@article {pmid41298252,
year = {2025},
author = {Shook-Sa, BE and Zivich, PN and Cole, SR and Rosenberg, NE and Hudgens, MG and Donnell, DJ and Moyo, S and Zuma, K and Ayles, H and Bock, P and Eron, JJ and Hayes, RJ and Edwards, JK},
title = {Examining the effect of universal testing and treatment strategies for HIV prevention in Zambia and South Africa: generalizing the results of the HPTN 071 (PopART) trial.},
journal = {Journal of the International AIDS Society},
volume = {28},
number = {12},
pages = {e70062},
doi = {10.1002/jia2.70062},
pmid = {41298252},
issn = {1758-2652},
support = {K01AI182506/NH/NIH HHS/United States ; R01AI157758/NH/NIH HHS/United States ; K01AI177102/NH/NIH HHS/United States ; R21MH134750/NH/NIH HHS/United States ; R37AI029168/NH/NIH HHS/United States ; P30AI50410/NH/NIH HHS/United States ; PRCRPG-Nov21∖100001/CRUK_/Cancer Research UK/United Kingdom ; },
mesh = {Humans ; *HIV Infections/prevention & control/diagnosis/drug therapy/epidemiology ; Male ; Zambia/epidemiology ; South Africa/epidemiology ; Adult ; Female ; Young Adult ; Adolescent ; *HIV Testing/methods ; Incidence ; Anti-HIV Agents/therapeutic use ; },
abstract = {INTRODUCTION: HIV Prevention Trials Network (HPTN) 071 (PopART) was a cluster-randomized trial to evaluate universal testing and treatment (UTT) strategies for HIV prevention. HPTN071 compared three arms: (A) combination prevention with UTT; (B) combination prevention with universal testing and antiretroviral therapy initiation according to local guidelines; and (C) standard of care (SOC). Interventions were implemented in entire randomized communities, with impacts on HIV incidence measured in "population cohorts," that is the HPTN071 sample. Unexpectedly, a significantly lower incidence was not observed in arm A relative to SOC. Importantly, rates of participation in the HPTN071 sample differed among population subgroups, for example men were underrepresented.

METHODS: To correct for underrepresented subgroups, PopART intervention effects are estimated in a population of interest, adults aged 18-44 in trial provinces, characterized with two nationally representative HIV-focused surveys. The HPTN071 sample is weighted to match the population of interest by demographics and HIV risk factors. Risk of HIV acquisition is compared across arms, both in the trial population (unweighted) and the population of interest (weighted). Both (1) the risk of HIV acquisition between 1 and 3 years and (2) the risk of HIV acquisition by 3 years are compared.

RESULTS: In the trial population, estimated risk in arm A is, counterintuitively, slightly higher than SOC (Year 1-3 Risk Difference [RD]: 0.10%; 95% CI: -1.15%, 1.25%). After weighting, risk in arm A is lower than SOC in the population of interest (RD: -0.34%; 95% CI: -2.04%, 0.96%). Weighting also strengthened the estimated effect in arm B relative to SOC (unweighted RD: -0.66%, 95% CI: -1.88%, 0.46%; weighted RD: -1.18%, 95% CI: -2.85%, 0.15%). Weighted year 3 risk difference estimates indicated even stronger possible intervention effects: A versus SOC -0.83% (95% CI: -2.94%, 0.99%), B versus SOC -1.86% (95% CI: -3.80%, -0.09%).

CONCLUSIONS: PopART interventions are estimated to be more protective in the population of interest than observed in the HPTN071 sample. These results partially explain the unexpected finding in arm A, providing further support for UTT strategies for HIV prevention. This analysis also highlights the importance of considering heterogeneous treatment effects among population subgroups when measuring the overall efficacy of HIV interventions.},
}

Humans
*HIV Infections/prevention & control/diagnosis/drug therapy/epidemiology
Male
Zambia/epidemiology
South Africa/epidemiology
Adult
Female
Young Adult
Adolescent
*HIV Testing/methods
Incidence
Anti-HIV Agents/therapeutic use

@article {pmid41297101,
year = {2025},
author = {Ronco, L and Tapscott, S and Voermans, NC and , },
title = {Meeting report: The FSHD society 2025 international research congress.},
journal = {Neuromuscular disorders : NMD},
volume = {58},
number = {},
pages = {106262},
doi = {10.1016/j.nmd.2025.106262},
pmid = {41297101},
issn = {1873-2364},
abstract = {Facioscapulohumeral muscular dystrophy (FSHD) is a genetic disorder marked by progressive muscle weakness and disability throughout life. Affecting about one million people worldwide, FSHD is among the most common forms of muscular dystrophy. To advance global collaboration, the FSHD Society hosted the 32nd International Research Congress (IRC) on June 12-13, 2025, in Amsterdam, the Netherlands. More than 250 researchers, clinicians, patients, and industry representatives attended, highlighting key developments in FSHD research. The Congress comprised six scientific sessions: (1) Population Genetics & Modifiers, (2) Measures of Disease Activity & Progression, (3) Novel Clinical Outcome Measures, (4) Mechanisms of Disease & Interventional Strategies, (5) Clinical Care & Related Issues, and (6) Clinical Studies & Trial Design. Keynote presentations were delivered by Leendert Trouw (Leiden University Medical Center, Netherlands) and Karen Chen (SMA Foundation, USA), who shared perspectives from their respective research domains. Preceding the IRC, the Industry Collaborative (IC) for Therapeutic Development united experts in clinical science, biomarkers, and industry to identify knowledge gaps and strengthen strategies for developing effective FSHD therapies. Following the IRC, the inaugural FSHD Connect Europe meeting brought together patients and families from across Europe to exchange experiences and gain updates on emerging clinical and scientific advances. The FSHD Society continues to foster research and community engagement to accelerate treatment breakthroughs. The next International Research Congress will be held in Chicago, Illinois, on June 25-26, 2026.},
}

@article {pmid41296990,
year = {2025},
author = {Liao, R and Fay, M and Mian, OY},
title = {Reply to: Toward Clinical Readiness: Critical Reflections on PATHOMIQ_PRAD and Artificial Intelligence Histologic Classifiers in Prostate Cancer.},
journal = {JCO clinical cancer informatics},
volume = {9},
number = {},
pages = {e2500261},
doi = {10.1200/CCI-25-00261},
pmid = {41296990},
issn = {2473-4276},
}

@article {pmid41296783,
year = {2025},
author = {Xu, S and Hudson, A and Janes, HE and Tomaras, GD and Ackerman, ME},
title = {Candidate correlates of protection in the HVTN505 HIV-1 vaccine efficacy trial identified by positive-unlabeled learning.},
journal = {PLoS computational biology},
volume = {21},
number = {11},
pages = {e1013705},
pmid = {41296783},
issn = {1553-7358},
mesh = {*AIDS Vaccines/immunology/therapeutic use ; Humans ; *HIV Infections/prevention & control/immunology ; *HIV-1/immunology ; *Machine Learning ; HIV Antibodies/immunology ; *Vaccine Efficacy ; Computational Biology ; },
abstract = {With a goal of unveiling mechanisms by which vaccines can provide protection against HIV-1 acquisition, several studies have explored correlates of risk of HIV-1 acquisition in HVTN 505, which was a phase IIb trial conducted to assess the safety and efficacy of a DNA plasmid and recombinant adenovirus serotype 5-vectored HIV vaccine regimen among individuals in the United States who were vulnerable to acquiring HIV. While this trial failed to meet its predetermined efficacy criteria, both immunological and virological correlates of reduced risk of acquisition have been reported, suggesting that at least some vaccine recipients were protected from some viruses. In this work, we describe application of a novel Positive-Unlabeled machine learning-based approach to infer protection status among vaccine recipients that did not acquire HIV, resulting in improved power to detect potential correlates of immunity. Having established the analytical robustness of protection status predictions using cross-validation and permutation testing strategies, we report increased confidence in previously identified correlates of risk, such as vaccine-elicited anti-HIV-1 Env glycoprotein IgG3 antibodies and antibody-dependent phagocytosis, and the new observation of an inverse correlation between inferred vaccine-mediated protection and virus-specific IgA responses. Though its biological validity is not established, this inference approach offers a new means to use case-control datasets to identify candidate markers of effective immune responses in the context of low vaccine efficacy.},
}

*AIDS Vaccines/immunology/therapeutic use
Humans
*HIV Infections/prevention & control/immunology
*HIV-1/immunology
*Machine Learning
HIV Antibodies/immunology
*Vaccine Efficacy
Computational Biology

@article {pmid41294288,
year = {2025},
author = {Furlong, J and Goya, S and Nawrocki, EP and Calhoun, V and Hatcher, E and Yankie, L and Greninger, AL},
title = {Automated annotation and validation of human respiratory virus sequences using VADR.},
journal = {Database : the journal of biological databases and curation},
volume = {2025},
number = {},
pages = {},
pmid = {41294288},
issn = {1758-0463},
support = {NU50CK000630//National Center for Zoonotic, Vector-borne, and Enteric Diseases/ ; 1R03LM014965-01/LM/NLM NIH HHS/United States ; /NH/NIH HHS/United States ; },
mesh = {Humans ; *Molecular Sequence Annotation/methods ; *Genome, Viral/genetics ; Phylogeny ; },
abstract = {Accurate annotation of viral genomes is essential for reliable downstream analysis and public data sharing. While National Center for Biotechnology Information's (NCBI's) Viral Annotation DefineR (VADR) pipeline provides standardized annotation and quality control, it only supports six viral groups to date. Here, we developed and validated 12 new reference sequence-based VADR models targeting key human respiratory viruses: measles virus, mumps virus, rubella virus, human metapneumovirus, human parainfluenza virus types 1-4, and seasonal coronaviruses (229E, NL63, OC43, and HKU1). Model construction was guided by a comprehensive analysis of intra-species genomic and phylogenetic diversity, enabling the development of genotype-specific models associated with reference genomes that defined expected genome structure and annotation. Models were trained on 5327 publicly available complete viral genomes and tested on 372 viral genomes not yet submitted to GenBank. VADR passed 96.3% of publicly available viral genomes and 98.1% of viral genomes not in the training set, correctly identifying overlapping ORFs, mature peptides, and transcriptional slippage as well as genome misassemblies. VADR detected novel viral biology including the first reported HCoV-OC43 NS2 knockout in a human infection and novel G and SH coding sequence lengths in human metapneumovirus. These VADR models are publicly available and are used by NCBI curators as part of the GenBank submission pipeline, supporting high-quality, scalable viral genome annotation for research and public health.},
}

Humans
*Molecular Sequence Annotation/methods
*Genome, Viral/genetics
Phylogeny

@article {pmid41291065,
year = {2025},
author = {Chan, M and Gujral, TS},
title = {Beyond genomics: 3D microtumor assays for rapid, clinically relevant functional drug testing.},
journal = {Oncogene},
volume = {},
number = {},
pages = {},
pmid = {41291065},
issn = {1476-5594},
support = {R01CA273081//U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)/ ; U01FD007925//U.S. Department of Health & Human Services | U.S. Food and Drug Administration (U.S. Food & Drug Administration)/ ; },
abstract = {Precision oncology is increasingly moving beyond genomics alone to approaches that directly test how patient tumors respond to therapy. This shift reflects a central challenge in oncology, where sequencing alone often fails to identify effective therapies for rare, treatment-resistant, or genomically ambiguous tumors. Here, we highlight three-dimensional (3D) microtumor models as a powerful functional platform that preserves the architecture, cell types, and microenvironment of intact tumors for drug screening. By capturing biology that 2D models and genomics alone miss, this approach enables more accurate prediction of therapeutic vulnerabilities and expands the precision-oncology toolkit for patients who currently lack actionable options.},
}

@article {pmid41290584,
year = {2025},
author = {Elias, S and Brown, S and Egini, O and Walji, M and Homsy, S and Velayati, A and Devlin, S and Ponce, DM and Kennedy, V and Bharadwaj, S and Shiraz, P and Jakubowski, AA and Papadopoulos, EB and Muffly, L and Perales, MA and Giralt, SA and Smith, M and Gyurkocza, B},
title = {Allogeneic hematopoietic cell transplantation in acute myeloid leukemia not in complete remission: outcomes and prognostic factors in a contemporary cohort.},
journal = {Blood cancer journal},
volume = {15},
number = {1},
pages = {208},
pmid = {41290584},
issn = {2044-5385},
}

@article {pmid41289158,
year = {2025},
author = {Rayes, A and Logan, BR and Liu, X and Dara, J and Buckley, RH and Oved, JH and Kapoor, N and Kapadia, M and Chandra, S and Martinez, CA and Bunin, N and Chandrakasan, S and Chen, K and Bednarski, JJ and Haines, HL and Eissa, H and Talano, JM and Keller, MD and Ebens, CL and Chaudhury, S and Shereck, EB and Aquino, VM and Knutsen, AP and Alexander, JL and Gillio, AP and Chellapandian, D and Shah, AJ and Miller, HK and Vander Lugt, MT and Seroogy, CM and Dorsey, MJ and Mousallem, T and Parrott, RE and O'Reilly, RJ and Aguayo-Hiraldo, PI and Prockop, SE and Dávila Saldaña, BJ and Thakar, MS and Burroughs, LM and Torgerson, TR and Leiding, JW and Marsh, RA and Griffith, LM and Pulsipher, MA and Kohn, DB and Notarangelo, LD and Cowan, MJ and Puck, JM and Cuvelier, GDE and Heimall, J and Haddad, E and Pai, SY and Dvorak, CC},
title = {Outcomes Following Matched Sibling Donor Transplantation for Severe Combined Immunodeficiency: A Report from the PIDTC.},
journal = {Blood advances},
volume = {},
number = {},
pages = {},
doi = {10.1182/bloodadvances.2025016812},
pmid = {41289158},
issn = {2473-9537},
abstract = {The Primary Immune Deficiency Treatment Consortium (PIDTC) performed a retrospective analysis of 133 patients with severe combined immunodeficiency (SCID) receiving matched sibling donor (MSD) hematopoietic cell transplantation (HCT) between 1980 and 2023 at 30 North American institutions. In this largest cohort of MSD outcomes in SCID patients to date, we examined the impact of conditioning regimen and graft-versus-host disease (GVHD) prophylaxis on survival and immune recovery. Outcomes after MSD HCT for SCID were excellent. Patients without an active infection or failure to thrive (FTT) at the time of HCT had 5-year overall survival (OS) superior to those with infection or FTT. Acute and chronic GVHD outcomes were independent of GVHD prophylaxis, conditioning regimen, SCID type, or presence of maternal engraftment. Patients without active infection at the time of HCT had superior chronic GVHD free event-free survival vs. those with infection. T cell reconstitution at 6 months was less likely achieved with use of GVHD prophylaxis or serotherapy, and in leaky SCID or Omenn syndrome patients. At 6 months, 1 year, and 2-5 years T cell reconstitution was less likely with ADA, DCLRE1C or RAG genotype. B cell reconstitution at 1 year and 2-5 years was negatively impacted by development of grade II-IV or III-IV acute GVHD. Conditioning did not impact T or B cell reconstitution. Our data suggest omitting conditioning and GVHD prophylaxis for patients with typical SCID did not negatively impact 5-year outcomes following MSD HCT, but the data are insufficient to recommend this approach for best long-term outcomes. (ClinicalTrials.gov NCT01186913).},
}

@article {pmid41289154,
year = {2025},
author = {Ruan, J and Bond, DA and Shah, BD and Allan, JN and Rutherford, SC and Gribbin, C and Chen, Z and Bhinder, B and Tam, W and Rossi, D and Xiang, JZ and Hobbie, B and Harbhajan, M and Sahni, TK and Chen, GZ and Sigouros, M and Inghirami, GG and Chen-Kiang, S and Elemento, O and Maddocks, KJ and Leonard, JP and Martin, P},
title = {MRD-driven Initial Therapy of Acalabrutinib and Lenalidomide plus Rituximab (ALR) or Obinutuzumab (ALO) for Mantle Cell Lymphoma.},
journal = {Blood advances},
volume = {},
number = {},
pages = {},
doi = {10.1182/bloodadvances.2025017760},
pmid = {41289154},
issn = {2473-9537},
abstract = {This phase 2 study evaluated the efficacy and safety of combining acalabrutinib (A) and lenalidomide (L) with either rituximab (ALR) or obinutuzumab (ALO), with longitudinal minimal residual disease (MRD) monitoring in frontline MCL treatment (ClinicalTrials.gov - NCT03863184). The primary objective was molecular CR after 12 cycles of induction, defined by Lugano criteria and undetectable MRD <10-6 (uMRD6) by clonoSEQ. Secondary objectives included safety, responses and survival. Exploratory objectives included tumor mutation profiles and cell-free DNA (cfDNA) by CAPP-Seq. Patients in uMRD6 molecular CR were eligible for discontinuation of A+L after 24 cycles; all patients received a minimum of 36 cycles of anti-CD20 antibody treatment. In the ALR cohort, grade 3-4 hematologic toxicities included neutropenia (38%), thrombocytopenia (4%) and anemia (4%). Non-hematologic toxicities included rash (42%), fatigue (4%), nausea (4%), and vomiting (4%). The ORR was 100%, CR 83% and molecular CR 67% after 12 cycles of induction, with best molecular CR at 83%. At a median follow-up of 53 months (range 46-60), the 4-yr OS and PFS for ALR were 91% and 76%, respectively. TP53 mutations were adversely associated with PFS (p=0.026). For ALO, ORR, CR and molecular CR were 90% following induction, and 2-yr OS and PFS were both at 100%. Longitudinal cfDNA analysis in ALR revealed clonal evolution during response and progression. This safe and active regimen is feasible as a time-limited initial therapy for MCL patients and warrants further evaluation in response-adapted strategy.},
}

@article {pmid41288979,
year = {2025},
author = {Li, A and Jafari, O and Lam, BD and Jiang, JY and Kim, RB and Ma, S and Zhou, E and Tiong, JW and Chiang, EC and Ryu, J and Amos, CI and La, J and Fillmore, NR},
title = {Validation of a Risk Score for Cancer-Associated Thrombosis Using Nationwide EHR Data.},
journal = {JAMA network open},
volume = {8},
number = {11},
pages = {e2544428},
pmid = {41288979},
issn = {2574-3805},
mesh = {Humans ; Female ; *Neoplasms/complications/epidemiology ; Male ; *Electronic Health Records/statistics & numerical data ; Middle Aged ; Risk Assessment/methods ; Aged ; *Venous Thromboembolism/epidemiology/etiology ; Risk Factors ; *Thrombosis/etiology/epidemiology ; },
abstract = {IMPORTANCE: Venous thromboembolism (VTE) is associated with increased mortality and morbidity in patients with cancer. Existing risk prediction models are typically validated within individual sites, a fragmented approach that limits clinical adoption.

OBJECTIVE: To validate the electronic health record cancer-associated thrombosis (EHR-CAT) score compared with the benchmark Khorana score in a contemporary cohort of patients with cancer across the nation, before and after treatment, excluding those at high risk of bleeding.

This prognostic study included patients in a nationwide longitudinal EHR database from January 2018 to December 2023 with follow-up continuing to April 2025. Patients with newly diagnosed, invasive, solid, or hematologic malignant neoplasms (defined using validated International Statistical Classification of Diseases, Tenth Revision, Clinical Modification [ICD-10-CM] algorithms) receiving systemic therapy (defined using the first antineoplastic medication) were included. Those with recent history of acute VTE diagnosis or anticoagulant prescription were excluded.

EXPOSURES: Demographics, risk model variables, and common anticoagulant trial exclusion criteria (as a proxy for identifying people at high risk of bleeding) were extracted on or before index therapy initiation date.

MAIN OUTCOMES: Incident VTE and bleeding outcomes at 6 months were defined using validated ICD-10-CM algorithms.

RESULTS: A total of 732 594 patients (median [IQR] age, 65.0 [56.9-73.0] years; 425 124 female [58.0%]; 25 634 Asian [3.5%], 94 269 Black [12.9%], 48 266 Hispanic [6.6%], 583 047 White [76.9%]) with active cancer receiving systemic therapy between 2018 and 2023 from 184 health systems were identified. With a median (IQR) follow-up of 676 (340-1151) days, the incidence of 6-month VTE, bleeding, and mortality was 4.7% (34 499 patients), 3.7% (26 993 patients), and 8.4% (60 239 patients), respectively. Bleeding risk was higher in the 26.0% of patients (190 413) meeting anticoagulant trial exclusion criteria (7.2% vs 2.4%; hazard ratio, 2.5 [95% CI, 2.5-2.5]). The EHR-CAT score stratified patients into discriminative risk groups (C statistic, 0.70-0.71) both before and after exclusion for bleeding risk. When compared with the benchmark Khorana score (C statistic, 0.63), EHR-CAT reclassified 20% of patients into revised categories with improved prediction accuracy. Furthermore, EHR-CAT had consistent calibration in subgroups by age, sex, race, ethnicity, and individual health system sites.

CONCLUSIONS: This prognostic study of the EHR-CAT risk score demonstrated the external validity and feasibility of using readily available structured EHR data to estimate VTE risk in patients with cancer.},
}

Humans
Female
*Neoplasms/complications/epidemiology
Male
*Electronic Health Records/statistics & numerical data
Middle Aged
Risk Assessment/methods
Aged
*Venous Thromboembolism/epidemiology/etiology
Risk Factors
*Thrombosis/etiology/epidemiology

@article {pmid41288462,
year = {2025},
author = {Dotson, EH and Elmariah, SB and Bergerat, AM and James, K and Luo, T and Reed, SD and Guthrie, KA and Mitchell, CM},
title = {A pilot study of vaginal nerve fiber and blood vessel density in postmenopausal women with genitourinary syndrome of menopause.},
journal = {Menopause (New York, N.Y.)},
volume = {},
number = {},
pages = {},
pmid = {41288462},
issn = {1530-0374},
support = {R01AG048209//National Institute of Aging/ ; },
abstract = {OBJECTIVE: Menopause is accompanied by decreased circulating estrogen for all people; however, only some develop genitourinary syndrome of menopause, the cause of which is unknown. In this pilot study, we measured vaginal blood vessel and nerve fiber density, as well as vaginal fluid immune markers to identify a potential cause of vaginal symptoms.

METHODS: This is a secondary analysis of samples from a randomized trial of vaginal estradiol or moisturizer versus placebo for moderate-severe postmenopausal vaginal discomfort. Fourteen participants were selected from the placebo tablet/vaginal moisturizer or dual placebo arms of the original study: eight with a ≥2-point reduction in most bothersome symptom severity (responders) and six with a <2-point reduction in symptom severity (nonresponders). At 0, 4, and 12 weeks, we characterized vaginal protein gene product 9.5-positive nerve fiber and CD31+ vessel length and density from vaginal wall biopsies (immunofluorescent staining) and vaginal fluid immune markers (MesoScale Discovery). We compared responders versus nonresponders at baseline and across visits using linear mixed models to evaluate associations between symptoms, nerve/vessel length and density, and immune markers.

RESULTS: There were no significant differences in baseline characteristics between responders and nonresponders. Mean CD31+ vessel length at 12 weeks was higher in responders than nonresponders (P = 0.034), while all other measurements were similar between the two groups. No clear patterns were observed across proinflammatory or chemoattractant cytokine concentrations with biopsy measures.

CONCLUSIONS: Vaginal blood supply and extent of vascularization may contribute to vaginal discomfort symptoms in postmenopausal people; however, the results of this small study need to be confirmed with a larger sample size.},
}

@article {pmid41287634,
year = {2025},
author = {Kikawa, C and Huddleston, J and Loes, AN and Turner, SA and Lee, J and Barr, IG and Cowling, BJ and Englund, JA and Greninger, AL and Harvey, R and Hasegawa, H and Ho, F and Lacombe, K and Leung, NHL and Lewis, NS and Peck, H and Watanabe, S and Smith, DJ and Bedford, T and Bloom, JD},
title = {Near real-time data on the human neutralizing antibody landscape to influenza virus to inform vaccine-strain selection in September 2025.},
journal = {Virus evolution},
volume = {11},
number = {1},
pages = {veaf086},
pmid = {41287634},
issn = {2057-1577},
abstract = {The hemagglutinin of human influenza virus evolves rapidly to erode neutralizing antibody immunity. Twice per year, new vaccine strains are selected with the goal of providing maximum protection against the viruses that will be circulating when the vaccine is administered ~8-12 months in the future. To help inform this selection, here we quantify how the antibodies in recently collected human sera neutralize viruses with hemagglutinins from contemporary influenza strains. Specifically, we use a high-throughput sequencing-based neutralization assay to measure how 188 human sera collected from Oct 2024 to April 2025 neutralize 140 viruses representative of the H3N2 and H1N1 strains circulating in humans as of the summer of 2025. This data set, which encompasses 26 148 neutralization titre measurements, provides a detailed portrait of the current human neutralizing antibody landscape to influenza A virus. The full data set and accompanying visualizations are available for use in vaccine development and viral forecasting.},
}

@article {pmid41287255,
year = {2025},
author = {Follmann, D and Dang, L and Chu, E and Fintzi, J and Janes, H and Gilbert, PB and Andrews, LIB and Serebryannyy, L and Carroll, R and Lin, B and Koup, R and Toma, J and Deng, LW and Priddy, F and Dixit, A and Zhou, H and Baden, L and El Sahly, HM},
title = {A Test-Negative Design for Immune Correlates Approximates a Traditional Exposure Proximal Design but Requires Far Fewer Blood Samples.},
journal = {The Journal of infectious diseases},
volume = {},
number = {},
pages = {},
doi = {10.1093/infdis/jiaf572},
pmid = {41287255},
issn = {1537-6613},
abstract = {Traditional vaccine clinical trials sample blood from all participants. In contrast, the test-negative immune correlates design only samples blood from participants who develop symptoms. We compared traditional to test-negative immune correlates methods in the mRNA-1273 SARS-CoV-2 vaccine efficacy clinical trial. Using a neutralizing antibody assay, hazard ratios were 0.48 (95% CI: 0.29, 0.73) and 0.55 (95% CI: 0.28, 1.06) respectively for traditional and test-negative methods. Analogous ratios for binding antibody assay were 0.69 (95% CI: 0.52, 0.94) and 0.78 (95% CI 0.50, 1.20. The results support use of the logistically simpler test-negative immune correlates design.},
}

@article {pmid41286512,
year = {2025},
author = {Al-Ali, RW and Gui, G and Ravindra, N and Andrew, G and Mukherjee, D and Wong, ZC and Huang, Y and Gerhold, J and Holman, M and Jacobsen, A and D'Angelo, J and Miller, J and Elias, K and Auletta, JJ and El Chaer, F and Devine, SM and Jimenez, AMJ and De Lima, MJG and Litzow, MR and Kebriaei, P and Saber, W and Spellman, SR and Zeger, SL and Page, KM and Radich, JP and Lindsley, RC and Dillon, LW and Hourigan, CS},
title = {Measurable residual mutated NPM1 before allogeneic transplant for acute myeloid leukemia.},
journal = {Bone marrow transplantation},
volume = {},
number = {},
pages = {},
pmid = {41286512},
issn = {1476-5365},
support = {1-ZIA-HL006163//U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)/ ; },
}

@article {pmid41286306,
year = {2025},
author = {Li, Y and Zhou, Z and Zhang, Y and Jia, D and Wang, D and Reiger, MC and Creighton, CJ and Nelson, PS and Corey, E and Morrissey, C and Xin, L},
title = {Targeting FZD6 creates therapeutically actionable vulnerabilities for advanced prostate cancer.},
journal = {Oncogene},
volume = {},
number = {},
pages = {},
pmid = {41286306},
issn = {1476-5594},
support = {W81XWH-22-1-0752//U.S. Department of Defense (United States Department of Defense)/ ; 19CHAL11//Prostate Cancer Foundation (PCF)/ ; R01CA271457//U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)/ ; P50CA97186//U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)/ ; R21CA277368//U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)/ ; },
abstract = {Wnt signaling is a complex pathway consisting of numerous ligands and frizzled (FZD) receptors. These signaling components are widely expressed in human prostate tissues and often undergo upregulation or mutation in advanced prostate cancers. Enhanced Wnt signaling promotes prostate cancer cell proliferation, metastasis, and resistance to therapy. However, targeting pan-Wnt signaling poses challenges due to tissue toxicity. We show that FZD6 is the most highly expressed and frequently amplified Wnt receptor in advanced human prostate cancers. Knockdown of FZD6 suppresses both in vitro and in vivo growth of various prostate cancer cell lines and patient-derived xenograft models. FZD6 knockdown impairs DNA double-strand break (DSB) repair, as determined by both resolution of γH2AX foci and DNA DSB repair reporter assays. Mechanistically, FZD6 knockdown-induced growth suppression is linked to reduced activities of SRC kinase and STAT3, while DNA damage repair deficiency is mediated through WEE1 downregulation via PLK1. Knockdown of FZD6 enhances the therapeutic efficacy of genotoxic agents for prostate cancer cells. A kinome-wide CRISPR-Cas9 knockout screen reveals that FZD6 inhibition sensitizes prostate cancer cells to the inhibition of PKMYT1, a WEE kinase family member. Collectively, we demonstrate that targeting a single FZD receptor highly expressed in prostate cancers can yield significant therapeutic efficacy, and uncover therapeutic vulnerabilities associated with FZD6 inhibition.},
}

@article {pmid41286102,
year = {2025},
author = {Smith, JL and Adebamowo, CA and Adebamowo, SN and Darst, BF and Fullerton, SM and Gogarten, SM and Hamed, ME and Hirbo, JB and Hysong, MR and Johar, AS and Khan, AT and Kullo, IJ and Konigsberg, IR and Kraft, P and Lange, LA and Li, Y and Martin, AR and Nelson, SC and Choudhury, A and Ramsay, M and Cobran, EK and Schaid, DJ and Sharma, J and Wang, Y and Wojcik, GL and , and Sun, Q},
title = {Recommendations for responsible use of population descriptors in polygenic risk score development.},
journal = {Nature genetics},
volume = {},
number = {},
pages = {},
pmid = {41286102},
issn = {1546-1718},
support = {HL07111-45//U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)/ ; U01HG011717//U.S. Department of Health & Human Services | NIH | National Human Genome Research Institute (NHGRI)/ ; U01HG011715//U.S. Department of Health & Human Services | NIH | National Human Genome Research Institute (NHGRI)/ ; U01HG011723//U.S. Department of Health & Human Services | NIH | National Human Genome Research Institute (NHGRI)/ ; U01HG011720//U.S. Department of Health & Human Services | NIH | National Human Genome Research Institute (NHGRI)/ ; U01HG011719//U.S. Department of Health & Human Services | NIH | National Human Genome Research Institute (NHGRI)/ ; U01CA261339//U.S. Department of Health & Human Services | NIH | National Human Genome Research Institute (NHGRI)/ ; U01HG011710//U.S. Department of Health & Human Services | NIH | National Human Genome Research Institute (NHGRI)/ ; U01HG011697//U.S. Department of Health & Human Services | NIH | National Human Genome Research Institute (NHGRI)/ ; },
abstract = {The recent report from the National Academies of Sciences, Engineering and Medicine emphasizes the importance of detailed and tailored use of population descriptors in genomic analyses, but specific guidance for genomic data analysts is still lacking. In this Perspective, we focus on polygenic risk score (PRS) development and demonstrate that population descriptors are explicitly or implicitly involved in every step of the process. Attention to this matter is both an analytical concern and an ethical concern, as each decision has an impact on PRS results and performance across diverse populations. Drawing from the experience of the Polygenic Risk Methods Development (PRIMED) Consortium, we offer recommendations for applying population descriptors throughout the entire process of PRS development, validation and application. We urge the research community, particularly data analysts, to critically evaluate and justify their choices when using these descriptors to ensure both scientific rigor and research integrity.},
}

@article {pmid41285840,
year = {2025},
author = {Jackson, LA and Coler, RN and Deye, GA and Carter, D and Gray, SA and Pecor, T and Davis, J and Larsen, SE and Posavad, CM and Cox, C and Watanabe, A and Lundeen, JS and Gill, R and Kalyanasundaram, A and Siddiqui, AA},
title = {Safety and immunogenicity of the Sm-p80 GLA-SE schistosomiasis vaccine.},
journal = {NPJ vaccines},
volume = {10},
number = {1},
pages = {247},
pmid = {41285840},
issn = {2059-0105},
support = {UM1AI148684//National Institute of Allergy and Infectious Diseases/ ; UM1AI148684//National Institute of Allergy and Infectious Diseases/ ; UM1AI148684//National Institute of Allergy and Infectious Diseases/ ; UM1AI148684//National Institute of Allergy and Infectious Diseases/ ; UM1AI148684//National Institute of Allergy and Infectious Diseases/ ; },
abstract = {Schistosomiasis is a neglected tropical disease with the greatest burden in sub-Saharan Africa. An efficacious and safe vaccine would have a major global public health impact. The investigational SchistoShield® (Sm-p80 [antigen] + GLA-SE [adjuvant]) vaccine targets the Sm-p80 surface membrane antigen of Schistosoma mansoni and in nonhuman primate challenge studies was shown to be highly effective in killing pathogenic female worms and reducing host organ pathology and egg excretion. In this Phase 1 first-in-human, dose-escalation trial with sequential assignment, we evaluated the safety and immunogenicity of the vaccine in healthy adults in the United States. The vaccine formulations, given as a three dose intramuscular series, were well tolerated and adjuvanted formulations induced robust IgG ELISA responses against the Sm-p80 antigen. The vaccine has been advanced to a Phase 1b trial among adults in endemic areas of Africa.Clinicaltrials.gov registration: NCT05292391 https://Clinicaltrials.gov/study/NCT05292391 .},
}

@article {pmid41285650,
year = {2025},
author = {Ho, C and Kennedy, N and Di, M and Gopal, AK and Lynch, RC and Ng, K and Wu, QV and Poh, C and Raghunathan, V and Rasmussen, H and Shadman, M and Till, BG and Ujjani, CS and Smith, SD},
title = {Barriers to Investigator-Initiated Clinical Trial Enrollment in Frontline Large B-Cell Lymphoma.},
journal = {Clinical lymphoma, myeloma & leukemia},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.clml.2025.11.002},
pmid = {41285650},
issn = {2152-2669},
abstract = {BACKGROUND: Frontline therapy fails to cure ∼ 25% of patients with large B-cell lymphoma (LBCL), underscoring the need for clinical trials to improve outcomes. However, enrollment remains limited by logistical and structural barriers. Investigator-initiated trials (IITs) at our center enroll patients 5 to 10 times faster than industry-sponsored trials, yet the influence of geography and socioeconomic status on participation remains poorly understood.

METHODS: We retrospectively reviewed adults with newly diagnosed large B-cell lymphoma (LBCL) referred to Fred Hutchinson Cancer Center (FHCC) between October 2022 and June 2024. Patients were prescreened by a clinical research nurse and investigators for frontline IIT eligibility. Demographic, geographic, and socioeconomic data were collected, including sex, race, ethnicity, distance from FHCC, area deprivation index, insurance, and interpreter need. Logistic and elastic net regression were used to evaluate predictors of trial enrollment. Trial-ineligible patients were analyzed descriptively.

RESULTS: Of 153 patients, 68 (44%) were trial-eligible; 24 (35%) enrolled. Enrolled patients lived closer to FHCC (median 15 vs. 50 miles; P = .00015) and had lower ADI scores (median 8 vs. 21; P = .006) than non-enrolled eligible patients. In univariate analysis, both distance and ADI were associated with enrollment; in multivariable stepwise regression, only distance remained significant. Elastic net regression identified both distance and ADI as frequently selected predictors. Among 85 trial-ineligible patients, 61% had already initiated treatment; these patients also lived farther away and in more deprived areas.

CONCLUSION: Geographic distance and neighborhood deprivation significantly influenced trial enrollment, even in investigator-initiated trials (IITs). Decentralized trial models, telemedicine triage, and system-level interventions are needed to reduce these inequities.},
}

@article {pmid41285296,
year = {2025},
author = {Harper, K and Adintori, PA and Heimgartner, J and Schmidt, E and Carpenter, PA and Ullrich, C},
title = {Best Practice Considerations in Nutritional Care for Adult Patients Undergoing Hematopoietic Cell Transplantation.},
journal = {Transplantation and cellular therapy},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jtct.2025.11.021},
pmid = {41285296},
issn = {2666-6367},
abstract = {The American Society of Transplantation and Cellular Therapy partnered with established registered dietitian experts in hematopoietic cell transplantation (HCT). Committee members and the expert dietitians developed frequently asked questions (FAQs) held by HCT providers. The expert dietitians drafted the list of FAQs, which were then reviewed by the Practice Guidelines Committee and organized by the representatives assigned as partners on this paper. The FAQs are organized by phase in the peri-HCT period. The FAQs cover pre- and early post-HCT nutrition assessment (FAQ 1-4), early post-HCT nutrition interventions (FAQ 5-11), and chronic post-HCT nutrition interventions (FAQ 13-16). Finally, emerging topics in nutritional care with HCT recipients are highlighted as future directions with opportunities for further research (FAQ 17-20).},
}

@article {pmid41284631,
year = {2025},
author = {Banerjee, R and Khouderchah, C and Akhtar, OS and Liang, EC and Gauthier, J and Dhodapkar, MV and Portuguese, AJ},
title = {Prior transplantation and idecabtagene vicleucel in multiple myeloma: a secondary analysis of CIBMTR data.},
journal = {Blood},
volume = {},
number = {},
pages = {},
doi = {10.1182/blood.2025031426},
pmid = {41284631},
issn = {1528-0020},
abstract = {N/A.},
}

@article {pmid41280050,
year = {2025},
author = {Langley, CA and Lilly, M and Malik, HS and Emerman, M},
title = {Fitness Landscapes of APOBEC3G Antagonism by HIV-1 Vif proteins.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {41280050},
issn = {2692-8205},
abstract = {Host immune factors shape viral evolution. The HIV-1 Vif protein counteracts viral hypermutation caused by the host cytidine deaminase APOBEC3G (A3G), ensuring productive infection. Using deep mutational scanning (DMS) across two divergent HIV-1 clade B Vif proteins, we systematically mapped the mutational landscape governing their antagonism of A3G. These high-resolution fitness maps define conserved and adaptable regions of Vif, illuminating core principles of host-virus coevolution. Most missense mutations were strongly deleterious, reflecting pervasive purifying selection. Yet several highly conserved residues at binding interfaces with A3G, RNA, and CBFβ exhibited unexpected mutational tolerance, revealing structural flexibility at these sites. Comparative analysis revealed shared constraints and striking differences between HIV-1 strains, shaped by epistatic interactions and additional selective pressures, including Vif antagonism of A3H and PP2A. By pinpointing evolutionary vulnerabilities and adaptive mechanisms, this study provides a framework for understanding viral plasticity and developing targeted strategies to disrupt Vif-mediated immune evasion.},
}

@article {pmid41279534,
year = {2025},
author = {McCrone, JT and Baele, G and Omah, IF and Kinganda-Lusamaki, E and Brew, JA and Carvalho, LM and Dudas, G and Mbala-Kingebeni, P and Suchard, MA and Rambaut, A},
title = {Evidence of latency reshapes our understanding of Ebola virus reservoir dynamics.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {41279534},
issn = {2692-8205},
abstract = {Ebola virus (EBOV) has caused severe outbreaks of haemorrhagic fever in Central and West Africa since the first observed zoonotic epidemic in the late 1970s. While recent outbreaks have revealed much about the epidemiological dynamics that sustain human-to-human transmission, the mechanisms by which the virus persists between outbreaks are unknown. Previously, phylogenetic approaches have been used to characterise the EBOV reservoir from the evolutionary relationships among observed human outbreaks. We here employ a novel phylogenetic latency model - inspired by recent observations of extreme EBOV evolutionary rate heterogeneity in humans - to characterise the natural history of EBOV and by extension its reservoir. We find the prevailing model of EBOV reservoir dynamics is deficient, and the long-term EBOV evolutionary rate is slower than previously believed. The hypothesis that EBOV diversity dates back to a bottleneck event just prior to the first human outbreak is not supported by the data. Further, our results suggest that EBOV undergoes extended periods of quiescence in the reservoir, similar to that observed in a small fraction of human infections. These findings have significant implications for understanding the source of EBOV outbreaks, characterising the EBOV reservoir, and uncovering the factors that contribute to EBOV outbreaks in humans.},
}

@article {pmid41278697,
year = {2025},
author = {Chang, CH and Handler, T and Fuda, N and Pascua, D and Mouton, T and Larracuente, AM},
title = {Pervasive suppressors halt the spread of selfish Segregation Distorter in a natural population.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {41278697},
issn = {2692-8205},
abstract = {Meiotic drivers are selfish genetic elements that subvert Mendelian inheritance to increase their own transmission, yet they are typically found at low frequencies across natural populations. The factors that limit their spread remain unclear. To investigate this paradox, we studied the Segregation Distorter (SD) system, a selfish coadapted gene complex in Drosophila melanogaster. SD biases its transmission by killing sperm carrying a homologous chromosome bearing a target locus, Responder (Rsp), which appear as satellite repeats. Such selfish killing impairs male fertility and imposes selective pressure on the host genome to evolve resistance, either by deleting Rsp copies or acquiring unlinked suppressors. To characterize the spectrum of Rsp alleles and the frequency of segregating suppressors, we surveyed 90 strains from the Drosophila Genome Reference Panel. Rather than loss of Rsp, we found that over half of the strains (52/90) harbor suppressors located on the X chromosome or autosomes, but not the Y chromosome. The widespread presence of strong suppressors limited the resolution of our genome-wide association mapping; however, recombination analysis identified a strong X-linked suppressor to a ~300 kb interval on the chromosome. Together, our findings suggest that pervasive, multilocus suppression constrains the spread of SD in natural populations.},
}

@article {pmid41281626,
year = {2026},
author = {Sarria, GR and Torales, S and Rossi, F and Ricagni, L and Baldeon, D and Felix, A and Li, B and Gkika, E and Ferraris, G and Sarria, GJ},
title = {Radiotherapy access in Latin America: Socio-economic determinants and equity challenges socio-economic determinants in Latin America for radiotherapy.},
journal = {Clinical and translational radiation oncology},
volume = {56},
number = {},
pages = {101062},
pmid = {41281626},
issn = {2405-6308},
abstract = {INTRODUCTION: Radiotherapy (RT) is essential for cancer treatment, yet access in Latin America remains highly unequal due to socio-economic and systemic disparities. This study aims to identify and analyze the key socio-economic determinants influencing RT access, infrastructure, and workforce distribution across 11 Latin American countries.

METHODS: A comprehensive database was created using 29 demographic, economic, and healthcare-related variables from public sources and expert input. Countries included were Argentina, Bolivia, Brazil, Chile, Colombia, Ecuador, Mexico, Paraguay, Peru, Uruguay, and Venezuela. Variables were categorized under access, demand, and supply of RT services. Correlation analyses and linear/exponential regression models were applied in an exploratory way to evaluate relationships between socio-economic indicators and RT availability.

RESULTS: Higher GDP per capita and adjusted GDP (PPP) correlated significantly with better RT infrastructure, including EBRT and megavoltage units (r > 0.68, p < 0.05). Urban population percentage strongly correlated with RT access (r = -0.77, p = 0.005), while social security coverage was linked to lower inhabitants per RT center (r = -0.67, p = 0.025). Notably, the number of radiation oncologists correlated perfectly with patients requiring EBRT (r = 1.0, p < 0.001), but showed no correlation with poverty or urbanization, highlighting workforce capacity constraints. Rural areas were underserved due to infrastructure centralization in urban zones. High out-of-pocket expenditure and low public health investment would be associated with limited access to these treatments.

CONCLUSION: Socio-economic disparities-particularly GDP, healthcare coverage, and urbanization-are strongly associated with RT access inequities in Latin America. For the medical community and public policymakers, confirming these assumptions requires a different scope about discussions regarding access to these highly complex services, when they are not associated with the population's health needs but rather with the countries' mere organizational and financial capabilities. Some possible formats require the definition of new clinical and financial management models. Our findings underscore the need for targeted health policies, investment in infrastructure and workforce, and decentralized care models. Expanding RT services beyond urban centers and improving funding models are critical to ensuring equitable cancer treatment across the region.},
}

@article {pmid41279355,
year = {2025},
author = {Khan, SA and Faerber, D and Kirkey, D and Raffel, S and Hadland, B and Deininger, M and Buettner, F and Zhao, HG},
title = {Cross-Species Morphology Learning Enables Nucleic Acid-Independent Detection of Live Mutant Blood Cells.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {41279355},
issn = {2692-8205},
abstract = {In hematology/oncology clinics, molecular diagnostics based on nucleic acid sequencing or hybridization are routinely employed to detect malignancy-associated genetic mutations and are instrumental in therapeutic stratification and prognostication. However, their limited cost-efficiency constrains their use in pre-malignant screening-specifically, the detection of rare circulating mutant blood cells in asymptomatic individuals. In both neonates and adults, the presence of malignancy-associated mutations in peripheral blood correlates with an elevated risk of future neoplastic transformation, with certain mutations, such as KMT2A rearrangements, exhibiting near-complete penetrance. If feasible, pre-malignant screening could enable early intervention and even disease prevention. Here, we introduce a high-throughput, single-cell computer vision platform capable of identifying mutant peripheral blood cells by recognizing mutation-specific morphological features. The morphology recognition module was developed through cross-species learning from murine to human datasets, enabling a generalizable and cost-effective approach for detecting mutations in live blood cells. The platform holds promise for translation into pre-malignant screening applications in asymptomatic neonates and adults as well as measurable residual disease monitoring in malignancies. Furthermore, it provides a novel single-cell morphological data modality that complements existing molecular layers, including genomics, epigenomics, transcriptomics, and proteomics.},
}

@article {pmid41277126,
year = {2025},
author = {Powles, T and Tagawa, ST and Vulsteke, C and Gross-Goupil, M and Park, SH and Necchi, A and De Santis, M and Duran, I and Morales-Barrera, R and Guo, J and Sternberg, CN and Bellmunt, J and Goebell, PJ and Kovalenko, M and Boateng, F and Sierecki, M and Wang, L and Sima, CS and Waldes, J and Bangs, R and Loriot, Y and Grivas, P},
title = {A plain language summary of the TROPiCS-04 study: sacituzumab govitecan use after platinum-based chemotherapy and immunotherapy in people with locally advanced or metastatic cancer of the bladder, urethra, or upper urinary tract.},
journal = {Future oncology (London, England)},
volume = {},
number = {},
pages = {1-18},
doi = {10.1080/14796694.2025.2579003},
pmid = {41277126},
issn = {1744-8301},
}

@article {pmid41276459,
year = {2025},
author = {Yang, E and Salerno, S and Dahlerus, C and Hirth, RA and Xu, T and Eckard, A and Agbenyikey, W and Horton, GM and Clark, S and Messana, JM and Li, Y},
title = {The Impact of Transplant Waitlisting Measures on Dialysis Facilities' Star Ratings.},
journal = {Health services research},
volume = {},
number = {},
pages = {e70071},
doi = {10.1111/1475-6773.70071},
pmid = {41276459},
issn = {1475-6773},
support = {75FCMC18D0041-75FCMC18F0001//Centers for Medicare and Medicaid Services/ ; HHSM-500-2013-13017I-HHSM-500-T001//Centers for Medicare and Medicaid Services/ ; },
abstract = {OBJECTIVE: To evaluate how adding kidney transplantation waitlisting measures-the Standardized First Kidney Transplant Waitlist Ratio for Incident Dialysis Patients (SWR) and Percentage of Prevalent Patients Waitlisted (PPPW)-affects Dialysis Facility Care Compare Star Ratings.

STUDY SETTING AND DESIGN: In this observational, cross-sectional study, we calculated the difference between facilities' published (with waitlisting measures) and counterfactual (without waitlisting measures) Star Ratings. We used multinomial regression to examine associations between Star Rating changes after waitlisting measure inclusion and facility characteristics and calculated corresponding average risk differences.

We used comprehensive clinical and administrative data from the Centers for Medicare/Medicaid Services from 2021 to investigate the impact of waitlisting measure addition on Star Ratings. Facility characteristics included demographic and patient mix, area deprivation index (ADI), dialysis organization affiliation, and urbanicity.

PRINCIPAL FINDINGS: 36.5% of facilities' ratings changed after waitlisting measures were added. Facility characteristics associated with a higher average risk of Star increase included location in low-ADI (0.091; 95% CI: 0.072, 0.109) or urban areas (0.061; 95% CI: 0.034, 0.087), independent/small dialysis organization affiliation (0.062; 95% CI: 0.041, 0.083), and having more PD patients (0.115; 95% CI: 0.093, 0.138). Characteristics associated with a higher average risk of Star decrease included high-ADI (0.075; 95% CI: 0.054, 0.095) or rural (0.056; 95% CI: 0.028, 0.083) location, large dialysis organization affiliation (0.058; 95% CI: 0.039, 0.078), having more patients with dual Medicare/Medicaid eligibility (0.052; 95% CI: 0.032, 0.071), and having fewer peritoneal dialysis patients (0.100; 95% CI: 0.081, 0.120).

CONCLUSIONS: Including waitlisting measures significantly impacts the Star Ratings and captures a new dimension of care quality. Worse socioeconomic status-related facility characteristics were strongly associated with worse Star Rating outcomes. These findings can inform future discussions about risk adjustment among the developers of the SWR and PPPW measures.},
}

@article {pmid41275868,
year = {2025},
author = {Silhol, R and Booton, RD and Mitchell, KM and Stannah, J and Stevens, O and Dimitrov, D and Bershteyn, A and Johnson, LF and Kelly, SL and Kim, HY and Maheu-Giroux, M and Martin-Hughes, R and Mishra, S and Stone, J and Stuart, R and Stover, J and Vickerman, P and Wilson, DP and Baral, S and Donnell, D and Imai-Eaton, JW and Boily, MC},
title = {Identifying priority populations for HIV interventions using acquisition and transmission indicators: a combined analysis of 15 mathematical models from ten African countries.},
journal = {The lancet. HIV},
volume = {},
number = {},
pages = {},
doi = {10.1016/S2352-3018(25)00199-7},
pmid = {41275868},
issn = {2352-3018},
abstract = {BACKGROUND: Characterising disparities in HIV infection across populations by gender, age, and HIV risk is key information to guide intervention priorities. We aimed to assess how indicators measuring HIV acquisitions, transmissions, or potential long-term infections influence estimates of the contribution of different populations to new infections, including key populations (including female sex workers, their clients, men who have sex with men).

METHODS: In this mathematical model comparison analysis, we evaluated four indicators using nine models representing 15 different settings across Africa. The acquisition indicator (I1) measured the annual proportion of all new infections acquired by a specific population, the direct transmission indicator (I2) measured the annual proportion of all new infections directly transmitted by a specific population, and the 1-year transmission population-attributable fractions (tPAFs; I3) and 10-year tPAFs (I4) measured the proportion of new infections averted if transmission involving a specific population was blocked over a specific time period. We compared estimates of the four indicators across seven populations and 15 settings and assessed if the contribution of specific populations ranked differently across indicators for ten settings.

FINDINGS: Different indicators identified distinct priority populations as the largest contributors: I1 identified women aged 25 years and older outside key populations as contributing the most to acquired infections in eight of ten settings in 2020, but to direct transmissions (I2) in only two settings. In six of ten settings, I4 identified non-key population men aged 25 years and older and clients of female sex workers as the largest contributors to HIV transmission. Notably, non-key population women aged 15-24 years acquired (I1) more infections in 2020 (median of 1·7 times higher across models) than they directly transmitted (I2), whereas more infections were transmitted than acquired in non-key population men aged 25 years and older (median 1·4 times more) and clients of female sex workers (1·6 times more) in all but one model. Estimates of the 10-year tPAFs accounting for transmission in the long-term were substantially larger than the direct transmission indicator for all populations, especially for female sex workers (2·0 times higher).

INTERPRETATION: Indicators that reflect HIV acquisitions and transmissions in the short and long term can be used to capture the complexity of HIV epidemics across different populations and timeframes. The added nuance would improve the effectiveness of the HIV prevention response across all populations at risk.

FUNDING: US National Institutes of Health and UK Medical Research Council.

TRANSLATION: For the French translation of the abstract see Supplementary Materials section.},
}

@article {pmid41274869,
year = {2025},
author = {Liu, C and Joehanes, R and Ma, J and Xie, J and Yang, J and Wang, M and Huan, T and Hwang, SJ and Wen, J and Sun, Q and Demirkale, CY and Heard-Costa, NL and Orchard, P and Carson, AP and Haessler, JW and Raffield, LM and Reiner, AP and Franceschini, N and Auer, PL and Kooperberg, C and Li, Y and O'Connor, G and Murabito, JM and Munson, P and Levy, D},
title = {Integrating whole genome and transcriptome sequencing to characterize the genetic architecture of isoform variation.},
journal = {Nature communications},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41467-025-64336-8},
pmid = {41274869},
issn = {2041-1723},
abstract = {We present a whole-blood isoform ratio QTL (irQTL) resource by analyzing genome-wide isoform-to-gene expression ratios using sequencing data. In Framingham Heart Study (FHS, n = 2622) discovery, we identify over 1.1 million cis-irQTLs (minor allele frequency [MAF] ≥ 0.01, ±1 Mb of 10,883 isoform transcripts, P < 5 × 10[-8]) across 4,971 genes. Among 11,425 sentinel cis-irQTLs, 72% replicate (P < 1 × 10[-4]) in the Women's Health Initiative (WHI; n = 2005). Notably, 20% of cis-irQTLs have no significant association with overall gene expression, indicating isoform-specific regulation. These variants are enriched at splice donor/acceptor sites and genome-wide association study loci (P < 1 × 10[-10]). We also identify 1870 sentinel trans-irQTLs (MAF ≥ 0.01, P < 1.5 × 10[-13]) for 1,084 isoforms across 590 genes, and 2327 rare cis-irQTLs (0.003 < MAF < 0.01) for 2467 isoforms of 1428 genes in FHS, with external replication rates of 61% and 41% in WHI, respectively. We highlight rs12898397 in ULK3, which alters splice site usage and reduces expression of a full-length isoform. Mendelian randomization supports a causal role between this isoform shift and reduced diastolic blood pressure. These findings highlight the power of irQTL mapping to uncover transcript-specific regulatory mechanisms underlying complex traits.},
}

@article {pmid41273917,
year = {2025},
author = {Leger, KJ and Stratton, KL and Sachdeva, R and Armenian, SH and Bhat, AH and Boyle, PM and Edwards, LA and Meacham, LR and Narasimhan, S and Nathan, PC and Sadak, KT and Sharma, S and Border, WL and Leisenring, WM and Chow, EJ},
title = {Enhancing Prediction of Cancer Therapy-Related Cardiomyopathy From Surveillance Echocardiograms: A Children's Oncology Group Study.},
journal = {JACC. Advances},
volume = {4},
number = {12 Pt 2},
pages = {102363},
doi = {10.1016/j.jacadv.2025.102363},
pmid = {41273917},
issn = {2772-963X},
abstract = {BACKGROUND: Early echocardiographic indicators of cardiac remodeling may enhance cardiomyopathy risk prediction in childhood cancer survivors (CCS).

OBJECTIVES: The objective of the study was to assess whether influential echocardiographic measures can be combined to develop a robust cardiomyopathy risk prediction model in CCS.

METHODS: Multicenter retrospective study of ≥1-year CCS with digitally archived surveillance echocardiograms, enrolled cardiomyopathy cases (left ventricular [LV] fractional shortening ≤28% or LV ejection fraction ≤50% on ≥2 occasions) and noncases (≥5-year CCS who maintained fractional shortening ≥ 30% and ejection fraction ≥55% without initiation of cardiac medications). Echocardiograms were centrally quantitated in a blinded fashion. Least absolute shrinkage and selection operator regression identified the most influential 2-year predictors of cardiomyopathy among 27 echocardiographic parameters. Logistic regression was used to generate ORs with 95% CIs. Estimates were applied to the training and test data sets to generate area under the receiver operating characteristic curves (AUC).

RESULTS: Data from 146 CCS (52 cases; 94 noncases) with a median follow-up of 9.3 years post-cancer diagnosis and a total of 281 echocardiograms were included. A set of 7 echocardiographic measures were identified as the most influential predictors, with AUC of 0.82 (95% CI: 0.74-0.89) and 0.85 (95% CI: 0.74-0.95) in the training and test data sets, respectively. LV end-systolic dimension (ORmm: 1.2; 95% CI: 1.1-1.4), apical 4-chamber longitudinal strain (OR%: 1.2; 95% CI: 1.0-1.3), and septal A' velocity (ORcm/s: 1.3; 95% CI: 1.1-1.6) were strongly predictive of cardiomyopathy. AUCs were similar if cancer treatment exposures were included.

CONCLUSIONS: Early abnormalities in echocardiographic parameters of structure and function predict subsequent cardiomyopathy in CCS and can identify high-risk survivors who warrant early intervention.},
}

@article {pmid41272850,
year = {2025},
author = {Mariapun, S and Eriksson, M and Tai, MC and Mohd Taib, NA and Yip, CH and Rahmat, K and Vachon, CM and Lindstrom, S and Li, J and Hartman, M and Hall, P and Easton, DF and Ho, WK and Teo, SH},
title = {Genome-wide association study of Asian women identifies putative mammographic density-associated loci.},
journal = {Breast cancer research : BCR},
volume = {27},
number = {1},
pages = {207},
pmid = {41272850},
issn = {1465-542X},
support = {/WT_/Wellcome Trust/United Kingdom ; UM.C/HIR/MOHE/06//Malaysian Ministry of Higher Education High Impact Research Grant/ ; MR/P012930/1//Newton - Ungku Omar Fund/ ; v203477/Z/16/Z/WT_/Wellcome Trust/United Kingdom ; },
mesh = {Humans ; Female ; *Genome-Wide Association Study ; *Breast Density/genetics ; *Breast Neoplasms/genetics/diagnostic imaging/pathology ; *Asian People/genetics ; Middle Aged ; Polymorphism, Single Nucleotide ; Genetic Predisposition to Disease ; Mammography ; Aged ; Adult ; *Genetic Loci ; White People/genetics ; Risk Factors ; },
abstract = {BACKGROUND: Mammographic density (MD) is a strong, heritable risk factor for breast cancer. To date, 55 independent MD-associated genetic loci have been identified through genome-wide association studies (GWASs) in women of European ancestry; however, no studies have been reported in Asian women.

METHODS: To identify novel loci, we conducted genome-wide association studies (GWASs) of absolute dense, absolute nondense, and percentage area and volumetric densities, adjusting for age, body mass index (BMI), and ancestry-informative principal components, in a multi-ethnic cohort of 2,951 Asian women attending opportunistic mammography screening. We selected 175 novel loci that were associated with at least one MD phenotype at P < 5 × 10[- 6] for (a) replication in an independent set of 401 Asian breast cancer cases, using density measurements from the unaffected breasts, (b) evaluation in a GWAS meta-analysis of MD in 27,900 women of European ancestry and (c) evaluation with breast cancer risk in Asian women.

RESULTS: Four of the 175 loci were replicated in women of Asian ancestry at P < 0.05, with directions of association that were consistent with those observed in the GWAS. The rs7018644 SNP at the 9p13.1 locus was the only loci replicated in both Asian and European cohorts. In addition, eight SNPs were also associated with breast cancer risk (P < 0.05) in a GWAS meta-analysis of Asian women.

CONCLUSION: This study identifies potential novel MD-associated loci in Asian women. Replication in a larger Asian study is needed to confirm these findings.},
}

Humans
Female
*Genome-Wide Association Study
*Breast Density/genetics
*Breast Neoplasms/genetics/diagnostic imaging/pathology
*Asian People/genetics
Middle Aged
Polymorphism, Single Nucleotide
Genetic Predisposition to Disease
Mammography
Aged
Adult
*Genetic Loci
White People/genetics
Risk Factors

@article {pmid41271835,
year = {2025},
author = {Chamberlin, S and Graham, J and Jeng, S and Swarts, J and Ferris, M and Heise, M and Baric, RS and McWeeney, S and Lund, J and Mooney, M},
title = {Adaptive immune response to West Nile virus infection in the Collaborative Cross mouse model: A database of cellular phenotypes and Quantitative Trait Loci.},
journal = {Scientific data},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41597-025-06293-x},
pmid = {41271835},
issn = {2052-4463},
support = {U19AI100625//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; U19AI100625//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; U19AI100625//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; U19AI100625//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; U19AI100625//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; U19AI100625//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; U19AI100625//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; U19AI100625//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; U19AI100625//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; U19AI100625//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; },
abstract = {West Nile virus (WNV) infection can lead to a wide range of clinical outcomes, from asymptomatic to self-limiting febrile and serious neuro-invasive disease. Knowledge of the genetic factors contributing to the heterogeneity of this disease can inform pathogenic mechanisms, help guidethe development of cell based therapeutics, vaccines and inform lifestyle choices. Yet this knowledge is incomplete in humans. Here we present data from a large-scale experiment aimed at identifying quantitative trait loci (QTL) associated with adaptive immune cellular phenotypes observed in response to infection with WNV. This data was generated using the Collaborative Cross (CC) mouse model, previously demonstrated as a representative model for human WNV infection and homeostatic immune states. In addition, due to challenges of QTL mapping with the large number of intermediate, highly coordinated immune and virologic phenotypes, we also provide a computational pipeline for the prioritization of gene candidates designed to leverage those characteristics for downstream mechanistic studies.},
}

@article {pmid41271741,
year = {2025},
author = {Huppert, LA and Gliwa, AS and Tait, M and Quintal, L and Starzinski, S and Cheung, A and Moasser, M and Majure, M and Melisko, M and Munster, P and Rugo, HS and Campbell, M and Fong, L and Chien, AJ},
title = {Phase Ib study of intratumoral talimogene laherparepvec (T-VEC) in combination with chemotherapy or endocrine therapy in patients with advanced HER2-negative breast cancer.},
journal = {NPJ breast cancer},
volume = {11},
number = {1},
pages = {130},
pmid = {41271741},
issn = {2374-4677},
abstract = {Talimogene laherparepvec (T-VEC) is an oncolytic virus that is hypothesized to enhance responses to systemic therapy. This Phase 1b trial evaluated the safety and efficacy of intratumoral T-VEC plus chemotherapy (CT) or endocrine therapy (ET) for patients with hormone receptor positive (HR +)/HER2- and triple negative (TN) advanced breast cancer (ABC) with injectable locoregional/chest wall disease. The primary endpoint was safety/tolerability. Secondary endpoints were objective response rate by irRECIST 1.1 and clinical assessment of local response. 19 patients enrolled (9 HR + /HER2-; 10 TN; median two lines of prior CT). Intratumoral T-VEC was administered with the following partners: gemcitabine/carboplatin (n = 8), nab-paclitaxel (n = 7), paclitaxel (n = 2), or ET (n = 2). Eight patients in the T-VEC + gemcitabine/carboplatin arm were formally evaluated for dose limiting toxicities (DLTs) based on pre-specified protocol criteria, and one DLT (grade 3 neutropenia leading to carboplatin dose reduction) was identified. Response per irRECIST 1.1 was evaluated in 16 patients: partial response (n = 2, 12.5%), stable disease (n = 7, 43.8%), progressive disease (n = 7, 43.8%). Patients with higher pre-treatment tumor infiltrating lymphocytes (TILs) were more likely to respond, and clinical responders had induction of Ki-67 in multiple peripheral myeloid populations. In conclusion, the addition of intratumoral T-VEC to CT or ET was safe in patients with ABC and injectable locoregional disease, supporting the continued investigation of direct intratumoral immunomodulatory strategies that can enhance local and systemic immune responses. NCT03554044.},
}

@article {pmid41269781,
year = {2025},
author = {Artz, AS and Logan, BR and Saber, W and Geller, N and Bellach, A and Kou, J and Wood, WA and McCarty, J and Knight, TG and Runaas, L and Johnston, L and Walston, JD and Nakamura, R and Mishra, A and Uberti, J and Dahi, PB and Saultz, JN and McCurdy, SR and Morris, LE and Imus, P and Hogan, WJ and Nadiminti, KV and Bhatt, VR and Olin, RL and Maakaron, JE and Sobecks, RM and Wall, SA and Mattila, D and Protz, B and Devine, SM and Horowitz, MM and Sorror, ML},
title = {CHARM is Prognostic of Geriatric Morbidity and Toxicity after Allogeneic Transplant for Older Adults: BMT CTN 1704 Study.},
journal = {Blood advances},
volume = {},
number = {},
pages = {},
doi = {10.1182/bloodadvances.2025018340},
pmid = {41269781},
issn = {2473-9537},
abstract = {Despite concerns about the toxicity of allogeneic hematopoietic cell transplantation (alloHCT) in older patients, prospective data are limited characterizing prevalence or risk-stratification for geriatric morbidity such as disability or frailty. We prospectively assessed the prognostic impact of the novel composite health assessment risk model (CHARM), a score established to predict 1-year non-relapse mortality (NRM), among 1105 patients aged ≥60 years enrolled on the Bone Marrow Transplant-Clinical Trials Network Study 1704. Secondary endpoints were assessed post-alloHCT at day (D) 100, 180 and 365 in multivariable models adjusted with predetermined clinical variables. Among alloHCT survivors, the prevalence of disability by instrumental activities of daily living (IADL), frailty by the Physical Frailty Phenotype and physical function impairment by PROMIS was highest at D100, and lower D180 and D365. Higher CHARM scores were independently associated with greater IADL disability [coefficient=-0.64, 95% confidence interval (CI): -0.85 to -0.43, p<0.001], increased frailty (coefficient=0.19, CI: 0.081 to 0.31, p<0.001), worse PROMIS physical function, greater PROMIS depression, increased serious organ toxicity by D100, more cognitive decline at D100, higher mortality after acute GVHD but not significantly associated with PROMIS anxiety or acute GVHD. Higher CHARM score predicted for worse disability-free survival (OR = 2.03, CI: 1.66 - 2.48, p<0.001) and lower frailty-free survival (OR =2.00, CI: 1.61 - 2.49). In summary, CHARM is an independent prognostic scoring system not only for NRM, but also for geriatric morbidity and functional limitation-free survival through 1-year after alloHCT. Pre-alloHCT CHARM is a novel tool to aid shared decision-making for older patients. NCT03992352.},
}

@article {pmid41269777,
year = {2025},
author = {Phillips, TJ and Di, M and Miller, T and Wang, J and Pierre, A and Maglinte, GA and Seymour, EK and Wang, Y},
title = {Real-World Comparative Effectiveness of Bruton Tyrosine Kinase Inhibitors in Relapsed/Refractory Mantle Cell Lymphoma.},
journal = {Blood advances},
volume = {},
number = {},
pages = {},
doi = {10.1182/bloodadvances.2025017160},
pmid = {41269777},
issn = {2473-9537},
abstract = {This real-world retrospective cohort study evaluated utilization and comparative effectiveness of covalent Bruton tyrosine kinase inhibitor (cBTKi) monotherapies in relapsed/refractory mantle cell lymphoma (R/R MCL) from electronic health records in the United States. Adults with R/R MCL who received second- or third-line (2L/3L) zanubrutinib, acalabrutinib, or ibrutinib monotherapy, on or after January 1, 2018, were included. Inverse probability of treatment weighting was used in adjusted Cox models to compare real-world time-to-next treatment (rwTTNT) and overall survival (rwOS). Among 698 patients who received 2L/3L cBTKi monotherapy, 49%, 32%, and 19% received acalabrutinib, ibrutinib, and zanubrutinib, respectively. Unadjusted analyses showed median rwTTNT for 2L zanubrutinib, acalabrutinib, and ibrutinib was 14.5 (95%CI 11.0-23.2), 12.8 (95%CI 10.5-15.6), and 10.3 (95%CI 7.6-13.7) months and median rwOS was 26.4 (95%CI 23.2-not reached [NR]), 29.2 (95%CI 22.9-38.1), and 29.3 (95%CI 21.8-41.6) months, respectively. Median rwTTNT for 3L zanubrutinib, acalabrutinib, and ibrutinib was 21.1 (95%CI 3.9-NR), 9.2 (95%CI 6.8-14.7), and 9.6 (95%CI 4.8-18.0) months and median rwOS was NR (95%CI 27.3-NR), 27.4 (95%CI 15.1-42.2), and 27.0 (95%CI 15.6-NR) months, respectively. Adjusted models in the 2L/3L cohorts combined showed numerically longer rwTTNT and statistically significantly longer rwOS for zanubrutinib versus ibrutinib (hazard ratio 0.63, 95%CI 0.42-0.96), and trends for improved rwTTNT and rwOS for zanubrutinib over acalabrutinib. Toxicity was a frequent reason for changing to another cBTKi. These findings suggest potential improvements in rwTTNT and rwOS with the use of second- and next-generation cBTKis for R/R MCL from 2018 and beyond.},
}

@article {pmid41268646,
year = {2025},
author = {Heng, F and Sun, Y and Xu, J and Gilbert, PB},
title = {Generalized nonparametric temporal modeling of recurrent events with application to a malaria vaccine trial.},
journal = {Biometrics},
volume = {81},
number = {4},
pages = {},
pmid = {41268646},
issn = {1541-0420},
support = {R37 AI054165/NH/NIH HHS/United States ; DMS-1915829//National Science Foundation/ ; },
mesh = {*Malaria Vaccines/therapeutic use ; Humans ; *Models, Statistical ; *Malaria/prevention & control/epidemiology ; Computer Simulation ; Algorithms ; Statistics, Nonparametric ; Likelihood Functions ; Recurrence ; Biometry/methods ; },
abstract = {Motivated by a malaria vaccine efficacy trial, this paper investigates generalized nonparametric temporal models of intensity processes with multiple time scales. Through the choice of link functions, the proposed models encompass a wide range of models such as the multiplicative temporal intensity model and the additive temporal intensity model. A maximum likelihood estimation procedure is developed to estimate the effects of two time-scales via the local linear smoothing with double kernels. Computational algorithms are developed to facilitate applications of the proposed method. An adaptive algorithm is developed to overcome the challenges of overlapping covariates. A cross-validation bandwidth selection procedure based on the logarithm of likelihood criteria is discussed. The asymptotic properties of the proposed estimators are investigated. Our simulation study shows that the proposed methods have satisfactory finite sample performance for both the multiplicative temporal intensity model and additive temporal intensity model. The proposed methods are applied to analyze the MAL-094/MAL-095 malaria vaccine efficacy trial data to investigate how the new malaria infection risk changes over time and how a prior infection or vaccination changes the future infection risk. The proposed method provides new insight into the protective effects of the malaria vaccine against new malaria infections and how the vaccine efficacy is modified by the history of prior malaria infection over time.},
}

*Malaria Vaccines/therapeutic use
Humans
*Models, Statistical
*Malaria/prevention & control/epidemiology
Computer Simulation
Algorithms
Statistics, Nonparametric
Likelihood Functions
Recurrence
Biometry/methods

@article {pmid41268055,
year = {2025},
author = {Salerno, S and Li, Y},
title = {A Pseudo-Value Approach to Causal Deep Learning of Semi-Competing Risks.},
journal = {Arabian journal of mathematics},
volume = {},
number = {},
pages = {},
pmid = {41268055},
issn = {2193-5351},
support = {R01 CA249096/CA/NCI NIH HHS/United States ; },
abstract = {While mortality is often the main focus of cancer studies, non-fatal events, such as disease progression, can vitally impact patient outcomes. For example, recurrence after curative treatment is a crucial endpoint in lung cancer, affecting available second-line treatments and personalized care. Estimating the de-confounded effect of interventions on disease recurrence is a key aspect of assessing cancer treatments. However, semi-competing risks complicate causal inference when death prevents disease recurrence. Existing approaches for estimating causal quantities in semi-competing survival functions rely on complex objective functions with strong assumptions and are challenging to estimate accurately. To address these challenges, we propose a deep learning approach for estimating the causal effect of treatment on non-fatal outcomes in the presence of dependent censoring and complex covariate relationships. Our three-stage approach involves estimating the marginal survival function using an Archimedean copula representation, and a jackknife pseudo-value approach that estimates pseudo-survival probabilities at fixed time points. These pseudo-survival probabilities serve as target values for developing causal estimators that are consistent and do not rely on assumptions like proportional hazards across all time points. In the final stage, we employ a deep neural network to link pseudo-outcomes, the causal variable, and additional confounders. This enables us to estimate survival average causal effects through direct standardization. We evaluate our approach through numerical studies and apply it to the Boston Lung Cancer Study, specifically examining the effect of surgical tumor resection in patients with early-stage non-small cell lung cancer.},
}

@article {pmid41266432,
year = {2025},
author = {Day, PM and Thompson, CD and Scherer, EM and Carter, JJ and Galloway, DA and Lowy, DR and Schiller, JT},
title = {Post-attachment neutralization of HPV16 by antibodies derived from Gardasil-vaccinated women.},
journal = {NPJ vaccines},
volume = {10},
number = {1},
pages = {239},
pmid = {41266432},
issn = {2059-0105},
abstract = {HPV vaccines exhibit high type-specific and antibody-mediated protection against anogenital infection, even after a single dose. Complete and long-term "sterilizing" immunity against incident infection appears to be established in most HPV vaccinees, suggesting that not only are persistent levels of virus-inhibiting antibodies routinely generated but that they are also exceptionally potent at preventing infection. The process of HPV infection is unusually protracted at several steps, including slow internalization after the virions bind to the cell surface. This observation prompted us to comprehensively evaluate the ability of neutralizing antibodies to prevent infection subsequent to HPV pseudovirion attachment to cells. Using sera and memory B cell-derived monoclonal antibodies from Gardasil-vaccinated women, we observed almost complete post-attachment neutralization of HPV16 pseudovirion infection of HaCaT cells three hours after attachment, even when vaccinees' sera were diluted 250-fold, with a gradual loss of activity up to 18 h. Unexpectedly, three distinct mechanisms of post-attachment neutralization were discovered, capsid shedding from the cell surface, capsid retention on the cell surface, and rapid capsid degradation after internalization.},
}

@article {pmid41266372,
year = {2025},
author = {Barnes, DR and Tyrer, JP and Dennis, J and Leslie, G and Bolla, MK and Lush, M and Aeilts, AM and Aittomäki, K and Andrieu, N and Andrulis, IL and Anton-Culver, H and Arason, A and Arun, BK and Balmaña, J and Bandera, EV and Barkardottir, RB and Berger, LPV and Berrington de Gonzalez, A and Berthet, P and Białkowska, K and Bjørge, L and Blanco, AM and Blok, MJ and Bobolis, KA and Bogdanova, NV and Brenton, JD and Butz, H and Buys, SS and Caligo, MA and Campbell, I and Castillo, C and Claes, KBM and Colonna, SV and Cook, LS and Daly, MB and Dansonka-Mieszkowska, A and de la Hoya, M and deFazio, A and DePersia, A and Ding, YC and Doherty, JA and Domchek, SM and Dörk, T and Einbeigi, Z and Engel, C and Evans, DG and Foretova, L and Fortner, RT and Fostira, F and Foti, MC and Friedman, E and Frone, MN and Ganz, PA and Gentry-Maharaj, A and Glendon, G and Godwin, AK and González-Neira, A and Greene, MH and Gronwald, J and Guerrieri-Gonzaga, A and Hamann, U and Hansen, TVO and Harris, HR and Hauke, J and Heitz, F and Hogervorst, FBL and Hooning, MJ and Hopper, JL and Huff, CD and Huntsman, DG and Imyanitov, EN and Izatt, L and Jakubowska, A and James, PA and Janavicius, R and John, EM and Kar, S and Karlan, BY and Kennedy, CJ and Kiemeney, LALM and Konstantopoulou, I and Kupryjanczyk, J and Laitman, Y and Lavie, O and Lawrenson, K and Lester, J and Lesueur, F and Lopez-Pleguezuelos, C and Mai, PL and Manoukian, S and May, T and McNeish, IA and Menon, U and Milne, RL and Modugno, F and Mongiovi, JM and Montagna, M and Moysich, KB and Neuhausen, SL and Nielsen, FC and Noguès, C and Oláh, E and Olopade, OI and Osorio, A and Papi, L and Pathak, H and Pearce, CL and Pedersen, IS and Peixoto, A and Pejovic, T and Peng, PC and Peshkin, BN and Peterlongo, P and Powell, CB and Prokofyeva, D and Pujana, MA and Radice, P and Rashid, MU and Rennert, G and Richenberg, G and Sandler, DP and Sasamoto, N and Setiawan, VW and Sharma, P and Sieh, W and Singer, CF and Snape, K and Sokolenko, AP and Soucy, P and Southey, MC and Stoppa-Lyonnet, D and Sutphen, R and Sutter, C and Tan, YY and Teixeira, MR and Terry, KL and Thomsen, LCV and Tischkowitz, M and Toland, AE and Van Gorp, T and Vega, A and Velez Edwards, DR and Webb, PM and Weitzel, JN and Wentzensen, N and Whittemore, AS and Winham, SJ and Wu, AH and Yadav, S and Yu, Y and Ziogas, A and Berchuck, A and Couch, FJ and Goode, EL and Goodman, MT and Monteiro, AN and Offit, K and Ramus, SJ and Risch, HA and Schildkraut, JM and Thomassen, M and Simard, J and Easton, DF and Jones, MR and Chenevix-Trench, G and Gayther, SA and Antoniou, AC and Pharoah, PDP},
title = {Genome-wide association study of 398,238 women unveils seven loci associated with high-grade serous ovarian cancer.},
journal = {NPJ genomic medicine},
volume = {10},
number = {1},
pages = {73},
pmid = {41266372},
issn = {2056-7944},
support = {R01 CA074850/CA/NCI NIH HHS/United States ; P50 CA105009/CA/NCI NIH HHS/United States ; P30 CA076292/CA/NCI NIH HHS/United States ; P50 CA116201/CA/NCI NIH HHS/United States ; R01 CA126841/CA/NCI NIH HHS/United States ; U10 CA180868/CA/NCI NIH HHS/United States ; U01 CA069417/CA/NCI NIH HHS/United States ; R03 CA130065/CA/NCI NIH HHS/United States ; R01 CA140323/CA/NCI NIH HHS/United States ; UM1 CA164973/CA/NCI NIH HHS/United States ; R01 CA260132/CA/NCI NIH HHS/United States ; R01 CA176785/CA/NCI NIH HHS/United States ; N01 PC067010/PC/NCI NIH HHS/United States ; P50 CA159981/CA/NCI NIH HHS/United States ; RC4 CA153828/CA/NCI NIH HHS/United States ; P30 CA016056/CA/NCI NIH HHS/United States ; R01 CA087538/CA/NCI NIH HHS/United States ; R01 CA142996/CA/NCI NIH HHS/United States ; P50 CA125183/CA/NCI NIH HHS/United States ; Z01 ES044005/ImNIH/Intramural NIH HHS/United States ; P01 CA087969/CA/NCI NIH HHS/United States ; R01 CA067262/CA/NCI NIH HHS/United States ; R01 CA106414/CA/NCI NIH HHS/United States ; P30 CA072720/CA/NCI NIH HHS/United States ; R01 CA095023/CA/NCI NIH HHS/United States ; PPRPGM-Nov20\100002//Cancer Research UK (CRUK)/ ; P30 CA168524/CA/NCI NIH HHS/United States ; U01 CA161032/CA/NCI NIH HHS/United States ; UM1 CA176726/CA/NCI NIH HHS/United States ; K05 CA154337/CA/NCI NIH HHS/United States ; R37 CA070867/CA/NCI NIH HHS/United States ; R03 CA113148/CA/NCI NIH HHS/United States ; R01 CA058598/CA/NCI NIH HHS/United States ; K22 CA138563/CA/NCI NIH HHS/United States ; R01 CA058860/CA/NCI NIH HHS/United States ; Z01 ES049033/ImNIH/Intramural NIH HHS/United States ; R01 CA080742/CA/NCI NIH HHS/United States ; S10 RR025141/RR/NCRR NIH HHS/United States ; U10 CA027469/CA/NCI NIH HHS/United States ; R01 CA063678/CA/NCI NIH HHS/United States ; UL1 TR000124/TR/NCATS NIH HHS/United States ; K07 CA080668/CA/NCI NIH HHS/United States ; U01 CA116167/CA/NCI NIH HHS/United States ; P30 CA008748/CA/NCI NIH HHS/United States ; R01 CA214545/CA/NCI NIH HHS/United States ; R01 CA128978/CA/NCI NIH HHS/United States ; N02 CP011019/CP/NCI NIH HHS/United States ; N02 CP065504/CP/NCI NIH HHS/United States ; P30 CA014089/CA/NCI NIH HHS/United States ; U19 CA148537/CA/NCI NIH HHS/United States ; P30 CA051008/CA/NCI NIH HHS/United States ; R01 CA116167/CA/NCI NIH HHS/United States ; R01 CA083918/CA/NCI NIH HHS/United States ; R01 CA063464/CA/NCI NIH HHS/United States ; R03 CA115195/CA/NCI NIH HHS/United States ; PRCPJT-May21\100006//Cancer Research UK (CRUK)/ ; U10 CA037517/CA/NCI NIH HHS/United States ; P20 GM130423/GM/NIGMS NIH HHS/United States ; UM1 CA186107/CA/NCI NIH HHS/United States ; R25 CA112486/CA/NCI NIH HHS/United States ; R01 CA054419/CA/NCI NIH HHS/United States ; R01 CA122443/CA/NCI NIH HHS/United States ; P30 CA015083/CA/NCI NIH HHS/United States ; R01 CA076016/CA/NCI NIH HHS/United States ; R01 CA054281/CA/NCI NIH HHS/United States ; U01 CA063464/CA/NCI NIH HHS/United States ; P30 CA016520/CA/NCI NIH HHS/United States ; R01 CA160669/CA/NCI NIH HHS/United States ; U01 CA058860/CA/NCI NIH HHS/United States ; R01 CA248288/CA/NCI NIH HHS/United States ; U01 CA164920/CA/NCI NIH HHS/United States ; R35 CA253187/CA/NCI NIH HHS/United States ; U19 CA148112/CA/NCI NIH HHS/United States ; R01 CA149429/CA/NCI NIH HHS/United States ; P01 CA017054/CA/NCI NIH HHS/United States ; N01 CN025403/CA/NCI NIH HHS/United States ; R01 CA142081/CA/NCI NIH HHS/United States ; U19 CA148065/CA/NCI NIH HHS/United States ; /WT_/Wellcome Trust/United Kingdom ; R01 CA049449/CA/NCI NIH HHS/United States ; R01 CA063682/CA/NCI NIH HHS/United States ; R01 CA192393/CA/NCI NIH HHS/United States ; K07 CA095666/CA/NCI NIH HHS/United States ; U10 CA180888/CA/NCI NIH HHS/United States ; R01 CA112523/CA/NCI NIH HHS/United States ; U10 CA180822/CA/NCI NIH HHS/United States ; U01 CA164973/CA/NCI NIH HHS/United States ; R37 CA054281/CA/NCI NIH HHS/United States ; P50 CA136393/CA/NCI NIH HHS/United States ; },
abstract = {Nineteen genomic regions have been associated with high-grade serous ovarian cancer (HGSOC). We meta-analyzed >22 million variants for 398,238 women from the Ovarian Cancer Association Consortium (OCAC), UK Biobank (UKBB) and Consortium of Investigators of Modifiers of BRCA1/BRCA2 (CIMBA) to identify novel HGSOC susceptibility loci. Eight novel variants were associated with HGSOC risk. An interesting discovery biologically was TP53 3'-UTR SNP rs78378222-T's association with HGSOC (per-T-allele relative risk (RR) = 1.44, 95% CI:1.28-1.62, P = 1.76 × 10[-9]). Polygenic scores (PGS) were developed using OCAC and CIMBA data and trained on FinnGen data. The optimal PGS included 64,518 variants and was associated with an odds ratio of 1.46 (95% CI:1.37-1.54) per standard deviation when validated in the UKBB. This study represents the largest HGSOC GWAS to date - demonstrating that improvements in imputation reference panels and increased sample sizes help to identify HGSOC associated variants that previously went undetected, ultimately improving PGS which can improve personalized HGSOC risk prediction.},
}

@article {pmid41262227,
year = {2025},
author = {Banerjee, R and Das, MK and Smith, KD},
title = {Amyloid Deposits in a Bone Marrow Biopsy Alongside a Presumed Causative Clone.},
journal = {EJHaem},
volume = {6},
number = {6},
pages = {e70180},
pmid = {41262227},
issn = {2688-6146},
}

@article {pmid41256718,
year = {2025},
author = {Ukogu, OA and Montague, Z and Altan-Bonnet, G and Nourmohammad, A},
title = {Design principles of the cytotoxic CD8[+] T-cell response.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {41256718},
issn = {2692-8205},
support = {R35 GM142795/GM/NIGMS NIH HHS/United States ; ZIA BC012007/ImNIH/Intramural NIH HHS/United States ; },
abstract = {Cytotoxic T lymphocytes eliminate infected or malignant cells, safeguarding surrounding tissues. Although experimental and systems-immunology studies have cataloged many molecular and cellular actors involved in an immune response, the design principles governing how the speed and magnitude of T-cell responses emerge from cellular decision-making remain elusive. Here, we recast the T-cell response as a feedback-controlled program, wherein the rates of activation, proliferation, differentiation and death are regulated through antigenic, pro- and anti-inflammatory cues. By exploring a broad class of feedback-controller designs as potential immune programs, we demonstrate how the speed and magnitude of T-cell responses emerge from optimizing signal-feedback to protect against diverse infection settings. We recover an inherent trade-off: infection clearance at the cost of immunopathology. We show how this trade-off is encoded into the logic of T-cell responses by hierarchical sensitivity to different immune signals. Notably, we find that designs that balance harm from acute infections and autoimmunity produce immune responses consistent with experimentally observed patterns of T-cell effector expansion in mice. Extending our model to immune-based T-cell therapies for cancer tumors, we identify a trade-off between the affinity for tumor antigens ("quality") and the abundance ("quantity") of infused T-cells necessary for effective treatment. Finally, we show how therapeutic efficacy can be improved by targeted genetic perturbations to T-cells. Our findings offer a unified control-logic for cytotoxic T-cell responses and point to specific regulatory programs that can be engineered for more robust T-cell therapies.},
}

@article {pmid41256432,
year = {2025},
author = {Favor, A and Quijano, R and Chernova, E and Kubaney, A and Weidle, C and Esler, MA and McHugh, L and Carr, A and Hsia, Y and Juergens, D and Carr, KD and Kim, PT and Politanska, Y and Sehgal, E and Kwon, PS and Pecoraro, RJ and Glasscock, C and Borst, AJ and DiMaio, F and Stoddard, BL and Baker, D},
title = {De novo design of RNA and nucleoprotein complexes.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {41256432},
issn = {2692-8205},
support = {P30 GM124169/GM/NIGMS NIH HHS/United States ; R35 GM148166/GM/NIGMS NIH HHS/United States ; S10 OD028581/OD/NIH HHS/United States ; },
abstract = {Nucleic acids fold into sequence-dependent tertiary structures and carry out diverse biological functions, much like proteins. However, while considerable advances have been made in the de novo design of protein structure and function, the same has not yet been achieved for RNA tertiary structures of similar intricacy. Here, we describe a generative diffusion framework, RFDpoly, for generalized de novo biopolymer (RNA, DNA and protein) design, and use it to create diverse and designable RNA structures. We design RNA structures with novel folds and experimentally validate them using a combination of chemical footprinting (SHAPE-seq) and electron microscopy. We further use this approach to design protein-nucleic acid assemblies; the crystal structure of one such design is nearly identical to the design model. This work demonstrates that the principles of structure-based de novo protein design can be extended to nucleic acids, opening the door to creating a wide range of new RNA structures and protein-nucleic acid complexes.},
}

@article {pmid41256175,
year = {2025},
author = {Cheng, S and Suger, AH and Goss, LB and Zhang, J and Fuller, H and Guo, B and Lindström, S and Darst, BF},
title = {Validation and context-dependent effects of a prostate cancer polygenic risk score in the All of Us Research Program.},
journal = {medRxiv : the preprint server for health sciences},
volume = {},
number = {},
pages = {},
pmid = {41256175},
support = {P30 CA015704/CA/NCI NIH HHS/United States ; P50 CA097186/CA/NCI NIH HHS/United States ; U01 CA261339/CA/NCI NIH HHS/United States ; R00 CA246063/CA/NCI NIH HHS/United States ; R03 CA287235/CA/NCI NIH HHS/United States ; },
abstract = {Polygenic risk scores (PRSs) have demonstrated strong potential for improving prostate cancer risk stratification. However, it is unknown whether the clinical utility of prostate cancer PRS vary by demographic, lifestyle, and socioeconomic factors. We validated a previously developed multi-ancestry PRS of 451 prostate cancer risk variants and evaluated context-dependent effects using genetic and clinical data from the diverse All of Us Research Program, including 7,577 cases and 90,608 controls across six genetic ancestry groups. In ancestry-stratified testing, the PRS showed strong associations with prostate cancer risk, with odds ratios (ORs) per standard deviation (SD) increase ranging from 1.61 (95% CI=1.02-2.64, P=0.05) in Middle Eastern to 2.19 (95% CI=1.98-2.42, P=2.2×10[-51]) in American populations. Age-stratified analyses showed an overall reduced PRS effect with increasing age. Across modifiable lifestyle and healthcare access factors, PRS effects were larger in those with higher body mass index (OR ranging from 1.71-2.17 in underweight to obese individuals, P=0.02), in never or former smokers vs. current smokers (OR=2.06, 2.37, and 1.93, respectively, P=0.06), and in those recently accessing healthcare (OR=2.21 vs. 1.88, P=0.05), highlighting important context-specific modifiers. We did not observe context-dependent effects by other socioeconomic factors, such as income, education, and insurance. In a phenome-wide association study (PheWAS), the PRS was associated with 14 clinical outcomes, including known prostate cancer-related conditions. These findings confirm the predictive strength of the multi-ancestry prostate cancer PRS across diverse populations and underscore the importance of accounting for demographic, lifestyle, and healthcare-related contexts when applying PRS in clinical and public health settings.},
}

@article {pmid41261961,
year = {2025},
author = {Chen, J and Francis, P and Martinez, A and Marre, E and Thornton, S and Loggers, ET and Shinohara, MM},
title = {Exploring sexual health in patients with cutaneous T-cell lymphoma: a mixed methods study.},
journal = {The British journal of dermatology},
volume = {},
number = {},
pages = {},
doi = {10.1093/bjd/ljaf466},
pmid = {41261961},
issn = {1365-2133},
}

@article {pmid41261829,
year = {2025},
author = {Wu, HV and Oeffinger, KC and Chou, JF and Henderson, TO and Hudson, MM and Diller, LR and McDonald, AJ and Ford, J and Mubdi, NZ and Rinehart, D and Vukadinovich, C and Elkin, EB and Leisenring, WM and Armstrong, GT and Ford, JS and Moskowitz, CS},
title = {Assessing delivery of and attitudes toward a randomized intervention to increase mammography uptake among childhood cancer survivors: A report from the Childhood Cancer Survivor Study.},
journal = {Journal of psychosocial oncology},
volume = {},
number = {},
pages = {1-16},
doi = {10.1080/07347332.2025.2586559},
pmid = {41261829},
issn = {1540-7586},
abstract = {OBJECTIVE: This study characterizes utilization of, and attitudes toward, a two-part intervention of (1) mailed materials, including educational laminated cards for patients and healthcare providers, and (2) telephone counseling, that aimed to increase screening mammography uptake among adult female survivors of childhood cancer compared to attention controls.

METHODS: Participants (n = 136, median age 35 years, range 25-49 years) were diagnosed with cancer between 1976 and 1999 before age 21 years and had been treated with chest radiation. At study end, participants completed a questionnaire asking about their use of and attitudes toward the intervention components. Fisher's exact tests assessed associations.

RESULTS: Among 130 survivors who completed the survey, 45 (35%) received a mammogram. Eighty-five (65%) survivors recalled receiving both intervention components; about half (n = 73, 56%) found the laminated cards helpful and/or described the telephone counseling as positive or activating (n = 81, 62%). Of the 96 women who provided responses, approximately two-thirds (n = 64, 67%) reported little to no fear/anxiety regarding the intervention. Women were more likely to obtain a mammogram if they remembered receiving both intervention components compared to women who reported receiving one or no components (45% vs. 24%, p = 0.050), reported using the laminated card to discuss screening with a healthcare provider (72% vs. 51%, p = 0.086), or found the telephone counseling motivational (61% vs. 30%, p = 0.003).

CONCLUSIONS: In summary, the two-part intervention was well-received and elicited minimal fear/anxiety. Receiving intervention messaging in multiple forms and sharing it with a healthcare provider was associated with intervention efficacy.},
}

@article {pmid41261512,
year = {2025},
author = {Greenlee, H and Crew, KD and Maurer, M and Kalinsky, K and Cremers, S and Naini, A and Tsai, WY and Shi, Z and Brogan, F and Hershman, DL},
title = {Phase I Randomized, Placebo-Controlled, Cross-Over Dose-Finding Study of Coenzyme Q10 on Doxorubicin Pharmacokinetics during Breast Cancer Treatment.},
journal = {Integrative cancer therapies},
volume = {24},
number = {},
pages = {15347354251388014},
doi = {10.1177/15347354251388014},
pmid = {41261512},
issn = {1552-695X},
mesh = {Humans ; Female ; *Ubiquinone/analogs & derivatives/administration & dosage/blood/pharmacology ; *Doxorubicin/pharmacokinetics/administration & dosage/adverse effects/therapeutic use ; *Breast Neoplasms/drug therapy ; Middle Aged ; Cross-Over Studies ; Adult ; Aged ; Dose-Response Relationship, Drug ; Cyclophosphamide/administration & dosage ; Antineoplastic Combined Chemotherapy Protocols/pharmacokinetics/therapeutic use ; Maximum Tolerated Dose ; Antibiotics, Antineoplastic/pharmacokinetics/administration & dosage ; },
abstract = {AIM: To determine effects of Coenzyme Q10 (CoQ10) supplementation in breast cancer patients receiving doxorubicin treatment.

METHODS: Phase I randomized, placebo-controlled, cross-over, dose-finding study among women with stage I-III breast cancer receiving 4 cycles of doxorubicin plus cyclophosphamide. The study was designed to test effects on doxorubicin pharmacokinetic parameters when administering up to the maximum tolerated dose of CoQ10 of 1200 mg/day. Eligible patients were randomized to Arm A (CoQ10 after Cycle 3, followed by placebo after Cycle 4) or Arm B (placebo after Cycle 3, followed by CoQ10 after Cycle 4). CoQ10 concentrations and total antioxidant capacity (TAC) were measured before and after chemotherapy cycles. Non-compartmental pharmacokinetic parameters of doxorubicin and its active metabolites were measured with and without CoQ10. Paired t-tests assessed intra-patient differences in pharmacokinetic parameters, serum CoQ10 concentrations, TAC, and adverse events.

RESULTS: Six patients received 300 mg/day of CoQ10 (Arm A [n = 3], Arm B [n = 3]). One patient received 600 mg/day of CoQ10 but was discontinued due to non-adherence. Serum CoQ10 concentrations were increased in patients receiving 300 mg/day (mean ± SD change: CoQ10, 1.6 ± 0.9 µg/mL; placebo, -0.01 ± 0.3 µg/mL; P = .01). There were no clinically significant pharmacokinetic interactions between 300 mg/day CoQ10 and doxorubicin and no differences in TAC or adverse events during treatment and nontreatment periods. The trial was closed early due to slow accrual.

CONCLUSION: 300 mg/day of CoQ10 with doxorubicin did not change doxorubicin pharmacokinetics and was not associated with treatment-related adverse events. Future studies should evaluate the long-term effects of CoQ10 at 300 mg/day and safety studies should examine higher doses.

TRIAL REGISTRATION: ClinicalTrials.gov: NCT00976131.},
}

Humans
Female
*Ubiquinone/analogs & derivatives/administration & dosage/blood/pharmacology
*Doxorubicin/pharmacokinetics/administration & dosage/adverse effects/therapeutic use
*Breast Neoplasms/drug therapy
Middle Aged
Cross-Over Studies
Adult
Aged
Dose-Response Relationship, Drug
Cyclophosphamide/administration & dosage
Antineoplastic Combined Chemotherapy Protocols/pharmacokinetics/therapeutic use
Maximum Tolerated Dose
Antibiotics, Antineoplastic/pharmacokinetics/administration & dosage

@article {pmid41260881,
year = {2026},
author = {Valieris, R and Rosa, L and Martins, L and Defelicibus, A and Carraro, DM and Nunes, DN and Dias-Neto, E and Rosales, R and da Silva, IT},
title = {Regulators of homologous recombination deficiency identified by machine learning using somatic multi-omics data.},
journal = {Life science alliance},
volume = {9},
number = {2},
pages = {},
pmid = {41260881},
issn = {2575-1077},
mesh = {Humans ; *Machine Learning ; DNA Copy Number Variations/genetics ; DNA Methylation/genetics ; *Neoplasms/genetics ; *Homologous Recombination/genetics ; Genomics/methods ; Polymorphism, Single Nucleotide/genetics ; Mutation ; Biomarkers, Tumor/genetics ; Gene Expression Regulation, Neoplastic ; Multiomics ; },
abstract = {Homologous recombination deficiency (HRD) is a critical biomarker for guiding targeted therapies, yet the full range of somatic alterations driving HRD across cancers remains incompletely characterized. Here, we present a tumor-agnostic machine learning framework that integrates somatic multi-omics data, including copy-number variations, single-nucleotide variants, DNA methylation, and gene expression from over 8,000 patients in The Cancer Genome Atlas. Using a genome-wide mutational signature-based HRD score as ground truth, our model achieved high predictive performance and leveraged SHAP-based explainability to uncover HRD regulators beyond BRCA1/2 Cross-tumor analysis revealed both shared and cancer type-specific molecular determinants, whereas functional enrichment highlighted key molecular and cellular processes. These findings expand the known repertoire of HRD-associated alterations, provide a resource for mechanistic investigation, and demonstrate the potential of integrative AI approaches to improve patient stratification for HR-targeted therapies across diverse malignancies.},
}

Humans
*Machine Learning
DNA Copy Number Variations/genetics
DNA Methylation/genetics
*Neoplasms/genetics
*Homologous Recombination/genetics
Genomics/methods
Polymorphism, Single Nucleotide/genetics
Mutation
Biomarkers, Tumor/genetics
Gene Expression Regulation, Neoplastic
Multiomics

@article {pmid41260765,
year = {2026},
author = {Rojanasopondist, P and Kaz, A and Yu, M and Grady, WM},
title = {Emerging Biomarkers for Managing Barrett's Esophagus.},
journal = {Gastrointestinal endoscopy clinics of North America},
volume = {36},
number = {1},
pages = {149-170},
doi = {10.1016/j.giec.2025.05.005},
pmid = {41260765},
issn = {1558-1950},
mesh = {Humans ; *Barrett Esophagus/genetics/metabolism/diagnosis/pathology/therapy ; *Adenocarcinoma/genetics/metabolism/diagnosis ; *Esophageal Neoplasms/genetics/diagnosis/metabolism ; *Biomarkers, Tumor/metabolism/genetics ; DNA Methylation ; Biomarkers ; MicroRNAs ; },
abstract = {Comparative analyses of normal esophageal tissue, Barrett's Esophagus (BE), and esophageal adenocarcinoma have identified distinctive molecular alterations in genomic DNA, epigenetics, non-coding RNA, and proteins that have shown promise as disease-specific biomarkers. Some of the best characterized and promising biomarkers for managing BE are multi-target esophageal cytology DNA assays based on methylated-DNA and immunohistochemical staining of Trefoil factor 3. Additional biomarkers including microRNA, measures of genomic instability, mixed-method panels, and other novel biomarkers (e.g. volatile organic compounds and saliva microbiome) remain in early development and will need further validation in large, prospective studies prior to clinical use.},
}

Humans
*Barrett Esophagus/genetics/metabolism/diagnosis/pathology/therapy
*Adenocarcinoma/genetics/metabolism/diagnosis
*Esophageal Neoplasms/genetics/diagnosis/metabolism
*Biomarkers, Tumor/metabolism/genetics
DNA Methylation
Biomarkers
MicroRNAs

@article {pmid41260264,
year = {2025},
author = {Hurvitz, SA and Loi, S and O'Shaughnessy, J and Okines, AFC and Tolaney, SM and Sohn, J and Saura, C and Zhu, X and Cameron, D and Bachelot, T and Hamilton, E and Curigliano, G and Wolff, AC and Harbeck, N and Masuda, N and Vahdat, L and Zaman, K and Valdes-Albini, F and Block, M and Pluard, T and Tan, TJ and Gawryletz, C and Chan, A and Bedard, PL and Yerushalmi, R and Xu, B and Schmitt, M and Xie, D and Borges, VF and , },
title = {Tucatinib and trastuzumab emtansine for patients with previously treated HER2-positive locally advanced and metastatic breast cancer: primary analysis of the randomized phase III trial HER2CLIMB-02.},
journal = {Annals of oncology : official journal of the European Society for Medical Oncology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.annonc.2025.11.005},
pmid = {41260264},
issn = {1569-8041},
abstract = {BACKGROUND: Trastuzumab emtansine (T-DM1) is a standard treatment option in patients with previously treated human epidermal growth factor receptor 2-positive (HER2+) locally advanced or metastatic breast cancer (LA/MBC). Here, we report the efficacy and safety of tucatinib in combination with T-DM1 compared with T-DM1 alone from the phase III HER2CLIMB-02 study (NCT03975647).

PATIENTS AND METHODS: Eligible patients had HER2+ LA/MBC that had been previously treated with trastuzumab and a taxane in any setting; these included patients with brain metastases (BMs). Patients were randomly assigned 1:1 to receive T-DM1 (3.6 mg/kg intravenously every 21 days) combined with either tucatinib (300 mg orally twice daily) in the tucatinib arm or placebo (orally twice daily) in the control arm.

RESULTS: In total, 463 patients were randomly assigned. After a median follow-up duration of 24.4 months, the median progression-free survival (PFS) was 9.5 months in the tucatinib arm and 7.4 months in the control arm (hazard ratio [HR]=0.76; 95% CI, 0.61-0.95; P=0.0163). A PFS benefit was observed across all prespecified subgroups, including in patients with BMs. Interim overall survival analysis results were immature. The median OS was not reached in the tucatinib arm and was 38.0 months in the control arm (HR=1.23; 95% CI, 0.87-1.74). The incidences of treatment-emergent adverse events (TEAEs) associated with any treatment discontinuation and of grade ≥3 TEAEs were higher in the tucatinib arm than in the control arm (22.1% versus 11.6% and 68.8% versus 41.2%, respectively). The most common grade ≥3 TEAEs in the tucatinib arm were elevated alanine aminotransferase (16.5%) and aspartate aminotransferase levels (16.5%) (versus 2.6% for both in the control arm).

CONCLUSION: The addition of tucatinib to T-DM1 improved PFS in patients with previously treated HER2+ LA/MBC, including patients with BMs, and exhibited a manageable safety profile.},
}

@article {pmid41260262,
year = {2025},
author = {Saura, C and Cortés, J and Modi, S and Kim, SB and Hamilton, E and Hurvitz, SA and Krop, IE and Curigliano, G and Iwata, H and Im, SA and Herbolsheimer, P and Karnoub, M and Boran, A and Kuwahara, Y and Egorov, A and André, F},
title = {Pooled analysis by best confirmed response to trastuzumab deruxtecan and related biomarkers in patients with HER2-positive metastatic breast cancer from DESTINY-Breast01, DESTINY-Breast02, and DESTINY-Breast03.},
journal = {Annals of oncology : official journal of the European Society for Medical Oncology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.annonc.2025.11.007},
pmid = {41260262},
issn = {1569-8041},
abstract = {BACKGROUND: Objective response rates in the DESTINY-Breast01/02/03 trials, which evaluated trastuzumab deruxtecan (T-DXd) in human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (mBC), were 62%/70%/79%, respectively.

PATIENTS AND METHODS: This exploratory pooled analysis investigated associations between best confirmed response to T-DXd and baseline characteristics/long-term outcomes in patients who received 5.4 mg/kg T-DXd in DESTINY-Breast01/02/03. Endpoints included best confirmed response per (blinded) independent central review ([B]ICR) using RECIST v1.1, progression-free survival (PFS) by (B)ICR, overall survival (OS), safety, and biomarker analyses of expression levels/alterations of genes relevant to HER2-positive mBC or T-DXd activity.

RESULTS: 834 patients who received T-DXd in DESTINY-Breast01/02/03 were evaluable for response; 125 (15.0%) experienced complete response (CR), 477 (57.2%) experienced partial response (PR), and 232 (27.8%) were considered non-responders (stable disease/progressive disease). Median number of prior regimens in the metastatic setting was 2 for patients with CR versus 3 for patients with PR and non-responders; visceral disease and baseline brain or bone metastases were less frequently observed in patients with CR. 24-month PFS rates in patients with CR, PR, and non-responders, respectively, were 77.8%, 46.3%, and 20.6%, and 36-month OS rates were 88.6%, 54.0%, and 35.9%. Rates of serious adverse events, T-DXd discontinuation, and interstitial lung disease/pneumonitis were numerically lower in patients with CR. In exploratory biomarker analyses, responders had tumors with numerically higher HER2 plasma copy number, lower ESR1 gene expression and ESR1 mutation frequency, and lower circulating tumor DNA levels at baseline.

CONCLUSIONS: Patients with objective response to T-DXd, particularly those with CR, showed prolonged median PFS and OS. These results support T-DXd use across broad patient groups with HER2-positive mBC, including those with lower disease burden. Patients whose disease does not respond to T-DXd represent an unmet medical need, and research into more effective treatment approaches for these patients is warranted.},
}

@article {pmid41260224,
year = {2025},
author = {Roy, V and Kellman, BP and Hsu, WL and Nziza, N and Parker, L and Germosen, D and Bonifer, R and Pfeiffer, RM and Yu, KJ and Michels, B and Chen, TC and Chen, CJ and Goldstein, AM and Waterboer, T and Wang, CP and Kumar, N and Jain, A and Newell, EW and Streeck, H and Alter, G and Hildesheim, A and Liu, Z and Julg, B},
title = {Epstein-Barr-virus-specific functional antibody signatures in the context of nasopharyngeal carcinoma development.},
journal = {Med (New York, N.Y.)},
volume = {},
number = {},
pages = {100925},
doi = {10.1016/j.medj.2025.100925},
pmid = {41260224},
issn = {2666-6340},
abstract = {BACKGROUND: Nasopharyngeal carcinoma (NPC) in endemic areas is strongly linked to Epstein-Barr virus (EBV) infection. EBV-specific immunoglobulin (Ig)A and IgG titers have been used for diagnosis and prognosis, but their full potential for prediction and protection remains unclear.

METHODS: We analyzed samples from 353 individuals, including patients with NPC at diagnosis or patients with NPC years prior to diagnosis, matched controls, and family members from NPC multiplex families from Taiwan, along with 50 patients with NPC from Singapore with survival data. We used systems serology, a comprehensive approach to assess antibody subclass, isotype, and fragment crystallizable gamma receptor (FcγR) binding, along with effector functions such as complement deposition, cellular phagocytosis, and natural killer (NK) cell activation.

FINDINGS: Patients with NPC showed a broad expansion of antibody levels, FcγR binding, and Fc effector functions, especially neutrophil phagocytosis and complement deposition, compared to controls. Prior to NPC onset, individuals exhibited elevated EBV-specific IgM levels and higher FcγRIIA and FcγRIIIB binding, suggesting an early immune response to viral activity. IgMs appeared as potential correlative markers for NPC. In contrast, controls showed increased IgG2 levels and FcγRIIB binding, indicating lower inflammatory responses. On a per-antibody level, controls exhibited stronger Fc effector functions, suggesting a protective role in preventing NPC. Additionally, we identified a multivariate antibody signature associated with survival after treatment.

CONCLUSIONS: This study provides valuable insights into EBV-specific antibodies as predictive biomarkers of NPC progression, offering opportunities for improved disease management.

FUNDING: This work was supported by the Ragon Institute of Mass General, MIT, and Harvard with support from the National Cancer Institute (CA264646 to E.W.N.).},
}

@article {pmid41259899,
year = {2025},
author = {Maiorano, BA and Cigliola, A and Tateo, V and Mercinelli, C and Pastorino, GL and Dizman, N and Ebrahimi, H and Pal, SK and Gupta, S and Grivas, P and Kamat, AM and Spiess, PE and Agarwal, N and Necchi, A},
title = {Outcomes of immune checkpoint inhibitor rechallenge in advanced urothelial carcinoma: results from a global real-world evidence study.},
journal = {ESMO open},
volume = {10},
number = {12},
pages = {105862},
doi = {10.1016/j.esmoop.2025.105862},
pmid = {41259899},
issn = {2059-7029},
abstract = {BACKGROUND: Several immune checkpoint inhibitors (ICIs) are approved for urothelial carcinoma (UC), but limited information is currently available regarding the efficacy of rechallenging ICIs in patients with previous ICI exposure.

PATIENTS AND METHODS: A retrospective study was carried out using the TriNetX® database for a large-scale search of patients with advanced UC (aUC) who had received two separate courses of ICIs (either alone or in combinations). Kaplan-Meier analysis was used to estimate progression-free and overall survival (PFS, OS) of ICI rechallenge. Propensity score matching analysis was run to balance and compare groups based on the duration of ICI rechallenge and stage at diagnosis.

RESULTS: Out of 35 789 patients, a cohort of 292 (0.81%) treated with ≥2 ICI-including lines between 2014 and 2024 was identified. There were 86% bladder versus 14% upper tract UC. At initial diagnosis, 49% had stage IV, whereas 51% had stage I-III disease. The median time on prior ICI treatment was 19.5 months; the median time from the end of ICI to the start of ICI rechallenge was 9.4 months. After a median follow-up of 21.7 months, the median OS of ICI rechallenge was 20.5 months, the median PFS was 10.3 months. Previous use of an ICI in a nonmetastatic setting was associated with longer median OS than both lines given in aUC (P < 0.001). Among those who received a previous ICI in a metastatic setting, a cut-off of 12 months for the ICI rechallenge was associated with a longer median OS (P = 0.027). The longest duration of rechallenge treatment was achieved with anti-programmed cell death protein 1 given after anti-programmed death-ligand 1 therapy (18.2 months, P < 0.001).

CONCLUSIONS: Although it is an uncommon and not standard strategy, previous ICI in nonmetastatic UC and a period of ≥12 months after previous ICI in the metastatic setting were associated with better outcomes after ICI rechallenge in patients with aUC.},
}

@article {pmid41259538,
year = {2025},
author = {Slein, MD and Backes, IM and Jiménez, LM and Kelkar, NS and Garland, CR and Khanwalkar, US and Sholukh, AM and Johnston, C and Leib, DA and Ackerman, ME},
title = {Eliminating interactions with the viral Fc receptor improves antibody-mediated protection against neonatal HSV infection in mice.},
journal = {Science translational medicine},
volume = {17},
number = {825},
pages = {eadu8579},
doi = {10.1126/scitranslmed.adu8579},
pmid = {41259538},
issn = {1946-6242},
mesh = {Animals ; *Receptors, Fc/metabolism/immunology ; *Herpes Simplex/immunology/prevention & control/virology ; Humans ; Antibodies, Monoclonal/immunology ; Mice ; Herpesvirus 1, Human/immunology ; *Antibodies, Viral/immunology ; Immunoglobulin G/immunology ; Antibodies, Neutralizing/immunology ; Viral Envelope Proteins/immunology/metabolism ; Female ; Protein Binding ; Animals, Newborn ; Pregnancy Complications, Infectious ; },
abstract = {Herpes simplex virus (HSV) encodes surface glycoproteins that are host defense evasion molecules. For example, glycoproteins E and I (gE/gI) form a viral Fc receptor (vFcR) for most subclasses and allotypes of human IgG, promoting evasion of humoral immune responses. Although monoclonal antibodies (mAbs) protect mice from neonatal HSV (nHSV) infections, the impact of vFcR activity on mAb-mediated protection is unknown. Using HSV-1 with intact and ablated gE-mediated Fc binding, as well as Fc-engineered mAbs with modified ability to interact with gE/gI, we investigated the role of the vFcR in mAb-mediated protection from nHSV. HSV-specific mAbs modified to lack binding to gE exhibited enhanced neutralization in vitro and superior protection in vivo compared with their native IgG1 forms. Improved protection was dependent on the presence of vFcR activity and was observed for mAbs specific for both glycoprotein D and glycoprotein B, as well as for a nonneutralizing mAb, and for both laboratory-adapted and clinical isolates of HSV-1 and HSV-2. Further, human IgG3 allotypes, including those lacking vFcR binding, also exhibited enhanced antiviral activity in vivo, identifying a unique viral susceptibility to this subclass. In summary, this study demonstrates that rendering mAbs insensitive to the vFcR can improve protection against HSV, offering prospects for antibody-based interventions.},
}

Animals
*Receptors, Fc/metabolism/immunology
*Herpes Simplex/immunology/prevention & control/virology
Humans
Antibodies, Monoclonal/immunology
Mice
Herpesvirus 1, Human/immunology
*Antibodies, Viral/immunology
Immunoglobulin G/immunology
Antibodies, Neutralizing/immunology
Viral Envelope Proteins/immunology/metabolism
Female
Protein Binding
Animals, Newborn
Pregnancy Complications, Infectious

@article {pmid41259068,
year = {2025},
author = {Hathaway, CL and Brown, ER and Cherne, S and Sepulveda, AL and Chirenje, ZM and Jeenarain, N and Naidoo, L and Siva, S and Singh, N and Woeber, K and Gaffoor, Z and Mirembe, BG and Kiweewa, FM and Mansoor, LE and Chinula, L and Dadabhai, S and Mugo, NR and Palanee-Phillips, T and Barnabas, RV},
title = {Association of HPV on risk of HIV acquisition in african women: Analyses from MTN-020/ASPIRE.},
journal = {Journal of the National Cancer Institute},
volume = {},
number = {},
pages = {},
doi = {10.1093/jnci/djaf336},
pmid = {41259068},
issn = {1460-2105},
abstract = {BACKGROUND: Observational data on the synergy between HPV infection and risk for HIV acquisition are needed. HPV clearance, associated with an influx of cells targeted by HIV, may increase HIV risk. This study examined the association between HPV and HIV acquisition using endocervical swabs collected in MTN-020/ASPIRE.

METHODS: Healthy, sexually active women without HIV participating in the ASPIRE dapivirine ring study in Malawi, South Africa, Uganda, and Zimbabwe, provided endocervical swabs monthly, which were tested for HPV-DNA. HPV status was classified into: prevalent, persistent (HPV+ for at least 4 months), HPV clearance (HPV+ followed by HPV-), HPV acquisition (HPV- followed by HPV+), and remaining HPV positive (two subsequent HPV+). Cox time-varying regression models were used to assess associations between HPV states and HIV acquisition.

RESULTS: Among 91 HIV acquisition endpoints, HPV clearance increased HIV risk for high-risk types (16/18/31/33/35/45/52/58) (HR: 2.40, 95% CI: 1.59-3.62). Remaining HPV+ also showed a moderately increased risk (HR: 1.59, 95% CI: 1.07-2.35), while prevalent, persistent, and HPV acquisition events showed non-significant associations. Elevated HIV risk was also observed for clearance of HPV16/18, other high-risk types, low-risk types, and HPV6/11. There was also a dose-response relationship, with HIV risk increasing by 1.75-fold (95% CI: 1.55-1.96) for each additional HPV type cleared.

CONCLUSIONS: HPV clearance-related immune activation is strongly linked to HIV acquisition, likely due to increased CD4+ T cells and inflammation. These findings support HPV vaccination as a potential HIV prevention strategy and highlight the need to integrate HIV prevention into cervical cancer programs.},
}

@article {pmid41257522,
year = {2025},
author = {Sanderson, JB and Lin, YH and Su, K and Wang, Y and Portuguese, A and Gauthier, J and Durbin, M and Banerjee, R},
title = {Treatment-Emergent Parkinsonism in Four Patients Treated with Chimeric Antigen Receptor T-Cell Therapy.},
journal = {Movement disorders clinical practice},
volume = {},
number = {},
pages = {},
doi = {10.1002/mdc3.70452},
pmid = {41257522},
issn = {2330-1619},
abstract = {BACKGROUND: Treatment-emergent motor and neurocognitive adverse events (MNTs) are rare but increasingly well-documented complications of chimeric antigen receptor T-cell (CAR-T) therapy. Here, we describe the development of parkinsonism in four patients who received CAR-T therapy with either B-cell maturation antigen (BCMA)-targeting ciltacabtagene autoleucel for multiple myeloma (n = 3) or CD-19-targeting axicabtagene autoleucel for lymphoma (n = 1).

CASES: We report four cases of parkinsonism in patients who received CAR-T therapy. Two patients had evidence of underlying neurodegenerative parkinsonism, either clinically or through subsequent workup for their movement disorder. All patients received some combination of symptom-directed and immunomodulatory therapies.

CONCLUSION: This report describes features of CAR-T treatment-emergent parkinsonism, introduces parkinsonism as a potential effect of CD-19-targeted CAR-T therapy, and suggests utility of screening for underlying clinical or biomarker signs of pre-existing neurodegenerative parkinsonism prior to CAR-T infusion.},
}

@article {pmid41257223,
year = {2025},
author = {Sawyer, L and Suchy-Dicey, AM and Nelson, LA and Sarche, M and Reese, JA and Cole, S and Sitlani, CM and Umans, JG and Fretts, AM},
title = {Association of Social Support With Glycemic Control Among American Indians With Type 2 Diabetes: The Strong Heart Family Study.},
journal = {Diabetes spectrum : a publication of the American Diabetes Association},
volume = {38},
number = {4},
pages = {455-460},
pmid = {41257223},
issn = {1040-9165},
abstract = {Few studies have examined associations of social support with blood glucose control in American Indians (AIs), a population with a high burden of type 2 diabetes and related complications. This study examined the association of perceived social support with A1C among AIs in the Strong Heart Study. This cross-sectional study included 431 AI participants. Social support was measured using questions adapted from the National Comorbidity Survey and validated for use in AIs. A1C was measured using high-performance liquid chromatography. Generalized estimating equations were used to examine the association of social support with A1C. Participants who reported greater levels of social support had lower A1C levels. After adjustment for potential confounders, for every 1-SD increase in social support (6.8 points), A1C was 0.21% lower (β = -0.21%, 95% CI -0.40 to -0.01, P = 0.04). These data suggest that higher levels of social support are associated with better control of blood glucose. Further studies are needed to determine the mechanism by which perceived social support affects A1C.},
}

@article {pmid41256528,
year = {2025},
author = {Chun, J and Tripathi, P and Flores-Garcia, Y and Madan, B and Lee, GA and Fahad, AS and Lei, H and Teng, IT and Hurlburt, NK and Flynn, BJ and Pancera, M and Miura, K and Zhou, T and Idris, AH and Zavala, F and Seder, RA and Kwong, PD and DeKosky, BJ},
title = {Anti-Malaria Antibody Engineering Broadens Recognition Motifs and Reveals New Homotypic Interactions that Enhance Protective Breadth.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {41256528},
issn = {2692-8205},
abstract = {The monoclonal antibody L9 mediates high-level protection against malaria in children for up to 6 months in Africa. L9 preferentially binds with high affinity to the NVDP minor repeat on the P. falciparum circumsporozoite protein (PfCSP). Here, we sought to improve the affinity of L9 to enhance protection against rare strains with two spatially separated minor repeats or a single minor repeat. Site saturation mutagenesis and yeast display-screening identified a panel of affinity-improved variants. In vivo challenge showed one variant, L9_yd19, to be modestly more potent against a chimeric transgenic Plasmodium encoding PfCSP with two widely spaced minor repeats from a Kenyan parasite strain, with no loss in potency against the benchmark 3D7 strain with its standard complement of minor repeats. L9_yd19 also had high affinity against NANP major repeats and was protective against transgenic Plasmodium with PfCSP containing only NANP major repeats (NANP12). Cryo-EM studies revealed L9_yd19 to recognize PfCSP with two distinct homotypic interfaces, which combined to yield two trimeric layers of antibodies comprising asymmetric trimers that dimerized in a head-to-head fashion. These data reveal a new antibody mechanism that utilizes interfaces involving dual homotypic symmetry elements, a 2-fold and an asymmetric 3-fold, for potentially improved malaria prevention.},
}

@article {pmid41254224,
year = {2025},
author = {Masopust, D and Awasthi, A and Bosselut, R and Brooks, DG and Buggert, M and Chamoto, K and Cui, W and Dong, C and Farber, DL and Gebhardt, T and Gerlach, C and Goldrath, A and Greenberg, PD and Hale, JS and Hayday, A and Homann, D and Iannacone, M and Jameson, SC and Jenkins, MK and Joshi, NS and Kaech, SM and Kallies, A and Kamphorst, AO and Kaplan, MH and Klenerman, P and Künzli, M and Lanzavecchia, A and Lauer, GM and Lugli, E and Luster, AD and Mackay, LK and McElrath, MJ and Mueller, SN and Ndhlovu, Z and Ndung'u, T and Ohashi, PS and Oxenius, A and Pantaleo, G and Pepper, M and Picker, LJ and Quarnstrom, CF and Reyes-Terán, G and Roederer, M and Rosato, PC and de Oca, GS and Sallusto, F and Schumacher, TN and Schwartz, DM and Shin, EC and Soerens, AG and Thommen, DS and Vezys, V and Viola, JPB and Walker, BD and Watts, TH and Weaver, CT and Wherry, EJ and Xue, HH and Youngblood, B and Ahmed, R},
title = {Guidelines for T cell nomenclature.},
journal = {Nature reviews. Immunology},
volume = {},
number = {},
pages = {},
pmid = {41254224},
issn = {1474-1741},
abstract = {Advances in T cell biology have revealed heterogeneity among T cell populations that is not captured by existing general nomenclature. This issue has caused an ad hoc broadening of core T cell subset definitions and the invention of new subset designations that have not been uniformly delineated. To address this issue, in this Consensus Statement, we propose guidelines that serve three goals. First, they advocate that primary research reports define the experimental basis by which relevant subsets are designated in the methods section of each study. Second, they provide standardized definitions for existing subset designations in popular use, and common experimental criteria for defining each subset are noted. Last, they present an alternative 'modular nomenclature' paradigm. The newly proposed modular nomenclature eschews conceptualization of antigen-experienced T cells as belonging to a few idealized subsets, and the nomenclature instead simply indicates individual biological properties present in a T cell population with brief descriptors. Collectively, these guidelines intend to enhance transparency in the literature while facilitating clearer communication of findings and concepts to researchers, students and clinicians.},
}

@article {pmid41254197,
year = {2025},
author = {Yi, JC and Henrikson, NB and Panattoni, L and Liao, Y and Jones, SMW},
title = {Relationships between financial distress and anxiety and depression in cancer survivors.},
journal = {Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer},
volume = {33},
number = {12},
pages = {1084},
pmid = {41254197},
issn = {1433-7339},
support = {U24AT011310//Emotional Well-Being and Economic Burden Research Network (EMOT-ECON;)/ ; },
mesh = {Humans ; Female ; Male ; *Cancer Survivors/psychology ; Middle Aged ; *Depression/epidemiology/etiology/psychology ; *Financial Stress/psychology/epidemiology ; Adult ; *Anxiety/epidemiology/etiology/psychology ; Aged ; *Neoplasms/psychology/economics ; Surveys and Questionnaires ; Age Factors ; },
abstract = {PURPOSE: Many cancer survivors experience financial distress. This distress can be associated with anxiety and depressive symptoms in cancer survivors. The aim of the study was to examine how much unique variance in anxiety and depressive symptoms is accounted for by financial distress using a measure developed specifically for financial distress using item response theory.

METHODS: Participants were recruited either through a cancer survivorship program or through the Prolific survey panel. Measures included patient reports of demographic and clinical variables. Financial related anxiety/worry and depression were assessed. The Generalized Anxiety Disorder-7 (GAD-7) and the Patient Health Questionnaire-8 (PHQ-8) were used for general measures of anxiety and depression, respectively. Separate hierarchical regressions were performed with the GAD-7 and PHQ-8 as outcome variables.

RESULTS: A total of N = 459 cancer survivors completed the survey. The sample average age was 51.5 years (SD = 15.0), 67.5% female, 85.6% White, 7.4% Hispanic, and 6.5% Asian race. The most common cancer diagnosis was breast (27.9%). Age, income, education, and financial anxiety were associated with anxiety, and the overall model accounted for 31% of the variance. For depression, only female sex and financial depression were significantly associated and accounted for 46% of the variance.

CONCLUSION: Financial distress in combination with demographic and clinical variables operated differently in models of anxiety and depression in cancer survivors. More demographic variables were associated with anxiety symptoms than with depressive symptoms. Interventions such as financial navigation could reduce overall distress.},
}

Humans
Female
Male
*Cancer Survivors/psychology
Middle Aged
*Depression/epidemiology/etiology/psychology
*Financial Stress/psychology/epidemiology
Adult
*Anxiety/epidemiology/etiology/psychology
Aged
*Neoplasms/psychology/economics
Surveys and Questionnaires
Age Factors

@article {pmid41253492,
year = {2025},
author = {Kimble, EL and Wright, JH and Torkelson, A and Kirchmeier, DR and Braathen, K and Ruff, RO and Shimp, KR and Seaton, BW and Gauthier, J and Kolokythas, O and Boiani, NE and Jellyman, D and Yeung, CC and Tam, E and Price, JP and Hirayama, A and Turtle, CJ},
title = {Novel antibodies for identification, selection, and manipulation of T cells expressing Whitlow linker-containing CARs.},
journal = {Journal for immunotherapy of cancer},
volume = {13},
number = {11},
pages = {},
doi = {10.1136/jitc-2025-013123},
pmid = {41253492},
issn = {2051-1426},
mesh = {Humans ; Animals ; *Receptors, Chimeric Antigen/immunology/metabolism/genetics ; Mice ; *T-Lymphocytes/immunology/metabolism ; *Antibodies, Monoclonal/immunology ; *Single-Chain Antibodies/immunology ; *Immunotherapy, Adoptive/methods ; *Receptors, Antigen, T-Cell/immunology/metabolism ; },
abstract = {BACKGROUND: The translational study of chimeric antigen receptor (CAR) T-cell function, persistence, immunophenotype, and spatial localization after infusion is crucial for understanding factors that influence clinical outcomes. However, research has been limited by a lack of optimized tools to reliably detect CAR-engineered cells. To address this, we developed a novel platform to generate monoclonal antibodies (mAbs) targeting a linker peptide incorporated in single-chain variable fragments (scFvs) of most CAR constructs.

METHODS: Using recombinant proteins and scFv linker peptides as immunogens, we generated murine mAbs against the Whitlow linker peptide, capable of binding cells expressing Whitlow linker-containing CARs in both fresh and formalin-fixed paraffin-embedded (FFPE) tissues. We evaluated these antibodies in multiple in vitro translational applications relevant to CAR T-cell research and manufacturing.

RESULTS: We identified five unique mAbs reactive against the Whitlow linker and characterized their binding properties and three-dimensional structural conformation. One clone was evaluated in depth, demonstrating comparable capacity to identify CAR T cells in peripheral blood relative to other methods using anti-idiotype antibodies or recombinant CAR-target proteins. In contrast to these reagents, the anti-Whitlow mAb detects cells expressing Whitlow linker-containing CARs with different antigen specificities, including those harboring the widely employed anti-CD19 FMC63-derived scFv as well as other scFvs, such as those targeting B-cell maturation antigen (BCMA) or CD33. Importantly, the anti-Whitlow mAb identified CAR T cells in situ in archival FFPE tissues, and a DNA-barcoded format enabled their spatial characterization and immunophenotyping in highly multiplexed immunohistochemistry. We also assessed the functional consequences of antibody binding on CAR T cells in vitro and demonstrated the feasibility of anti-Whitlow mAb-mediated selective enrichment of CAR-expressing T cells for potential utility in manufacturing workflows.

CONCLUSIONS: Anti-Whitlow mAb clones exhibited distinct structural and functional properties that can be leveraged for multiple applications, providing versatile tools for detection, selection and manipulation of a broad range of clinical and preclinical CAR T-cell products.},
}

Humans
Animals
*Receptors, Chimeric Antigen/immunology/metabolism/genetics
Mice
*T-Lymphocytes/immunology/metabolism
*Antibodies, Monoclonal/immunology
*Single-Chain Antibodies/immunology
*Immunotherapy, Adoptive/methods
*Receptors, Antigen, T-Cell/immunology/metabolism

@article {pmid41252670,
year = {2026},
author = {Drevdahl, DJ and Canales, MK and Dorcy, KS},
title = {Contesting Professional Nursing Values.},
journal = {Nursing inquiry},
volume = {33},
number = {1},
pages = {e70064},
doi = {10.1111/nin.70064},
pmid = {41252670},
issn = {1440-1800},
support = {//The authors received no specific funding for this work./ ; },
mesh = {Humans ; *Ethics, Nursing/history ; United States ; *Codes of Ethics/history ; *Professionalism ; *Social Values ; History, 20th Century ; },
abstract = {A code of ethics, as proof of nursing professionalism, is used to promote nursing's core values. In the United States, the American Nurses Association's (ANA) Code of Ethics is accepted as the primary source for professional nursing values. Particular processes are used within nursing to embed professional values into nursing discourse. A historical review of the ANA Code of Ethics, a review of published articles about professional nursing values, and an examination of the development and globalization of the Nurses Professional Values Scale informed our examination of nursing's efforts to delineate, instill, and measure professional nursing values. The analysis was informed theoretically by Bourdieu and his concept of "playing the game." Constructing and reinforcing professional nursing values reveals difficulties about what constitutes core nursing values and what they mean, particularly with respect to values that comprise the good nurse; the inability to measure and evaluate said values; and the colonization of Western values globally. The inordinate amount of time and energy spent on nursing values surfaced the vexing nature of such efforts. The concept of profession and its accompanying values must be regarded with suspicion.},
}

Humans
*Ethics, Nursing/history
United States
*Codes of Ethics/history
*Professionalism
*Social Values
History, 20th Century

@article {pmid41252205,
year = {2025},
author = {MacLean, F and Zemek, RM and Tsegaye, AT and Graham, JB and Swarts, JL and Vick, SC and Potchen, NB and Cruz Talavera, I and Warrier, L and Dubrulle, J and Schroeder, LK and Elz, A and Sowerby, D and Saito, A and Thomas, KK and Mack, M and Schiffer, JT and McClelland, RS and Jerome, KR and Chohan, BH and Ngure, K and Mugo, NR and Newell, EW and Lingappa, JR and Lund, JM},
title = {Genital herpes shedding episodes associate with altered spatial organization and activation of mucosal immune cells.},
journal = {JCI insight},
volume = {},
number = {},
pages = {},
doi = {10.1172/jci.insight.197491},
pmid = {41252205},
issn = {2379-3708},
abstract = {Herpes Simplex Virus 2 (HSV-2) infection results in variable rates of local viral shedding in anogenital skin. The impact of episodic viral exposures on immune cells in adjacent mucosal tissues, including the genital tract, is unknown. However, any immune responses at this site could impact protective mucosal immunity, tissue homeostasis, and adverse health outcomes. To investigate the impact of HSV-2 on cervicovaginal tract immunity, we applied flow cytometry, immunofluorescent imaging, analysis of soluble immune factors, and spatial transcriptomics to cervicovaginal tissue and blood samples provided by a total of 232 HSV-2-seropositive and seronegative participants, with genital HSV-2 shedding evaluated at the time of biopsy. This unique dataset was used to define and spatially map immune cell subsets and localized gene expression via spatial transcriptomics. HSV-2-seropositivity alone was associated with minimal differences in cervicovaginal and circulating T cell phenotypes. However, the vaginal mucosa during active HSV-2 shedding was associated with alterations in T cell, macrophage, and dendritic cell localization and gene expression consistent with increased immune surveillance, with immune activating and suppressing signals potentially reinforcing mucosal tissue homeostasis.},
}

@article {pmid41252152,
year = {2025},
author = {Sergeeva, OA and Jin, G and Sarkar, M and Zeiger, J and Dhindwal, S and Chin, SS and Abulizi, A and Lai, Z and Brown, C and DeMaria, WG and Ryan, D and An, X and Karp, HJ and Teran, E and Yuan, C and Klaskin, D and Reeve, TA and Yu, GK and Tam, EM and Kaech, SM and Preyer, M and Matis, L and Fine, JS and Martomo, SA and Myers, JS},
title = {EVOLVE platform, a trispecific T cell engager with integrated CD2 costimulation, for the treatment of solid and hematologic tumors.},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
volume = {122},
number = {47},
pages = {e2510829122},
doi = {10.1073/pnas.2510829122},
pmid = {41252152},
issn = {1091-6490},
mesh = {Humans ; Animals ; Mice ; *T-Lymphocytes/immunology ; *CD2 Antigens/immunology ; *Antibodies, Bispecific/immunology/pharmacology ; CD3 Complex/immunology ; Cell Line, Tumor ; Lymphocyte Activation/immunology ; *Hematologic Neoplasms/immunology/therapy/drug therapy ; *Neoplasms/immunology/therapy ; Xenograft Model Antitumor Assays ; CD58 Antigens/immunology ; Female ; },
abstract = {Ten CD3 T cell engagers (TCEs) have received regulatory approval for the treatment of hematologic and solid tumors. However, limited costimulatory signaling essential for sustained T cell effector activity may limit CD3 TCE clinical efficacy and response duration. The CD2 receptor is an attractive costimulation target owing to its association with T cell receptor signaling and favorable expression profile. We show that CD2 costimulation is superior in maintaining T cell viability and effector function relative to other pathways in in vitro chronic stimulation assays. The extracellular domain of CD58, the predominant CD2 ligand, is functional as an antibody fusion, improving bispecific potency. We observe that higher CD3 affinity molecules have the potential for superagonism in the context of an integrated CD2 agonist. Evaluation of TCEs with integrated CD2 costimulation and attenuated CD3 binding identified optimal CD3 affinity agonists that avoid target-independent T cell activation and demonstrated an increased therapeutic index relative to nonattenuated CD3 agonists. This platform shows increased tumor-killing efficacy as compared to CD3 affinity-matched bispecifics for known tumor targets such as HER2, CD20, B7-H4, and UL16-binding protein 2 (ULBP2). We demonstrate that ULBP2-targeted trispecifics with integrated CD2 costimulation and optimized CD3 affinity are superior to higher-affinity CD3 molecules in in vivo mouse efficacy studies. This integrated CD2 costimulation platform, which we termed EVOLVE, represents a next-generation TCE platform to increase T cell effector function in the tumor microenvironment and has the potential to address unmet patient needs by improving the depth and durability of clinical antitumor T cell responses.},
}

Humans
Animals
Mice
*T-Lymphocytes/immunology
*CD2 Antigens/immunology
*Antibodies, Bispecific/immunology/pharmacology
CD3 Complex/immunology
Cell Line, Tumor
Lymphocyte Activation/immunology
*Hematologic Neoplasms/immunology/therapy/drug therapy
*Neoplasms/immunology/therapy
Xenograft Model Antitumor Assays
CD58 Antigens/immunology
Female

@article {pmid41249067,
year = {2025},
author = {Leichter, S and Ahmad, K and Henikoff, S},
title = {Polycomb misregulation in enterocytes drives tissue decline in the aging Drosophila intestine.},
journal = {Genome research},
volume = {},
number = {},
pages = {},
doi = {10.1101/gr.281058.125},
pmid = {41249067},
issn = {1549-5469},
abstract = {Aging compromises intestinal integrity, yet the chromatin changes driving this decline remain unclear. Polycomb-mediated repression is essential for silencing developmental genes, but this regulatory mechanism becomes dysregulated with age. Although shifts in Polycomb regulation within intestinal stem cells have been linked to gut aging, the Polycomb landscape of differentiated cell types remains unexplored. Differentiated cells comprise the majority of the gut epithelium and directly impact both tissue and whole organismal aging. Using single-cell chromatin profiling of the Drosophila intestine, we identify cell type-specific chromatin landscape changes during aging. We find that old enterocytes aberrantly repress genes essential for transmembrane transport and chitin metabolism, contributing to intestinal barrier decline - an example of antagonistic pleiotropy in a regenerative tissue. Barrier decline leads to derepression of JAK/STAT ligands in all cell types and increased proliferation of aging stem cells, with elevated RNA Polymerase II (RNAPII) at S-phase-dependent histone genes. Specific upregulation of histone genes during aging stem cell proliferation resembles RNAPII hypertranscription of histone genes in aggressive human cancers. Our work reveals that misregulation of the Polycomb-mediated H3K27me3 histone modification in differentiated cells during aging not only underlies tissue decline but also mirrors transcriptional changes in cancer, suggesting a common mechanism linking aging and cancer progression.},
}

@article {pmid41248759,
year = {2025},
author = {Thonglert, K and Apisarnthanarax, S and Yeap, BY and Havard, ME and Schaub, SK and Nyflot, MJ and Bowen, SR and He, Y and Tsai, J and De, BS and Chamseddine, I and Pursley, J and Roberts, H and Wo, J and Prayongrat, A and Alisanant, P and Amornwichet, N and Khorprasert, C and Hong, T and Koay, EJ and Grassberger, C},
title = {Establishing Albumin-Bilirubin (ALBI) score changes as predictors of radiation-induced liver disease (RILD) in hepatocellular carcinoma (HCC) patients post external beam radiotherapy (EBRT).},
journal = {International journal of radiation oncology, biology, physics},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.ijrobp.2025.11.009},
pmid = {41248759},
issn = {1879-355X},
abstract = {PURPOSE: To determine ALBI score change thresholds that indicate hepatotoxicity and predict poorer overall survival (OS) in HCC patients post-EBRT.

EXPERIMENTAL DESIGN: The development cohort consisted of 329 HCC patients treated with liver-targeted EBRT across two centers from 2008 to 2023, with 71% classified as Child-Pugh (CP) A and 29% as CP-B/C. Recursive partitioning analysis identified thresholds associated with OS, which were evaluated using Cox regression, compared to a 2-point increase in CP score (CP2+) and externally validated using data from two independent centers (n = 248). The primary outcome was to establish ALBI score change thresholds associated with poorer OS. Secondary outcomes included comparing the prognostic accuracy of ALBI score change thresholds with the CP2+ criterion, analyzing the predictive value across different baseline liver functions, and examining the association between radiation dose to the normal liver and ALBI score changes.

RESULTS: ALBI changes of >0.25 (ALBI change grade 1) and >0.5 (ALBI change grade 2) were identified as optimal thresholds. CP2+ showed superior discriminative performance in the overall cohort; however, when stratifying by baseline liver status, ALBI change grade 1 outperformed CP2+ in CP-B/C patients (HR 4.4, 95%CI 2.4-7.8). Overall, these findings were confirmed in the external validation cohort. Multivariable Cox models including CP2+ or ALBI changes and baseline liver status demonstrated higher or similar concordance for ALBI score changes across all datasets. Mean liver dose correlated more strongly with ALBI score changes (logistic regression OR=1.09/1.07 for grade 1/2) than with CP2+ (OR=1.04).

CONCLUSIONS: ALBI score changes of >0.25 and >0.5 are alternatives to CP2+ to evaluate radiation-induced hepatotoxicity, with the potential for more accurate assessment based on baseline liver function. Their objectivity and stronger correlation with normal liver dose makes ALBI score changes more suitable for dose-response models aimed at minimizing the risk of liver complications following EBRT.},
}

@article {pmid41243521,
year = {2025},
author = {Hirsch, J and Cadet, T and Wells, K and Thompson, B and Bullock, K and Nedjat-Haiem, FR},
title = {Perspectives of Advance Care Planning for Latinos During COVID-19.},
journal = {The American journal of hospice & palliative care},
volume = {},
number = {},
pages = {10499091251396828},
doi = {10.1177/10499091251396828},
pmid = {41243521},
issn = {1938-2715},
abstract = {Latinos face challenges in accessing care for serious illness and lack preparedness for healthcare crises which were exacerbated by the COVID-19 pandemic. Following a social ecological model, this study explored perceptions of advanced care planning (ACP) for Latinos from key informants including community members and health care providers. A total of 12 focus groups including 25 community members and 24 providers were completed in both English and Spanish from April to July of 2020. Using a grounded theory approach and constant comparison, we identified 4 primary themes: underlying vulnerabilities and barriers to ACP, the pandemic context, unique Latino pandemic experience, and urgency to do ACP because of COVID. The Latino experience reflects a complex interplay between 2 macro systems, a unique Latino experience and the pandemic, which included significant communication gaps, isolation, mistrust, and anxiety. The pandemic was an eye-opening experience for many Latinos which has made ACP more relevant as awareness and knowledge of death and dying shifted.},
}

@article {pmid41239501,
year = {2025},
author = {Terashima, M and Nakayama, K and Shirai, S and Ugai, S and Lee, HY and Matsui, H and Mizuno, H and Tanaka, S and Song, M and Sasamoto, N and Kawachi, I and Giovannucci, EL and Ugai, T},
title = {Diverging global incidence trends of early-onset cancers: comparisons with incidence trends of later-onset cancers and mortality trends of early-onset cancers.},
journal = {Military Medical Research},
volume = {12},
number = {1},
pages = {79},
pmid = {41239501},
issn = {2054-9369},
support = {R50 CA274122/NH/NIH HHS/United States ; 23K20052//Japan Society for the Promotion of Science/ ; },
mesh = {Humans ; Incidence ; Female ; *Neoplasms/epidemiology/mortality ; Male ; Adult ; Middle Aged ; *Age of Onset ; Global Health/statistics & numerical data ; *Mortality/trends ; },
abstract = {BACKGROUND: The global increase in the incidence of early-onset cancers (defined as cancers diagnosed at 20-49 years old) is a serious public health problem. We investigated 1) whether the incidence trend of early-onset cancers differs from that of later-onset cancers and 2) whether both the incidence and mortality of early-onset cancers have increased concurrently.

METHODS: We utilized age-standardized incidence and mortality rates for early-onset and later-onset cancers diagnosed between 2000 and 2017 from the Cancer Incidence in Five Continents and World Health Organization (WHO) mortality databases. The national obesity prevalence among adults aged 20-49 years was obtained from the National Clinical Database. Using joinpoint regression models, we calculated average annual percentage changes (AAPCs) for cancer incidence and mortality by cancer types and countries. We additionally conducted human development index (HDI)-stratified analyses and assessed the correlation between the obesity prevalence in younger populations and early-onset cancer incidence by country. To investigate the more recent trend of early-onset cancer mortality, we extended our mortality analysis after 2017 for cancer types and countries with statistically significant positive AAPCs in both incidence and mortality of early-onset cancers between 2000 and 2017.

RESULTS: Our analysis showed that 10 early-onset cancer types (thyroid cancer, breast cancer, melanoma, uterine cancer, colorectal cancer, kidney cancer, cervical cancer, pancreatic cancer, multiple myeloma, Hodgkin lymphoma) in females and 7 early-onset cancer types (thyroid cancer, kidney cancer, testis cancer, prostate cancer, colorectal cancer, melanoma, leukemia) in males had statistically significant positive AAPCs in at least 10 countries. Among these, the following early-onset cancer types had significantly higher AAPCs than later-onset cancer types in females: colorectal cancer (6 countries; AAPC range: 1.8-3.8%), cervical cancer (6 countries; AAPC range: 1.2-3.3%), pancreatic cancer (5 countries; AAPC range: 2.3-13.0%), and multiple myeloma (5 countries; AAPC range: 3.1-9.8%); in males: prostate cancer (12 countries; AAPC range: 3.9-18.4%), colorectal cancer (8 countries; AAPC range: 1.8-3.2%), and kidney cancer (6 countries; AAPC range: 2.0-6.0%). We observed statistically significant positive AAPCs in both the incidence and mortality of the following early-onset cancer types: uterine cancer (5 countries) and colorectal cancer (3 countries in females and 5 countries in males). The steeper increases in early-onset cancers compared with later-onset cancers were mainly observed in the very high-HDI country group, including early-onset colorectal cancer (AAPC = 2.4%, 95% CI 2.1-2.6 in females; AAPC = 2.0%, 95% CI 1.7-2.4 in males) to later-onset colorectal cancer (AAPC = -0.1%, 95% CI -0.2 to 0 in females; AAPC = -0.2%, 95% CI -0.3 to 0 in males). We observed strong positive correlations between the increasing obesity prevalence and the rising incidence of early-onset obesity-related cancers in several countries, including Australia (7 cancer types), United Kingdom (7 cancer types), Canada (7 cancer types), Republic of Korea (7 cancer types), and USA (6 cancer types) in females and United Kingdom (7 cancer types), Canada (6 cancer types), Australia (5 cancer types), Sweden (5 cancer types), and Republic of Korea (4 cancer types) in males. Although we did not observe an apparent spike after 2017 in many countries, we observed continued increases in the mortality of certain cancer types, such as uterine cancer (Japan, Republic of Korea, United Kingdom, USA, and Ecuador) in females and colorectal cancer (Argentina, Canada, United Kingdom, and USA) in males.

CONCLUSIONS: The increase in many early-onset cancer types was significantly higher than that of later-onset cancers, and the incidence and mortality of certain early-onset cancer types (such as colorectal cancer) increased simultaneously. Our study highlights global differences in cancer incidence and mortality trends of early-onset and later-onset cancers.},
}

Humans
Incidence
Female
*Neoplasms/epidemiology/mortality
Male
Adult
Middle Aged
*Age of Onset
Global Health/statistics & numerical data
*Mortality/trends

@article {pmid41237667,
year = {2025},
author = {Voillet, V and van Duijn, J and Vanshylla, K and Dintwe, OB and Pattacini, L and Omar, FL and Khuzwayo, S and Euler, Z and Schwedhelm, K and MacMillan, HR and Gilbert, PB and Fiore-Gartland, A and Newell, EW and Hendriks, J and McElrath, MJ and Stieh, DJ and De Rosa, SC and Andersen-Nissen, E},
title = {Unbiased cell clustering analysis of vaccine-induced T cell responses in the Imbokodo HIV-1 vaccine trial.},
journal = {EBioMedicine},
volume = {122},
number = {},
pages = {106017},
doi = {10.1016/j.ebiom.2025.106017},
pmid = {41237667},
issn = {2352-3964},
abstract = {BACKGROUND: HIV-1 T cell responses are associated with viral control and may be protective in a prophylactic vaccination setting. Traditional methods for analysing these responses might be biased towards specific functionalities or epitopes. This study presents an unsupervised and unbiased clustering analysis workflow, using the Leiden algorithm followed by selection of antigen-specific clusters using MIMOSA positivity calls, for high-dimensional flow cytometry data to identify distinct T cell populations associated with protection in the HVTN 705/HPX2008/Imbokodo HIV-1 vaccine efficacy trial.

METHODS: Participants were vaccinated with Ad26.Mos4.HIV (M0, M3) and Ad26.Mos4.HIV + Clade C gp140 (M6, M12), and a validated 28-colour intracellular cytokine staining assay was performed on PBMC isolated at M7, M13 and M24 in a pilot immunogenicity (n = 60) and case-control cohort (n = 283). 28-colour phenotyping assays were also performed on PBMC from the case-control cohort (n = 334).

FINDINGS: Our clustering analysis workflow allowed identification of vaccine-induced subpopulations of both CD4+ and CD8+ T cells expressing combinations of the 28 markers. Durable HIV-1 antigen-specific CD4+ and CD8+ T cell responses were observed for up to 2 years, comprising mainly clusters of polyfunctional T cells expressing anti-viral cytokines and activation markers. Eight CD4+ and six CD8+ HIV-1 antigen-specific T cell clusters were induced by vaccination; only one CD4+ T cell cluster specific for Gag was mildly elevated in cases (acquiring HIV) compared to controls.

INTERPRETATION: Our study introduces an innovative analysis approach to identify vaccine-induced T cell subpopulations in vaccine trials. Comparison of T cell clusters between cases and controls holds promise for improving the efficacy of future HIV-1 vaccination strategies.

FUNDING: This work was funded by the National Institute of Allergy and Infectious Diseases (NIAID) and the Division of AIDS (DAIDS), both of the US National Institutes of Health (NIH) [NIAID grants to the HIV Vaccine Trials Network (HVTN) (Fred Hutchinson Cancer Center): UM1AI068618 (HVTN LC to M.J.M.) and UM1AI068635 (HVTN SDMC to P.B.G.)] and by Janssen Vaccines & Prevention B.V. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health or Janssen.},
}

@article {pmid41237309,
year = {2025},
author = {Kanellopoulou, A and Bouras, E and Chan, AT and Marchand, LL and Wolk, A and Wu, AH and Gunter, MJ and Nimptsch, K and Haycock, P and Lewis, SJ and Martin, RM and Zuber, V and Phipps, AI and Peters, U and Van Duijnhoven, FJB and Tsilidis, KK},
title = {Investigating the association between anthropometry and colorectal cancer survival: a two-sample Mendelian randomization analysis.},
journal = {International journal of epidemiology},
volume = {54},
number = {6},
pages = {},
pmid = {41237309},
issn = {1464-3685},
support = {C18281/A29019//Cancer Research UK programme grant, the Integrative Cancer Epidemiology Programme/ ; NIHR202411//Cancer Research UK programme grant, the Integrative Cancer Epidemiology Programme/ ; //NIHR Bristol Biomedical Research Centre/ ; },
mesh = {Humans ; Mendelian Randomization Analysis ; *Colorectal Neoplasms/mortality/genetics ; Male ; Female ; Body Mass Index ; Middle Aged ; Waist Circumference/genetics ; Waist-Hip Ratio ; Aged ; *Anthropometry ; Birth Weight/genetics ; Body Height/genetics ; Proportional Hazards Models ; },
abstract = {BACKGROUND: Observational epidemiologic studies on the association of anthropometric traits and colorectal cancer (CRC) survival provide inconsistent results, and potential limitations prohibit the investigation of causality. We examined the associations between seven genetically predicted anthropometric traits [height, body mass index (BMI), waist circumference (WC), hip circumference (HC), waist-hip circumference ratio, birth weight and body fat percentage] and CRC-specific mortality among CRC cases using two-sample Mendelian randomization (MR).

METHODS: Analyses were performed using 16 964 CRC cases, out of which 4010 died due to their disease, from the Genetics and Epidemiology of Colorectal Cancer Consortium and Colon Cancer Family Registry. We further conducted stratified analyses by anatomical site and stage. We applied the inverse variance weighted approach, and sensitivity analyses were conducted to assess the impact of potential violations of MR assumptions and adjust for collider bias.

RESULTS: One standard deviation (SD 13.4 cm) higher genetically predicted levels of WC were associated with worse CRC survival [hazard ratio (HR); 1.22, 95% confidence interval (CI); 1.02-1.47]. Positive associations were further observed for a SD higher genetically predicted BMI (SD; 4.8 kg/m2, HR; 1.5, 95% CI; 1.15-1.95) and HC (SD; 9.2 cm, HR; 1.32, 95% CI; 1.02-1.73) and CRC-specific mortality in cases of stages II/III. The latter associations were generally robust to sensitivity analyses. Positive but imprecisely estimated associations were found for most other anthropometric traits.

CONCLUSIONS: Despite the limitations of cancer survival research, our findings support that CRC cases should avoid obesity. Further research should inform the development of recommendations targeting overweight/obesity management during cancer surveillance.},
}

Humans
Mendelian Randomization Analysis
*Colorectal Neoplasms/mortality/genetics
Male
Female
Body Mass Index
Middle Aged
Waist Circumference/genetics
Waist-Hip Ratio
Aged
*Anthropometry
Birth Weight/genetics
Body Height/genetics
Proportional Hazards Models

@article {pmid41236449,
year = {2025},
author = {Kim, NJ and Li, M and Vutien, P and Mecham, B and Borgerding, J and Swarts, K and Atuluru, P and Michel, MC and Barnard Giustini, A and Mezzacappa, C and Berry, K and VoPham, T and Marsh, TL and Feng, Z and Johnson, KM and Beste, LA and Kaplan, DE and Taddei, TH and Ioannou, GN},
title = {Changes in Liver Disease Etiology Support a Lower Alpha-Fetoprotein Threshold for Hepatocellular Carcinoma Screening.},
journal = {Gastroenterology},
volume = {},
number = {},
pages = {},
doi = {10.1053/j.gastro.2025.08.021},
pmid = {41236449},
issn = {1528-0012},
abstract = {BACKGROUND & AIMS: Serum alpha-fetoprotein (AFP) is a key component of hepatocellular carcinoma (HCC) screening, but its test characteristics are uncertain as alcohol-associated liver disease (ALD) and metabolic dysfunction-associated steatotic liver disease (MASLD) rates increase.

METHODS: We evaluated AFP trends at HCC diagnosis and estimated its test performance for HCC screening in cirrhosis using Veterans Health Administration (VHA) and United Network for Organ Sharing data.

RESULTS: Among the 40,399 VHA patients diagnosed with HCC between 2001 and 2021, median AFP at HCC diagnosis declined over time and was highest in active-hepatitis C (HCV) (32.7 vs cured-HCV 8.3, ALD 9.0, MASLD 7.7 ng/mL). Among the 28,170 VHA patients with cirrhosis receiving care in 2019 (9.6% active-HCV, 43% cured-HCV, 24% ALD, 14% MASLD), 1,029 developed HCC in 2019. At AFP thresholds ≥20 and ≥10 ng/mL, the overall sensitivity/specificity for HCC screening was 31.7%/98.5% and 41.9%/94.1%, respectively. Lowering the AFP threshold to ≥10 ng/mL increased sensitivity with minimal reductions in specificity across all liver disease etiologies: active-HCV (sensitivity/specificity: 43.7% to 60.7%/92.6% to 83.0%), cured-HCV (32.5% to 41.5%/99.0% to 94.7%), ALD (22.8% to 32.3%/99.2% to 95.1%), and MASLD (21.7% to 29.9%/99.4% to 96.7%). Analysis of United Network for Organ Sharing (26,213 patients with HCC) resulted in similar increases in test sensitivity as the AFP threshold declined from ≥20 to ≥10 ng/mL (overall: 31.8% to 48.7%; active-HCV: 36.7% to 58.6%, cured-HCV: 21.4% to 36.4%, MASLD: 19.1% to 33.4%, and ALD: 15.9% to 27.1%).

CONCLUSIONS: For HCC screening in MASLD, ALD, and cured-HCV cirrhosis, reducing the AFP threshold to ≥10 ng/mL would substantially increase sensitivity while maintaining very high specificity.},
}

@article {pmid41235976,
year = {2025},
author = {Hunter, BD and Lunning, M and Shadman, M and Ahmed, S and Abramson, JS and Perales, MA and Ahmed, N and Mirza, AS and Isufi, I and Frigault, MJ and Crombie, JL and Miklos, DB and Vasconcelos, A and Crotta, A and Bernasconi, D and Roy, D and Bleickardt, E and Pasquini, MC and Kamdar, M},
title = {CRS or ICANS Are Rare Beyond 2 Weeks After Lisocabtagene Maraleucel Infusion: Data From Clinical Trials and the Real-World Setting.},
journal = {Transplantation and cellular therapy},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jtct.2025.10.024},
pmid = {41235976},
issn = {2666-6367},
abstract = {Improved understanding of the timing of cytokine release syndrome (CRS) and immune effector cell-mediated neurotoxicity syndrome (ICANS)/neurological events (NE) after chimeric antigen receptor (CAR) T-cell therapy infusion can inform patient safety monitoring. To report CRS and ICANS/NE outcomes, including incidence, onset, and resolution, in patients treated with lisocabtagene maraleucel (liso-cel) in clinical trials and the real-world setting. This analysis included patients treated with liso-cel in 5 clinical trials across different B-cell non-Hodgkin lymphoma indications (n = 702) and in the real-world setting for large B-cell lymphoma, as captured in the Center for International Blood and Marrow Transplant Research (CIBMTR) Registry (n = 877). All outcomes are reported descriptively. Among 702 patients in clinical trials, 54% had any-grade CRS (grade ≥3 at onset, 1%), with 98% of events occurring ≤day 15 after infusion; median time to resolution was 5 days. Any-grade NEs occurred in 31% of patients (grade ≥3 at onset, 5%), with 88% of events occurring ≤day 15 after infusion; median time to resolution was 7 days. Among 877 patients in the real-world setting, 49% had any-grade CRS (maximum grade ≥3, 3%), with 97% of events occurring ≤day 15 after infusion; median time to resolution was 4 days. Any-grade ICANS occurred in 27% of patients (maximum grade ≥3, 10%). Of 150 patients with reported onset date, 95% had onset ≤day 15 after infusion; median time to resolution was 5.5 days. The vast majority of CRS or ICANS/NEs occurred ≤day 15 after liso-cel infusion. These results support the recently updated United States Food and Drug Administration monitoring requirements aimed to improve treatment access while maintaining patient safety.},
}

@article {pmid41040691,
year = {2025},
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 Maxwell, GL 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 = {Beyond BRCA deficiency: Clinical and molecular predictors of survival in patients with BRCA-deficient tubo-ovarian high-grade serous carcinoma.},
journal = {medRxiv : the preprint server for health sciences},
volume = {},
number = {},
pages = {},
pmid = {41040691},
support = {R21 CA267050/CA/NCI NIH HHS/United States ; R01 CA172404/CA/NCI NIH HHS/United States ; K07 CA080668/CA/NCI NIH HHS/United States ; P30 CA015083/CA/NCI NIH HHS/United States ; R01 CA248288/CA/NCI NIH HHS/United States ; M01 RR000056/RR/NCRR NIH HHS/United States ; R01 CA095023/CA/NCI NIH HHS/United States ; R01 CA168758/CA/NCI NIH HHS/United States ; P50 CA136393/CA/NCI NIH HHS/United States ; },
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 unexpectedly poor outcomes. We profiled 154 tumors, enriched for patients with BRCA-deficient tumors that experienced short overall survival (≤3 years, n=42), using whole-genome, transcriptome, and methylation analyses. All but one BRCA-deficient tumor exceeded an accepted HRD genomic scarring threshold. However, patients with BRCA1-deficient HGSC with a more elevated HRD score survived significantly longer. Patients with BRCA2-deficient HGSC and loss of NF1 survived twice as long as those without NF1 loss, whereas PIK3CA or RAD21 amplification defined BRCA2-deficient HGSC with exceptionally short survival. BRCA1-deficient tumors in short survivors had evidence of immunosuppressive c-kit signaling and EMT. In a large HGSC cohort (n=1,389) including 282 individuals with pathogenic germline BRCA variants (gBRCApv), the location of the mutation within functional domains stratified clinical outcomes. Notably, residual disease after primary surgery had limited prognostic effect in gBRCApv-carriers compared to non-carriers. Our findings indicate that tumor HR proficiency in the context of therapy response and survival is not a binary property, and highlight genomic and immune modifiers of outcomes in BRCA-deficient HGSC.},
}

@article {pmid41233693,
year = {2025},
author = {Dussault, N and Henderson, K and Daniel, K and Mitchell, NM and Nickolopoulos, E and Hemming, P and Casarett, D and Cho, A and Ma, JE},
title = {Reply to the Letter to the Editor re: Evaluating a Clinical Chaplain Pilot Intervention to Facilitate Advance Care Planning in a Primary Care Clinic.},
journal = {Journal of general internal medicine},
volume = {},
number = {},
pages = {},
doi = {10.1007/s11606-025-10044-4},
pmid = {41233693},
issn = {1525-1497},
}

@article {pmid41228468,
year = {2025},
author = {Teruel Camargo, J and Recinos, G and Hinerman, AS and Duong, C and Rodriquez, EJ and Juarez, JJ and McClain, AC and Alver, SK and Daviglus, ML and Van Horn, L and Pérez-Stable, EJ},
title = {Pulse Consumption and Metabolic Syndrome: Findings from the Hispanic Community Health Study/Study of Latinos.},
journal = {Nutrients},
volume = {17},
number = {21},
pages = {},
pmid = {41228468},
issn = {2072-6643},
support = {N01HC65233, N01HC65234, N01HC65235, N01HC65236, N01HC65237/HL/NHLBI NIH HHS/United States ; },
mesh = {Humans ; *Metabolic Syndrome/epidemiology/ethnology/physiopathology/prevention & control ; Female ; Middle Aged ; Male ; *Hispanic or Latino/statistics & numerical data ; *Diet ; Aged ; Risk Factors ; White ; },
abstract = {Background/Objectives: Metabolic syndrome affects half of middle-aged (ages 45-64) Hispanic or Latino (Latino) adults. Pulses, fiber-rich plant proteins common in Latino diets (e.g., dry beans and lentils), may mitigate metabolic syndrome. We evaluated the association between pulse intake and metabolic syndrome. Methods: We analyzed data from 6,958 adults aged ≥ 50 in the Hispanic Community Health Study/Study of Latinos (2008-2011) Visit 1. Pulse intake was assessed using two 24 h dietary recalls and categorized into no, low (<1/2 cup), moderate (≥1/2 to 3/4 cup), and high pulse (>3/4 cup) daily intake groups. Metabolic syndrome was defined by criteria including blood pressure ≥130/85 mmHg or medication use, triglycerides ≥150 mg/dL or medication use, high-density lipoprotein cholesterol (men <40 mg/dL and women <50 mg/dL), and waist circumference (men ≥102 cm and women ≥88 cm). We used multivariate logistic regression models with predicted probability proportions to assess the association adjusted for sociodemographic factors, acculturation, diet quality, energy intake, and physical activity. Results: Of the 6,958 participants, 53.1% had metabolic syndrome and 53.4% had a moderate or high pulse intake. Pulse intake varied, where 19.4% had a high intake, 33.9% had a moderate intake, 12.5% had a low intake, and 34.2% had no intake. Moderate (predicted marginal = 0.52, 95% confidence interval [CI] = 0.49, 0.55) and high (predicted marginal = 0.49, 95%CI = 0.45, 0.53) intakes were associated with a lower prevalence of metabolic syndrome. Conclusions: Among Latino adults ≥50 years old, a moderate or high pulse intake was associated with a lower prevalence of metabolic syndrome. Increasing the pulse intake in the population may be linked to reduced metabolic syndrome.},
}

Humans
*Metabolic Syndrome/epidemiology/ethnology/physiopathology/prevention & control
Female
Middle Aged
Male
*Hispanic or Latino/statistics & numerical data
*Diet
Aged
Risk Factors
White

@article {pmid41224138,
year = {2025},
author = {Minus, E and Coley, RY and Shortreed, SM and Williamson, BD},
title = {Behavior of prediction performance metrics with rare events.},
journal = {Journal of clinical epidemiology},
volume = {},
number = {},
pages = {112046},
doi = {10.1016/j.jclinepi.2025.112046},
pmid = {41224138},
issn = {1878-5921},
abstract = {OBJECTIVE: Area under the receiving operator characteristic curve (AUC) is commonly reported alongside prediction models for binary outcomes. Recent articles have raised concerns that AUC might be a misleading measure of prediction performance in the rare event setting. This setting is common since many events of clinical importance are rare. We aimed to determine whether the bias and variance of AUC are driven by the number of events or the event rate. We also investigated the behavior of other commonly used measures of prediction performance, including positive predictive value, accuracy, sensitivity, and specificity.

STUDY DESIGN AND SETTING: We conducted a simulation study to determine when or whether AUC is unstable in the rare event setting by varying the size of datasets used to train and evaluate prediction models. This plasmode simulation study was based on data from the Mental Health Research Network; the data contained 149 predictors and the outcome of interest, suicide attempt, which had event rate 0.92% in the original dataset.

RESULTS: Our results indicate that poor AUC behavior-as measured by empirical bias, variability of cross-validated AUC estimates, and empirical coverage of confidence intervals-is driven by the number of events in a rare-event setting, not event rate. Performance of sensitivity is driven by the number of events, while that of specificity is driven by the number of non-events. Other measures, including positive predictive value and accuracy, depend on the event rate even in large samples.

CONCLUSION: AUC is reliable in the rare event setting provided that the total number of events is moderately large; in our simulations, we observed near zero bias with 1000 events.},
}

@article {pmid41222477,
year = {2025},
author = {Takashima, Y and Dias Costa, A and Akimoto, N and Ugai, T and Bell, P and Väyrynen, JP and Hornick, JL and Mino-Kenudson, M and Zhong, Y and Ugai, S and Haruki, K and Yao, Q and Matsuda, K and Higashioka, M and Buchanan, DD and Phipps, AI and Peters, U and Giannakis, M and Song, M and Chan, AT and Fuchs, CS and Nowak, JA and Ogino, S},
title = {T-cell Subset Features and Distributions Evolve Across the Colorectal Precancer-Cancer Spectrum.},
journal = {Cancer immunology research},
volume = {},
number = {},
pages = {},
pmid = {41222477},
issn = {2326-6074},
support = {R35 CA197735/CA/NCI NIH HHS/United States ; R01 CA248857/CA/NCI NIH HHS/United States ; U01 CA167552/CA/NCI NIH HHS/United States ; UM1 CA186107/CA/NCI NIH HHS/United States ; UM1 CA167552/CA/NCI NIH HHS/United States ; R21 CA230873/CA/NCI NIH HHS/United States ; P01 CA087969/CA/NCI NIH HHS/United States ; P01 CA055075/CA/NCI NIH HHS/United States ; R01 CA151993/CA/NCI NIH HHS/United States ; R50 CA274122/CA/NCI NIH HHS/United States ; },
abstract = {The immune microenvironment is a crucial component of colorectal carcinoma (CRC) that has been well characterized, but much less is known about the immune microenvironment of CRC precursors. We hypothesized that T-cell infiltrates might differ across the colorectal neoplastic spectrum. We leveraged the prospective cohort incident-tumor biobank method, which provided formalin-fixed paraffin-embedded tumor tissue specimens (N=1,825) from 790 CRC precursors (including hyperplastic polyps, sessile serrated adenomas, traditional serrated adenomas, tubular adenomas, tubulovillous adenomas, and villous adenomas) and 1,035 CRCs. We performed an in situ multispectral immunofluorescence assay for CD3, CD4, CD8, FOXP3 (negative, low, or high expression), PTPRC (CD45RO, CD45RA), MKI67 (Ki-67), and KRT combined with supervised machine learning. CD3+CD4+ cells were more abundant than CD3+CD8+ cells in most precursors. In conventional adenomas, greater villous component correlated with fewer intraepithelial CD3+CD8+ cells. Serrated lesions, including hyperplastic polyps and sessile serrated lesions, exhibited higher densities of intraepithelial CD3+CD8+ cells compared to other precursors and carcinomas. Age strata of patients with precursors (including early-onset precursors) were not associated with differential T-cell infiltration patterns. Compared to invasive CRC, precursors generally showed higher densities of CD3+CD4+ cells and CD3+CD8+ cells with phenotypes of naive (CD45RA+CD45RO-), memory (CD45RA-CD45RO+), and regulatory (FOXP3+Low and FOXP3+High) in intraepithelial and lamina propria/stromal regions. In conclusion, T-cell infiltration patterns vary across different histopathological types of the colorectal neoplastic spectrum from precursors to invasive carcinomas. Our findings shed light on how the tumor-immune microenvironment evolves during precursor development and progression to CRC.},
}

@article {pmid41221958,
year = {2025},
author = {Rees, MJ and Khouri, J and Grajales-Cruz, AF and Zanwar, SS and Goel, U and Midha, S and Kelley, J and Puglianini, OC and Corraes, AMS and Raza, S and Davis, JA and Green, K and Hansen, DK and Banerjee, R and Sidana, S and Patel, KK and Bianchi, G and Sborov, DW and Lee, S and Kumar, SK and Baz, R and Anwer, F and Mikkilineni, L and Nadeem, O and Lin, Y and Anderson, LD},
title = {The Real-World Safety and Efficacy of Bispecific T-Cell Engager Therapy in Systemic AL Amyloidosis.},
journal = {American journal of hematology},
volume = {},
number = {},
pages = {},
doi = {10.1002/ajh.70140},
pmid = {41221958},
issn = {1096-8652},
}

@article {pmid41219045,
year = {2025},
author = {Chen, F and Sheng, X and Wang, A and Xu, Y and Hughley, R and Xiong, W and Pooler, L and Wan, P and Gundell, SM and Kigozi, G and Nakigozi, G and Nalugoda, F and Kagaayi, J and Kigozi, GN and Mugamba, S and Kyasanku, E and Nkale, J and Olwa, VO and Lubwama, A and Daama, A and Nakajugo, R and Adusei, B and Jalloh, M and Gueye, SM and Adjei, AA and Mensah, J and Fernandez, PW and Adebiyi, AO and Olufemi Ogunbiyi, J and Aisuodionoe-Shadrach, OI and Petersen, L and Chen, WC and McBride, J and Bensen, JT and Mohler, JL and Taylor, JA and Andrews, C and Kigongo, M and Colline, A and Kiddu, V and Namugambe, J and Owamaani, S and Job, K and Masaba, BJ and Asiimwe, F and Muwanga, P and Namulondo, J and Nagawa, F and Kayiraba, C and Ogwang, M and Okidi, R and Oweka, D and Kitara, E and Obonyo, J and Lajul, D and Matovu, P and Muheki, PA and Natumanya, J and Agaba, E and Aculokin, E and Twongyeirwe, A and Mutema, G and Bitamazire, D and Butler, EN and Ingles, SA and Rybicki, BA and Stanford, JL and Zheng, W and Berndt, SI and Chanock, SJ and Huff, CD and Lachance, J and Multigner, L and Darst, BF and Rebbeck, TR and Brureau, L and Watya, S and Conti, DV and Haiman, CA},
title = {Integrating Pathogenic Variants, Polygenic Risk Score, and Family History for Prostate Cancer Risk Estimation in Men of African Ancestry.},
journal = {European urology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.eururo.2025.09.4161},
pmid = {41219045},
issn = {1873-7560},
abstract = {BACKGROUND AND OBJECTIVE: The impact of germline pathogenic variants (PVs) in cancer predisposition genes on risk of prostate cancer (PCa) remains understudied in large populations of African ancestry. This study aims to characterize the range of genetic risk of PCa and aggressive disease phenotypes in men of African ancestry.

METHODS: We analyzed 7176 PCa cases and 4873 controls from seven countries across North America and Africa to assess the association between PVs in 37 cancer predisposition genes and the risk of overall, aggressive, and metastatic PCa. Genes significantly associated with PCa risk were used to estimate lifetime absolute risk based on family history, polygenic risk score (PRS), and PV carrier status.

KEY FINDINGS AND LIMITATIONS: PVs in ATM, BRCA2, CHEK2, HOXB13, and PALB2 were presented in 4% of aggressive/metastatic PCa cases and were significantly associated with an increased risk of aggressive PCa (odds ratio 2.18-5.96, p < 0.05). Lifetime absolute risk varied widely depending on PV carrier status, PRS, and family history, ranging from 3.0% to 74% for overall PCa, 0.6% to 41% for aggressive PCa, and 0.2% to 37% for metastatic PCa. PV carriers with a positive family history and a PRS in the 90th percentile had seven, 18, and 34 times the risks of overall, aggressive, and metastatic PCa, respectively, compared with average-risk individuals. Oversampling of aggressive cases may limit the generalizability of these findings to screening populations.

Integration of PV status, PRS, and family history enables more refined PCa risk estimates. The wide range of PCa risk observed among men of African ancestry in our study supports future prospective studies in the development of risk-stratified cancer screening programs to identify high-risk individuals who may benefit from screening at an earlier age.},
}

@article {pmid41218661,
year = {2025},
author = {Ford, EC and Evans, S and Salter, B and Bazan, JG and Weintraub, SM and Moran, JM and Olsen, JR and Dalton, AP and Kujundzic, K and Wilson, E and Marks, LB},
title = {Operations and impact of a specialty-specific national incident learning system: Ten years of RO-ILS: Radiation Oncology Incident Learning System.},
journal = {International journal of radiation oncology, biology, physics},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.ijrobp.2025.10.027},
pmid = {41218661},
issn = {1879-355X},
abstract = {Incident learning is recognized by national and international organizations as a key component of maintaining safety and quality in healthcare. In 2014, RO-ILS: Radiation Oncology Incident Learning System was launched by the American Society for Radiation Oncology and the American Association of Physicists in Medicine with the goal of facilitating safer and higher quality care in radiation oncology. This review discusses the structure of the RO-ILS program, its foundations and operations, as well as outcomes in terms of engagement and learning opportunities. RO-ILS operates under the auspices and protection of patient safety organization (PSO) in the United States (US). As of the end of 2024, 781 facilities have enrolled in the program representing a mixture of US practice settings (private practice community/academic, free-standing/hospital-based, small/large). A cumulative 41,516 events have been reported to the PSO, the largest volume of events compared to other national and international aggregated ILS systems in radiation oncology. A minority of events (24%) are incidents, i.e. events that actually reached a patient regardless of harm. Approximately 10% of events were rated as potentially severe or critical. A key feature of the RO-ILS program are reports and other releases aimed at education and quality improvement. Over 100 releases have been issued including case studies, great catches, safety notices and themed reports, as well as industry webinars and user meetings. While there is evidence of success and engagement in the RO-ILS program, current and future challenges include the quantity and quality of reported data, the ability to effectively extract information, further engagement of key stakeholders, and program sustainability. These must be addressed for RO-ILS to continue to fulfill the mission of supporting safer and higher quality care in radiation oncology.},
}

@article {pmid41217670,
year = {2025},
author = {Liu, ZY and Chen, GC and LaMonte, MJ and Kamensky, V and Evenson, KR and Shadyab, AH and Luo, J and Allison, M and Wild, RA and Going, SB and Eaton, CB and Stone, KL and Bea, JW and Seguin-Fowler, RA and Johnson, KC and Kaplan, RC and Rohan, TE and Wassertheil-Smoller, S and Qi, Q},
title = {Longitudinal transitions in sedentary behavior and physical activity in relation to all-cause and cause-specific mortality among postmenopausal women.},
journal = {GeroScience},
volume = {},
number = {},
pages = {},
pmid = {41217670},
issn = {2509-2723},
support = {K01HL129892/HL/NHLBI NIH HHS/United States ; R01HL060712/HL/NHLBI NIH HHS/United States ; R01HL140976/HL/NHLBI NIH HHS/United States ; R01-HL146132-01/HL/NHLBI NIH HHS/United States ; R01DK119268/DK/NIDDK NIH HHS/United States ; R01DK120870/DK/NIDDK NIH HHS/United States ; 5R01CA227122//Division of Cancer Epidemiology and Genetics, National Cancer Institute/ ; },
abstract = {To evaluate longitudinal transitions in sedentary behavior and physical activity for the associations with all-cause and cause-specific mortality (i.e., cardiovascular disease [CVD], cancer, respiratory, and Alzheimer's disease/dementia mortality) among postmenopausal women. This prospective cohort study included 58,168 multiethnic US postmenopausal women from the Women's Health Initiative Observational Study, who had self-reported data on various sedentary behaviors and recreational physical activity at baseline (Y0: 1993-1998; age range: 50-79 years) and after 6 years (Y6). According to sedentary time (≥ 8 h/day or not) or physical activity (≥ 8.5 MET-h/week or not) at Y0 and Y6 assessments, participants were grouped by transition in sedentary behavior (consistently non-sedentary, sedentary to non-sedentary, non-sedentary to sedentary, and consistently sedentary) or physical activity levels (consistently low, high to low, low to high, and consistently high). Over a median follow-up of 15.0 years (from Y6 to March 2019), 17,354 all-cause deaths occurred, ranging from 1336 respiratory to 5111 CVD deaths. Compared to the consistently non-sedentary group, the two groups with unfavorable transitions in sedentary behavior (i.e., from non-sedentary to sedentary or being consistently sedentary) both had a higher risk of all-cause mortality and mortality from CVD, cancer, and respiratory disease. Conversely, the two groups with favorable transitions in physical activity (i.e., transitioning to or maintaining high activity), as compared with the consistently-low activity group, both had a lower risk mortality from all causes and several specific causes. Significant interactions were observed between transitions in sedentary behavior and physical activity on the risk of all-cause and CVD mortality (P-interaction < 0.01). Specifically, unfavorable sedentary transitions were associated with an elevated risk only among women with unfavorable transitions in physical activity. Among US postmenopausal women, maintaining or transiting to a sedentary lifestyle over 6 years was associated with a higher risk of mortality, predominantly among those not achieving regular physical activity over the years.},
}

@article {pmid41216598,
year = {2025},
author = {Wang, R and Stempel, JM and Shallis, RM and Huntington, SF and Zeidan, AM and Neparidze, N and Di, M and Bewersdorf, JP and Mendez, L and Ma, X and Podoltsev, NA},
title = {Second malignancies among older patients with classical myeloproliferative neoplasms treated with ruxolitinib.},
journal = {Blood neoplasia},
volume = {2},
number = {4},
pages = {100159},
pmid = {41216598},
issn = {2950-3280},
support = {N01 PC035136/CA/NCI NIH HHS/United States ; N01 PC035139/CA/NCI NIH HHS/United States ; N02 PC015105/PC/NCI NIH HHS/United States ; T32 CA233414/CA/NCI NIH HHS/United States ; },
abstract = {Polycythemia vera (PV), essential thrombocythemia (ET), and myelofibrosis (MF) are classical Philadelphia chromosome-negative myeloproliferative neoplasms (MPNs) associated with an increased risk of development of second primary malignancies (SMs). The reasons for solid and lymphoid SMs are unclear, but a therapy-related effect has been invoked. Although an increased risk of nonmelanoma skin cancers is associated with the use of ruxolitinib (RUX), its influence on the development of other forms of SMs remains controversial. We conducted a retrospective cohort analysis to assess associations between RUX and SMs among older patients diagnosed with MPN from 2012 to 2019 in the Surveillance, Epidemiology, and End Results-Medicare-linked database. We identified 6043 patients (2396 with PV, 2944 with ET, 703 with MF) with a median age of 76 years (interquartile range [IQR], 71-82). After a median follow-up of 3.66 (IQR, 2.25-5.17) and 3.02 years (IQR, 1.84-4.75) for 513 RUX users and 5530 nonusers, respectively, 469 patients developed an SM: 383 solid and 86 lymphoid. In the multivariable proportional subdistribution hazard regression model with death as a competing risk, the risk of developing any SM did not differ by RUX use status (hazard ratio [HR], 0.96; 95% confidence interval [CI], 0.65-1.42; P = .84) or by proportion of days covered by RUX (every 10% increase; HR, 1.00; 95% CI, 0.96-1.05; P = .95). RUX exposure did not affect the risk of solid SM (HR, 0.77; 95% CI, 0.48-1.23; P = .27) or lymphoid SM (HR, 1.73; 95% CI, 0.79-3.80; P = .17). Our results suggest that RUX use does not increase the risk of SM in older patients with MPN.},
}

@article {pmid41213499,
year = {2025},
author = {Dehn, JG and Logan, B and Lee, SJ and Shaw, BE and Devine, S and Ciurea, SO and Horowitz, M and He, N and Pusic, I and Srour, SA and Arai, S and Juckett, M and Uberti, J and Hill, L and Vasu, S and Hogan, WJ and Hayes-Lattin, B and Westervelt, P and Bashey, A and Farhadfar, N and Grunwald, MR and Leifer, E and Symons, H and Saad, A and Vogel, J and Erickson, C and Buck, K and Pidala, J},
title = {Access to Allogeneic Cell Transplantation Based on Donor Search Prognosis: BMT CTN 1702 Trial.},
journal = {Transplantation and cellular therapy},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jtct.2025.11.010},
pmid = {41213499},
issn = {2666-6367},
abstract = {BACKGROUND: Patients requiring allogeneic hematopoietic cell transplantation (HCT) have variable likelihoods of identifying an 8/8 HLA-matched unrelated donor (MUD). A Search Prognosis calculator can estimate the likelihood.

OBJECTIVE: This study (NCT#03904134; https://clinicaltrials.gov/study) evaluates if using a Search Prognosis algorithm results in similar incidence of transplant between patients Very Likely (>90%) vs Very Unlikely (<10%) to have a MUD. An additional objective included understanding barriers resulting in a delay or cancellation of a patient transplant.

STUDY DESIGN: The national multi-center Blood and Marrow Transplant Clinical Trial Network (BMT CTN) 1702 interventional trial utilized Search Prognosis-based biologic assignment to guide donor selection. HCT eligible patients at participating transplant centers were invited to enroll. Patients assigned to the Very Likely arm were to proceed with MUD, while Very Unlikely were to utilize alternative donors. A third stratum, Less Likely (∼25%), were observed under standard center practices, but were not part of the primary objective. We report here the cumulative incidence of HCT by Search Prognosis group and barriers to HCT.

RESULTS: Evaluable patients included 1751 of which 413 (24%) were from racial/ethnic minorities. Seach Prognosis was 958 (55%) Very Likely, 517 (30%) Less Likely and 276 (16%) Very Unlikely. 1171 (67%) received HCT, 384 (22%) died without HCT, and 196 (11%) remained alive without HCT. Among the 1,234 patients (Very Likely vs Very Unlikely), the adjusted cumulative incidence (95% CI) of HCT at 6-months was 59.8% (56.7-62.8) in Very Likely versus 52.3% (46.1-58.5) in Very Unlikely (P=0.113). Median time to HCT were similar in all Seach Prognosis groups. The predominant barriers resulting in a delay or cancellation of transplant were due to poor patient health (59%). Around 9% of delays and cancellations were attributed to excellent patient disease response, with only 14% of delays and 2% of cancellations due to donor reasons.

CONCLUSION: A prospective Search Prognosis-based algorithm can be effectively implemented in a national multicenter clinical trial, with donor related barriers to transplant representing a small proportion of cases. This approach resulted in rapid alternative donor identification and no statistical difference in rates of HCT in patients Very Likely and Very Unlikely to find a MUD.},
}

@article {pmid41213454,
year = {2025},
author = {Rioseco, A and Puschel, K and Soto, G and Vescovi, Z and Fuentes, I and Dibiase, F and Ulloa, G and Goic, C and Emery, J and Thompson, B and Martinez-Gutierrez, J},
title = {National cancer plans and primary care a systematic analysis comparing Latin American and non-Latin American countries.},
journal = {Journal of cancer policy},
volume = {46},
number = {},
pages = {100659},
doi = {10.1016/j.jcpo.2025.100659},
pmid = {41213454},
issn = {2213-5383},
abstract = {BACKGROUND: Cancer is a growing global health issue, particularly in middle- and high-income countries. National Cancer Control Plans (NCCPs) have emerged as a strategic response to reduce this burden. Primary care plays a crucial role across the cancer care continuum, yet its systematic inclusion in NCCPs remains unclear-especially in countries facing significant epidemiological challenges.

METHODS: This study employed a systematic qualitative design based on document analysis. Using the READ (Ready material, Extract data, Analyze, Distil) model, we examined the integration of primary care policies and practices in eight NCCPs: four from non-Latin American high-income countries (NLAHIc-Australia, Canada, the United States, and the United Kingdom) and four from Latin American middle-income countries (LATAMc-Argentina, Colombia, Chile, and Mexico). Covidence software facilitated the systematic text review, and a set of evidence-based key performance indicators (KPIs) was developed to guide the analysis.

RESULTS: Primary care integration varied across countries. LATAMc NCCPs showed greater inclusion of primary care than NLAHIc. Health promotion strategies were more consistently present in NLAHIc, while LATAMc better integrated primary prevention into primary care. However, only 50 % of KPIs for secondary prevention and 15 % for survivorship care were included in LATAMc. Palliative care was more consistently integrated in LATAMc (75 %) than in NLAHIc (33 %). Policy Summary This is the first study to benchmark NCCPs from Latin American and high-income countries using evidence-based KPIs to assess primary care involvement in cancer control. Findings highlight an urgent need to strengthen primary care integration. LATAMc should improve secondary prevention and survivorship care, while NLAHIc need to better incorporate primary prevention and palliative care into their NCCPs.},
}

@article {pmid41213032,
year = {2025},
author = {El-Khoueiry, AB and Kim, RD and Harris, WP and Sung, MW and Waldschmidt, D and Cabrera, R and Garosi, VL and Ploeger, BA and Zebger-Gong, H and Brennan, BJ and Wang, YA and Mueller, U and Weispfenning, A and Seidel, H and Coppieters, S and Ishida, TC and Galle, PR},
title = {A multicenter dose-defining/expansion phase 1b study of first-line regorafenib plus pembrolizumab in patients with advanced hepatocellular carcinoma.},
journal = {Hepatology (Baltimore, Md.)},
volume = {},
number = {},
pages = {},
doi = {10.1097/HEP.0000000000001585},
pmid = {41213032},
issn = {1527-3350},
abstract = {BACKGROUND AND AIMS: Combinations including an immune checkpoint inhibitor are preferred first-line treatments for advanced hepatocellular carcinoma (HCC). We investigated the safety of regorafenib plus pembrolizumab as first-line systemic therapy for advanced HCC.

APPROACH AND RESULTS: This was a dose-defining/expansion phase 1b study in adults with advanced HCC without prior systemic treatment. Patients received regorafenib 80 or 120 mg/day for 3 weeks plus pembrolizumab 200 mg every 3 weeks in 4-week cycles (rego-80/pembro or rego-120/pembro): rego-80/pembro in the dose-defining phase; rego-80/pembro or rego-120/pembro in two dose-expansion cohorts. The primary objective was to assess safety; antitumor activity was a secondary objective. The MTD of regorafenib was 120 mg/day plus pembrolizumab; 4/19 patients receiving rego-120/pembro experienced DLTs (grade 3 increased aspartate aminotransferase [AST] with grade 1/2 increased bilirubin [n=2], and grade 3 rash [n=2]). The most common treatment-emergent adverse events (TEAEs) in the overall safety cohort (n=57) were diarrhea (53%) and fatigue (51%). The most common grade ≥3 TEAEs were increased AST (18%) and hypertension (16%). Dose modifications due to study drug-related adverse events were less frequent with rego-80/pembro than with rego-120/pembro. The objective response rate (ORR) in 54 response-evaluable patients was 31% and the disease control rate (DCR) was 89%. Exploratory analyses suggested an association between lower angiogenesis and transforming growth factor-β signalling before treatment and response.

CONCLUSION: Treatment with rego/pembro is feasible in patients with advanced HCC with a manageable safety profile. ORR and DCR are promising and consistent with other immunotherapy combinations in this setting.},
}

@article {pmid41210956,
year = {2025},
author = {Luedtke, A and Fong, Y and van der Laan, L and Heng, F and Huang, Y and Lu, Y and Yu, C and Carpp, LN and Roels, S and Le Gars, M and Van Roey, GA and Stieh, DJ and Van Dromme, I and Kenny, A and Carone, M and Hyrien, O and Ayala, V and Jayashankar, L and Castellino, F and Amoa-Awua, O and Basappa, M and Flach, B and Lin, BC and Moore, C and Naisan, M and Naqvi, M and Narpala, S and O'Connell, S and Mueller, A and Serebryannyy, L and Castro, M and Wang, J and Dziubla, G and Randhawa, AK and Andrasik, MP and Hendriks, J and Truyers, C and Struyf, F and Schuitemaker, H and Douoguih, M and Kublin, JG and Corey, L and Neuzil, KM and Bekker, LG and Garrett, N and Cardoso, SW and DelaFontaine, P and Magaret, CA and Vingerhoets, J and Casapia, M and Losso, MH and Little, SJ and Gaur, A and Swann, E and Petropoulos, CJ and McDermott, AB and Sadoff, J and Gray, GE and Grinsztejn, B and Goepfert, PA and Follmann, D and Roychoudhury, P and Greninger, AL and Koup, RA and Donis, RO and Gilbert, PB and , and , and , },
title = {Immune correlates analysis of antibody responses against SARS-CoV-2 variants in the ENSEMBLE vaccine efficacy trial.},
journal = {iScience},
volume = {28},
number = {11},
pages = {113660},
pmid = {41210956},
issn = {2589-0042},
abstract = {In Latin American sites of the ENSEMBLE trial of the Ad26.COV2.S vaccine vs. placebo, binding antibodies and neutralizing antibodies measured 4 weeks post-vaccination (∼peak) against circulating lineages (Ancestral, Gamma, Lambda, Mu, Zeta) were assessed as a correlate of risk of, and correlate of protection against, lineage-specific COVID-19. Comparison of lineage-matched controlled vaccine efficacy (VE) curves showed similar relationships across lineages of lineage-specific antibody with VE against lineage-matched COVID-19, supporting a "variant-invariant correlate of protection model" that undergirds immunobridging inferences of efficacy against new variants based on variant-matched neutralizing antibody titers. Lambda departed from this model at undetectable/just-detectable titers: at ∼ peak Reference-specific titers of 2.7 arbitrary units (AU)/mL (just-detectable) and 30 AU/ml, VE against Ancestral COVID-19 was 53.0% (95% CI: 30.7%, 67.9%) and 84.5% (73.6%, 93.0%), respectively; at the same Lambda-specific titers, VE against Lambda COVID-19 was 12.3% (-54.1%, 50.3%) and 91.1% (68.9%, 98.0%). Additional research is needed for Omicron variants.},
}

@article {pmid41210691,
year = {2025},
author = {Meng, L and Psutka, SP and Gheeya, J and Li, M and Noonavath, M and Orcutt, D and Gross, E and Collier, KA and Mortazavi, A and Folefac, E and Monk, P and Yang, Y},
title = {Tyrosine Kinase Inhibitors Outperform Immune Checkpoint Inhibitors in Bone-Predominant Metastatic Renal Cell Carcinoma: A Multicenter Real-World Analysis.},
journal = {Journal of Cancer},
volume = {16},
number = {14},
pages = {4047-4054},
pmid = {41210691},
issn = {1837-9664},
abstract = {Background: Bone-predominant metastatic renal cell carcinoma (mRCC) presents significant clinical challenges due to its associated morbidities and poor prognosis. Optimal first-line treatment remains unclear, largely because these patients are often excluded from clinical trials due to difficulties in measuring bone lesions. Emerging evidence suggests that bone metastases exhibit high angiogenesis gene signatures, potentially predicting favorable responses to tyrosine kinase inhibitors (TKIs). Methods: We conducted a multicenter retrospective analysis of patients with bone-predominant mRCC treated at The Ohio State University Comprehensive Cancer Center and Fred Hutchinson Cancer Center from January 2008 to June 2021. Bone predominance was defined as having a greater number of osseous metastases compared to extra-osseous sites using computed tomography or bone scans. Patients receiving first-line TKIs or immune checkpoint inhibitors (ICIs) were included; those treated with combination TKI-ICI therapies were excluded due to limited numbers. Demographic, clinical, and treatment data were collected. Progression-free survival (PFS) and overall survival (OS) were analyzed using Kaplan-Meier methods and compared using the log-rank test. Univariate Cox regression analysis was conducted to identify factors associated with OS. Results: A total of 69 patients with bone-predominant mRCC were identified, with 40 receiving TKIs and 29 receiving ICIs as first-line therapy. Baseline characteristics were comparable between groups. The median OS was significantly longer for patients treated with TKIs compared to those receiving ICIs (41.3 months vs. 19.3 months; log-rank P = 0.036). A trend toward improved median PFS was observed in the TKI group (7.9 months vs. 4.9 months; P = 0.075). Univariate analysis showed that treatment with ICIs was associated with an increased risk of death compared to TKIs (hazard ratio = 1.96; P = 0.040). Objective response rates were higher in the TKI group (22.9% vs. 12.0%), although this difference was not statistically significant (P = 0.332). Conclusions: In this multicenter real-world analysis, first-line treatment with TKIs was associated with significantly improved OS compared to ICIs in patients with bone-predominant mRCC. These findings suggest that TKI-containing regimens may be the preferred front-line therapy for this patient subgroup. Prospective studies are warranted to validate these results and to optimize treatment strategies for bone-predominant mRCC.},
}

@article {pmid41207385,
year = {2025},
author = {Richardson, AB and Ng, K and Gooley, TA and Cheng, GS and Salit, RB},
title = {Pulmonary Complications Following Hematopoietic Cell Transplantation in Patients with Myelofibrosis: A Single-center Retrospective Cohort Analysis.},
journal = {Transplantation and cellular therapy},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jtct.2025.10.027},
pmid = {41207385},
issn = {2666-6367},
abstract = {BACKGROUND: Myelofibrosis (MF) is a clonal hematopoietic stem-cell disorder which frequently results in extramedullary hematopoiesis. Hematopoietic cell transplantation (HCT) is the only cure. While a two-fold increase in pneumonia and respiratory-related mortality was recently reported in MF patients compared to the general population, incidence and etiology of HCT-related pulmonary complications has not been well studied.

METHODS: We performed a retrospective chart review of consecutive MF patients who received an HCT between 2002-2022. Patients with evidence of pulmonary impairment on pulmonary function tests, defined as ≥10-point decline in FEV1 compared to pre-HCT or a decline in FEV1/FVC ratio to < 0.7 or both, received further chart review to determine the etiology of this decline.

RESULTS: Of 228 patients evaluated, 126 (55%) met either FEV1 or FEV1/FVC criteria for pulmonary impairment. After further chart review, 35 patients (15.4%) were determined to have BOS by a pulmonologist or GVHD specialist. Other common causes of impairment included respiratory infections (n =10), cryptogenic organizing pneumonia (n = 8), and deconditioning (n = 8).

CONCLUSION: MF patients have a >50% likelihood of developing pulmonary impairment following HCT and a higher-than-expected incidence of BOS. This study supports increased pulmonary monitoring post-HCT in patients with MF.},
}

@article {pmid41207382,
year = {2025},
author = {Locke, FL and Nikiforow, S and Frigault, MJ and Maloney, DG and Davila, M and Miklos, DB and Lin, Y and Vong, J and Shah, NN and Neelapu, SS and Welch, J and Ng, E and Jacobson, C and Maus, MV},
title = {Recommendations for Defining Chimeric Antigen Receptor T-Cell (CAR T) Dose-Limiting Toxicities (DLTs) for Future Early-Phase CAR T Therapy Studies.},
journal = {Transplantation and cellular therapy},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jtct.2025.11.004},
pmid = {41207382},
issn = {2666-6367},
abstract = {Chimeric antigen receptor T-cell (CAR T) therapies have demonstrated potential to provide long-term remission in incurable hematologic malignancies, and novel approaches for CAR T therapy continue to be developed for treating cancer and other indications. Acute class-effect toxicities, such as cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome, and immune effector cell-associated hemophagocytic lymphohistiocytosis-like syndrome, remain significant concerns despite their potential reversibility. Given the complexities of balancing safety and efficacy of CAR T therapies, the US Food and Drug Administration (FDA) recently published Guidance for Industry, which included suggested definitions for dose-limiting toxicities (DLTs) for clinical trials of emerging CAR T therapies. However, the DLT definitions in the guidance do not reflect what was used in the phase 1 and/or registrational studies for the approved CAR Ts; for example, these studies defined DLTs as treatment-related, included exceptions, and/or allowed for time to resolve the adverse event. Using DLT definitions from the guidance could have prematurely stopped the early-phase studies of the now approved CAR Ts. In 2023, while designing a first-in-human, phase 1 study of a logic-gated cell therapy, an expert panel of academic cell therapists collaborated with industry partners at A2 Biotherapeutics to assess the practical implications of the FDA guidance. This led the panel to draft the revised recommendations contained herein, which integrate the permissibility of reversible events during dose-escalation for trial sponsors, investigators, health authorities, and other parties who may be involved in future CAR T therapy trials. These expert recommendations balance the safety of patients in early-phase trials with the potential long-term therapeutic opportunities for patients with terminal malignancies.},
}

@article {pmid41207381,
year = {2025},
author = {Wolff, D and Cutler, C and Mercep, I and Jaki, T and Robertson, DS and Schultz, KR and Lee, SJ and Martin, PJ and Pavletic, SZ},
title = {Towards better and more effective clinical trials for Chronic Graft-versus-Host Disease.},
journal = {Transplantation and cellular therapy},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jtct.2025.11.008},
pmid = {41207381},
issn = {2666-6367},
abstract = {While the incidence of chronic Graft-versus-Host Disease (chronic GVHD) is declining due to advances in prophylaxis and survival is improving due to better supportive care, first-line treatment of chronic GVHD continues to be based on corticosteroids. Numerous attempts to establish more effective or less toxic treatment alternatives have largely failed, likely due to the biological heterogeneity of chronic GVHD and uncontrolled use of systemic corticosteroids, indicating the need for new approaches. The 2020 NIH consensus conference proposed the systematic evaluation of steroid-free initial treatment combining clinical and biological assessment to establish personalized approaches. While the first generation of trials evaluating steroid-free single agent first-line therapy approaches are recruiting, they are still not able to consider the biological heterogeneity of chronic GVHD in deciding therapeutic approaches. To advance the field, we propose a two-stage adaptive trial design starting with an intervention under consideration followed by a replication phase after the first phase has identified candidate clinical features and or biomarker predicting success. For second and subsequent lines of treatment, current treatment decisions regarding the use of the four FDA approved agents are based on the product label or a trial-and-error approach, sometimes in combination regimens despite the lack of prospective data. Future trials and prospective observational studies should focus on the development of predictive markers to provide a biological rationale for sequencing treatment options and to identify synergistic combination treatments. The recently released FDA draft guidance document for developing drugs and treatments in GVHD serves as the starting point for clinical trials planning that should yield results during the next several years.},
}

@article {pmid41092927,
year = {2025},
author = {, },
title = {Global age-sex-specific all-cause mortality and life expectancy estimates for 204 countries and territories and 660 subnational locations, 1950-2023: a demographic analysis for the Global Burden of Disease Study 2023.},
journal = {Lancet (London, England)},
volume = {406},
number = {10513},
pages = {1731-1810},
pmid = {41092927},
issn = {1474-547X},
support = {R01 AG030153/AG/NIA NIH HHS/United States ; R03 AG043052/AG/NIA NIH HHS/United States ; R21 AG032572/AG/NIA NIH HHS/United States ; },
mesh = {Humans ; *Life Expectancy/trends ; Male ; Female ; *Global Burden of Disease/trends ; Middle Aged ; Adult ; Adolescent ; Aged ; Child ; Child, Preschool ; Young Adult ; Global Health/statistics & numerical data ; *Mortality/trends ; Cause of Death/trends ; Infant ; Aged, 80 and over ; Infant, Newborn ; COVID-19/epidemiology ; Age Distribution ; Sex Distribution ; },
abstract = {BACKGROUND: Comprehensive, comparable, and timely estimates of demographic metrics-including life expectancy and age-specific mortality-are essential for evaluating, understanding, and addressing trends in population health. The COVID-19 pandemic highlighted the importance of timely and all-cause mortality estimates for being able to respond to changing trends in health outcomes, showing a strong need for demographic analysis tools that can produce all-cause mortality estimates more rapidly with more readily available all-age vital registration (VR) data. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) is an ongoing research effort that quantifies human health by estimating a range of epidemiological quantities of interest across time, age, sex, location, cause, and risk. This study-part of the latest GBD release, GBD 2023-aims to provide new and updated estimates of all-cause mortality and life expectancy for 1950 to 2023 using a novel statistical model that accounts for complex correlation structures in demographic data across age and time.

METHODS: We used 24 025 data sources from VR, sample registration, surveys, censuses, and other sources to estimate all-cause mortality for males, females, and all sexes combined across 25 age groups in 204 countries and territories as well as 660 subnational units in 20 countries and territories, for the years 1950-2023. For the first time, we used complete birth history data for ages 5-14 years, age-specific sibling history data for ages 15-49 years, and age-specific mortality data from Health and Demographic Surveillance Systems. We developed a single statistical model that incorporates both parametric and non-parametric methods, referred to as OneMod, to produce estimates of all-cause mortality for each age-sex-location group. OneMod includes two main steps: a detailed regression analysis with a generalised linear modelling tool that accounts for age-specific covariate effects such as the Socio-demographic Index (SDI) and a population attributable fraction (PAF) for all risk factors combined; and a non-parametric analysis of residuals using a multivariate kernel regression model that smooths across age and time to adaptably follow trends in the data without overfitting. We calibrated asymptotic uncertainty estimates using Pearson residuals to produce 95% uncertainty intervals (UIs) and corresponding 1000 draws. Life expectancy was calculated from age-specific mortality rates with standard demographic methods. For each measure, 95% UIs were calculated with the 25th and 975th ordered values from a 1000-draw posterior distribution.

FINDINGS: In 2023, 60·1 million (95% UI 59·0-61·1) deaths occurred globally, of which 4·67 million (4·59-4·75) were in children younger than 5 years. Due to considerable population growth and ageing since 1950, the number of annual deaths globally increased by 35·2% (32·2-38·4) over the 1950-2023 study period, during which the global age-standardised all-cause mortality rate declined by 66·6% (65·8-67·3). Trends in age-specific mortality rates between 2011 and 2023 varied by age group and location, with the largest decline in under-5 mortality occurring in east Asia (67·7% decrease); the largest increases in mortality for those aged 5-14 years, 25-29 years, and 30-39 years occurring in high-income North America (11·5%, 31·7%, and 49·9%, respectively); and the largest increases in mortality for those aged 15-19 years and 20-24 years occurring in Eastern Europe (53·9% and 40·1%, respectively). We also identified higher than previously estimated mortality rates in sub-Saharan Africa for all sexes combined aged 5-14 years (87·3% higher in GBD 2023 than GBD 2021 on average across countries and territories over the 1950-2021 period) and for females aged 15-29 years (61·2% higher), as well as lower than previously estimated mortality rates in sub-Saharan Africa for all sexes combined aged 50 years and older (13·2% lower), reflecting advances in our modelling approach. Global life expectancy followed three distinct trends over the study period. First, between 1950 and 2019, there were considerable improvements, from 51·2 (50·6-51·7) years for females and 47·9 (47·4-48·4) years for males in 1950 to 76·3 (76·2-76·4) years for females and 71·4 (71·3-71·5) years for males in 2019. Second, this period was followed by a decrease in life expectancy during the COVID-19 pandemic, to 74·7 (74·6-74·8) years for females and 69·3 (69·2-69·4) years for males in 2021. Finally, the world experienced a period of post-pandemic recovery in 2022 and 2023, wherein life expectancy generally returned to pre-pandemic (2019) levels in 2023 (76·3 [76·0-76·6] years for females and 71·5 [71·2-71·8] years for males). 194 (95·1%) of 204 countries and territories experienced at least partial post-pandemic recovery in age-standardised mortality rates by 2023, with 61·8% (126 of 204) recovering to or falling below pre-pandemic levels. There were several mortality trajectories during and following the pandemic across countries and territories. Long-term mortality trends also varied considerably between age groups and locations, demonstrating the diverse landscape of health outcomes globally.

INTERPRETATION: This analysis identified several key differences in mortality trends from previous estimates, including higher rates of adolescent mortality, higher rates of young adult mortality in females, and lower rates of mortality in older age groups in much of sub-Saharan Africa. The findings also highlight stark differences across countries and territories in the timing and scale of changes in all-cause mortality trends during and following the COVID-19 pandemic (2020-23). Our estimates of evolving trends in mortality and life expectancy across locations, ages, sexes, and SDI levels in recent years as well as over the entire 1950-2023 study period provide crucial information for governments, policy makers, and the public to ensure that health-care systems, economies, and societies are prepared to address the world's health needs, particularly in populations with higher rates of mortality than previously known. The estimates from this study provide a robust framework for GBD and a valuable foundation for policy development, implementation, and evaluation around the world.

FUNDING: Gates Foundation.},
}

Humans
*Life Expectancy/trends
Male
Female
*Global Burden of Disease/trends
Middle Aged
Adult
Adolescent
Aged
Child
Child, Preschool
Young Adult
Global Health/statistics & numerical data
*Mortality/trends
Cause of Death/trends
Infant
Aged, 80 and over
Infant, Newborn
COVID-19/epidemiology
Age Distribution
Sex Distribution

@article {pmid41206949,
year = {2025},
author = {Zhang, T and Hua, X and Mohindroo, C and Wang, X and Dutta, D and Liu, J and Katta, S and Li, SA and Wang, J and Antwi, SO and Arslan, AA and Beane Freeman, LE and Bracci, PM and Canzian, F and Du, M and Gallinger, S and Goodman, PJ and Katzke, V and Kooperberg, C and Le Marchand, L and Neale, RE and Patel, AV and Perdomo, S and Shu, XO and Visvanathan, K and Van Den Eeden, SK and White, E and Zheng, W and Albanes, D and Andreotti, G and Bamlet, WR and Brennan, P and Buring, JE and Chanock, SJ and Chen, Y and Darst, B and Ferrari, P and Giovannucci, EL and Goggins, M and Haiman, C and Hassan, M and Holly, EA and Hung, RJ and Jones, MR and Kraft, P and Kurtz, RC and Malats, N and Moore, SC and Ng, K and Oberg, AL and Orlow, I and Peters, U and Porta, M and Rabe, KG and Rothman, N and Sánchez, MJ and Sesso, HD and Silverman, DT and Southey, MC and Um, CY and Yarmolinsky, J and Yu, H and Yuan, C and Zhong, J and Wolpin, BM and Risch, HA and Amundadottir, LT and Klein, AP and Yu, K and Zhang, H and Stolzenberg-Solomon, RZ},
title = {Different diabetes types and pancreatic ductal adenocarcinoma: a Mendelian randomization and pathway/gene-set analysis.},
journal = {Journal of the National Cancer Institute},
volume = {},
number = {},
pages = {},
doi = {10.1093/jnci/djaf308},
pmid = {41206949},
issn = {1460-2105},
abstract = {BACKGROUND: The associations between different types of diabetes, characterized by distinct pathophysiology and genetic architecture, and pancreatic ductal adenocarcinoma (PDAC) risk are not understood.

METHODS: We investigated associations of genetic susceptibility to type 2 diabetes (T2D), eight T2D mechanistic clusters, type 1 diabetes (T1D), and maturity-onset diabetes of the young (MODY) with PDAC risk. We used genome-wide association study (GWAS) summary-level statistics for T2D (242,283 cases, 1,569,734 controls), T1D (18,942 cases, 501,638 controls), and PDAC (10,244 cases and 360,535 controls) in individuals of European ancestry.

RESULTS: Two-sample Mendelian randomization (MR) using the Robust Adjusted Profile Score (MR-RAPS) method indicated that genetically predicted T2D was associated with PDAC risk (OR = 1.10; 95% CI 1.05-1.15), particularly the T2D obesity (OR = 1.28; 95% CI 1.15-1.42) and lipodystrophy (OR = 1.25; 95% CI 1.03-1.51) clusters. No association was observed for T1D with PDAC risk (OR = 1.01; 95% CI 0.99-1.02). Pathway/gene-set analysis using the summary-based Adaptive Rank Truncated Product (sARTP) method revealed a significant association between the MODY gene-sets and PDAC risk (P = 1.5 × 10-8), which remained after excluding 20 known PDAC GWAS loci (P = 7.6 × 10-4). HNF1A, FOXA3, and HNF4A were the top contributing genes after excluding the previously identified GWAS loci regions.

CONCLUSIONS: Our results from this genetic association study support that T2D, particularly the obesity and lipodystrophy mechanistic clusters, and MODY genomic susceptibility regions play a role in the etiology of PDAC.},
}

@article {pmid41206919,
year = {2025},
author = {El Kassar, N and DeZern, AE and Abkowitz, J and Artz, A and Beerman, I and Bolton, K and Brooks, MM and Borate, U and Ershler, WB and Ganz, T and Kalfa, TA and Kuaban, A and Leng, S and Nakada, D and Nazha, A and Grossmann, C and Pfeilstöcker, M and Qiu, C and Sauver, JS and Sekeres, MA and Simonsick, EM and White, KE and Zhang, D and Ferrucci, L and Kuchel, GA},
title = {A Proposed Path to Explaining the Unexplained Anemia of Aging.},
journal = {The journals of gerontology. Series A, Biological sciences and medical sciences},
volume = {},
number = {},
pages = {},
doi = {10.1093/gerona/glaf251},
pmid = {41206919},
issn = {1758-535X},
abstract = {Approximately 17% of people aged 65 years and older are anemic, and 10% of death certificates report anemia as a secondary cause of death in the US. Nonetheless, anemia remains unexplained in 30-50% of older adults. This unexplained anemia of aging (UAA) is a diagnosis of exclusion. The mechanism, impact, and progression of UAA remain unknown. At older ages, anemia adds to pre-existing co-morbidities with significant adverse health consequences, representing a compelling unmet clinical concern. The National Institute on Aging held a workshop in 2024 to discuss current knowledge and research opportunities. Topics included the epidemiology of anemia at older age, its clinical implications; probable mechanism(s) underlying UAA, ie; low grade inflammation's effects on erythropoiesis; the role of microbiota in iron regulation in bone marrow; the importance of ruling out a diagnosis of leukemic clonal hematopoiesis (CH), which is more prevalent in older age; the role of senescence and aging governing hematopoiesis, and effects of sex hormones on hematopoietic stem cell aging. Understanding the roles of these factors could reduce the proportion of the older anemic population whose anemia remains unexplained and offer insights into new potential diagnostic and intervention strategies. Speakers reviewed previous clinical trials in patients with UAA and CH. They discussed lessons learned, and future research priorities ., including efforts to develop new diagnostic algorithms and potential uses of machine learning.},
}

@article {pmid41092926,
year = {2025},
author = {, },
title = {Burden of 375 diseases and injuries, risk-attributable burden of 88 risk factors, and healthy life expectancy in 204 countries and territories, including 660 subnational locations, 1990-2023: a systematic analysis for the Global Burden of Disease Study 2023.},
journal = {Lancet (London, England)},
volume = {406},
number = {10513},
pages = {1873-1922},
pmid = {41092926},
issn = {1474-547X},
support = {P01 HD031921/HD/NICHD NIH HHS/United States ; R01 AG044917/AG/NIA NIH HHS/United States ; R01 AG030153/AG/NIA NIH HHS/United States ; HHSN271201300071C/AG/NIA NIH HHS/United States ; /WT_/Wellcome Trust/United Kingdom ; R03 AG043052/AG/NIA NIH HHS/United States ; R01 AG034479/AG/NIA NIH HHS/United States ; R01 AG018016/AG/NIA NIH HHS/United States ; R21 AG032572/AG/NIA NIH HHS/United States ; U01 AG009740/AG/NIA NIH HHS/United States ; R01 AG031716/AG/NIA NIH HHS/United States ; R21 AG034263/AG/NIA NIH HHS/United States ; },
mesh = {Humans ; *Global Burden of Disease/trends ; *Life Expectancy/trends ; Risk Factors ; Male ; Female ; Disability-Adjusted Life Years ; *Wounds and Injuries/epidemiology ; Middle Aged ; Adult ; Global Health/statistics & numerical data ; Child ; Aged ; Adolescent ; Infant ; Child, Preschool ; Young Adult ; Infant, Newborn ; COVID-19/epidemiology ; Persons with Disabilities/statistics & numerical data ; Quality-Adjusted Life Years ; Aged, 80 and over ; },
abstract = {BACKGROUND: For more than three decades, the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) has provided a framework to quantify health loss due to diseases, injuries, and associated risk factors. This paper presents GBD 2023 findings on disease and injury burden and risk-attributable health loss, offering a global audit of the state of world health to inform public health priorities. This work captures the evolving landscape of health metrics across age groups, sexes, and locations, while reflecting on the remaining post-COVID-19 challenges to achieving our collective global health ambitions.

METHODS: The GBD 2023 combined analysis estimated years lived with disability (YLDs), years of life lost (YLLs), and disability-adjusted life-years (DALYs) for 375 diseases and injuries, and risk-attributable burden associated with 88 modifiable risk factors. Of the more than 310 000 total data sources used for all GBD 2023 (about 30% of which were new to this estimation round), more than 120 000 sources were used for estimation of disease and injury burden and 59 000 for risk factor estimation, and included vital registration systems, surveys, disease registries, and published scientific literature. Data were analysed using previously established modelling approaches, such as disease modelling meta-regression version 2.1 (DisMod-MR 2.1) and comparative risk assessment methods. Diseases and injuries were categorised into four levels on the basis of the established GBD cause hierarchy, as were risk factors using the GBD risk hierarchy. Estimates stratified by age, sex, location, and year from 1990 to 2023 were focused on disease-specific time trends over the 2010-23 period and presented as counts (to three significant figures) and age-standardised rates per 100 000 person-years (to one decimal place). For each measure, 95% uncertainty intervals [UIs] were calculated with the 2·5th and 97·5th percentile ordered values from a 250-draw distribution.

FINDINGS: Total numbers of global DALYs grew 6·1% (95% UI 4·0-8·1), from 2·64 billion (2·46-2·86) in 2010 to 2·80 billion (2·57-3·08) in 2023, but age-standardised DALY rates, which account for population growth and ageing, decreased by 12·6% (11·0-14·1), revealing large long-term health improvements. Non-communicable diseases (NCDs) contributed 1·45 billion (1·31-1·61) global DALYs in 2010, increasing to 1·80 billion (1·63-2·03) in 2023, alongside a concurrent 4·1% (1·9-6·3) reduction in age-standardised rates. Based on DALY counts, the leading level 3 NCDs in 2023 were ischaemic heart disease (193 million [176-209] DALYs), stroke (157 million [141-172]), and diabetes (90·2 million [75·2-107]), with the largest increases in age-standardised rates since 2010 occurring for anxiety disorders (62·8% [34·0-107·5]), depressive disorders (26·3% [11·6-42·9]), and diabetes (14·9% [7·5-25·6]). Remarkable health gains were made for communicable, maternal, neonatal, and nutritional (CMNN) diseases, with DALYs falling from 874 million (837-917) in 2010 to 681 million (642-736) in 2023, and a 25·8% (22·6-28·7) reduction in age-standardised DALY rates. During the COVID-19 pandemic, DALYs due to CMNN diseases rose but returned to pre-pandemic levels by 2023. From 2010 to 2023, decreases in age-standardised rates for CMNN diseases were led by rate decreases of 49·1% (32·7-61·0) for diarrhoeal diseases, 42·9% (38·0-48·0) for HIV/AIDS, and 42·2% (23·6-56·6) for tuberculosis. Neonatal disorders and lower respiratory infections remained the leading level 3 CMNN causes globally in 2023, although both showed notable rate decreases from 2010, declining by 16·5% (10·6-22·0) and 24·8% (7·4-36·7), respectively. Injury-related age-standardised DALY rates decreased by 15·6% (10·7-19·8) over the same period. Differences in burden due to NCDs, CMNN diseases, and injuries persisted across age, sex, time, and location. Based on our risk analysis, nearly 50% (1·27 billion [1·18-1·38]) of the roughly 2·80 billion total global DALYs in 2023 were attributable to the 88 risk factors analysed in GBD. Globally, the five level 3 risk factors contributing the highest proportion of risk-attributable DALYs were high systolic blood pressure (SBP), particulate matter pollution, high fasting plasma glucose (FPG), smoking, and low birthweight and short gestation-with high SBP accounting for 8·4% (6·9-10·0) of total DALYs. Of the three overarching level 1 GBD risk factor categories-behavioural, metabolic, and environmental and occupational-risk-attributable DALYs rose between 2010 and 2023 only for metabolic risks, increasing by 30·7% (24·8-37·3); however, age-standardised DALY rates attributable to metabolic risks decreased by 6·7% (2·0-11·0) over the same period. For all but three of the 25 leading level 3 risk factors, age-standardised rates dropped between 2010 and 2023-eg, declining by 54·4% (38·7-65·3) for unsafe sanitation, 50·5% (33·3-63·1) for unsafe water source, and 45·2% (25·6-72·0) for no access to handwashing facility, and by 44·9% (37·3-53·5) for child growth failure. The three leading level 3 risk factors for which age-standardised attributable DALY rates rose were high BMI (10·5% [0·1 to 20·9]), drug use (8·4% [2·6 to 15·3]), and high FPG (6·2% [-2·7 to 15·6]; non-significant).

INTERPRETATION: Our findings underscore the complex and dynamic nature of global health challenges. Since 2010, there have been large decreases in burden due to CMNN diseases and many environmental and behavioural risk factors, juxtaposed with sizeable increases in DALYs attributable to metabolic risk factors and NCDs in growing and ageing populations. This long-observed consequence of the global epidemiological transition was only temporarily interrupted by the COVID-19 pandemic. The substantially decreasing CMNN disease burden, despite the 2008 global financial crisis and pandemic-related disruptions, is one of the greatest collective public health successes known. However, these achievements are at risk of being reversed due to major cuts to development assistance for health globally, the effects of which will hit low-income countries with high burden the hardest. Without sustained investment in evidence-based interventions and policies, progress could stall or reverse, leading to widespread human costs and geopolitical instability. Moreover, the rising NCD burden necessitates intensified efforts to mitigate exposure to leading risk factors-eg, air pollution, smoking, and metabolic risks, such as high SBP, BMI, and FPG-including policies that promote food security, healthier diets, physical activity, and equitable and expanded access to potential treatments, such as GLP-1 receptor agonists. Decisive, coordinated action is needed to address long-standing yet growing health challenges, including depressive and anxiety disorders. Yet this can be only part of the solution. Our response to the NCD syndemic-the complex interaction of multiple health risks, social determinants, and systemic challenges-will define the future landscape of global health. To ensure human wellbeing, economic stability, and social equity, global action to sustain and advance health gains must prioritise reducing disparities by addressing socioeconomic and demographic determinants, ensuring equitable health-care access, tackling malnutrition, strengthening health systems, and improving vaccination coverage. We live in times of great opportunity.

FUNDING: Gates Foundation and Bloomberg Philanthropies.},
}

Humans
*Global Burden of Disease/trends
*Life Expectancy/trends
Risk Factors
Male
Female
Disability-Adjusted Life Years
*Wounds and Injuries/epidemiology
Middle Aged
Adult
Global Health/statistics & numerical data
Child
Aged
Adolescent
Infant
Child, Preschool
Young Adult
Infant, Newborn
COVID-19/epidemiology
Persons with Disabilities/statistics & numerical data
Quality-Adjusted Life Years
Aged, 80 and over

@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},
doi = {10.1091/mbc.E25-05-0229},
pmid = {41060786},
issn = {1939-4586},
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 {pmid40815811,
year = {2025},
author = {Ligon, JA and Ji, L and Dang, A and Xu, X and Rheingold, SR and Bhojwani, D and Devidas, M and Kairalla, JA and Shago, M and Heerema, NA and Carroll, AJ and Borowitz, M and Wood, BL and Winick, NJ and Carroll, WL and Hunger, SP and Raetz, EA and Loh, ML and Gupta, S and Winestone, LE},
title = {Role of race and ethnicity in survival among children/young adults with relapsed ALL: a Children's Oncology Group report.},
journal = {Blood advances},
volume = {9},
number = {22},
pages = {5738-5751},
doi = {10.1182/bloodadvances.2025016670},
pmid = {40815811},
issn = {2473-9537},
support = {U10 CA180899/CA/NCI NIH HHS/United States ; },
mesh = {Humans ; Child ; Female ; Male ; Adolescent ; Child, Preschool ; Young Adult ; Recurrence ; *Precursor Cell Lymphoblastic Leukemia-Lymphoma/mortality/ethnology/therapy/epidemiology ; *Ethnicity ; Infant ; Prognosis ; Racial Groups ; Hispanic or Latino ; Adult ; White ; },
abstract = {Pediatric Hispanic and Black patients with newly diagnosed B-cell acute lymphoblastic leukemia (B-ALL) experience worse overall survival (OS). We hypothesized that differential outcomes by race and ethnicity following relapse may contribute to disparities. We examined 2053 patients with ALL enrolled in frontline Children's Oncology Group trials from 1996 to 2014 who relapsed. We assessed the association of race and ethnicity, disease characteristics, and socioeconomic status with relapse survival predictors and postrelapse OS. For noninfant B-ALL, postrelapse OS (P = .002) and disease-related prognosticators such as time to relapse (P = .0002) differed by race and ethnicity. After adjusting for disease and patient characteristics, the OS association with overall race and ethnicity was attenuated, and lost statistical significance; Hispanic ethnicity specifically remained associated with worse OS (hazard ratio [HR], 1.19; 95% confidence interval [CI], 1.01-1.41). Patients from highest annual median household income ZIP codes (>$85 000, approximately the highest quartile of patients) had better 5-year OS than those from the lowest (<$50 000; HR, 0.79; 95% CI, 0.63-0.99). Non-Hispanic Black and Hispanic patients more commonly lived in lower-income ZIP codes. For T-cell ALL, race, ethnicity, and socioeconomic status were not associated with OS. Worse postrelapse outcomes among racial and ethnic minority patients are largely driven by the prevalence of adverse disease-related factors at time of relapse, with a persistent disparity observed in Hispanic patients. The greatest impact in decreasing racial and ethnic B-ALL outcome disparities may be achieved by targeting frontline treatment interventions to address increased relapse among Black and Hispanic patients, and by developing and enabling equitable access to effective relapse treatments such as novel immunotherapies.},
}

Humans
Child
Female
Male
Adolescent
Child, Preschool
Young Adult
Recurrence
*Precursor Cell Lymphoblastic Leukemia-Lymphoma/mortality/ethnology/therapy/epidemiology
*Ethnicity
Infant
Prognosis
Racial Groups
Hispanic or Latino
Adult
White

@article {pmid41206886,
year = {2025},
author = {Seth, L and Bhave, A and Kollapaneni, S and Shah, V and Nahle, T and Blaes, A and Dent, S and Hurvitz, SA and Guha, A},
title = {Cardiotoxic Effects of Antibody Drug Conjugates vs Standard Chemotherapy in ERBB2-Positive Advanced Breast Cancer: A Systematic Review and Meta-Analysis.},
journal = {JAMA network open},
volume = {8},
number = {11},
pages = {e2540336},
pmid = {41206886},
issn = {2574-3805},
mesh = {Humans ; *Breast Neoplasms/drug therapy ; Female ; Receptor, ErbB-2 ; *Cardiotoxicity/etiology ; Trastuzumab/adverse effects/therapeutic use ; Ado-Trastuzumab Emtansine/adverse effects/therapeutic use ; *Immunoconjugates/adverse effects/therapeutic use ; *Antineoplastic Agents, Immunological/adverse effects ; Camptothecin/analogs & derivatives ; },
abstract = {IMPORTANCE: Antibody-drug conjugates (ADCs), such as trastuzumab emtansine and trastuzumab deruxtecan, are effective in treating erb-b2 receptor tyrosine kinase 2 (ERBB2)-positive breast cancer (BC) that has progressed on prior ERBB2-targeted therapy, warranting evaluation of their cardiotoxic profiles.

OBJECTIVE: To compare the incidence of cardiotoxic effects of ADCs vs standard-of-care chemotherapy regimens for ERBB2-positive locally advanced or metastatic BC.

DATA SOURCES: PubMed, ScienceDirect, Cochrane Library, and ClinicalTrials.gov databases were searched in December 2024 for studies published between 2000 and 2024.

STUDY SELECTION: The included studies were (1) phase 3 clinical trials that investigated locally advanced or metastatic ERBB2-positive BC; (2) clearly defined left ventricular ejection fraction (LVEF) decrease or heart failure definitions; (3) clearly defined LVEF monitoring frequency by echocardiography or multigated acquisition scan; (4) included studies consisted solely of either trastuzumab emtansine, trastuzumab deruxtecan, or one of the first-line to fourth-line chemotherapy regimens for unresectable stage IV ERBB2-positive breast cancer per the 2025 National Comprehensive Cancer Network guidelines; and (5) clearly defined cardiovascular eligibility criteria.

DATA EXTRACTION AND SYNTHESIS: Data from eligible studies were extracted by 3 reviewers. A random-effects model was used for the pooled analysis. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline was followed.

MAIN OUTCOMES AND MEASURES: The primary outcome was cardiotoxic effects, which were defined as the incidence of LVEF decrease. The pooled analysis was performed using logit-transformed proportions with the inverse variance method and a DerSimonian-Laird random-effects model for between-study variance, with Wilson score 95% CIs.

RESULTS: In this meta-analysis of 9538 patients, a pooled analysis demonstrated a 0.94% (95% CI, 0.56%-1.57%) incidence of LVEF decrease with trastuzumab emtansine, a 4.20% (95% CI, 2.91%-6.01%) incidence with trastuzumab deruxtecan, a 4.85% (95% CI, 3.73%-6.28%) incidence with trastuzumab plus chemotherapy, and a 5.52% (95% CI, 3.41%-8.83%) incidence with trastuzumab plus pertuzumab plus chemotherapy. A trim-and-fill analysis was used if evidence of publication bias was found.

CONCLUSIONS AND RELEVANCE: This meta-analysis found that trastuzumab emtansine was associated with the lowest incidence of LVEF decrease, and trastuzumab deruxtecan, trastuzumab plus chemotherapy, and trastuzumab plus pertuzumab plus chemotherapy had similar incidences. More research is needed into the cardiotoxic effects of these therapies.},
}

Humans
*Breast Neoplasms/drug therapy
Female
Receptor, ErbB-2
*Cardiotoxicity/etiology
Trastuzumab/adverse effects/therapeutic use
Ado-Trastuzumab Emtansine/adverse effects/therapeutic use
*Immunoconjugates/adverse effects/therapeutic use
*Antineoplastic Agents, Immunological/adverse effects
Camptothecin/analogs & derivatives

@article {pmid41206027,
year = {2025},
author = {Hanscom, B and Marzinke, MA and Li, X and Donnell, D and Bies, R and Hendrix, CW and Wang, Z and Acuipil, C and Rinehart, A and Collins, JW and Rooney, JF and Soto Torres, L and Richardson, P and Chariyalerstsak, S and Valdez Ramalho Madruga, J and Hurt, CB and Magnus, M and Frank, I and McCauley, M and Grinsztejn, B and Landovitz, RJ},
title = {Estimation of prevention-effective CAB-LA concentrations among men who have sex with men (MSM) and transgender women (TGW) in HPTN 083.},
journal = {The Journal of infectious diseases},
volume = {},
number = {},
pages = {},
doi = {10.1093/infdis/jiaf561},
pmid = {41206027},
issn = {1537-6613},
abstract = {BACKGROUND: The HIV Prevention Trials Network (HPTN) 083 Trial demonstrated the superiority of long-acting, injectable cabotegravir (CAB) over daily oral tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) for HIV pre-exposure prophylaxis among cisgender men (MSM) and transgender women (TGW) who have sex with men. Plasma CAB concentrations associated with HIV protection in humans are unknown.

METHODS: We conducted a nested case-control study among HPTN 083 participants to investigate the association between plasma CAB concentrations and HIV risk. Plasma CAB concentrations were estimated for participants with confirmed HIV and for HIV-negative controls, who were matched on region, gender, and race. The window of HIV acquisition for cases was defined as the time between the last HIV-negative visit and the first HIV-positive visit; this window was used to evaluate CAB exposure for cases and their matched controls. Participants were categorized by the minimum estimated CAB concentration (CABmin) during this window relative to the protein-adjusted 90% CAB inhibitory concentration (1x PA-IC90) and 4x PA-IC90. HIV risk was modeled using conditional logistic regression.

RESULTS: Plasma CABmin was ≥4x PA-IC90 in 26% of HIV-positive cases, compared to 76% of matched controls. Plasma CABmin ≥4x PA-IC90 was associated with a 93% reduction in risk of HIV acquisition compared to CABmin <1x PA-IC90 (95% CI: 76%, 98%, p<0.001). CABmin between 1x and 4x PA-IC90 had an estimated risk reduction of 79% compared to CABmin <1x PA-IC90 (95% CI: -19%, 96%, p=0.07).

CONCLUSIONS: Consistent plasma CAB concentrations ≥4x PA-IC90 were estimated to provide 93% protection against HIV in MSM and TGW.},
}

@article {pmid41205872,
year = {2025},
author = {Vaquera-Alfaro, HA and Jeon, Y and Wu, QV and Liang, EC and Portuguese, A and León, AG and Valdespino-Valdes, J and Gauthier, J},
title = {A Practical Guide to Competing Risk Analysis for Transplant and Cell Therapy Research.},
journal = {Transplantation and cellular therapy},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jtct.2025.11.003},
pmid = {41205872},
issn = {2666-6367},
abstract = {Competing risks are common in hematopoietic cell transplantation (HCT) and immune effector cell (IEC) therapy research. Competing risks refer to events that cannot co-occur and complicate time-to-event analyses. The typical example of competing risk in the context of HCT and IEC research is treatment-related mortality, which competes with disease relapse. In this primer, we first aim to introduce - in a clinician-friendly fashion - the core concepts underlying the statistical modelling of competing risks. Next, we propose a practical, step-by-step guide to analyze time-to-event outcomes in the context of competing risks using the open access R environment. Relevant R packages are introduced, enabling the generation of publication-ready tables and figures. We hope our manuscript will encourage more robust analyses in the fields of HCT and IEC therapy when competing risks are at play.},
}

@article {pmid41205698,
year = {2025},
author = {Dunk, MM and Delac, L and Rapp, SR and Driscoll, I and Latorre-Leal, M and Farland, LV and Haring, B and Harris, HR and Jung, SY and Manson, JE and Ochs-Balcom, HM and Shadyab, AH and Weitlauf, JC and Xu, H and Maioli, S},
title = {Exploring biomarkers of neurodegenerative risk: Associations of oxysterols, sex hormones, and reproductive characteristics in older women.},
journal = {Journal of lipid research},
volume = {},
number = {},
pages = {100938},
doi = {10.1016/j.jlr.2025.100938},
pmid = {41205698},
issn = {1539-7262},
abstract = {Women face a higher lifetime risk of developing neurodegenerative diseases such as Alzheimer's disease (AD) and related dementia (ADRD). The menopausal transition, characterized by a decline in estrogen levels, may affect cholesterol metabolism and neurodegenerative processes. Oxysterols, oxidized cholesterol derivatives, play a role in these pathways, with 24(S)-hydroxycholesterol (24HC) reflecting brain cholesterol turnover and 27-hydroxycholesterol (27HC) linked to systemic cholesterol metabolism. We investigated associations of plasma oxysterols with circulating sex hormones and characteristics of reproductive history in 1,974 postmenopausal women with no history of dementia from the Women's Health Initiative, taking into account APOE4 status and cholesterol-lowering medication. We found that higher levels of bioavailable estradiol were associated with higher 24HC and 27HC levels, and higher estrone was associated with higher 24HC (all p-values < 0.05). Associations of estradiol with 24HC and 27HC were stronger among those not using cholesterol medication and APOE4 carriers, with a significant interaction between 27HC and APOE4 in relation to 27HC (p for interaction = 0.04). Having an older age at menopause was associated with lower 24HC among those taking cholesterol medication (p for interaction = 0.03). Our findings suggest that 24HC and 27HC may be proxy biomarkers of neuronal health and estrogen status in postmenopausal women. The stronger associations between estradiol and oxysterols among APOE4 carriers and those not using cholesterol-lowering medication suggest the need to account for hormonal, genetic, and pharmacological factors when evaluating neurodegenerative risk. Longitudinal studies are warranted to further investigate oxysterols as potential early biomarkers of ADRD risk.},
}

@article {pmid41203676,
year = {2025},
author = {Duggan, C and de Dieu Tapsoba, J and Warner, J and Dash, A and Wang, CY and McTiernan, A},
title = {Effects of acute exercise on inflammatory and metabolic biomarkers in women: a randomized controlled trial.},
journal = {NPJ breast cancer},
volume = {11},
number = {1},
pages = {122},
pmid = {41203676},
issn = {2374-4677},
support = {P30 CA015704/CA/NCI NIH HHS/United States ; BRCF-18-107; BCRF-19-107; BCRF-20-107; BRCF-21-107; BRCF-22;107//Breast Cancer Research Foundation,United States/ ; },
abstract = {Mechanisms linking exercise to reduced breast cancer risk are poorly understood. 103 healthy women, 18-75, were randomized to 45-minutes of acute exercise at 60% VO2max (N = 54, intervention), or 45-minutes of rest (N = 49, control). Blood samples were collected at baseline, 45- and 105-minutes, analytes measured by immunoassay, and mean changes from baseline to 45- and 105-minutes modelled using generalized estimating equations, adjusted for confounders. Mean percent changes levels (Δ%) increased in exercisers vs. controls for monocyte chemoattractant protein (MCP)-1 Δ[45 min] + 17.1% (P < 0.0001), Δ[105 min] + 12.0% (P = 0.005); interleukin(IL)-6, Δ[45 min] + 103.5%, Δ[105 min] + 92.3%; and at 45-minutes for glucose Δ[45 min] + 8.8%; insulin Δ[45 min] + 82.4% (all P < 0.0001). Differences between arms for vascular endothelial growth factor (VEGF) Δ[45 min] + 9.8%; c-reactive protein Δ[45 min]-6.6%; irisin Δ[45 min]-5.1%; or plasminogen activator inhibitor (PAI)-1, Δ[45 min]-3.6% were non-statistically significant, with similar results at 105-minutes. Results suggest that acute exercise has specific effects on circulating metabolic and inflammatory biomarkers, implicated in breast cancer etiology, which differ from weight-loss-induced changes. Trial registration: Clincialtrials.gov identifier NCT03779867.},
}