP) after relapse on hormone therapy is well established for patients with prostate cancer with homologous recombination repair (HRR) gene alterations, but resistance often develops. We hypothesized that PARP inhibition within 6 months of starting androgen deprivation therapy for metastatic castration-sensitive prostate cancer (mCSPC) could be effective and improve radiographic progression-free survival when added to standard-of-care treatments. The double-blind AMPLITUDE trial evaluated combining niraparib, a potent and specific PARP inhibitor, with abiraterone acetate and prednisone (AAP) versus placebo and AAP in mCSPC with HRR gene alterations. Patients (n = 696) were randomized in a 1:1 ratio (348 per group). Median age was 68 years; 56% had BRCA1 or BRCA2 alterations; 78% had high-volume metastases; and 16% had received docetaxel. The primary endpoint was met, with a significant improvement in radiographic progression-free survival observed first in the BRCA subgroup (median not reached at the time of analysis for the niraparib and AAP group versus 26 months for the AAP group; hazard ratio = 0.52; 95% confidence interval: 0.37-0.72; P < 0.0001) and then in the intention-to-treat population (hazard ratio = 0.63; 95% confidence interval: 0.49-0.80; P = 0.0001). The data for overall survival, a key secondary endpoint, are immature (193/389 events) but favor niraparib (hazard ratio = 0.79 (95% confidence interval: 0.59-1.04); BRCA subgroup: hazard ratio = 0.75 (95% confidence interval: 0.51-1.11)). Incidence of grade 3 or 4 adverse events was 75% in the niraparib and AAP group and 59% in the AAP group; most frequent in the niraparib and AAP group were anemia (29%), with 25% of patients requiring a blood transfusion, and hypertension (27%). There were 14 treatment-emergent adverse events leading to deaths in the niraparib group and seven in the placebo group. Combining niraparib with AAP significantly improved radiographic progression-free survival in patients with mCSPC harboring BRCA1/BRCA2 or other HRR gene alterations, suggesting clinical benefit with this combination for these patients. ClinicalTrials.gov identifier: NCT04497844 .},
}

Aged
Aged, 80 and over
Humans
Male
Middle Aged
*Abiraterone Acetate/administration & dosage/adverse effects/therapeutic use
*Antineoplastic Combined Chemotherapy Protocols/therapeutic use/adverse effects
BRCA1 Protein/genetics
BRCA2 Protein/genetics
Double-Blind Method
*Indazoles/administration & dosage/adverse effects/therapeutic use
Neoplasm Metastasis
*Piperidines/administration & dosage/adverse effects/therapeutic use
Poly(ADP-ribose) Polymerase Inhibitors/administration & dosage
*Prednisone/administration & dosage/adverse effects/therapeutic use
Progression-Free Survival
*Prostatic Neoplasms, Castration-Resistant/drug therapy/genetics/pathology
*Recombinational DNA Repair/genetics/drug effects

@article {pmid41058534,
year = {2025},
author = {Peters, N and Haneda, E and Zhang, J and Karageorgos, G and Xia, W and Verburg, J and Wang, G and Paganetti, H and De Man, B},
title = {A hybrid training database and evaluation benchmark for assessing metal artifact reduction methods for X-ray CT imaging.},
journal = {Medical physics},
volume = {52},
number = {10},
pages = {e70020},
doi = {10.1002/mp.70020},
pmid = {41058534},
issn = {2473-4209},
mesh = {*Artifacts ; *Tomography, X-Ray Computed ; *Metals ; Benchmarking ; *Databases, Factual ; *Image Processing, Computer-Assisted/methods ; Humans ; Phantoms, Imaging ; Deep Learning ; Algorithms ; },
abstract = {BACKGROUND: Metal artifacts significantly degrade the image quality in computed tomography (CT) imaging, obscuring or even feigning pathology. While many different algorithms for metal artifact reduction (MAR) have been proposed, no comprehensive, clinically relevant evaluation benchmark exists. A major contributing factor to this is the lack of artifact-free ground truth data in clinical cases. Similarly, deep-learning based algorithms are hindered by the lack of paired training datasets with and without artifacts.

PURPOSE: We propose the simulation of a large training database for deep-learning based MAR algorithms as well as the definition of a comprehensive evaluation benchmark for MAR. For this we utilize and validate a framework for the realistic simulation of metal artifacts on clinical CT data.

METHODS: A clinical and a generic CT scanner geometry is modelled in the CatSim CT simulator within the open-access toolkit XCIST. Since most MAR research is performed in 2D, all datasets are simulated in 2D. The metal artifact simulation capability is experimentally validated in CT phantom scans containing various metal types and -geometries. The tool is then used to simulate metal artifact scenarios as training data for deep-learning algorithms utilizing two public CT databases. Lastly, a benchmark is defined for clinically realistic metal artifact scenarios and applied to a numerical and a deep-learning based MAR algorithm, respectively.

RESULTS: Within specified regions of interest, the mean CT number deviation between simulation and real data was less than 2%, making the simulation tool suitable for the aspired tasks. In total, 14,000 metal scenarios in the head, thorax and pelvis regions were simulated. For the clinical benchmark, a set of metrics covering CT number accuracy, noise, image sharpness, streak amplitude, structural integrity, and the effect on range in proton therapy, were defined for a range of clinical scenarios. Metal scenarios covered the most relevant clinical use cases, covering small metal implants such as fiducial markers up to large metal implants such as hip replacements. Both the simulation tools and the benchmark with the test cases were made publicly available.

CONCLUSIONS: We developed and distributed tools and datasets for the development and evaluation of MAR algorithms. This is the first comprehensive evaluation benchmark covering a large number of clinically realistic metal artifact scenarios.},
}

*Artifacts
*Tomography, X-Ray Computed
*Metals
Benchmarking
*Databases, Factual
*Image Processing, Computer-Assisted/methods
Humans
Phantoms, Imaging
Deep Learning
Algorithms

@article {pmid41058545,
year = {2025},
author = {Haneda, E and Peters, N and Zhang, J and Karageorgos, G and Xia, W and Paganetti, H and Wang, G and Guo, Y and Ma, J and Park, HS and Jeon, K and Fan, F and Thies, M and De Man, B},
title = {AAPM CT metal artifact reduction grand challenge.},
journal = {Medical physics},
volume = {52},
number = {10},
pages = {e70050},
pmid = {41058545},
issn = {2473-4209},
support = {R01 EB031102/EB/NIBIB NIH HHS/United States ; },
mesh = {*Artifacts ; *Metals ; *Tomography, X-Ray Computed ; *Image Processing, Computer-Assisted/methods ; Humans ; Algorithms ; },
abstract = {BACKGROUND: Metal artifact reduction (MAR) is a long-standing challenge in CT imaging. The presence of highly attenuating objects, such as dental fillings, hip prostheses, spinal screws/rods, and gold fiducial markers, can introduce severe streak artifacts in CT images, often reducing their diagnostic value. Existing CT MAR studies typically define their own test cases and evaluation metrics, making it difficult to objectively and comprehensively compare the performance of different MAR methods. There is a widespread need for a universal CT MAR image quality benchmark to evaluate the clinical impact of new MAR methods and compare them to state-of-the-art techniques.

PURPOSE: The goal of the AAPM CT Metal Artifact Reduction (CT-MAR) grand challenge was to create and distribute a clinically representative 2D MAR performance benchmark, and to invite participants to objectively compare the performance of their MAR methods based on this benchmark. A secondary goal was to facilitate MAR development by disseminating a MAR training database and tools. After completion of the grand challenge, the MAR benchmark and the MAR training database will remain publicly accessible for future MAR developments and benchmarking.

METHODS: Grand challenge participants were invited to submit results for their MAR algorithm. The challenge organizers provided 14,000 CT training datasets generated using a hybrid data simulation framework that combined real patient images-including lung, abdomen, liver, head, and pelvis-with virtual metal objects. Each training dataset included five types of data: CT sinograms (uncorrected and metal-free), CT reconstructed images (uncorrected and metal-free), and metal masks. In the final evaluation phase, 29 clinical uncorrected datasets with metal were provided in both the sinogram and image domains for participants to process with their MAR algorithms. Their results were evaluated using eight clinically relevant image quality metrics. The final ranking was determined and compared to an established normalized metal artifact reduction (NMAR) reference method. Additionally, we conducted a survey to better understand the methodologies used by participants.

RESULTS: A total of 106 teams registered for the challenge, with 26 teams completing all phases of the challenge. 92% of these-including all top ten teams-used a deep learning (DL) approach, employing a variety of network architectures such as UNet, ResNet, GAN, diffusion models, and transformers. Additionally, 22% of the teams-including the top three teams-utilized a combination of sinogram- and image-domain approaches. The results showed a broad distribution of the scores. Overall, the competition was marked by diverse methods and a wide range of results, including some truly exceptional results. More than 70% of the teams achieved a better overall score than the popular baseline NMAR method.

CONCLUSIONS: The CT-MAR grand challenge provided an opportunity to benchmark state-of-the-art MAR algorithms. Our hybrid data generation framework was a powerful tool for simulating large-scale realistic datasets for MAR algorithm development. A clinically relevant universal MAR benchmark offered an objective and meaningful way to compare different approaches. The training data and benchmark were published online to support future MAR development.},
}

*Artifacts
*Metals
*Tomography, X-Ray Computed
*Image Processing, Computer-Assisted/methods
Humans
Algorithms

@article {pmid41060040,
year = {2025},
author = {Nagarajan, R and Klotzman, V and Kondo, M and Godambe, S and Gold, A and Henderson, J and Martel, S},
title = {Taxonomy Portraits: Deciphering the Hierarchical Relationships of Medical Large Language Models.},
journal = {JMIR medical informatics},
volume = {13},
number = {},
pages = {e72918},
pmid = {41060040},
issn = {2291-9694},
mesh = {Humans ; *Language ; *Artificial Intelligence ; Benchmarking ; *Classification/methods ; Large Language Models ; },
abstract = {BACKGROUND: Large language models (LLMs) continue to enjoy enterprise-wide adoption in health care while evolving in number, size, complexity, cost, and most importantly performance. Performance benchmarks play a critical role in their ranking across community leaderboards and subsequent adoption.

OBJECTIVE: Given the small operating margins of health care organizations and growing interest in LLMs and conversational artificial intelligence (AI), there is an urgent need for objective approaches that can assist in identifying viable LLMs without compromising their performance. The objective of the present study is to generate taxonomy portraits of medical LLMs (n=33) whose domain-specific and domain non-specific multivariate performance benchmarks were available from Open-Medical LLM and Open LLM leaderboards on Hugging Face.

METHODS: Hierarchical clustering of multivariate performance benchmarks is used to generate taxonomy portraits revealing inherent partitioning of the medical LLMs across diverse tasks. While domain-specific taxonomy is generated using nine performance benchmarks related to medicine from the Hugging Face Open-Medical LLM initiative, domain non-specific taxonomy is presented in tandem to assess their performance on a set of six benchmarks and generic tasks from the Hugging Face Open LLM initiative. Subsequently, non-parametric Wilcoxon rank-sum test and linear correlation are used to assess differential changes in the performance benchmarks between two broad groups of LLMs and potential redundancies between the benchmarks.

RESULTS: Two broad families of LLMs with statistically significant differences (α=.05) in performance benchmarks are identified for each of the taxonomies. Consensus in their performance on the domain-specific and domain non-specific tasks revealed robustness of these LLMs across diverse tasks. Subsequently, statistically significant correlations between performance benchmarks revealed redundancies, indicating that a subset of these benchmarks may be sufficient in assessing the domain-specific performance of medical LLMs.

CONCLUSIONS: Understanding medical LLM taxonomies is an important step in identifying LLMs with similar performance while aligning with the needs, economics, and other demands of health care organizations. While the focus of the present study is on a subset of medical LLMs from the Hugging Face initiative, enhanced transparency of performance benchmarks and economics across a larger family of medical LLMs is needed to generate more comprehensive taxonomy portraits for accelerating their strategic and equitable adoption in health care.},
}

Humans
*Language
*Artificial Intelligence
Benchmarking
*Classification/methods
Large Language Models

@article {pmid41060772,
year = {2025},
author = {Sedovy, MW and Renton, MC and Roberts, K and Leng, X and Dennison, CL and Toler, CO and Leaf, MR and Lampe, PD and Best, AK and Isakson, BE and Johnstone, SR},
title = {Injury-induced connexin 43 expression regulates endothelial wound healing.},
journal = {American journal of physiology. Heart and circulatory physiology},
volume = {329},
number = {5},
pages = {H1361-H1377},
pmid = {41060772},
issn = {1522-1539},
support = {P01 HL120840/HL/NHLBI NIH HHS/United States ; NIH-HL137112//HHS | NIH | National Heart, Lung, and Blood Institute (NHLBI)/ ; AHA19CDA34630036//American Heart Association (AHA)/ ; F31 HL170721/HL/NHLBI NIH HHS/United States ; R21 HL168614/HL/NHLBI NIH HHS/United States ; AHA25POST1410066//American Heart Association (AHA)/ ; AHA23PRE1010870//American Heart Association (AHA)/ ; 25POST1410066/AHA/American Heart Association-American Stroke Association/United States ; R01 HL137112/HL/NHLBI NIH HHS/United States ; NIH-HL120840//HHS | NIH | National Heart, Lung, and Blood Institute (NHLBI)/ ; T32 HL007284/HL/NHLBI NIH HHS/United States ; 19CDA34630036/AHA/American Heart Association-American Stroke Association/United States ; NIH-F31HL170721//HHS | NIH | National Heart, Lung, and Blood Institute (NHLBI)/ ; NIH-R215R21HL168614-02//HHS | NIH | National Heart, Lung, and Blood Institute (NHLBI)/ ; },
mesh = {Animals ; *Connexin 43/genetics/metabolism ; *Wound Healing ; *Endothelial Cells/metabolism/pathology ; Mice, Knockout ; Mice ; *Carotid Artery Injuries/metabolism/pathology/genetics ; Cell Movement ; Mice, Inbred C57BL ; Cell Proliferation ; Disease Models, Animal ; Male ; Gap Junctions/metabolism ; },
abstract = {Endothelial cell (EC) injury is a major contributing factor to vascular surgical failure. As such, understanding the mechanisms of endothelial healing is essential to the development of vascular therapeutics and procedures. Gap junctions formed by connexin 43 (Cx43) are implicated in regulating skin wound healing, but their role in endothelial healing is unknown. Secondary analysis of RNA-seq data from in vivo injured mouse aortas (GEO: GSE115618) identified significant Cx43 upregulation in EC postinjury. We developed a novel in vivo model of EC injury using mouse carotid artery ligation to test the role of Cx43. We identified that EC immediately adjacent to the wound edge upregulate Cx43 protein expression, predominantly at cell-cell junctions. We show significantly delayed EC healing in a mouse model of inducible EC-specific Cx43 deletion [EC-Cx43 knockout (KO)] at 24 h post ligation. Single-cell RNA-seq analysis of 10,829 cells from 18 h injured EC-wild type (WT) and EC-Cx43 KO carotids revealed a Cx43-associated reduction in enrichment of EC pathways associated with migration, proliferation, and ERK/MAPK signaling pathways. Finally, the importance of Cx43 phosphorylation on EC healing was tested in mice with single-point alanine mutations (phospho-null) in known phosphorylation sites that alter Cx43 channel assembly and opening. Mice containing alanine mutations at ERK phosphorylated Cx43 serines (Cx43[S255/262/279/282A]) have reduced healing rates similar to EC-Cx43 KO mice. These data suggest that EC injury-induced Cx43 upregulation and subsequent Cx43 gap junction-mediated cell-to-cell communication are required for normal EC migration during wound healing after vascular injury.NEW & NOTEWORTHY These findings demonstrate for the first time that mechanical injury to large artery endothelium induces the expression of gap junction protein Cx43. This upregulation improves the migratory and proliferative capacity of endothelial cells at the wound edge, facilitating timely wound closure. This phenomenon is dependent on appropriate gap junction function and turnover.},
}

Animals
*Connexin 43/genetics/metabolism
*Wound Healing
*Endothelial Cells/metabolism/pathology
Mice, Knockout
Mice
*Carotid Artery Injuries/metabolism/pathology/genetics
Cell Movement
Mice, Inbred C57BL
Cell Proliferation
Disease Models, Animal
Male
Gap Junctions/metabolism

@article {pmid41060786,
year = {2025},
author = {Walsh, ME and Chetlapalli, K and Styler, BS and Upadhyayula, S and King, GA and Ünal, E},
title = {A conserved disruption of nucleocytoplasmic compartmentalization in meiosis is controlled by a kinase-phosphatase pair in Saccharomyces cerevisiae.},
journal = {Molecular biology of the cell},
volume = {36},
number = {12},
pages = {ar147},
pmid = {41060786},
issn = {1939-4586},
support = {R01 AG071801/AG/NIA NIH HHS/United States ; },
mesh = {*Saccharomyces cerevisiae/cytology/enzymology/metabolism/genetics ; *Meiosis/physiology ; *Saccharomyces cerevisiae Proteins/metabolism/genetics ; Nuclear Envelope/metabolism ; Cytoplasm/metabolism ; *Cell Nucleus/metabolism ; Nuclear Pore Complex Proteins/metabolism ; GTPase-Activating Proteins/metabolism ; Nuclear Pore/metabolism ; Schizosaccharomyces/metabolism ; },
abstract = {In eukaryotic organisms, the nucleus is remodeled to accommodate the space required for chromosome segregation. Remodeling strategies range from closed division, where the nuclear envelope remains intact, to open division, where the nuclear envelope is temporarily disassembled. While the budding yeast Saccharomyces cerevisiae (S. cerevisiae) undergoes closed mitosis, its meiotic nuclear division strategy is less understood. Here, we investigate nucleocytoplasmic compartmentalization during budding yeast meiosis and discover that meiosis II represents a semi-closed division marked by bidirectional mixing between the nucleus and cytoplasm. This includes nuclear entry of the Ran GTPase activating protein (RanGAP), typically cytoplasmic, although RanGAP relocalization appears to be a consequence, rather than a cause of permeability changes. This intercompartmental mixing occurs without nuclear envelope breakdown or dispersal of nucleoporins and is independent of known nuclear pore complex remodeling events. This phenomenon, termed virtual nuclear envelope breakdown (vNEBD), represents a unique mechanism distinct from other semi-closed divisions. We demonstrate that vNEBD is integrated into the meiotic program and regulated by the conserved meiotic kinase Ime2, and the meiosis-specific protein phosphatase 1 regulatory subunit, Gip1. Remarkably, the vNEBD event is conserved between S. cerevisiae and the distantly related Schizosaccharomyces pombe (S. pombe), indicating a fundamental role in meiosis.},
}

*Saccharomyces cerevisiae/cytology/enzymology/metabolism/genetics
*Meiosis/physiology
*Saccharomyces cerevisiae Proteins/metabolism/genetics
Nuclear Envelope/metabolism
Cytoplasm/metabolism
*Cell Nucleus/metabolism
Nuclear Pore Complex Proteins/metabolism
GTPase-Activating Proteins/metabolism
Nuclear Pore/metabolism
Schizosaccharomyces/metabolism

@article {pmid41061155,
year = {2026},
author = {Banerjee, R and Raje, NS},
title = {Vaccination during bispecific antibody treatment for myeloma.},
journal = {Blood advances},
volume = {10},
number = {2},
pages = {519-520},
pmid = {41061155},
issn = {2473-9537},
}

@article {pmid41061214,
year = {2025},
author = {McMurtry, CL and Givens, ML and Bailey, ZD and Graetz, N and Fleming, PJ and Petteway, RJ and Pacheco, J and Gollust, SE and Heller, JC and Lee, HE and Porter, KMP and Johnson, S and Michener, JD and LeBrón, AMW and Bailey, AK and Bloyd, J and Creary, M and Ornelas, IJ},
title = {Why Building Power Is Key to Protecting Academic Public Health and Advancing Health Equity.},
journal = {American journal of public health},
volume = {115},
number = {11},
pages = {1783-1788},
pmid = {41061214},
issn = {1541-0048},
}

@article {pmid41061233,
year = {2025},
author = {Dean, NE and Crisp, AM and Che-Mendoza, A and Kirstein, OD and Barrera-Fuentes, GA and Earnest, JT and Puerta-Guardo, HN and Collins, MH and Pavia-Ruz, N and Ayora-Talavera, G and González-Olvera, G and Medina-Barreiro, A and Bibiano-Marín, W and Jabbarzadeh, S and Halloran, ME and Longini, IM and Lenhart, A and Waller, LA and Correa-Morales, F and Palacio-Vargas, J and Gomez-Dantes, H and Manrique-Saide, P and Vazquez-Prokopec, GM},
title = {Randomized Trial of Targeted Indoor Spraying to Prevent Aedes-Borne Diseases.},
journal = {The New England journal of medicine},
volume = {393},
number = {14},
pages = {1387-1398},
pmid = {41061233},
issn = {1533-4406},
support = {R37 AI032042/AI/NIAID NIH HHS/United States ; U01 AI148069/AI/NIAID NIH HHS/United States ; U54 GM111274/GM/NIGMS NIH HHS/United States ; DFID: 30041-105//Bill and Melinda Gates Foundation/ ; },
mesh = {Adolescent ; Animals ; Child ; Child, Preschool ; Female ; Humans ; Male ; *Aedes/virology ; Chikungunya Fever/epidemiology/prevention & control/transmission ; Dengue/epidemiology/prevention & control/transmission ; Housing ; *Insecticides/administration & dosage ; Mexico/epidemiology ; *Mosquito Control/methods ; *Mosquito Vectors/virology ; *Mosquito-Borne Diseases/epidemiology/prevention & control/transmission ; Seasons ; Zika Virus Infection/epidemiology/prevention & control/transmission ; Incidence ; },
abstract = {BACKGROUND: Targeted indoor residual spraying focuses insecticide applications on common resting surfaces of Aedes aegypti mosquitoes (an arboviral disease vector) in houses, such as exposed lower sections of walls and under furniture.

METHODS: We conducted a two-group, parallel, unblinded, cluster-randomized trial in Merida, Mexico, to quantify the efficacy of targeted indoor residual spraying for preventing aedes-borne diseases (chikungunya, dengue, or Zika). Children 2 to 15 years of age were enrolled from households in 50 clusters of five-by-five city blocks. Households in 25 clusters received an annual application of targeted indoor residual spraying (intervention) before each season of aedes-borne disease (July through December). All clusters received routine Ministry of Health vector control. The primary end point was laboratory-confirmed, symptomatic aedes-borne disease. Community effects were assessed with the use of geolocated national surveillance data.

RESULTS: A total of 4461 children were monitored for up to three seasons (2021, 2022, and 2023). The indoor density of A. aegypti mosquitoes was 59% (95% confidence interval [CI], 51 to 65) lower with the intervention than with control. A total of 422 cases of aedes-borne disease were confirmed, primarily dengue in 2023. In the per-protocol analysis of cluster centers, 91 cases occurred among 1038 participants in the intervention group and 89 cases among 1037 participants in the control group (efficacy, -12.8%; 95% CI, -60.7 to 23.0). In an intention-to-treat analysis of entire clusters, 198 cases occurred among 2239 participants in the intervention group and 199 cases among 2222 participants in the control group (efficacy, 3.9%; 95% CI, -28.1 to 26.7). Adjustment of analyses for mobility or demographic characteristics did not change results. On the basis of 150 cases in the intervention clusters and 202 in the control clusters that were geolocated, the estimated community effect of the intervention was 24.0% (95% CI, 6.0 to 38.6). Two cases of multisymptom adverse events (e.g., nausea, watery eyes, diarrhea, and vomiting) were associated with the intervention.

CONCLUSIONS: Despite lower entomologic indexes with targeted indoor residual spraying than with routine vector control, the cumulative incidence of aedes-borne diseases was not significantly lower with targeted indoor residual spraying. (Funded by the National Institutes of Health and the Innovative Vector Control Consortium; ClinicalTrials.gov number, NCT04343521.).},
}

Adolescent
Animals
Child
Child, Preschool
Female
Humans
Male
*Aedes/virology
Chikungunya Fever/epidemiology/prevention & control/transmission
Dengue/epidemiology/prevention & control/transmission
Housing
*Insecticides/administration & dosage
Mexico/epidemiology
*Mosquito Control/methods
*Mosquito Vectors/virology
*Mosquito-Borne Diseases/epidemiology/prevention & control/transmission
Seasons
Zika Virus Infection/epidemiology/prevention & control/transmission
Incidence

@article {pmid41062463,
year = {2025},
author = {Ni, X and Richardson, RB and Godoy, AS and Ferla, MP and Kikawa, C and Scheen, J and Hannon, WW and Capkin, E and Lahav, N and Balcomb, BH and Marples, PG and Fairhead, M and Wang, S and Williams, EP and Tomlinson, CWE and Aschenbrenner, JC and Lithgo, RM and Winokan, M and Giroud, C and Dolci, I and Fernandes, RS and Oliva, G and Chandran, AV and Xavier, MA and Walsh, MA and Thompson, W and Bloom, JD and Kenton, NT and Lee, AA and von Delft, A and Barr, H and Kirkegaard, K and Koekemoer, L and Fearon, D and Evans, MJ and von Delft, F},
title = {Combined crystallographic fragment screening and deep mutational scanning enable discovery of Zika virus NS2B-NS3 protease inhibitors.},
journal = {Nature communications},
volume = {16},
number = {1},
pages = {8930},
pmid = {41062463},
issn = {2041-1723},
support = {U19 AI171399/AI/NIAID NIH HHS/United States ; U19AI171399//U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (NIAID)/ ; },
mesh = {*Zika Virus/drug effects/enzymology/genetics ; *Viral Nonstructural Proteins/genetics/antagonists & inhibitors/chemistry/metabolism ; *Protease Inhibitors/pharmacology/chemistry ; *Serine Endopeptidases/genetics/metabolism/chemistry ; Crystallography, X-Ray ; *Antiviral Agents/pharmacology/chemistry ; Mutation ; Drug Discovery/methods ; Binding Sites ; Models, Molecular ; Catalytic Domain ; Humans ; RNA Helicases/genetics/antagonists & inhibitors/chemistry/metabolism ; Protein Binding ; Viral Proteases ; Nucleoside-Triphosphatase ; DEAD-box RNA Helicases ; },
abstract = {The Zika viral protease NS2B-NS3 is essential for the cleavage of viral polyprotein precursor into individual structural and non-structural (NS) proteins and is therefore an attractive drug target. Generation of a robust crystal system of co-expressed NS2B-NS3 protease has enabled us to perform a crystallographic fragment screening campaign with 1076 fragments. 46 fragments with diverse scaffolds are identified to bind in the active site of the protease, with another 6 fragments observed in a potential allosteric site. To identify binding sites that are intolerant to mutation and thus suppress the outgrowth of viruses resistant to inhibitors developed from bound fragments, we perform deep mutational scanning of the NS2B-NS3 protease. Merging fragment hits yields an extensive set of 'mergers', defined as synthetically accessible compounds that recapitulate constellations of observed fragment-protein interactions. In addition, the highly sociable fragment hits enable rapid exploration of chemical space via algorithmic calculation and thus yield diverse possible starting points. In this work, we maximally explore the binding opportunities to NS2B-NS3 protease, facilitating its resistance-resilient antiviral development.},
}

*Zika Virus/drug effects/enzymology/genetics
*Viral Nonstructural Proteins/genetics/antagonists & inhibitors/chemistry/metabolism
*Protease Inhibitors/pharmacology/chemistry
*Serine Endopeptidases/genetics/metabolism/chemistry
Crystallography, X-Ray
*Antiviral Agents/pharmacology/chemistry
Mutation
Drug Discovery/methods
Binding Sites
Models, Molecular
Catalytic Domain
Humans
RNA Helicases/genetics/antagonists & inhibitors/chemistry/metabolism
Protein Binding
Viral Proteases
Nucleoside-Triphosphatase
DEAD-box RNA Helicases

@article {pmid41062500,
year = {2025},
author = {Jiménez-Vacas, JM and Westaby, D and Figueiredo, I and De Haven Brandon, A and Padilha, A and Yuan, W and Seed, G and Bogdan, D and Gurel, B and Bertan, C and Miranda, S and Lambros, M and Montero-Hidalgo, AJ and Coleman, I and Yu, IPL and Buroni, L and Zeng, W and Neeb, AJ and Welti, J and Rekowski, J and Paravati, R and Gabel, F and Pandell, N and Ferreira, A and Crespo, M and Riisnaes, R and Das, S and Taylor, J and Waldron, N and Hobern, E and Valenti, M and Ning, J and Bernett, I and Liodaki, K and Persse, T and Galipeau, P and Wilkinson, S and Trostel, SY and Karzai, F and Chau, CH and Beatson, EL and Zhang, X and Klumpp-Thomas, C and Varkaris, A and Luque, RM and Swain, A and Raynaud, F and Lack, NA and Thomas, CJ and Ha, G and Figg, WD and Bezzi, M and Sowalsky, AG and Nelson, PS and Carreira, S and Balk, SP and de Bono, JS and Sharp, A},
title = {Elucidating molecularly stratified single agent, and combination, therapeutic strategies targeting MCL1 for lethal prostate cancer.},
journal = {Nature communications},
volume = {16},
number = {1},
pages = {8806},
pmid = {41062500},
issn = {2041-1723},
support = {IES\R3\213131//Royal Society of Medicine (RSM)/ ; Clinical Research Career Development Fellowship//Wellcome Trust (Wellcome)/ ; R21 CA277368/CA/NCI NIH HHS/United States ; R50 CA274336/CA/NCI NIH HHS/United States ; /WT_/Wellcome Trust/United Kingdom ; P01 CA163227/CA/NCI NIH HHS/United States ; Challenge Award//Prostate Cancer Foundation (PCF)/ ; },
mesh = {*Myeloid Cell Leukemia Sequence 1 Protein/genetics/metabolism/antagonists & inhibitors ; Male ; Humans ; *Prostatic Neoplasms, Castration-Resistant/drug therapy/genetics/pathology/metabolism ; Animals ; Cell Line, Tumor ; Mice ; Proto-Oncogene Proteins c-akt/antagonists & inhibitors/metabolism ; Xenograft Model Antitumor Assays ; PTEN Phosphohydrolase/metabolism/genetics ; Phosphatidylinositol 3-Kinases/metabolism ; Gene Expression Regulation, Neoplastic/drug effects ; Apoptosis/drug effects ; bcl-Associated Death Protein/metabolism ; Bcl-2-Like Protein 11/metabolism ; },
abstract = {Metastatic castration-resistant prostate cancer (mCRPC) is a lethal disease requiring additional therapeutic strategies. MCL1, an anti-apoptotic BCL2 family member, promotes cancer-cell survival, but its role in mCRPC remains poorly understood. Here, we characterise MCL1 in multiple mCRPC biopsy cohorts and patient-derived models, assessing responses to MCL1 inhibition. MCL1 copy number gain (14%-34%) correlates with increased MCL1 expression and worse outcomes. MCL1 inhibition exhibits anti-tumour effects in MCL1-gained mCRPC models. Co-inhibition of MCL1 and AKT induces cancer-specific cell death in PTEN-loss/PI3K-activated models in vitro and in vivo, modulating BAD-BCLXL and BIM-MCL1 interactions, with durable anti-tumour activity in models with AKT inhibitor acquired resistance. Finally, CDK9-mediated MCL1 downregulation combined with AKT inhibition recapitulates these findings, providing further opportunities for clinical translation. These data support early phase clinical trials targeting MCL1, both as monotherapy for MCL1-gained mCRPC, and in combination with AKT inhibition for PTEN-loss/PI3K-activated mCRPC.},
}

*Myeloid Cell Leukemia Sequence 1 Protein/genetics/metabolism/antagonists & inhibitors
Male
Humans
*Prostatic Neoplasms, Castration-Resistant/drug therapy/genetics/pathology/metabolism
Animals
Cell Line, Tumor
Mice
Proto-Oncogene Proteins c-akt/antagonists & inhibitors/metabolism
Xenograft Model Antitumor Assays
PTEN Phosphohydrolase/metabolism/genetics
Phosphatidylinositol 3-Kinases/metabolism
Gene Expression Regulation, Neoplastic/drug effects
Apoptosis/drug effects
bcl-Associated Death Protein/metabolism
Bcl-2-Like Protein 11/metabolism

@article {pmid41062885,
year = {2025},
author = {Nayak, P and Kosiorek, H and Pai, RK and Shivji, S and Hagen, CE and Graham, RP and Buchanan, DD and Jenkins, MA and Phipps, AI and Le Marchand, L and Wu, C and Samadder, NJ and Swallow, CJ and Gallinger, SJ and Grant, RC and Westerling-Bui, T and Conner, J and Cyr, DP and Kirsch, R and Pai, RK},
title = {Utility of quantitative pathologic analysis of pT1 colorectal carcinomas to improve prediction of lymph node metastasis.},
journal = {Virchows Archiv : an international journal of pathology},
volume = {},
number = {},
pages = {},
pmid = {41062885},
issn = {1432-2307},
support = {U01CA167551//Division of Cancer Epidemiology and Genetics, National Cancer Institute/ ; },
abstract = {According to the National Comprehensive Cancer Network (NCCN), submucosally invasive (pT1) colorectal carcinomas (CRCs) should be evaluated for tumor grade, lymphatic invasion, and tumor budding to determine the risk of lymph node metastasis. The presence of any one of these high-risk features is an indication for surgery in endoscopically removed pT1 CRCs. In this study, we determined if quantitative pathologic analysis with the QuantCRC algorithm can augment NCCN risk stratification in a multi-institutional cohort of 512 surgically resected pT1 CRC. LASSO regression identified %high-grade, %inflammatory stroma (stromal area), and %tumor budding/poorly differentiated clusters (%TB/PDC) as important QuantCRC features and were used in subsequent logistic regression analysis. Five logistic regression models were built using NCCN and QuantCRC variables, with the combined NCCN + QuantCRC model providing the highest Area Under the Curve (AUC) of 0.74 (95% CI 0.68-0.81). A predicted probability cutoff of 0.092 provided a sensitivity of 78.3% and specificity of 62.1% in the NCCN + QuantCRC model with a 24.3% rate of lymph node positivity for high-risk (HR) tumors compared to 5.2% for low-risk (LR) CRCs. Fifteen pT1 CRCs were reclassified from NCCN LR to NCCN + QuantCRC HR and 3/15 (20%) demonstrated lymph node positivity. The median predicted probability of lymph node metastasis in the NCCN + QuantCRC model was used to define two HR groups (HR1: 0.092-0.218 and HR2: > 0.218). HR2 CRCs had a rate of lymph node positivity of 31.5% compared to 17.1% for HR1 CRCs (P = 0.02). Lastly, the NCCN + QuantCRC model was validated in a cohort of 29 endoscopically resected pT1 CRCs followed by surgical resection. In the NCCN + QuantCRC model, the 8 pN + CRCs in this cohort had a higher median predicted probability of lymph node metastasis compared to 21 pN0 CRCs (0.219 vs. 0.080, P = 0.04). In summary, the addition of variables from QuantCRC can improve risk stratification of pT1 CRCs over NCCN criteria alone.},
}

@article {pmid41063102,
year = {2025},
author = {Ebenezer, A and Iyaniwura, SA and Omame, A and Han, Q and Wang, X and Bragazzi, NL and Woldegerima, WA and Kong, JD},
title = {Understanding cholera dynamics in African countries with persistent outbreaks: a mathematical modeling approach.},
journal = {BMC public health},
volume = {25},
number = {1},
pages = {3395},
pmid = {41063102},
issn = {1471-2458},
support = {GPIN-2022-04559//NSERC Discovery Grant/ ; DGECR-2022-00454//NSERC Discovery Launch Supplement/ ; FRFE310 2021-00879//SSHRC-New Frontier in Research Fund- Exploratory/ ; 109981//Canada's International Development Research Centre (IDRC)/ ; },
mesh = {*Cholera/epidemiology/transmission ; Humans ; *Disease Outbreaks/statistics & numerical data ; Africa/epidemiology ; *Models, Theoretical ; Bayes Theorem ; Basic Reproduction Number ; Machine Learning ; },
abstract = {BACKGROUND: Cholera, caused by Vibrio cholerae, is a global health challenge, spreading through water in areas lacking clean water and sanitation. Since 2021, the reemergence of cholera cases has increased significantly in endemic regions in Africa. In particular, the continent experienced severe outbreaks between 2022 and 2024 due to droughts and cyclones, which have placed additional strain on healthcare systems.

OBJECTIVE: This study aims to investigate the dynamics of cholera outbreaks in eight African countries using mathematical modeling and machine learning and to provide information for public health decision making. By estimating key model parameters and epidemiological indicators, such as the basic reproduction number, we aim to identify and quantify the impacts of key transmission drivers. Using this together to socioeconomical factors, we will be classifying cholera persistent countries with similar dynamics using unsupervised learning. In addition, the study seeks to provide information on cholera outbreaks and management across the selected countries, identify key drivers of outbreak intensity, and propose targeted intervention strategies.

METHODS: A compartmentalized epidemiological model with indirect transmission routes is analyzed for cholera dynamics in eight African countries with persistent outbreaks. The key parameters and initial values of the model's variables were estimated using a Bayesian framework. We assessed some outcomes such as the reproduction number, "[Formula: see text]," outbreak peak duration and size. Moreover, environmental and socioeconomic data were used in hierarchical clustering to group countries by outbreak characteristics.

RESULTS: The study uncovered variation in cholera outbreak dynamics across the considered countries. Based on our model results, the median basic reproduction number ([Formula: see text]) across the endemic countries was 2.0 (SD : 0.454), which ranges from 1.41 in Zimbabwe to 2.80 in Mozambique. Furthermore, the results of the sensitivity analysis emphasized the significance of the maximum infection rate and the bacteria shedding rate in driving cholera outbreaks across the endemic regions in Africa. Hierarchical clustering revealed three distinct groups of countries based on outbreak dynamics and socioeconomic indicators: the chronic sanitation issues cluster (Somalia, Cameroon, and Comoros); the economic and infrastructure challenges cluster (Sudan, Zimbabwe, and Zambia); and the natural disaster cluster (Malawi and Mozambique).

CONCLUSION: This study highlights the drivers of cholera outbreaks across African countries, emphasizing the need for tailored interventions that consider underlying socio-demographic and environmental vulnerabilities. The findings underscore the importance of integrating data-driven approaches into cholera preparedness and response efforts to mitigate its impact.},
}

*Cholera/epidemiology/transmission
Humans
*Disease Outbreaks/statistics & numerical data
Africa/epidemiology
*Models, Theoretical
Bayes Theorem
Basic Reproduction Number
Machine Learning

@article {pmid41063387,
year = {2025},
author = {Chari, ST and Feng, Z and Wu, B and Fisher, W and Kambadakone, A and Zhao, YQ and Maitra, A and Kenner, B and Matrisian, LM},
title = {Heuriskance: a novel paradigm for systematic earlier detection of sporadic pancreatic cancer.},
journal = {Journal of the National Cancer Institute},
volume = {},
number = {},
pages = {},
pmid = {41063387},
issn = {1460-2105},
support = {U24 CA086368/CA/NCI NIH HHS/United States ; U01 DK126365/DK/NIDDK NIH HHS/United States ; U01 DK108328/DK/NIDDK NIH HHS/United States ; UG1 CA287013/CA/NCI NIH HHS/United States ; U01 DK108326/DK/NIDDK NIH HHS/United States ; },
abstract = {Early detection is key to improving survival and mortality from pancreatic cancer. Traditional periodic screening for cancer in an asymptomatic population is infeasible and not recommended for this low-incidence disease. We describe a novel approach we call "heuriskance" (hyou-ris-kance) wherein a systematic search for and onetime workup of a "heurisk" (hyou-risk) leads to earlier detection of cancer. A heurisk is an early warning sign with three defining characteristics: i) indicates higher-than-threshold-probability of having prevalent invasive cancer, ii) is associated with a meaningful lead time to diagnosis, and iii) is identifiable by a systematic and scalable process in the population. Heuriskance aims to systematically detect cancer with clinically meaningful lead time to clinical diagnosis, minimize proportion of patients with advanced disease, and maximize treatment options leading to increases in lead time-adjusted 1-, 3- and eventually 5- year survival. A specific example of a heurisk for pancreatic cancer is glycemically defined new onset diabetes (GNOD) and the Early Detection Initiative (NCT04662879) an example of GNOD-based heuriskance. As heuriskance has no precedent, we provide i) a tiered risk stratification approach (Define-Enrich-Find), ii) metrics for choosing a heurisk, iii) success metrics for strategy and iv) Phases 1-5 for evaluating the strategy in retrospective and prospective studies. Like all current cancer therapies, heuriskance aims to iteratively improve survival from a fatal disease using a pragmatic, evidence-based systematic approach to its earlier detection. The concept of heuriskance is applied to pancreatic cancer but could be extended to other cancer types.},
}

@article {pmid41063661,
year = {2026},
author = {Sesay, FA and Oware, K and Violette, LR and Donnell, D and Odoyo, JB and Omollo, V and Mogaka, FO and McClelland, RS and Balkus, JE and Bukusi, EA and Baeten, JM and Stewart, J},
title = {Trichomonas vaginalis Among Cisgender Women Taking Doxycycline Postexposure Prophylaxis.},
journal = {The Journal of infectious diseases},
volume = {233},
number = {2},
pages = {411-415},
pmid = {41063661},
issn = {1537-6613},
support = {K23 MH124466/MH/NIMH NIH HHS/United States ; P30 AI027757/AI/NIAID NIH HHS/United States ; R01 AI145971/AI/NIAID NIH HHS/United States ; R01AI145971/GF/NIH HHS/United States ; K23MH124466/GF/NIH HHS/United States ; P30AI027757/GF/NIH HHS/United States ; },
mesh = {Humans ; *Doxycycline/therapeutic use/administration & dosage ; Female ; *Trichomonas vaginalis/drug effects/isolation & purification ; Adult ; Kenya/epidemiology ; *Post-Exposure Prophylaxis ; *Anti-Bacterial Agents/therapeutic use ; Young Adult ; *Trichomonas Vaginitis/prevention & control/epidemiology/drug therapy ; Adolescent ; *Trichomonas Infections/prevention & control/epidemiology ; },
abstract = {Doxycycline treats and prevents several bacterial and parasitic infections and has been proposed as a possible treatment for Trichomonas vaginalis. Nested in a trial of doxycycline postexposure prophylaxis among cisgender women in Kenya, we conducted a secondary analysis of incident T. vaginalis infections. Among 224 cisgender women randomized to doxycycline postexposure prophylaxis and 225 to standard-of-care, there were 27 T. vaginalis diagnoses in the doxycycline postexposure prophylaxis group and 29 in the standard-of-care group (RR: 0.96, 95% CI: 0.54-1.73, P = .9). Understanding doxycycline postexposure prophylaxis's impact on T. vaginalis remains an important public health question that warrants further investigation.},
}

Humans
*Doxycycline/therapeutic use/administration & dosage
Female
*Trichomonas vaginalis/drug effects/isolation & purification
Adult
Kenya/epidemiology
*Post-Exposure Prophylaxis
*Anti-Bacterial Agents/therapeutic use
Young Adult
*Trichomonas Vaginitis/prevention & control/epidemiology/drug therapy
Adolescent
*Trichomonas Infections/prevention & control/epidemiology

@article {pmid41063982,
year = {2025},
author = {Mbuya, W and Horvath, A and Held, K and Maganga, L and Hoelscher, M and Bekker, LG and Duerr, A and Moodie, Z and Churchyard, G and Keefer, MC and Viegas, E and Moog, C and Geldmacher, C and Chachage, M},
title = {Effects of sex but not race and geographic origin on vaccine-induced HIV-specific antibody responses.},
journal = {Frontiers in immunology},
volume = {16},
number = {},
pages = {1601865},
pmid = {41063982},
issn = {1664-3224},
support = {UM1 AI068635/AI/NIAID NIH HHS/United States ; },
mesh = {Adult ; Female ; Humans ; Male ; Middle Aged ; Young Adult ; *AIDS Vaccines/immunology/administration & dosage ; Antibody Formation ; Double-Blind Method ; *HIV Antibodies/blood/immunology ; *HIV Infections/immunology/prevention & control/virology ; *HIV-1/immunology ; Immunoglobulin A/blood/immunology ; Immunoglobulin G/blood/immunology ; Sex Factors ; South Africa ; White/statistics & numerical data ; Black People/statistics & numerical data ; United States ; },
abstract = {BACKGROUND: Sex, race and geographic location may affect vaccine-induced immune responses, yet few preventive HIV vaccine trials have systematically evaluated such effects. The main objective of this study was therefore to examine the role of these factors on vaccine-induced HIV-specific immune responses within the HVTN 204 trial. This randomized, double-blinded, placebo-controlled phase 2 trial enrolled 480 Black and Caucasian adults from Africa and the Americas, who received a trivalent DNA-HIV-1 vaccine prime followed by a rAd5 vector HIV-1 vaccine boost.

METHODS: Available serum samples from baseline and four weeks after the final vaccination boost from Black (n=85, 59% female) and Caucasian (n=49, 51% female) HVTN 204 vaccine recipients from South Africa and the United States of America were studied using an Enzyme-Linked Immunosorbent Assay to determine titers of Envelope-specific IgG1, IgG3 and IgA antibodies. Recognition of linear Envelope peptide-specific IgG responses was mapped in a randomly selected subgroup analysis using a custom-designed peptide microarray (n = 41, 49% female). Associations between vaccine-induced Envelope-specific antibody responses and sex assigned at birth (female or male), race and geographic location were then analyzed by the Mann-Whitney U test, Fisher's exact test and multivariate logistic regression.

RESULTS: Four weeks post-final vaccination boost, we observed that Envelope-specific antibody titers were significantly increased for IgG1 but reduced for IgA in females (female vs. male median titer: 900 vs. 300, p=0.030 and <100 vs. 100, p=0.007, respectively). Multivariate logistic regression confirmed that female sex increased the odds for higher Envelope-specific IgG1 and low IgA titers compared to males. In terms of antibody epitopes, the V2 region was more frequently recognized in females than males (p=0.008). Race and geographic location had no apparent influence on antibody isotype titers investigated.

CONCLUSION: Female sex was associated with higher vaccine-induced IgG Envelope-specific binding antibody titers and recognition of V2 region of HIV Envelope in HVTN 204 volunteers. No such associations were detected for race or geographic location. Understanding biological factors driving these sex-based differences may improve the design of a new generation of HIV vaccine candidates.},
}

Adult
Female
Humans
Male
Middle Aged
Young Adult
*AIDS Vaccines/immunology/administration & dosage
Antibody Formation
Double-Blind Method
*HIV Antibodies/blood/immunology
*HIV Infections/immunology/prevention & control/virology
*HIV-1/immunology
Immunoglobulin A/blood/immunology
Immunoglobulin G/blood/immunology
Sex Factors
South Africa
White/statistics & numerical data
Black People/statistics & numerical data
United States

@article {pmid41065113,
year = {2025},
author = {Palacios, N and Gordon, S and Wang, T and Burk, R and Qi, Q and Huttenhower, C and Gonzalez, HM and Knight, R and De Carli, C and Daviglus, M and Lamar, M and Telavera, G and Tarraf, W and Kosciolek, T and Cai, J and Kaplan, RC},
title = {Gut microbiome and cognitive function in the Hispanic Community Health Study/Study of Latinos.},
journal = {Journal of Alzheimer's disease : JAD},
volume = {108},
number = {1},
pages = {84-97},
doi = {10.1177/13872877251376911},
pmid = {41065113},
issn = {1875-8908},
support = {R01 AG085320/AG/NIA NIH HHS/United States ; RF1 AG075922/AG/NIA NIH HHS/United States ; },
mesh = {Aged ; Female ; Humans ; Male ; Middle Aged ; *Cognition/physiology ; Cohort Studies ; Feces/microbiology ; *Gastrointestinal Microbiome/physiology ; *Hispanic or Latino/psychology ; },
abstract = {BackgroundThere is limited work on the association between the gut microbiome and Alzheimer's disease and related dementia (AD/ADRD) in Latinos.ObjectiveWe examined, within the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) cohort, the association between gut microbiome and cognitive function.MethodsWe analyzed the fecal metagenomes of 2471 HCHS/SOL participants to identify microbial taxonomic and functional features associated with global cognitive function. Omnibus (PERMANOVA) and feature-wise analyses (MaAsLin2) were conducted to identify microbiome-cognition associations, and specific microbial species and pathways (Kyoto Encyclopedia of Genes and Genomes (KEGG modules) associated with cognition.ResultsEubacterium species (E. siraeum and E. eligens), and C phoceensis, among other species were associated with better cognition. Several KEGG modules, most strongly Ornithine, Serine biosynthesis and Urea Cycle, were associated with worse cognition.ConclusionsIn a large Hispanic/Latino cohort, we identified several microbial taxa and KEGG pathways associated with cognition.},
}

Aged
Female
Humans
Male
Middle Aged
*Cognition/physiology
Cohort Studies
Feces/microbiology
*Gastrointestinal Microbiome/physiology
*Hispanic or Latino/psychology

@article {pmid41065373,
year = {2026},
author = {Pradere, B and Schuit, M and Guerrero-Ramos, F and Shariat, SF and Kitamura, H and Jacob, JM and Bao, Y and Heesakkers, J and Peters, KM and Cahn, DJ and De Troyer, B and Herrera Imbroda, B and Morris, DS and Pieczonka, CM and Wei, Q and Bhanvadia, S and Somer, R and Jessner, W and Triantos, S and Sánchez de Llano, C and Maffeo, JC and Sweiti, H and Psutka, SP},
title = {Side effect management and procedural best practices with indwelling intravesical drug-releasing systems in the treatment of bladder cancer: recommendations from expert panels.},
journal = {Current opinion in urology},
volume = {36},
number = {1},
pages = {123-133},
pmid = {41065373},
issn = {1473-6586},
mesh = {Humans ; *Urinary Bladder Neoplasms/drug therapy ; Administration, Intravesical ; Hematuria/therapy/chemically induced ; *Catheters, Indwelling/adverse effects/standards ; Urinary Tract Infections/therapy/chemically induced ; *Lower Urinary Tract Symptoms/therapy/chemically induced ; Practice Guidelines as Topic ; *Antineoplastic Agents/administration & dosage/adverse effects ; *Drug Delivery Systems/adverse effects ; Treatment Outcome ; },
abstract = {PURPOSE OF REVIEW: To provide expert recommendations for side effect management in patients with bladder cancer receiving intravesical-drug releasing system (iDRS) treatment and for optimizing iDRS insertion procedure success.

RECENT FINDINGS: Indwelling iDRS are designed to provide sustained local exposure to therapy. In clinical trials, frequent side effects of iDRS treatment were lower urinary tract symptoms (LUTS) (e.g., dysuria, pollakiuria, micturition urgency), urinary tract infections (UTIs), and hematuria. These side effects are generally low grade, but if not properly managed, may lead to treatment interruptions or discontinuations. As data are limited, practical recommendations based on expert opinion for the management of common side effects and best practices for iDRS insertion procedures may improve treatment adherence and optimize outcomes in patients with bladder cancer receiving iDRS.

SUMMARY: Two separate expert panels were convened to develop recommendations for side effect management with iDRS and optimizing iDRS insertion procedure success. Stepwise treatment-specific management strategies for LUTS, UTIs, and hematuria in patients receiving iDRS treatment that are familiar to practicing urologists are presented, including considerations for continuation or discontinuation of iDRS treatment. Several advanced techniques can be considered to improve iDRS insertions based on variations in patient anatomy.},
}

Humans
*Urinary Bladder Neoplasms/drug therapy
Administration, Intravesical
Hematuria/therapy/chemically induced
*Catheters, Indwelling/adverse effects/standards
Urinary Tract Infections/therapy/chemically induced
*Lower Urinary Tract Symptoms/therapy/chemically induced
Practice Guidelines as Topic
*Antineoplastic Agents/administration & dosage/adverse effects
*Drug Delivery Systems/adverse effects
Treatment Outcome

@article {pmid41066089,
year = {2025},
author = {O'Brien, KM and Keil, AP and Taylor, JA and Weinberg, CR and Polley, EC and Yadav, S and Boddicker, NJ and Hu, C and Ambrosone, CB and Anton-Culver, H and Auer, PL and Bodelon, C and Brantley, K and Burnside, ES and Chen, F and Domchek, SM and Eliassen, AH and Haiman, CA and Hodge, JM and Kraft, P and Lacey, JV and Lindstroem, S and Martinez, ME and Nathanson, KL and Neuhausen, SL and Olson, JE and Palmer, JR and Patel, AV and Penney, KL and Ruddy, KJ and Scott, CG and Teras, LR and Trentham-Dietz, A and Vachon, CM and Weitzel, JN and Yao, S and Zirpoli, G and Couch, FJ and Sandler, DP},
title = {Pathogenic Variants, Family History, and Cumulative Risk of Breast Cancer in US Women.},
journal = {JAMA oncology},
volume = {11},
number = {12},
pages = {1458-1469},
pmid = {41066089},
issn = {2374-2445},
mesh = {Humans ; Female ; United States/epidemiology ; Middle Aged ; Aged ; Aged, 80 and over ; *Genetic Predisposition to Disease/epidemiology/genetics ; *Breast Neoplasms/epidemiology/genetics ; Pedigree ; Case-Control Studies ; Risk Factors ; Incidence ; Models, Statistical ; Risk Assessment ; Medical History Taking ; Genetic Variation/genetics ; Ataxia Telangiectasia Mutated Proteins ; BRCA2 Protein ; Checkpoint Kinase 2 ; Fanconi Anemia Complementation Group N Protein ; BRCA1 Protein ; },
abstract = {IMPORTANCE: Inherited pathogenic variants (PVs) in known predisposition genes can greatly increase breast cancer risk, but the combined impact of PV status, family history, and other factors on breast cancer risk in the general US population has not been well described.

OBJECTIVE: To evaluate population-based breast cancer risk estimates for those with established PVs overall and stratified by first-degree family history of breast cancer and other factors.

This study used pooled data from 13 US-based breast cancer case-control studies participating in the Cancer Risk Estimates Related to Susceptibility (CARRIERS) consortium. Enrollment for individual studies occurred between 1976 and 2013, and results are based on data released March 2023, with analyses conducted from June 2022 to July 2025.

EXPOSURES: PVs, breast cancer family history, self-reported race and ethnicity, and established risk factors.

MAIN OUTCOMES AND MEASURES: Breast cancer rate ratios for PVs in 7 genes were estimated from the CARRIERS consortium. PV status and incidence and mortality statistics were combined using the Individualized Coherent Absolute Risk Estimation (iCARE) model to estimate conditional cumulative breast cancer risks and 95% CIs, stratified by family history and standardized to the US population. Models that incorporated population-based data and published estimates for established epidemiologic risk factors were also evaluated.

RESULTS: A total of 67 692 women were studied, including 33 841 who were diagnosed with breast cancer. PVs in ATM, BRCA1, BRCA2, CHEK2, and PALB2 were strongly associated with breast cancer risk, with BRCA1 and PALB2 PVs showing evidence of heterogeneity by family history. In models considering PVs, family history, and established risk factors, the estimated cumulative risks of breast cancer by age 50 years ranged from 2.4% (95% CI, 2.4-2.4) in women with no PVs and no family history to 35.5% (95% CI, 21.6-55.1) in PALB2 PV carriers with a family history. Among women who have not been diagnosed with breast cancer by age 50 years, the cumulative risk of breast cancer by age 80 years ranged from 11.1% (95% CI, 11.0-11.2) in noncarriers with no family history to 70.5% (95% CI, 52.8-83.5) for PALB2 carriers with a family history. PV-specific cumulative risk estimates varied across subgroups defined by race and ethnicity and potentially modifiable epidemiologic risk factors.

CONCLUSIONS AND RELEVANCE: In this study, population-based estimates of cumulative breast cancer risk for established PVs, as informed by the CARRIERS case-control sample, varied by family history and potentially modifiable risk factors. These estimates provide guidance for identifying individuals who will most benefit from enhanced screening and prevention strategies.},
}

Humans
Female
United States/epidemiology
Middle Aged
Aged
Aged, 80 and over
*Genetic Predisposition to Disease/epidemiology/genetics
*Breast Neoplasms/epidemiology/genetics
Pedigree
Case-Control Studies
Risk Factors
Incidence
Models, Statistical
Risk Assessment
Medical History Taking
Genetic Variation/genetics
Ataxia Telangiectasia Mutated Proteins
BRCA2 Protein
Checkpoint Kinase 2
Fanconi Anemia Complementation Group N Protein
BRCA1 Protein

@article {pmid41066125,
year = {2025},
author = {Gogebakan, KC and Lange, J and Owens, L and Pinderup, A and Gulati, R and Kessler, LG and Lyratzopoulos, G and Etzioni, R},
title = {Clinical Significance of a Multicancer Screening Trial With Stage-Based End Points.},
journal = {JAMA network open},
volume = {8},
number = {10},
pages = {e2536247},
pmid = {41066125},
issn = {2574-3805},
support = {R50 CA221836/CA/NCI NIH HHS/United States ; },
mesh = {Humans ; *Early Detection of Cancer/methods/statistics & numerical data ; Female ; Male ; Middle Aged ; *Neoplasms/diagnosis/epidemiology/mortality ; Aged ; Incidence ; England/epidemiology ; Neoplasm Staging ; *Mass Screening/methods ; Randomized Controlled Trials as Topic ; Clinical Relevance ; },
abstract = {IMPORTANCE: The first randomized screening trial of a multicancer early detection test is ongoing, with the primary end point being the incidence of late-stage cancer. The unprecedented use of a stage-based end point and short 3-year follow-up raise questions about how results should be interpreted and used in developing multicancer screening policy.

OBJECTIVE: To estimate outcomes of the trial and to identify information from the estimates that may aid in interpreting results of short-term trials evaluating multicancer screening tests.

This multicancer decision-analytic model estimated outcomes from registry data from the England National Cancer Registration and Analysis Service for cases diagnosed between January 2013 and December 2018. This model simulated a population-based multicancer screening trial of average-risk participants without a prior cancer diagnosis. The analysis was performed between April 2024 and April 2025.

INTERVENTIONS: Three annual multicancer screenings at months 0, 12, and 24. Cancers were assumed detectable 1 or 2 years before clinical diagnosis based on a published analysis, and cancer-specific early-stage sensitivities were set to either 100% or 50% of published sensitivities among clinically diagnosed cases.

MAIN OUTCOMES AND MEASURES: Reductions in late-stage (stage III-IV) cancer incidence over 3 years, cancer mortality over 5 years, and contributions of each cancer type to reductions in late-stage incidence and cancer mortality across the range of detectable intervals and early-stage sensitivities.

RESULTS: The model simulated 70 000 participants per arm (screening and control; median age, 66 years), and estimated that the overall late-stage incidence reductions at 3 years ranged from 6% to 23%, with corresponding reductions in 5-year cancer mortality from 6% to 9%. Colorectal cancer contributed the most to the reduction in late-stage incidence (28% to 39%), while lung cancer contributed the most to mortality reduction (40% to 42%).

CONCLUSIONS AND RELEVANCE: This independent decision-analytic model study found that the trial could achieve nontrivial cancer downstaging over 3 years, but modest mortality reduction over 5 years. These results were due to a limited number of target cancer types, underscoring the importance of transparent reporting of outcomes by cancer type, consideration of mortality implications, and careful preplanning for subsequent evaluation steps by the cancer research community.},
}

Humans
*Early Detection of Cancer/methods/statistics & numerical data
Female
Male
Middle Aged
*Neoplasms/diagnosis/epidemiology/mortality
Aged
Incidence
England/epidemiology
Neoplasm Staging
*Mass Screening/methods
Randomized Controlled Trials as Topic
Clinical Relevance

@article {pmid41067707,
year = {2025},
author = {Hines, MR and Knight, TE and McNerney, KO and Leick, MB and Jain, T and Ahmed, S and Frigault, MJ and Hill, JA and Jain, MD and Johnson, WT and Lin, Y and Mahadeo, KM and Maron, GM and Marsh, RA and Neelapu, SS and Nikiforow, S and Ombrello, AK and Shah, NN and Talleur, AC and Turicek, D and Vatsayan, A and Wong, SW and Maus, MV and Komanduri, KV and Berliner, N and Henter, JI and Perales, MA and Frey, NV and Teachey, DT and Frank, MJ and Shah, NN},
title = {Erratum to <Immune Effector Cell-Associated Hemophagocytic Lymphohistiocytosis-Like Syndrome><[Transplant Cell Ther. 2023 Jul;29(7):438.e1-438.e16. Epub 2023 Mar 9]>.},
journal = {Transplantation and cellular therapy},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jtct.2025.09.016},
pmid = {41067707},
issn = {2666-6367},
support = {ZIA BC011823/ImNIH/Intramural NIH HHS/United States ; ZIA BC012187/ImNIH/Intramural NIH HHS/United States ; },
}

@article {pmid41067857,
year = {2025},
author = {Gyurkocza, B and Sandmaier, BM},
title = {Salvage Allogeneic Hematopoietic Cell Transplantation for Primary Graft Failure.},
journal = {Transplantation and cellular therapy},
volume = {31},
number = {10},
pages = {725-726},
doi = {10.1016/j.jtct.2025.09.012},
pmid = {41067857},
issn = {2666-6367},
}

@article {pmid41068949,
year = {2025},
author = {Cao, J and Ferguson, M and Sun, J and Shen, M and Small, R and Hippe, DS and Zhao, X and Zhang, D and Watase, H and Yuan, C and Gao, P and DeMarco, JK and Nicosia, RF and Wang, Y and Li, H and Li, Z and Wang, Y and Kohler, T and Hatsukami, T and Sui, B},
title = {Composition of carotid plaques differs between Chinese and US patients: a histology study.},
journal = {Chinese neurosurgical journal},
volume = {11},
number = {1},
pages = {23},
pmid = {41068949},
issn = {2057-4967},
support = {R01 HL103609/HL/NHLBI NIH HHS/United States ; R01 HL073401/HL/NHLBI NIH HHS/United States ; 81361120402 and 62271061//National Natural Science Foundation of China/ ; L232130//Beijing Natural Science Foundation/ ; R01 NS083503/NS/NINDS NIH HHS/United States ; R01 NS083503, R01 HL61851, R01-HL60213, RO1 HL073401, and R01 HL103609/NH/NIH HHS/United States ; },
abstract = {BACKGROUND: The clinical manifestations of cerebrovascular disease are known to differ between the Chinese and United States (US) populations as do the plaque features on imaging.

OBJECTIVES: The aim of this study was to investigate and compare the histological features of excised carotid plaques from Chinese and US patients.

METHODS: Carotid endarterectomy specimens collected from two prospective studies were included. The entire plaque was serially sectioned (10-µm thickness) at 0.5-1 mm intervals. Hematoxylin and eosin staining and Mallory's trichrome staining were performed. The morphology and components of the plaques were measured and compared between the two groups.

RESULTS: A total of 1152 histological sections from 75 Chinese patients and 1843 sections from 111 US patients were analyzed. The Chinese group had significantly smaller minimum lumen diameters (median: 1.1 vs. 1.3 mm, p = 0.046) and a larger percent wall volume (median: 74% vs. 70%, p = 0.018) than the US group. After adjusting for confounding factors, carotid plaques in the Chinese population had larger lipid pools (β = 10.0%, 95% CI: 4.9 to 15.9%), more recent intraplaque hemorrhage (IPH; β = 8.4%, 95% CI: 4.5 to 12.7%), less late IPH (β = - 8.2%, 95% CI: - 11.3 to - 5.4), and fewer fibrous cap disruptions (45% vs. 67%, p = 0.061). Chinese plaques were more homogeneous and had a higher percentage of plaques with features of xanthomas than did US plaques (20% vs 2.7%, p < 0.001).

CONCLUSIONS: The histology of Chinese plaques differs significantly from that of U.S. plaques, suggesting substantial differences in the pathophysiology of atherosclerotic cerebrovascular disease between Chinese and North American populations, which indicates a need for a different management approach.},
}

@article {pmid41070684,
year = {2025},
author = {Lynch, RC and Cassaday, RD and Smith, SD and Cowan, AJ and Warren, EH and Shadman, MS and Till, BG and Ujjani, CS and Morris, K and Rasmussen, H and Voutsinas, J and Gopal, AK},
title = {Long-term follow-up of dose-dense brentuximab vedotin, ifosfamide, carboplatin and etoposide in second-line treatment of relapsed/refractory classical Hodgkin lymphoma.},
journal = {British journal of haematology},
volume = {207},
number = {4},
pages = {1599-1603},
doi = {10.1111/bjh.70052},
pmid = {41070684},
issn = {1365-2141},
support = {//Seagen/ ; P30 CA015704/CA/NCI NIH HHS/United States ; K24 CA184039/CA/NCI NIH HHS/United States ; },
mesh = {Humans ; *Hodgkin Disease/drug therapy/mortality/therapy ; Brentuximab Vedotin/administration & dosage/adverse effects ; Etoposide/administration & dosage/adverse effects ; Carboplatin/administration & dosage/adverse effects ; Ifosfamide/administration & dosage/adverse effects ; Female ; Male ; *Antineoplastic Combined Chemotherapy Protocols/therapeutic use/adverse effects/administration & dosage ; Adult ; Middle Aged ; Follow-Up Studies ; Adolescent ; Aged ; Young Adult ; Recurrence ; Salvage Therapy ; },
abstract = {This study presents the 5-year outcomes of a phase 1/2 trial (NCT02227199) evaluating dose-dense brentuximab vedotin (BV) combined with ifosfamide, carboplatin and etoposide (ICE) as second-line therapy in patients with relapsed classic Hodgkin lymphoma (cHL). Forty-five patients received at least one dose of BV-ICE, with the intention to proceed to autologous stem cell transplantation (ASCT). At a median follow-up of over 5 years, the progression-free survival was 77% (95% CI, 66%-91%) and overall survival was 91% (95% CI, 82%-100%). Of 37 patients who underwent ASCT, five relapsed; two received subsequent allogeneic transplantation and remain alive. Among eight patients who did not proceed to ASCT, four remain in complete remission long-term. Second malignancies developed in five patients post-ASCT, including two localized skin cancers and three non-skin cancers. These findings highlight BV-ICE as a highly active salvage regimen for relapsed cHL, with durable remissions in a majority of patients. The regimen may be especially relevant in the modern era for patients who relapse after Programmed Cell Death Protein 1 (PD-1) inhibitor-based front-line therapy and require additional treatment prior to planned ASCT.},
}

Humans
*Hodgkin Disease/drug therapy/mortality/therapy
Brentuximab Vedotin/administration & dosage/adverse effects
Etoposide/administration & dosage/adverse effects
Carboplatin/administration & dosage/adverse effects
Ifosfamide/administration & dosage/adverse effects
Female
Male
*Antineoplastic Combined Chemotherapy Protocols/therapeutic use/adverse effects/administration & dosage
Adult
Middle Aged
Follow-Up Studies
Adolescent
Aged
Young Adult
Recurrence
Salvage Therapy

@article {pmid41071311,
year = {2025},
author = {Carballo, EV and Gonzalez-Ericsson, P and Lehmann, BD and Taylor, BC and Wulfkuhle, JD and Ocampo, A and Gallagher, RI and Huang, DS and Maxey, C and Steele, JA and Kleinberg, K and Sun, X and Marshall, JL and Sanchez, V and Opalenik, SR and Petricoin, E and Rimel, BJ and Balko, JM and Penn, CA},
title = {The Impact of JAK1 Pathogenic Variants and MHC-I Expression on Response to Immune Checkpoint Inhibition in Endometrial Cancer.},
journal = {Clinical cancer research : an official journal of the American Association for Cancer Research},
volume = {31},
number = {24},
pages = {5294-5305},
pmid = {41071311},
issn = {1557-3265},
support = {G20 RR030956/RR/NCRR NIH HHS/United States ; P30 CA068485/CA/NCI NIH HHS/United States ; T32 CA009592/CA/NCI NIH HHS/United States ; UL1 RR024975/RR/NCRR NIH HHS/United States ; 1018894//Burroughs Wellcome Fund (BWF)/ ; },
mesh = {Progression-Free Survival ; *Immune Checkpoint Inhibitors/pharmacology/therapeutic use ; Histocompatibility Antigens Class I/genetics/metabolism ; Gene Expression Regulation, Neoplastic/drug effects/immunology ; *Janus Kinase 1/genetics ; *Endometrial Neoplasms/drug therapy/genetics/immunology/mortality ; Tumor Escape/genetics/immunology ; Microsatellite Instability ; CD56 Antigen/genetics/metabolism ; Humans ; Female ; Middle Aged ; Aged ; Retrospective Studies ; Endometrium/pathology ; Proteomics ; },
abstract = {PURPOSE: Immune checkpoint inhibitors (ICI) have increasing application in endometrial cancer, underscoring the need for robust biomarkers for patient selection. JAK1 pathogenic variants (PV) have previously been implicated in immune evasion. In this study, we identify biomarkers predictive of ICI response in endometrial cancer and the implications of JAK1 PVs in this context.

EXPERIMENTAL DESIGN: This is a translational study of tumors from 84 patients with endometrial cancer treated with ICIs. High-throughput proteomic-based profiling was used to quantify 193 phosphoprotein/protein expression levels, including key JAK/STAT signaling pathway components. Associations with clinical outcomes were assessed using multivariate regression analysis. The functional consequences of JAK1 PVs were explored through in vitro signaling assays and analyses of The Cancer Genome Atlas database.

RESULTS: MHC-I expression correlated with improved progression-free survival (P = 0.035), validated in orthogonal approaches. Notably, a subset of patients harboring JAK1 PVs demonstrated exceptional survival on ICIs. In The Cancer Genome Atlas cohort of microsatellite instability-high and DNA polymerase epsilon-mutated tumors, homozygous loss of JAK1 trended toward decreased survival, whereas heterozygous loss of JAK1 was associated with significantly improved survival (P = 0.026), suggesting partial retention of antigen presentation pathways. Among our ICI-treated microsatellite instability-high tumor samples, NK cell marker NCAM1 was associated with improved survival (P = 0.02).

CONCLUSIONS: These data support MHC-I as a potential predictive biomarker for ICI response in endometrial cancer. Additionally, we show that partial retention of JAK1 signaling in JAK1 tumors with heterozygous loss is associated with improved survival, potentially attributable to enhanced NK cell activity in tumors with low MHC-I expression.},
}

Progression-Free Survival
*Immune Checkpoint Inhibitors/pharmacology/therapeutic use
Histocompatibility Antigens Class I/genetics/metabolism
Gene Expression Regulation, Neoplastic/drug effects/immunology
*Janus Kinase 1/genetics
*Endometrial Neoplasms/drug therapy/genetics/immunology/mortality
Tumor Escape/genetics/immunology
Microsatellite Instability
CD56 Antigen/genetics/metabolism
Humans
Female
Middle Aged
Aged
Retrospective Studies
Endometrium/pathology
Proteomics

@article {pmid41071598,
year = {2026},
author = {Corvera, S and Rajan, A and Townsend, KL and Shamsi, F and Wu, J and Svensson, KJ and Zeltser, LM and Collins, S and Reis, T and Tseng, YH and Goodyear, LJ},
title = {Advances in Adipose Tissue Biology.},
journal = {Endocrine reviews},
volume = {47},
number = {1},
pages = {75-92},
pmid = {41071598},
issn = {1945-7189},
support = {K01 DK125608/DK/NIDDK NIH HHS/United States ; R35 GM124593/GM/NIGMS NIH HHS/United States ; R03 DK135786/DK/NIDDK NIH HHS/United States ; R01 DK112283/DK/NIDDK NIH HHS/United States ; 23IPA1042031/AHA/American Heart Association-American Stroke Association/United States ; R01 DK137403/DK/NIDDK NIH HHS/United States ; DP1 DK139570/DK/NIDDK NIH HHS/United States ; P30 DK116074/DK/NIDDK NIH HHS/United States ; P01 AG032959/AG/NIA NIH HHS/United States ; R01 DK136724/DK/NIDDK NIH HHS/United States ; R01 DK125260/DK/NIDDK NIH HHS/United States ; R56 DK140355/DK/NIDDK NIH HHS/United States ; R01 DK099511/DK/NIDDK NIH HHS/United States ; R01 DK125094/DK/NIDDK NIH HHS/United States ; P30 DK036836/DK/NIDDK NIH HHS/United States ; R43 AG097164/AG/NIA NIH HHS/United States ; },
mesh = {Humans ; *Adipose Tissue/physiology/metabolism ; Animals ; Obesity/metabolism ; Adipocytes/physiology ; Energy Metabolism/physiology ; },
abstract = {Adipose tissue has emerged as a central regulator of human physiology, with its dysfunction driving the global rise in obesity-associated diseases, such as type 2 diabetes, cardiovascular and liver diseases, and several cancers. Once thought to be inert, adipocytes are now recognized as dynamic, responsive cells essential for energy homeostasis and interorgan communication, including the brain. Distinct adipose depots support specialized functions across development, sex, and aging. Technologies like single-cell RNA sequencing are unraveling depot-specific mechanisms, with the potential of identifying new therapeutic targets. This review highlights major scientific advancements leading to our current appreciation of the pivotal role of adipose tissue in health and disease. Many key discoveries in this field have been catalyzed by National Institutes of Health funding, particularly through the National Institute of Diabetes, Digestive and Kidney Diseases, now celebrating its 75th anniversary.},
}

Humans
*Adipose Tissue/physiology/metabolism
Animals
Obesity/metabolism
Adipocytes/physiology
Energy Metabolism/physiology

@article {pmid41071741,
year = {2025},
author = {Dionne, JA and Campbell, JD and Salim, J and Atmar, RL and Healy, CM and Posavad, CM and Flach, B and Brown, ER and Farley, MM and Stephens, DS},
title = {Baptism in a Pandemic: Infectious Diseases Clinical Research Consortium Network Design for Readiness and Response.},
journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America},
volume = {81},
number = {Supplement_2},
pages = {S109-S116},
pmid = {41071741},
issn = {1537-6591},
support = {UM1 AI148684/AI/NIAID NIH HHS/United States ; },
}

@article {pmid41071904,
year = {2025},
author = {Malladi, SK and Jaiswal, D and Ying, B and Alsoussi, WB and Darling, TL and Dadonaite, B and Civljak, A and Horvath, SC and Zhou, JQ and Kim, W and Turner, JS and Schmitz, AJ and Han, F and Scheaffer, SM and Farnsworth, CW and Nachbagauer, R and Nestorova, B and Chalkias, S and Klebert, MK and Edwards, DK and Paris, R and Strnad, BS and Middleton, WD and O'Halloran, JA and Presti, RM and Bloom, JD and Boon, ACM and Diamond, MS and Bajic, G and Ellebedy, AH},
title = {Germinal center-mediated broadening of B cell responses to SARS-CoV-2 booster immunization.},
journal = {Science immunology},
volume = {10},
number = {112},
pages = {eadu4107},
doi = {10.1126/sciimmunol.adu4107},
pmid = {41071904},
issn = {2470-9468},
support = {P30 CA016087/CA/NCI NIH HHS/United States ; R01 AI168178/AI/NIAID NIH HHS/United States ; P01 AI172531/AI/NIAID NIH HHS/United States ; S10 OD026880/OD/NIH HHS/United States ; UL1 TR004419/TR/NCATS NIH HHS/United States ; S10 OD030463/OD/NIH HHS/United States ; },
mesh = {*Germinal Center/immunology ; *SARS-CoV-2/immunology ; Humans ; Animals ; *B-Lymphocytes/immunology ; Immunization, Secondary ; *COVID-19/immunology/prevention & control ; Spike Glycoprotein, Coronavirus/immunology ; *COVID-19 Vaccines/immunology ; Antibodies, Viral/immunology ; Adult ; Antibodies, Neutralizing/immunology ; Cricetinae ; Antibodies, Monoclonal/immunology ; Male ; Female ; },
abstract = {Germinal centers (GCs) are key sites for antibody diversification and affinity maturation. SARS-CoV-2 messenger RNA (mRNA) vaccines elicit robust GC B cell responses in humans, but how these responses influence the breadth of immunity against viral variants remains unclear. We analyzed GC B cell responses in nine healthy adults after mRNA booster immunization. We show that 77.8% of the B cell clones in the GC expressed representative monoclonal antibodies (mAbs) recognizing the spike protein, with 37.8% of these targeting the receptor binding domain (RBD). One RBD-targeting mAb, mAb-52, neutralized all tested SARS-CoV-2 strains, including the recent XEC variant. mAb-52 used the IGHV3-66 public clonotype, protected hamsters challenged against the EG.5.1 variant, and targeted the class I/II RBD epitope, closely mimicking the binding footprint of ACE2. Its broad reactivity was driven by extensive somatic hypermutation, underscoring the critical role of GC reactions in shaping cross-variant B cell immunity after SARS-CoV-2 booster vaccination.},
}

*Germinal Center/immunology
*SARS-CoV-2/immunology
Humans
Animals
*B-Lymphocytes/immunology
Immunization, Secondary
*COVID-19/immunology/prevention & control
Spike Glycoprotein, Coronavirus/immunology
*COVID-19 Vaccines/immunology
Antibodies, Viral/immunology
Adult
Antibodies, Neutralizing/immunology
Cricetinae
Antibodies, Monoclonal/immunology
Male
Female

@article {pmid41072416,
year = {2025},
author = {Di Meo, F and Albano, F and Cesarano, A and Wang, Y and Kale, B and Shain, K and Silva, A and Kurihara, N and Tenshin, H and Jellyman, D and Song, X and Ghaffari, S and Mesa, H and Creelan, B and Freeman, C and Zhao, X and Meads, MB and Rodriguez, PC and Marino, S and Locke, F and Hwu, P and Roodman, D and Mansilla-Soto, J and Perna, F},
title = {Developing SEMA4A-directed CAR T cells to overcome low BCMA antigen density in multiple myeloma.},
journal = {Cancer cell},
volume = {43},
number = {12},
pages = {2298-2310.e6},
pmid = {41072416},
issn = {1878-3686},
support = {P30 CA076292/CA/NCI NIH HHS/United States ; R37 CA276939/CA/NCI NIH HHS/United States ; },
mesh = {Humans ; *Multiple Myeloma/therapy/immunology/pathology ; *B-Cell Maturation Antigen/immunology/metabolism ; Animals ; *Semaphorins/immunology/metabolism/genetics ; Mice ; *Immunotherapy, Adoptive/methods ; *Receptors, Chimeric Antigen/immunology/metabolism ; Cell Line, Tumor ; Xenograft Model Antitumor Assays ; *T-Lymphocytes/immunology ; },
abstract = {Chimeric antigen receptor (CAR) T cell therapy targeting B cell maturation antigen (BCMA) for multiple myeloma (MM) is effective, but relapses associated with low-to-negative BCMA expression are common, indicating the need for additional targets. We quantitatively profile antigen density in a cohort of patients relapsed after BCMA CAR T therapy, showing high number of SEMA4A molecules/cell where BCMA density is low. SEMA4A deletion limits MM cell growth, migration, tissue infiltration, and osteoclast formation, while extending mouse survival. We generate monoclonal antibodies targeting SEMA4A-extracellular domain for CAR construction, screen engineered T cells for expansion, cytokine release, and cytotoxicity against MM cells. Lead constructs lack reactivity against normal non-hematopoietic tissues. SEMA4A CAR T cells show superior efficacy than BCMA CAR T cells eliminating patient-derived BCMA[low] tumors and MM cells progressing under suboptimal doses of BCMA CAR T cells. This study prepares for a phase 1 clinical trial with SEMA4A-directed CAR T cells for MM.},
}

Humans
*Multiple Myeloma/therapy/immunology/pathology
*B-Cell Maturation Antigen/immunology/metabolism
Animals
*Semaphorins/immunology/metabolism/genetics
Mice
*Immunotherapy, Adoptive/methods
*Receptors, Chimeric Antigen/immunology/metabolism
Cell Line, Tumor
Xenograft Model Antitumor Assays
*T-Lymphocytes/immunology

@article {pmid41073857,
year = {2026},
author = {Cannon, V and Wright, JH and Yeung, CCS and Grady, WM and Yu, M},
title = {Multiplex Digital PCR Assay Targeting DNA Methylation for Early Detection of Cancer.},
journal = {Methods in molecular biology (Clifton, N.J.)},
volume = {2969},
number = {},
pages = {29-42},
pmid = {41073857},
issn = {1940-6029},
support = {U2C CA271902/CA/NCI NIH HHS/United States ; },
mesh = {*DNA Methylation ; Humans ; *Multiplex Polymerase Chain Reaction/methods ; *Early Detection of Cancer/methods ; *Esophageal Neoplasms/genetics/diagnosis ; Biomarkers, Tumor/genetics ; *Adenocarcinoma/genetics/diagnosis ; },
abstract = {Digital PCR has been demonstrated to enable the precise nucleic acid absolute quantification across a wide range of applications. Historically, dPCR technology was limited to two channels for fluorescence detection. Recent advances in digital PCR have made it possible to multiplex and allow for simultaneous analysis of multiple targets within a PCR reaction. Here, we describe a multiplex dPCR assay for the detection and quantification of methylated DNA (also known as DNA-methylation-specific multiplex digital PCR, or DNA-methylation specific dPCR). We also demonstrate the application of this technology for the development of a candidate DNA methylation-based biomarker panel for the early detection of high-grade dysplasia and esophageal adenocarcinoma. Further, we discuss common technical challenges and troubleshooting for performing successful DNA-methylation-specific MS-dPCR assays.},
}

*DNA Methylation
Humans
*Multiplex Polymerase Chain Reaction/methods
*Early Detection of Cancer/methods
*Esophageal Neoplasms/genetics/diagnosis
Biomarkers, Tumor/genetics
*Adenocarcinoma/genetics/diagnosis

@article {pmid41073880,
year = {2025},
author = {Koufigar, S and Ford, E and He, Y and Olsen, S and Fagerstrom, JM},
title = {A case study on SSD to SAD linear acceleartor calibration transition.},
journal = {Journal of applied clinical medical physics},
volume = {26},
number = {10},
pages = {e70298},
pmid = {41073880},
issn = {1526-9914},
mesh = {Calibration/standards ; Humans ; *Radiotherapy Planning, Computer-Assisted/methods/standards ; *Particle Accelerators/instrumentation/standards ; Radiotherapy Dosage ; *Quality Assurance, Health Care/standards ; *Neoplasms/radiotherapy ; *Radiotherapy, Intensity-Modulated/methods ; Retrospective Studies ; *Phantoms, Imaging ; },
abstract = {PURPOSE: Modifying calibration conditions of linear accelerators is infrequent and potentially a high-risk procedure. This study outlines a systematic approach used to transition a linear accelerator's calibration condition in an active clinical environment from source-to-surface (SSD) to source-to-axis (SAD), while maintaining treatment accuracy and avoiding interruption of clinical operations.

METHODS: A satellite clinic within a university radiation oncology service operated an Elekta Versa HD linear accelerator with SSD calibration, while other system C-arm accelerators used SAD. With a single installation of the treatment planning system used across all sites, it was decided to convert the machine to SAD calibration. Representative plans with diverse delivery techniques were comprehensively evaluated in advance. Over a single weekend, beams were recommissioned in the treatment planning system (TPS), and output was adjusted per AAPM's TG-51 protocol. Monitor units (MUs) for on-treatment patients were scaled manually in the oncology information system, MOSAIQ. Quality assurance (QA) checks, as well as independent peer-reviewing of each field, were performed to ensure safety and quality for this high-risk procedure. A retrospective failure modes and effects analysis (FMEA) was subsequently conducted. To evaluate the clinical relevance and broader impact of this work, a targeted survey was conducted via the Wayne State MedPhysUSA LISTSERV.

RESULTS: As a result of the change in output calibration condition, field MU required scaling, ranging from 2.7% to 6.4%. Patient-specific QA measurements demonstrated consistent gamma pass rates, and both solid-water phantom and external audit results verified machine output accuracy within 2%. No patient treatments were interrupted during the process. The FMEA identified insufficient expertise and staffing as the highest-risk failure mode. Survey results indicated that 80% of respondents had never personally performed a calibration transition with patients on treatment, and the majority of respondents characterized the procedure as extremely rare and of higher risk than standard TG-51 annual QA.

CONCLUSIONS: The absolute output calibration condition was successfully transitioned from SSD to SAD without interruptions of patient treatments. Multiple verification steps were implemented to ensure quality and safety. This project contributed to improved standardization across multiple sites of practice.},
}

Calibration/standards
Humans
*Radiotherapy Planning, Computer-Assisted/methods/standards
*Particle Accelerators/instrumentation/standards
Radiotherapy Dosage
*Quality Assurance, Health Care/standards
*Neoplasms/radiotherapy
*Radiotherapy, Intensity-Modulated/methods
Retrospective Studies
*Phantoms, Imaging