@article {pmid41106380,
year = {2025},
author = {Galeano Niño, JL and Ponath, F and Ajisafe, VA and Becker, CR and Kempchinsky, AG and Zepeda-Rivera, MA and Gomez, JA and Wu, H and Terrazas, JG and Bouzek, H and Cromwell, E and Chanana, P and Wong, M and Damania, A and White, MG and You, YN and Kopetz, S and Ajami, NJ and Wargo, JA and Johnston, CD and Bullman, S},
title = {Tumor-infiltrating bacteria disrupt cancer epithelial cell interactions and induce cell-cycle arrest.},
journal = {Cancer cell},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.ccell.2025.09.010},
pmid = {41106380},
issn = {1878-3686},
abstract = {Tumor-infiltrating bacteria are increasingly recognized as modulators of cancer progression and therapy resistance. We describe a mechanism by which extracellular intratumoral bacteria, including Fusobacterium, modulate cancer epithelial cell behavior. Spatial imaging and single-cell spatial transcriptomics show that these bacteria predominantly localize extracellularly within tumor microniches of colorectal and oral cancers, characterized by reduced cell density, transcriptional activity, and proliferation. In vitro, Fusobacterium nucleatum disrupts epithelial contacts, inducing G0-G1 arrest and transcriptional quiescence. This state confers 5-fluorouracil resistance and remodels the tumor microenvironment. Findings were validated by live-cell imaging, spatial profiling, mouse models, and a 52-patient colorectal cancer cohort. Transcriptomics reveals downregulation of cell cycle, transcription, and antigen presentation genes in bacteria-enriched regions, consistent with a quiescent, immune-evasive phenotype. In an independent rectal cancer cohort, high Fusobacterium burden correlates with reduced therapy response. These results link extracellular bacteria to cancer cell quiescence and chemoresistance, highlighting microbial-tumor interactions as therapeutic targets.},
}

@article {pmid41106280,
year = {2025},
author = {Tower, A and Owens, K and Esmaeili, S and Schiffer, JT and Reeves, DB and Schwartz, EJ},
title = {Quantitative viral dynamics: Methods for parameter estimation.},
journal = {Virology},
volume = {613},
number = {},
pages = {110631},
doi = {10.1016/j.virol.2025.110631},
pmid = {41106280},
issn = {1096-0341},
abstract = {Fitting mathematical models of viral dynamics to serial, quantitative viral load data provides inferences on the mechanisms in virus infection. This process can reveal the speed and magnitude of viral replication, cell proliferation and death, immune responses, and/or treatment efficacy. Viral dynamics modeling involves developing conceptual models, translating them into equations, and applying the appropriate statistical tools to determine the optimal parameters such that the model recapitulates observations from human and animal infections. In this review, we outline the theoretical foundations needed to understand model fitting, parameter estimation, and what it means to achieve a good fit. We provide examples and explain the strengths and limitations of three commonly used model fitting approaches: individual fitting, population mixed effects fitting, and feature fitting. We briefly review fitting algorithms and highlight powerful available computer software packages that can be used for fitting and parameter estimation. We discuss different model types, parameter identifiability, and how future modeling efforts can leverage advances in multi-dimensional data. Finally, we conclude with simple guidelines for choosing the best approach based on available data and scientific questions.},
}

@article {pmid41105919,
year = {2025},
author = {Ji, X and Hu, X and Nathan, PC and Leisenring, WM and Armstrong, GT and Castellino, SM and Kirchhoff, AC},
title = {Changes in Medicaid Enrollment Among Adult Survivors of Childhood Cancer After Medicaid Expansion: A Report From the Childhood Cancer Survivor Study.},
journal = {JCO oncology practice},
volume = {},
number = {},
pages = {OP2401056},
doi = {10.1200/OP-24-01056},
pmid = {41105919},
issn = {2688-1535},
abstract = {PURPOSE: Little is known about whether Medicaid expansion under the Affordable Care Act affects insurance coverage among adult survivors of childhood cancer, a high-risk population requiring lifetime follow-up care. We examined the association of Medicaid expansion with Medicaid enrollment among participants in the Childhood Cancer Survivor Study.

METHODS: We identified 13,355 adult survivors (age 18-64 years) diagnosed with cancer at age <21 years between 1970 and 1999 and linked these survivors to Medicaid administrative data from 2010 to 2019. Outcomes included the percentage of survivors with any Medicaid enrollment and Medicaid-covered days (total number of days when a survivor was enrolled in Medicaid) each year. Multivariable difference-in-differences (DD) models were used to examine outcome changes (post- v pre-expansion) in expansion versus nonexpansion states.

RESULTS: Medicaid enrollment rates among survivors increased in expansion states (17.1% pre-expansion to 22.8% postexpansion) but decreased in nonexpansion states (16.6%-15.7%), leading to a net increase of 7.1 percentage points (ppts; 95% CI, 6.1 to 8.1). The DD model also showed a net mean increase of 18.7 days/year (95% CI, 15.0 to 22.4) in Medicaid-covered days in expansion relative to nonexpansion states. The expansion-associated increase in enrollment was greatest among survivors who were age 18-29 years (11.2 ppts; 95% CI, 8.3 to 14.1), non-Hispanic Black (13.6 ppts, 95% CI, 8.8 to 18.4) or Hispanic (13.4 ppts, 95% CI, 7.0 to 19.8), with <$20K in US dollars (USD) self-reported household income (13.5 ppts, 95% CI, 10.7 to 16.3), and noncollege graduates (9.3 ppts, 95% CI, 7.7 to 10.9). Similar patterns were observed when examining Medicaid-covered days.

CONCLUSION: To our knowledge, we provide the first evidence of increased Medicaid enrollment and longer coverage duration among adult survivors of childhood cancer after Medicaid expansion. Greater increases were seen among survivors from underrepresented racial/ethnic backgrounds, young adult survivors, and those with lower socioeconomic status, providing a mechanism to reduce disparities and ensure long-term medical care for childhood cancer survivors.},
}

@article {pmid41105890,
year = {2025},
author = {Zwaan, CM and Tasian, SK and Aplenc, R and Brodersen, LE and Buldini, B and De Moerloose, B and Dworzak, MN and Fogelstrand, L and Gibson, BE and Goemans, BF and Hasle, H and Hirsch, BA and Kaspers, GJ and Klusmann, JH and Kutny, MA and Lehrnbecher, T and Locatelli, F and Meshinchi, S and Petit, A and Pigazzi, M and Tierens, A and Kolb, EA and Reinhardt, D and Tomizawa, D and Cooper, TM},
title = {Diagnosis and Management of AML in Pediatric Patients: Consensus Recommendations from an International Expert Panel.},
journal = {Blood},
volume = {},
number = {},
pages = {},
doi = {10.1182/blood.2024027904},
pmid = {41105890},
issn = {1528-0020},
abstract = {The European LeukemiaNet has periodically issued guidelines for the diagnosis and management of acute myeloid leukemia (AML) in adults. These consensus recommendations, most recently updated in 2022, incorporate recent advances in genomic testing, disease detection methods, target identification, and response assessment. Whilst similarities exist between AML in children and adults, pediatric AML is frequently characterized by unique cytogenetic and molecular features, which require distinct genetic and immunophenotypic diagnostics, therapeutic approaches, response assessment criteria, and supportive care strategies. To address these specific needs, an international panel of pediatric hematologist-oncologists, biologists, geneticists, and laboratory medicine scientists convened to develop recommendations for the diagnosis and management of AML in children, adolescents, and young adults (hereafter termed pediatric AML) that are discussed in this special report.},
}

@article {pmid41105630,
year = {2025},
author = {Beyrer, C and Remien, RH and Eshleman, SH and Gamble, TR and De Dieu Tapsoba, J and Labbett, RL and Sullivan, PA and Laeyendecker, O and Anderson, PL and Agravat, D and Hughes, JP and Driffin, DD and Hutchinson, CS and Hucks-Ortiz, C and Adair, M and Curry, M and Jones, SB and Haddock, IL and Boyd, D and Burwen, DR and Johnson, AS and Nelson, LE and , },
title = {Investigating the HIV epidemic among Black gay and bisexual men in the Southern United States: Results of the HPTN 096 pilot cross-sectional assessment.},
journal = {PloS one},
volume = {20},
number = {10},
pages = {e0334031},
pmid = {41105630},
issn = {1932-6203},
mesh = {Humans ; Male ; *HIV Infections/epidemiology/prevention & control/drug therapy ; Cross-Sectional Studies ; Adult ; *Homosexuality, Male/statistics & numerical data ; Pilot Projects ; *Black or African American/statistics & numerical data ; Middle Aged ; United States/epidemiology ; Pre-Exposure Prophylaxis ; *Bisexuality/statistics & numerical data ; Young Adult ; Adolescent ; Incidence ; *Epidemics ; White ; },
abstract = {BACKGROUND: The HIV Prevention Trials Network (HPTN) 096 study was designed to address the markedly higher rates of HIV incidence among Black men who have sex with men (MSM) in the Southern United States (US). A cross-sectional assessment was conducted during the pilot phase of the study to determine its feasibility and collect key HIV-related metrics for the study population.

METHODS AND FINDINGS: Four hundred and twenty-two Black MSM, ≥ 15 years old and living in the four pilot communities (Dallas, TX; Houston, TX; Montgomery, AL; Greenville, SC), were enrolled via starfish sampling into the cross-sectional assessment. Each participant completed two questionnaires and had blood samples collected at a single study visit. Laboratory testing was performed to determine HIV status and use of oral pre-exposure prophylaxis (PrEP). HIV drug resistance and viral suppression were also assessed for two of the four pilot communities (Dallas and Houston). Categorical variables were summarized using frequency and percentage. Continuous variables were summarized using mean, standard deviation, median and interquartile range. Univariable and multivariable logistic regression models were used to assess various associations. HIV status was determined for 403 of the 422 participants (95.5%); 212 (52.6%) men were living with HIV, including one with acute HIV. For these participants, 163 (76.9%) reported that they were in HIV care. In Dallas and Houston, 71 of the 101 living with HIV (70.3%) were virally suppressed. Of the 191 not living with HIV, 57 (29.8%) reported ever taking PrEP, 41 (21.5%) reported being currently on PrEP, and eight (4.2%) reported never having heard of PrEP. PrEP use was documented through laboratory testing in 36 (19.1%) of 188 participants tested; of the 41 participants reporting current PrEP use, five did not have laboratory evidence of PrEP use.

CONCLUSION: During the pilot, we successfully recruited Black MSM using starfish sampling and demonstrated the feasibility of collecting primary study outcomes using a cross-sectional assessment. We found a high burden of HIV and those living with HIV had only a moderate rate of viral suppression. In addition, PrEP use was uncommon among the men living without HIV. Reducing HIV incidence in Black MSM remains a key element to addressing the HIV epidemic in the US.},
}

Humans
Male
*HIV Infections/epidemiology/prevention & control/drug therapy
Cross-Sectional Studies
Adult
*Homosexuality, Male/statistics & numerical data
Pilot Projects
*Black or African American/statistics & numerical data
Middle Aged
United States/epidemiology
Pre-Exposure Prophylaxis
*Bisexuality/statistics & numerical data
Young Adult
Adolescent
Incidence
*Epidemics
White

@article {pmid41105497,
year = {2025},
author = {Gavate, R and Zepeda-Rivera, MA and Jones, DS and LaCourse, KD and Bullman, S and Johnston, CD},
title = {Complete genome sequence of Peptostreptococcus anaerobius SB204, isolated from a human colonic adenocarcinoma.},
journal = {Microbiology resource announcements},
volume = {},
number = {},
pages = {e0080425},
doi = {10.1128/mra.00804-25},
pmid = {41105497},
issn = {2576-098X},
abstract = {We report the complete genome sequence of Peptostreptococcus anaerobius SB204, a strain isolated from the resected tumor of a treatment-naive patient with colorectal cancer. The genome comprises a single chromosomal contig of 2.15 Mbp with an overall GC content of 36.1%.},
}

@article {pmid41104107,
year = {2025},
author = {Tom, A and Gomez-Acosta, C and Henderson, V and McDougall, J and Mendoza, JA and Carosso, E and Cohn, EB and Barrington, WE and Bigelow-Chavez, L and Nyame, YA and Lion, KC},
title = {Advancing equity in cancer care: a pilot explanatory mixed methods study of a racially, ethnically, and linguistically concordant model of patient navigation.},
journal = {Journal of health equity},
volume = {2},
number = {1},
pages = {},
pmid = {41104107},
issn = {2994-4694},
support = {F31 CA157045/CA/NCI NIH HHS/United States ; P30 CA015704/CA/NCI NIH HHS/United States ; T32 CA092408/CA/NCI NIH HHS/United States ; },
abstract = {Disparities in cancer outcomes persist among systemically marginalized patients. A new racially, ethnically, or linguistically concordant (RELC) model of patient navigation (PN) was piloted at Fred Hutchinson Cancer Center in 2019. An explanatory mixed-methods observational study assessed patient-centered outcomes of RELC PN, traditional PN, and no PN. Patients from these models completed surveys at baseline and follow-up to measure changes in satisfaction, discrimination, resilience, stress, trust, and discussion of clinical trials. Interviews with patients receiving RELC PN were analyzed using thematic analysis. A total of 118 participants completed surveys. Satisfaction with care improved by 4.2 points (SD 7.0) on an 18-item 5-point Likert scale for those receiving RELC navigation, with no change in traditional or no PN groups. Discrimination based on race dropped from 40% (n = 2) to 20% (n = 1) in the RELC model. A higher proportion of RELC PN patients (80%; n = 4) discussed clinical trials compared to traditional PN (17%; n = 3) and no PN (20% n = 19). Thematic analysis of 29 interviews indicated the model was crucial in overcoming racism, improving trust, and empowering patients. This study highlights the potential of RELC PN to improve patient satisfaction, increase participation in clinical trials, and reduce experiences of discrimination.},
}

@article {pmid41103457,
year = {2025},
author = {Zhu, K and Zheng, Y and Chan, KCG},
title = {Weighted Brier Score - an Overall Summary Measure for Risk Prediction Models with Clinical Utility Consideration.},
journal = {Statistics in biosciences},
volume = {},
number = {},
pages = {},
pmid = {41103457},
issn = {1867-1764},
support = {R01 CA236558/CA/NCI NIH HHS/United States ; U24 CA086368/CA/NCI NIH HHS/United States ; },
abstract = {As advancements in novel biomarker-based algorithms and models accelerate their use in disease risk prediction, it is crucial to evaluate these models within the context of their intended clinical application. Prediction models output the absolute risk of disease; subsequently, patient counseling and shared decision-making are based on the estimated individual risk and cost-benefit assessment. The overall impact of the application is referred to as clinical utility, which received significant attention and desire to incorporate into model assessment lately. The classic Brier score is a popular measure of prediction accuracy; however, it is insufficient for effectively assessing clinical utility. To address this limitation, we propose a class of weighted Brier scores that aligns with the decision-theoretic framework of clinical utility. Additionally, we decompose the weighted Brier score into discrimination and calibration components, and we link the weighted Brier score to the H measure, which has been proposed as an alternative to the area under the receiver operating characteristic curve. This theoretical link to the H measure further supports our weighting method and underscores the essential elements of discrimination and calibration in risk prediction evaluation. The practical use of the weighted Brier score as an overall summary is demonstrated using data from a prostate cancer study.},
}

@article {pmid41102612,
year = {2025},
author = {Heldman, MR and Boeckh, MJ and Ison, MG},
title = {Influenza Antivirals for Prevention and Treatment in Immunocompromised People.},
journal = {The Journal of infectious diseases},
volume = {232},
number = {Supplement_3},
pages = {S243-S253},
doi = {10.1093/infdis/jiaf217},
pmid = {41102612},
issn = {1537-6613},
mesh = {Humans ; *Immunocompromised Host ; *Influenza, Human/prevention & control/drug therapy ; *Antiviral Agents/therapeutic use ; Dibenzothiepins/therapeutic use ; Neuraminidase/antagonists & inhibitors ; Pyridones/therapeutic use ; Thiepins/therapeutic use ; Morpholines ; Pyridines/therapeutic use ; Drug Resistance, Viral ; Triazines ; },
abstract = {Antivirals form a foundation for protecting immunocompromised individuals (ICIs) from influenza complications. Neuraminidase inhibitors have demonstrated benefit for both prophylaxis and treatment in ICIs, including when given >48 hours after symptom onset. Baloxavir is a newer antiviral that has potent effects on viral kinetics in immunocompetent people, but data on baloxavir in ICIs are currently limited. Optimization of antiviral therapy to minimize viral replication within ICIs and reduce the risk of treatment-emergent antiviral resistance (eg, through combination regimens) may prevent viral evolution within ICIs and mitigate transmission of virulent or resistant variants to the general public. Unfortunately, ICIs have been excluded from most clinical trials evaluating novel influenza preventive and therapeutic strategies. Inclusion of ICIs in such clinical trials is essential to facilitate acquisition of clinical and virologic data in patients with specific immunocompromising conditions and ensure that ICIs have equitable access to valuable interventions.},
}

Humans
*Immunocompromised Host
*Influenza, Human/prevention & control/drug therapy
*Antiviral Agents/therapeutic use
Dibenzothiepins/therapeutic use
Neuraminidase/antagonists & inhibitors
Pyridones/therapeutic use
Thiepins/therapeutic use
Morpholines
Pyridines/therapeutic use
Drug Resistance, Viral
Triazines

@article {pmid41102222,
year = {2025},
author = {Ellison, ST and Hayman, I and Derr, K and Derr, P and Frebert, S and Itkin, Z and Shen, M and Jones, A and Olson, W and Corey, L and Wald, A and Johnston, C and Fong, Y and Ferrer, M and Zhu, J},
title = {Limitations of acyclovir and identification of potent HSV antivirals using 3D bioprinted human skin equivalents.},
journal = {Nature communications},
volume = {16},
number = {1},
pages = {9200},
pmid = {41102222},
issn = {2041-1723},
support = {U18 TR0033208//U.S. Department of Health & Human Services | NIH | National Center for Advancing Translational Sciences (NCATS)/ ; T32 AI007140/AI/NIAID NIH HHS/United States ; U18 TR003208/TR/NCATS NIH HHS/United States ; T32 AI07140//U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (NIAID)/ ; R01 AI143773/AI/NIAID NIH HHS/United States ; },
mesh = {Humans ; *Antiviral Agents/pharmacology ; *Acyclovir/pharmacology ; Keratinocytes/drug effects/virology ; *Skin/cytology/drug effects/virology ; Fibroblasts/drug effects/virology ; Printing, Three-Dimensional ; *Herpes Simplex/drug therapy/virology ; Bioprinting/methods ; *Simplexvirus/drug effects ; Virus Replication/drug effects ; },
abstract = {Herpes simplex virus (HSV) infection poses global public health concerns with lifelong impacts. Acyclovir, the standard therapy, has limited efficacy in preventing subclinical shedding, and drug resistance occurs in immunocompromised patients, highlighting the need for novel therapeutics. Here we show that acyclovir is significantly less effective in skin-derived keratinocytes than donor-matched fibroblasts. Using 3D bioprinted human skin equivalents (HSEs) in a 96-well plate format, we have screened 738 compounds with broad targets and mechanisms of action, identifying potent antivirals, including 23 known or experimental HSV treatments. Unlike acyclovir, antivirals against HSV helicase/primase or host replication pathways display similar potency across cell types and donor sources in both 2D and 3D models. The reduced potency in keratinocytes may explain acyclovir's limited clinical efficacy. Our 3D bioprinted HSE assay platform enables the integration of patient-derived cells early in drug development and offers a physiologically relevant approach for HSV drug discovery.},
}

Humans
*Antiviral Agents/pharmacology
*Acyclovir/pharmacology
Keratinocytes/drug effects/virology
*Skin/cytology/drug effects/virology
Fibroblasts/drug effects/virology
Printing, Three-Dimensional
*Herpes Simplex/drug therapy/virology
Bioprinting/methods
*Simplexvirus/drug effects
Virus Replication/drug effects

@article {pmid41102182,
year = {2025},
author = {Weinstock, JS and Chaudhry, SA and Ioannou, M and Viskadourou, M and Reventun, P and Jakubek, YA and Liggett, LA and Laurie, C and Broome, JG and Khan, A and Taylor, KD and Guo, X and Peyser, PA and Boerwinkle, E and Chami, N and Kenny, EE and Loos, RJ and Psaty, BM and Tracy, RP and Brody, JA and Yun, JH and Cho, MH and Vasan, RS and Kardia, SL and Smith, JA and Raffield, LM and Bidulescu, A and O'Brien, EC and de Andrade, M and Rotter, JI and Rich, SS and Tracy, RP and Chen, YI and Gu, CC and Hsiung, CA and Kooperberg, C and Haring, B and Nassir, R and Mathias, R and Reiner, A and Sankaran, VG and Lowenstein, CJ and Blackwell, TW and Abecasis, GR and Smith, AV and Kang, HM and Natarajan, P and Jaiswal, S and Bick, A and Post, WS and Scheet, P and Auer, P and Karantanos, T and Battle, A and Arvanitis, M},
title = {Genetic determinants and genomic consequences of non-leukemogenic somatic point mutations.},
journal = {Nature communications},
volume = {16},
number = {1},
pages = {9194},
pmid = {41102182},
issn = {2041-1723},
support = {R01 HL120393/HL/NHLBI NIH HHS/United States ; K08 HL166690/HL/NHLBI NIH HHS/United States ; U01 HL120393/HL/NHLBI NIH HHS/United States ; R35 GM139580/GM/NIGMS NIH HHS/United States ; R01 HL117626/HL/NHLBI NIH HHS/United States ; },
mesh = {Humans ; *Point Mutation/genetics ; Genome-Wide Association Study ; *Clonal Hematopoiesis/genetics ; Genomics/methods ; Germ-Line Mutation ; },
abstract = {Clonal hematopoiesis (CH) is defined by the expansion of a lineage of genetically identical cells in blood. Genetic lesions that confer a fitness advantage, such as leukemogenic point mutations or mosaic chromosomal alterations (mCAs), are frequent mediators of CH. However, recent analyses of both single cell-derived colonies of hematopoietic cells and population sequencing cohorts have revealed CH frequently occurs in the absence of known driver genetic lesions. To characterize CH without known driver genetic lesions, we use 51,399 deeply sequenced whole genomes from the NHLBI TOPMed sequencing initiative to perform simultaneous germline and somatic mutation analyses among individuals without leukemogenic point mutations (LPM), which we term CH-LPMneg. We quantify CH by estimating the total mutation burden. Because estimating somatic mutation burden without a paired-tissue sample is challenging, we develop a novel statistical method, the Genomic and Epigenomic informed Mutation (GEM) rate, that uses external genomic and epigenomic data sources to distinguish artifactual signals from true somatic mutations. We perform a genome-wide association study of GEM to discover the germline determinants of CH-LPMneg. We identify seven genes associated with CH-LPMneg (TCL1A, TERT, SMC4, NRIP1, PRDM16, MSRA, SCARB1).Functional analyses of SMC4 and NRIP1 implicated altered hematopoietic stem cell self-renewal and proliferation as the primary mediator of mutation burden in blood. We then perform comprehensive multi-tissue transcriptomic analyses, finding that the expression levels of 404 genes are associated with GEM. Finally, we perform phenotypic association meta-analyses across four cohorts, finding that GEM is associated with increased white blood cell count, but is not significantly associated with incident stroke or coronary disease events. Overall, we develop GEM for quantifying mutation burden from WGS and use GEM to discover the genetic, genomic, and phenotypic correlates of CH-LPMneg.},
}

Humans
*Point Mutation/genetics
Genome-Wide Association Study
*Clonal Hematopoiesis/genetics
Genomics/methods
Germ-Line Mutation

@article {pmid41101975,
year = {2025},
author = {Miller, SR and Chung, DH and Gonzalez, RT and Jackson, WC and Caram, MEV and Tsao, PA and Stensland, K and Gulati, R and Shah, Y and Wale, D and Elliott, D and Caverly, T and Hofer, TP and Saini, S and Green, MD and Schipper, M and Dess, RT and Bryant, AK},
title = {Impact of PSMA PET Staging on Initial Treatment in Newly Diagnosed Prostate Cancer.},
journal = {Journal of nuclear medicine : official publication, Society of Nuclear Medicine},
volume = {},
number = {},
pages = {},
doi = {10.2967/jnumed.125.270825},
pmid = {41101975},
issn = {1535-5667},
abstract = {Prostate-specific membrane antigen (PSMA) PET/CT has become a common staging modality for newly diagnosed high-risk and unfavorable intermediate-risk prostate cancer after showing improved sensitivity and specificity compared with conventional imaging in clinical trials. We aimed to assess the causal impact of PSMA PET staging on initial treatment selection in real-world practice. Methods: We used observational data from the U.S. Veterans Health Administration to emulate a randomized controlled trial in which patients with newly diagnosed, unfavorable intermediate-, high-, and very-high-risk prostate cancer from January 2022 to December 2023 would have been randomized to undergo either upfront [18]F- or [68]Ga-PSMA PET staging or conventional imaging ([99m]Tc bone scan and pelvic CT or MRI). Outcomes of interest included use of frontline androgen deprivation therapy (ADT), second-generation androgen receptor pathway inhibitors (ARPIs), radiotherapy, and radical prostatectomy. Weighted univariable Cox regression was performed to assess the effect of treatment group on each outcome, and 95% CIs were generated from 1,000 bootstrap replicates. Results: In total, 9,049 patients met the criteria for inclusion. PSMA PET staging was associated with higher rates of any ADT use relative to conventional staging (adjusted hazard ratio [aHR], 1.26; 95% CI, 1.19-1.44), higher rates of ARPI use (aHR, 1.52; 95% CI, 1.33-1.78), lower rates of prostatectomy (aHR, 0.69; 95% CI, 0.56-0.83), and no significant effect on the use of radiotherapy (aHR, 1.10; 95% CI, 0.99-1.25). Compared with patients with PSMA stage N0M0, ARPI use was more common in patients with PSMA stage N1M0 (aHR, 6.87; 95% CI, 5.41-8.73) and PSMA stage M1 (aHR, 10.13; 95% CI, 8.16-1.2.58). Patients with PSMA N1M0 disease were much less likely to undergo prostatectomy compared with PSMA N0M0. Conclusion: PSMA PET staging may be leading to fewer prostatectomies and higher use rates of ADT and ARPIs in the Veterans Health Administration.},
}

@article {pmid41101869,
year = {2025},
author = {Apisarnthanarax, S and Kim, EY},
title = {SBRT: The Most Precise and Least Invasive Tool in the Liver Cancer Toolbox.},
journal = {International journal of radiation oncology, biology, physics},
volume = {123},
number = {4},
pages = {919},
doi = {10.1016/j.ijrobp.2025.08.023},
pmid = {41101869},
issn = {1879-355X},
}

@article {pmid41101390,
year = {2025},
author = {Chen, J and Belew, MD and Wei, J and Chow, EJ and Cheng, Z},
title = {Pediatric doxorubicin exposure induces persistent pathological changes in mice.},
journal = {Toxicology and applied pharmacology},
volume = {505},
number = {},
pages = {117600},
doi = {10.1016/j.taap.2025.117600},
pmid = {41101390},
issn = {1096-0333},
abstract = {Over 50 % of pediatric cancer patients undergo treatment with chemotherapy regimens containing anthracyclines, such as doxorubicin (DOX). However, the long-term effects of childhood DOX exposure remain poorly understood, and protective strategies are limited. To establish a mouse model that recapitulates the chronic health conditions in adult survivors of childhood cancer, 14-day-old C57BL/6N mice received DOX (2.5 mg/kg, twice weekly for 2 weeks, i.p.) and were monitored for 32 weeks. Pediatric DOX injection induced late cardiotoxicity including systolic and diastolic dysfunction, cardiac fibrosis and cardiomyocyte atrophy, which were alleviated by treatment with the CDK7/12/13 inhibitor THZ1. Pediatric DOX also reduced heart, liver and spleen weight, while sparing the lung and kidney. Mechanistically, DOX induced persistent activation of p38 in the heart and diminished physiological cardiomyocyte hypertrophy. Pediatric DOX caused slow body weight gain and late mortality, which were surprisingly exacerbated by THZ1. Notably, pediatric THZ1 exposure also hindered body weight gain and reduced heart and liver weight. In conclusion, pediatric DOX exposure resulted in chronic cardiac dysfunction, underweight and premature death during adulthood in mice. Pharmacologic inhibition of CDK7/12/13 with THZ1 partially protected against pediatric DOX-induced cardiotoxicity, but aggravated growth delay and accelerated mortality.},
}

@article {pmid41100801,
year = {2025},
author = {Neelapu, SS and Chavez, JC and Sehgal, AR and Epperla, N and Ulrickson, ML and Bachy, E and Munshi, PN and Casulo, C and Maloney, DG and de Vos, S and Reshef, R and Leslie, LA and Oluwole, OO and Yakoub-Agha, I and Khanal, R and Rosenblatt, JD and Wulff, J and Shen, RR and Zhang, W and Poddar, S and Miao, H and Nikolajeva, O and Jacobson, CA},
title = {Five-Year Follow-Up Analysis of ZUMA-5: Axicabtagene Ciloleucel in Relapsed/Refractory Indolent Non-Hodgkin Lymphoma.},
journal = {Journal of clinical oncology : official journal of the American Society of Clinical Oncology},
volume = {},
number = {},
pages = {JCO2500668},
doi = {10.1200/JCO-25-00668},
pmid = {41100801},
issn = {1527-7755},
abstract = {Axicabtagene ciloleucel (axi-cel) is an autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy approved for relapsed/refractory (R/R) follicular lymphoma (FL). Here, we report updated clinical outcomes from ZUMA-5 in 159 enrolled patients with R/R indolent non-Hodgkin lymphoma (iNHL; 127 with FL and 31 with marginal zone lymphoma) after a median follow-up of 64.6 months. Patients underwent leukapheresis and received lymphodepleting chemotherapy and axi-cel (2 × 10[6] CAR T cells/kg). The overall response rate was 90% (75% complete response rate). The median duration of response was 60.4 months, and the median progression-free survival (PFS) was 62.2 months; median time to next treatment and overall survival were not reached (NR). At data cutoff, 55% of patients were alive without requiring subsequent anticancer therapy. Median lymphoma-specific PFS in patients with FL was NR; 34% had progression or death due to lymphoma or study treatment. Notably, after 30 months postinfusion, progression or lymphoma-related deaths were rare. Late-onset toxicities were infrequent and largely unrelated to axi-cel. Durable response and prolonged survival in FL were associated with robust early CAR T-cell expansion and naïve product phenotype. These findings confirm sustained responses and manageable safety with axi-cel in the long term among patients with R/R iNHL and its potential as a curative therapy in FL.},
}

@article {pmid41100668,
year = {2025},
author = {Visani, GM and Pun, MN and Minervina, AA and Bradley, P and Thomas, PG and Nourmohammad, A},
title = {T cell receptor specificity landscape revealed through de novo peptide design.},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
volume = {122},
number = {42},
pages = {e2504783122},
doi = {10.1073/pnas.2504783122},
pmid = {41100668},
issn = {1091-6490},
support = {R35GM142795//HHS | National Institutes of Health (NIH)/ ; R35 GM141457/GM/NIGMS NIH HHS/United States ; AI136514//HHS | National Institutes of Health (NIH)/ ; A153352//UW | Office of Research Central, University of Washington (ORC)/ ; 2045054//National Science Foundation (NSF)/ ; PHY-2210452//National Science Foundation (NSF)/ ; PHY-2309135//National Science Foundation (NSF)/ ; 2919.02//Gordon and Betty Moore Foundation (GBMF)/ ; },
mesh = {*Receptors, Antigen, T-Cell/immunology/metabolism/chemistry ; *Peptides/immunology/chemistry ; Humans ; Machine Learning ; T-Lymphocytes/immunology ; Major Histocompatibility Complex ; Histocompatibility Antigens Class I/immunology ; Protein Binding ; },
abstract = {T cells play a key role in adaptive immunity by mounting specific responses against diverse pathogens. Effective bindings between T cell receptors (TCRs) and pathogen derived peptides presented on major histocompatibility complexes (MHCs) mediate immune responses. However, predicting these interactions remains challenging due to limited functional data on T cell reactivities. Here, we introduce a computational approach to predict TCR interactions with peptides presented on MHC-I alleles, and to design immunogenic peptides for specified TCR-MHC complexes. Our method leverages HERMES, a structure-based machine learning model trained on the protein universe to predict amino acid preferences based on local structural environments. Despite no direct training on TCR-pMHC data, HERMES's implicit physical reasoning enables us to make accurate predictions of both TCR-pMHC binding affinities and T cell activities across diverse viral and cancer epitopes, achieving up to 0.72 correlation with experimental data. Leveraging our TCR recognition model, we develop a computational protocol for de novo design of immunogenic peptides. Through experimental validation in three TCR-MHC systems, we demonstrate that our designs-with up to five substitutions from the native sequence-activate T cells at success rates of up to 50%. Last, we use our generative framework to quantify the diversity of the peptide recognition landscape for various TCR-MHC's, offering key insights into T cell specificity. Our approach provides a platform for immunogenic peptide and neoantigen design, as well as for evaluating TCR specificity, offering a computational framework to inform design of engineered T cell therapies and vaccines.},
}

*Receptors, Antigen, T-Cell/immunology/metabolism/chemistry
*Peptides/immunology/chemistry
Humans
Machine Learning
T-Lymphocytes/immunology
Major Histocompatibility Complex
Histocompatibility Antigens Class I/immunology
Protein Binding

@article {pmid41099706,
year = {2025},
author = {Hu, C and Popchock, AR and Latino, AA and Asbury, CL and Biggins, S},
title = {Direct observation of interdependent and hierarchical kinetochore assembly on individual centromeres.},
journal = {Nucleic acids research},
volume = {53},
number = {19},
pages = {},
pmid = {41099706},
issn = {1362-4962},
support = {P30 CA015704/CA/NCI/HH/HHS/United States ; R35 GM149357/GM/NIGMS/NH/NIH HHS/United States ; F32GM136010/NH/NIH HHS/United States ; //Jane Coffin Childs Memorial Fund/ ; /HHMI/Howard Hughes Medical Institute/United States ; },
mesh = {*Kinetochores/metabolism ; *Saccharomyces cerevisiae Proteins/metabolism/genetics ; *Centromere/metabolism/genetics ; Saccharomyces cerevisiae/genetics/metabolism ; DNA-Binding Proteins/metabolism/genetics ; Chromosomal Proteins, Non-Histone/metabolism/genetics ; Microtubules/metabolism ; Protein Binding ; Cell Cycle Proteins ; },
abstract = {Kinetochores are megadalton protein machines that harness microtubules to segregate chromosomes during cell division. The kinetochores must assemble after DNA replication during every cell cycle onto specialized regions of chromosomes called centromeres, but the order and regulation of their assembly remains unclear due to the complexity of kinetochore composition and the difficulty resolving individual kinetochores in vivo. Here, by adapting a prior single-molecule method for monitoring kinetochore assembly in budding yeast lysates, we identify a sequential order of assembly and uncover previously unknown interdependencies between subcomplexes. We show that inner kinetochore assembly depends partly on outer kinetochore components, and that outer kinetochore branches do not assemble independently of one another. Notably, Mif2 assembly is a rate-limiting step that can be accelerated by binding to the Mtw1 subcomplex, thereby promoting rapid assembly of many inner and outer kinetochore components. The importance of controlling kinetochore assembly kinetics is supported by a Mif2 mutant lacking both autoinhibition and Mtw1 subcomplex binding activity, which leads to defective kinetochore-microtubule attachments when the centromeric histone variant Cse4 is overexpressed. Altogether, our work provides a direct view of kinetochore assembly and reveals highly interdependent regulatory events that control its order and timing.},
}

*Kinetochores/metabolism
*Saccharomyces cerevisiae Proteins/metabolism/genetics
*Centromere/metabolism/genetics
Saccharomyces cerevisiae/genetics/metabolism
DNA-Binding Proteins/metabolism/genetics
Chromosomal Proteins, Non-Histone/metabolism/genetics
Microtubules/metabolism
Protein Binding
Cell Cycle Proteins

@article {pmid41099265,
year = {2025},
author = {McKenney, JK and Brooks, JD and Nguyen, JK and Ding, CKC and Newcomb, LF and Myles, JL and Alaghehbandan, R and Przybycin, CG and Chan, E and Simko, JP and Greenland, NY and Schwen, Z and Weight, CJ and Cooperberg, MR and Carroll, PR},
title = {In reply to: 'Prostate cancer with favorable histology is not synonymous with prostate cancer indolence'.},
journal = {Histopathology},
volume = {},
number = {},
pages = {},
doi = {10.1111/his.70023},
pmid = {41099265},
issn = {1365-2559},
}

@article {pmid41098153,
year = {2025},
author = {Ikoma-Colturato, MRV and Magalhães Furtado, F and Bertolucci, CM and Severino, AR and Souto, EX and Ferreira Dos Santos, TC and Dametto, APF and Beltrame, MP and Bacal, NS and Avelar, DMV and Fernandes, RA and Gomes, BE and da Costa, ES and Santos, BEFDS and Mendonça de Pontes, R and Périco, MDH and Gevert, F and de Siqueira, PFR and Marquezotti, F and Wagner, AOM and Soares, ACCV and Duarte, FB and Flowers, ME and Vigorito, AC},
title = {Standardization of Measurable Residual Disease in Acute Myeloid Leukemia by Flow Cytometry: A Multicenter Study.},
journal = {EJHaem},
volume = {6},
number = {5},
pages = {e70163},
pmid = {41098153},
issn = {2688-6146},
abstract = {INTRODUCTION: Measurable residual disease (MRD) is a strong predictor of the risk of relapse of acute myeloid leukemia (AML). Therefore, for use in clinical decision-making, methods for MRD assessment must achieve adequate accuracy, sensitivity, specificity, and reproducibility. Multiparametric flow cytometry (MFC) is the most widely used method for assessing AML-MRD, but its sensitivity varies considerably due to the differing approaches used across centers, in addition to the different experiences of flow cytometrists, especially during clonal evolution. This study aimed to standardize AML-MRD by MFC in a multicenter project involving 16 Brazilian laboratories.

METHODS: In the first phase, specialists were trained in pre-analytical standard operating procedures (SOPs) and analysis strategies of pre-validated 8- and 10-color protocols, followed by a data-only, that is, a Dry Phase of flow cytometry standard (FCS) file exchange by the coordinating laboratory in a comparability assessment. In the second or Wet Phase, laboratories prepared and analyzed their samples, and the FCS files were submitted for central analysis.

RESULTS: The agreement of MRD results was 81% and 80% between laboratories and central analysts in the Dry and Wet Phases, respectively. However, non-suitable application of pre-analytical SOPs hampered MRD interpretation for 30% of the laboratories in the Wet Phase.

CONCLUSIONS: This study demonstrated that standardized flow cytometry protocols are reproducible as long as rigorous SOPs are implemented. The project's results underscore that continuous education and external quality control are essential to build expertise and ensure reliable AML-MRD results in clinical practice. Trial Registration:The authors have confirmed clinical trial registration is not needed for this submission.},
}

@article {pmid41096533,
year = {2025},
author = {Munarriz, D and López-Godino, O and Martinez-Cibrian, N and Albiol, N and Brillembourg, H and Navarro-Velázquez, S and Español-Rego, M and Casanueva, S and García-Tomás, L and Muñoz-Sanchez, G and Alserawan, L and Benitez-Ribas, D and Magnano, L and Correa, JG and Rivero, A and Mozas, P and Gine, E and Rodríguez-Lobato, LG and Martínez-Roca, A and Montoro-Lorite, M and Ayora, P and Esteve, J and Frutos, L and Balagué-Ponz, O and Urbano-Ispizua, A and González-Navarro, EA and Juan, M and Delgado, J and Ortiz-Maldonado, V},
title = {Combining CAR T-Cell Therapy and Nivolumab to Overcome Immune Resistance in THRLBCL: A Case Report.},
journal = {International journal of molecular sciences},
volume = {26},
number = {19},
pages = {},
pmid = {41096533},
issn = {1422-0067},
mesh = {Humans ; Female ; Adult ; *Nivolumab/therapeutic use ; *Lymphoma, Large B-Cell, Diffuse/therapy/immunology/pathology ; *Immunotherapy, Adoptive/methods ; *Antineoplastic Agents, Immunological/therapeutic use ; Antigens, CD19/immunology ; B7-H1 Antigen/metabolism ; Combined Modality Therapy ; Drug Resistance, Neoplasm ; Tumor Microenvironment ; },
abstract = {T-cell/histiocyte-rich large B-cell lymphoma (THRLBCL) is a rare, aggressive subtype of diffuse large B-cell lymphoma characterized by a profoundly immunosuppressive tumor microenvironment. PD-L1 overexpression by tumor cells is a recognized immune escape mechanism and may underlie resistance to cellular therapies, including CAR T-cell therapy. We report a case of a 29-year-old woman with refractory stage IV-B THRLBCL treated with anti-CD19 CAR T-cell therapy (varnimcabtagene autoleucel), who achieved an initial response (day +28) but experienced disease progression by day +100 despite robust CAR T-cell expansion. Peripheral blood analysis revealed persistent absolute B-cell aplasia, while bone marrow biopsy confirmed CD19-positive disease. Comparative immunohistochemistry demonstrated markedly increased PD-L1 expression in post-CAR T-cell samples, suggesting adaptive immune resistance via PD-1/PD-L1-mediated CAR T-cell inhibition. Nivolumab was initiated at month +4 to overcome this checkpoint-mediated resistance. Notably, a complete metabolic response was documented on PET/CT after four doses of nivolumab (month +6). The patient remains in sustained remission, with persistent B-cell aplasia, four years post-intervention. This case provides clinical and pathological evidence supporting the use of immune checkpoint blockade to rescue CAR T-cell efficacy, highlighting the potential of this synergistic approach in THRLBCL and possibly other B-cell malignancies exhibiting similar immune evasion.},
}

Humans
Female
Adult
*Nivolumab/therapeutic use
*Lymphoma, Large B-Cell, Diffuse/therapy/immunology/pathology
*Immunotherapy, Adoptive/methods
*Antineoplastic Agents, Immunological/therapeutic use
Antigens, CD19/immunology
B7-H1 Antigen/metabolism
Combined Modality Therapy
Drug Resistance, Neoplasm
Tumor Microenvironment

@article {pmid41093689,
year = {2025},
author = {Goetz, MP and Toi, M and Huober, J and Sohn, J and Trédan, O and Park, IH and Campone, M and Chen, SC and Manso, LM and Paluch-Shimon, S and Freedman, OC and O'Shaughnessy, J and Pivot, X and Tolaney, SM and Hurvitz, SA and Llombart-Cussac, A and André, V and Saha, A and van Hal, G and Shahir, A and Iwata, H and Johnston, SRD},
title = {Corrigendum to "Abemaciclib plus a nonsteroidal aromatase inhibitor as initial therapy for HR+, HER2- advanced breast cancer: final overall survival results of MONARCH 3": [Ann Oncol 2024; 35: 718-727].},
journal = {Annals of oncology : official journal of the European Society for Medical Oncology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.annonc.2025.07.002},
pmid = {41093689},
issn = {1569-8041},
}

@article {pmid41092928,
year = {2025},
author = {, },
title = {Global burden of 292 causes of death in 204 countries and territories and 660 subnational locations, 1990-2023: a systematic analysis for the Global Burden of Disease Study 2023.},
journal = {Lancet (London, England)},
volume = {},
number = {},
pages = {},
doi = {10.1016/S0140-6736(25)01917-8},
pmid = {41092928},
issn = {1474-547X},
abstract = {BACKGROUND: Timely and comprehensive analyses of causes of death stratified by age, sex, and location are essential for shaping effective health policies aimed at reducing global mortality. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2023 provides cause-specific mortality estimates measured in counts, rates, and years of life lost (YLLs). GBD 2023 aimed to enhance our understanding of the relationship between age and cause of death by quantifying the probability of dying before age 70 years (70q0) and the mean age at death by cause and sex. This study enables comparisons of the impact of causes of death over time, offering a deeper understanding of how these causes affect global populations.

METHODS: GBD 2023 produced estimates for 292 causes of death disaggregated by age-sex-location-year in 204 countries and territories and 660 subnational locations for each year from 1990 until 2023. We used a modelling tool developed for GBD, the Cause of Death Ensemble model (CODEm), to estimate cause-specific death rates for most causes. We computed YLLs as the product of the number of deaths for each cause-age-sex-location-year and the standard life expectancy at each age. Probability of death was calculated as the chance of dying from a given cause in a specific age period, for a specific population. Mean age at death was calculated by first assigning the midpoint age of each age group for every death, followed by computing the mean of all midpoint ages across all deaths attributed to a given cause. We used GBD death estimates to calculate the observed mean age at death and to model the expected mean age across causes, sexes, years, and locations. The expected mean age reflects the expected mean age at death for individuals within a population, based on global mortality rates and the population's age structure. Comparatively, the observed mean age represents the actual mean age at death, influenced by all factors unique to a location-specific population, including its age structure. As part of the modelling process, uncertainty intervals (UIs) were generated using the 2·5th and 97·5th percentiles from a 250-draw distribution for each metric. Findings are reported as counts and age-standardised rates. Methodological improvements for cause-of-death estimates in GBD 2023 include a correction for the misclassification of deaths due to COVID-19, updates to the method used to estimate COVID-19, and updates to the CODEm modelling framework. This analysis used 55 761 data sources, including vital registration and verbal autopsy data as well as data from surveys, censuses, surveillance systems, and cancer registries, among others. For GBD 2023, there were 312 new country-years of vital registration cause-of-death data, 3 country-years of surveillance data, 51 country-years of verbal autopsy data, and 144 country-years of other data types that were added to those used in previous GBD rounds.

FINDINGS: The initial years of the COVID-19 pandemic caused shifts in long-standing rankings of the leading causes of global deaths: it ranked as the number one age-standardised cause of death at Level 3 of the GBD cause classification hierarchy in 2021. By 2023, COVID-19 dropped to the 20th place among the leading global causes, returning the rankings of the leading two causes to those typical across the time series (ie, ischaemic heart disease and stroke). While ischaemic heart disease and stroke persist as leading causes of death, there has been progress in reducing their age-standardised mortality rates globally. Four other leading causes have also shown large declines in global age-standardised mortality rates across the study period: diarrhoeal diseases, tuberculosis, stomach cancer, and measles. Other causes of death showed disparate patterns between sexes, notably for deaths from conflict and terrorism in some locations. A large reduction in age-standardised rates of YLLs occurred for neonatal disorders. Despite this, neonatal disorders remained the leading cause of global YLLs over the period studied, except in 2021, when COVID-19 was temporarily the leading cause. Compared to 1990, there has been a considerable reduction in total YLLs in many vaccine-preventable diseases, most notably diphtheria, pertussis, tetanus, and measles. In addition, this study quantified the mean age at death for all-cause mortality and cause-specific mortality and found noticeable variation by sex and location. The global all-cause mean age at death increased from 46·8 years (95% UI 46·6-47·0) in 1990 to 63·4 years (63·1-63·7) in 2023. For males, mean age increased from 45·4 years (45·1-45·7) to 61·2 years (60·7-61·6), and for females it increased from 48·5 years (48·1-48·8) to 65·9 years (65·5-66·3), from 1990 to 2023. The highest all-cause mean age at death in 2023 was found in the high-income super-region, where the mean age for females reached 80·9 years (80·9-81·0) and for males 74·8 years (74·8-74·9). By comparison, the lowest all-cause mean age at death occurred in sub-Saharan Africa, where it was 38·0 years (37·5-38·4) for females and 35·6 years (35·2-35·9) for males in 2023. Lastly, our study found that all-cause 70q0 decreased across each GBD super-region and region from 2000 to 2023, although with large variability between them. For females, we found that 70q0 notably increased from drug use disorders and conflict and terrorism. Leading causes that increased 70q0 for males also included drug use disorders, as well as diabetes. In sub-Saharan Africa, there was an increase in 70q0 for many non-communicable diseases (NCDs). Additionally, the mean age at death from NCDs was lower than the expected mean age at death for this super-region. By comparison, there was an increase in 70q0 for drug use disorders in the high-income super-region, which also had an observed mean age at death lower than the expected value.

INTERPRETATION: We examined global mortality patterns over the past three decades, highlighting-with enhanced estimation methods-the impacts of major events such as the COVID-19 pandemic, in addition to broader trends such as increasing NCDs in low-income regions that reflect ongoing shifts in the global epidemiological transition. This study also delves into premature mortality patterns, exploring the interplay between age and causes of death and deepening our understanding of where targeted resources could be applied to further reduce preventable sources of mortality. We provide essential insights into global and regional health disparities, identifying locations in need of targeted interventions to address both communicable and non-communicable diseases. There is an ever-present need for strengthened health-care systems that are resilient to future pandemics and the shifting burden of disease, particularly among ageing populations in regions with high mortality rates. Robust estimates of causes of death are increasingly essential to inform health priorities and guide efforts toward achieving global health equity. The need for global collaboration to reduce preventable mortality is more important than ever, as shifting burdens of disease are affecting all nations, albeit at different paces and scales.

FUNDING: Gates Foundation.},
}

@article {pmid41091803,
year = {2025},
author = {Wiley, HS and Lopez, CF and Rodin, AS and Rockne, RC and Yankeelov, TE and Sauro, HM and Hassan, G and Prabhakaran, S and Demir, E and Hu, M and Fuxman Bass, J and Luddy, KA and Newman, H and Mochel, JP and Costello, JC and Xing, J and Afify, SM and Acar, A and Hayden Gephart, M and Feng, S and Banks, O and Banerjee, J and Clayton, A and Hill, DE and Sweis, RF and Umeh-Garcia, MC and Su, Y and Meyer, AS},
title = {A Roadmap for the Future of Systems Biology in Cancer Research.},
journal = {Cancer research},
volume = {},
number = {},
pages = {},
doi = {10.1158/0008-5472.CAN-25-0700},
pmid = {41091803},
issn = {1538-7445},
abstract = {Cancer systems biology seeks to understand how cancer arises as a system of interconnected molecules, cells, and tissues, with the goal of understanding, predicting, and controlling the disease. In the last decade, the field has rapidly grown as advances in experimental, computational, and analytical technologies have improved our ability to capture and recapitulate the complexities of cancer at multiple scales. However, the field's promise to understand how specific molecular changes give rise to altered cancer outcomes remains incompletely fulfilled. Fortunately, an opportunity exists to accelerate progress by better coordinating modeling and data-gathering efforts across the cancer systems biology community. This will create the foundation for building accurate, multiscale cancer models that can better predict and identify improved therapeutic interventions. Here, we outline some of the current challenges in cancer systems biology research, how they can be addressed, and actions that the community can take to accelerate progress in the field.},
}

@article {pmid41088800,
year = {2025},
author = {Fuhrman, J and Yun, J and Indorf, A},
title = {Practical considerations and emerging approaches for the management of vasomotor and sexual symptoms in breast cancer patients on endocrine therapies.},
journal = {Expert review of clinical pharmacology},
volume = {},
number = {},
pages = {},
doi = {10.1080/17512433.2025.2573780},
pmid = {41088800},
issn = {1751-2441},
abstract = {INTRODUCTION: Vasomotor symptoms (VMS) and decreased libido are common menopausal symptoms. Patients with breast cancer receiving endocrine therapy experience new or worsening menopausal symptoms. Pharmacologic therapy for VMS has been centered on selective serotonin reuptake inhibitors and serotonin norepinephrine reuptake inhibitors, gabapentin, and clonidine. These therapeutic options fall short in obtaining adequate symptom relief, illustrating a therapeutic gap in efficacious treatment modalities. There are no historical systemic treatment options for low libido.

AREAS COVERED: This review summarizes the current pharmacologic therapy for VMS, focusing on the practical considerations for use of the novel VMS (fezolinetant, elinzanetant) and libido agents (flibanserin, bremelanotide). Literature search was completed with PUBMED, Cochrane Library, and Web of Science. Fezolinetant is a novel neurokinin 3 receptor antagonist that has demonstrated clinical benefit in patients without a history of breast cancer. For libido management, flibanserin and bremelanotide act as serotonin/dopaminergic modulators and melanocortin receptor agonists, respectively.

EXPERT OPINION: These novel agents are eagerly awaited therapeutic options; however, clinical trials excluded breast cancer patients. This review provides clinicians with relevant considerations to assess when recommending these therapies for patients with breast cancer, while awaiting ongoing research to give additional insights for best tailoring therapy for this patient population.},
}

@article {pmid41087806,
year = {2025},
author = {Yi, JC and Lee, E and Duggan, C and Baker, KS and Blythe, N and Cole, AM and Cushing-Haugen, KL and Gutierrez, AI and Linden, H and Mendoza, JA and Ohlsen, TJD and Ortblad, KF and Schwartz, SM and Yung, R and Ceballos, R and Chow, EJ},
title = {Perspective of Hispanic Cancer Survivors on Survivorship Care Plans: A Qualitative Study.},
journal = {Journal of immigrant and minority health},
volume = {},
number = {},
pages = {},
pmid = {41087806},
issn = {1557-1920},
support = {75N91020C00005/NH/NIH HHS/United States ; HHSN261201800004I/NH/NIH HHS/United States ; R21 CA258105/NH/NIH HHS/United States ; R21 CA258105/NH/NIH HHS/United States ; },
abstract = {Explore Hispanic cancer survivors' thoughts about survivorship care plans (SCPs), lay health educator (LHE)-delivered survivorship information, and general survivorship care among Hispanic cancer survivors. A subset of N = 95 participants (≥ 18 years) enrolled in a randomized controlled trial (RCT; March 2023 to August 2023) assessing the feasibility of LHE-delivered survivorship information completed phone-based interviews in which semi-structured guides probed their views on SCPs, the LHE call, and survivorship more broadly. Twenty participants (21% of the total enrolled) completed interviews (11 in English, 9 in Spanish). Most participants were female (70%), half were born in the United States (50%), and the majority had breast cancer (55%); the remaining had colorectal (5%), lymphoma (15%), and prostate cancers (25%). The average time since cancer diagnosis was 3.1 years (SD 1.8). Participants reported few issues transitioning from oncology to primary care and perceived that this transition was supported by easily accessible medical records that also help delineate the care responsibilities of different providers. Most participants thought the SCPs were easy to understand and helped them manage their survivorship care with confidence. They also found information on nutrition and physical activity helpful. Participants liked the LHE call but did not necessarily think it assisted with care coordination. Hispanic cancer survivors reported that the SCPs were helpful and easy to understand but that benefits of a survivorship-focused LHE session were less clear. Additional research may help to determine how best to utilize SCPs and LHEs for these survivors and their providers. Clinical Trials Registration: clinicaltrials.gov NCT04081779.},
}

@article {pmid41087744,
year = {2025},
author = {Abu-Shmais, AA and Freeman, G and Creanga, A and Vukovich, MJ and Malla, T and Mantus, GE and Shimberg, GD and Gillespie, RA and Guerra Canedo, V and Dadonaite, B and Rodgers, MD and Chopde, AJ and Bardwil-Lugones, E and Bylund, T and Henry, AR and Roberts-Torres, J and Johnston, TS and Smith, S and Yang, ES and Cheng, C and Walker, EL and Ravichandran, M and Gordon, IJ and Dittakavi, TS and Reed, DS and Pierson, TC and Dropulic, L and Bloom, JD and Tsybovsky, Y and Boritz, EA and Douek, DC and Zhou, T and Kanekiyo, M and Andrews, SF},
title = {Cross-neutralizing and potent human monoclonal antibodies against historical and emerging H5Nx influenza viruses.},
journal = {Nature microbiology},
volume = {},
number = {},
pages = {},
pmid = {41087744},
issn = {2058-5276},
support = {R01 AI141707/AI/NIAID NIH HHS/United States ; 75N93021C00015/AI/NIAID NIH HHS/United States ; UC7AI180311//U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (NIAID)/ ; UC7AI180311//U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (NIAID)/ ; R01 AI141707/AI/NIAID NIH HHS/United States ; 75N93021C00015/AI/NIAID NIH HHS/United States ; },
abstract = {Highly pathogenic avian influenza H5Nx viruses are an emerging threat for global health, especially clade 2.3.4.4b H5N1 virus which causes panzootic infections. Here we describe the isolation and characterization of broadly cross-neutralizing monoclonal antibodies (mAbs) against diverse H5Nx viruses from individuals who received a monovalent H5N1 vaccine 15 years ago. By screening over 500 mAbs, we identified 5 mAbs that neutralized the majority of H5 clades including 2.3.4.4b and target three distinct conserved epitopes within the HA globular head. Cryo-electron microscopy structures of these mAbs in complex with HA, deep mutational scanning and neutralization escape studies define the sites of vulnerability of H5 HA. These mAbs mediated stronger prophylactic protection against clade 2.3.4.4b H5N1 infection in mice than the best-in-class mAb targeting the HA stem. Our study identified several highly potent broadly neutralizing H5 mAbs from humans that either alone or in combination provide a pragmatic pandemic preparedness option against the threat of panzootic H5N1 influenza.},
}

@article {pmid41087376,
year = {2025},
author = {Edge, R and Matthews, S and Ahani, B and Aksyuk, AA and Clegg, L and Perez, JL and Esser, MT and Chang, LJ and Hirsch, I and Villafana, T and Pura, J and Stepanov, O and Streicher, K and White, T and Cohen, TS and Follmann, D and Gilbert, PB and Seegobin, S},
title = {A SARS-CoV-2 variant‑adjusted threshold of protection model for monoclonal antibody pre-exposure prophylaxis against COVID-19.},
journal = {Nature communications},
volume = {16},
number = {1},
pages = {9101},
pmid = {41087376},
issn = {2041-1723},
support = {Not applicable//AstraZeneca/ ; },
mesh = {Humans ; *COVID-19/prevention & control/immunology/virology ; *SARS-CoV-2/immunology/genetics/drug effects ; *Pre-Exposure Prophylaxis/methods ; *Antibodies, Monoclonal/immunology/therapeutic use/administration & dosage ; *Antibodies, Viral/immunology/blood ; Antibodies, Neutralizing/immunology/blood ; COVID-19 Drug Treatment ; Female ; Male ; Middle Aged ; Proportional Hazards Models ; Antibodies, Monoclonal, Humanized ; },
abstract = {Clinical development of monoclonal antibodies (mAbs) against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is challenging due to rapid changes in the variant landscape. This study identified a threshold model for neutralising antibody (nAb) titres associated with clinically relevant protection against symptomatic COVID-19 for vulnerable populations. Using efficacy data from the phase 3 PROVENT pre-exposure prophylaxis trial of tixagevimab-cilgavimab (NCT04625725), individual nAb ID50 titres were predicted by dividing serum mAb concentration by prevalence-adjusted tixagevimab-cilgavimab potency (from in vitro IC50 values combined with viral surveillance data) and related to efficacy with a Cox model. The Threshold of Protection (ToP) Cox model was externally validated using data from the phase 3 SUPERNOVA trial (NCT05648110), which assessed sipavibart efficacy against symptomatic COVID-19 in immunocompromised participants. The PROVENT ToP model estimated the variant-specific observed efficacies from SUPERNOVA for 3 and 6 months post any dose with Lin's concordance of 0.86 and 0.75, respectively. This approach integrates predicted nAb ID50 titres against multiple SARS-CoV-2 variants into a ToP model that can be applied across different variants and could serve as a surrogate endpoint in immunobridging studies to expedite clinical evaluation and regulatory approval for mAbs targeting SARS-CoV-2.},
}

Humans
*COVID-19/prevention & control/immunology/virology
*SARS-CoV-2/immunology/genetics/drug effects
*Pre-Exposure Prophylaxis/methods
*Antibodies, Monoclonal/immunology/therapeutic use/administration & dosage
*Antibodies, Viral/immunology/blood
Antibodies, Neutralizing/immunology/blood
COVID-19 Drug Treatment
Female
Male
Middle Aged
Proportional Hazards Models
Antibodies, Monoclonal, Humanized

@article {pmid40763278,
year = {2025},
author = {Simonin, M and Boissel, N and Petit, A and Mullighan, CG and Hunger, SP and Loh, ML and Winter, SS and Macintyre, E and Teachey, DT and Baruchel, A and Asnafi, V},
title = {Prognostic impact of the PredicT-ALL classifier in the AALL0434 trial: a model combining NGS, MRD, and WBC at diagnosis.},
journal = {Blood advances},
volume = {9},
number = {20},
pages = {5323-5326},
doi = {10.1182/bloodadvances.2025017399},
pmid = {40763278},
issn = {2473-9537},
}

@article {pmid41085624,
year = {2026},
author = {Finton, KAK and Foote-McNabb, UN and Wilcox, EC and Jones, LA and Gafken, PR and Strong, RK},
title = {Artemis: Mass Spectrometry-Based Identification of MHC-Presented Peptides Across Alleles, Classes, and Species Using Soluble Single-Chain MHC Constructs.},
journal = {Methods in molecular biology (Clifton, N.J.)},
volume = {2980},
number = {},
pages = {231-250},
pmid = {41085624},
issn = {1940-6029},
mesh = {Humans ; *Peptides/immunology/genetics ; Alleles ; *Mass Spectrometry/methods ; *Antigen Presentation/immunology ; Animals ; *Major Histocompatibility Complex ; },
abstract = {The current "gold standard" for the identification of MHC-restricted peptides is conventional immunoprecipitation/mass spectrometry (MS); however, this approach requires a relatively large amount of sample, complex purification procedures, and computational analyses to assign peptides to individual alleles. Here, we provide instructions for the expression, purification, and MS identification of MHC-presented peptides of human and non-human, classical and non-classical, class I and class II proteins using a readily expressible, soluble, and easily purifiable single-chain dimer construct. This procedure enables the identification of up to tens of thousands of allele-specific peptides per run for peptidomics, ligandomics, therapeutic targeting, and motif analyses. Also included are instructions for construct design, streamlined lentiviral transfection and transduction, and computational methods for high-throughput processing of MS results, yielding high confidence peptide lists, motifs, and multiple analytics.},
}

Humans
*Peptides/immunology/genetics
Alleles
*Mass Spectrometry/methods
*Antigen Presentation/immunology
Animals
*Major Histocompatibility Complex

@article {pmid41085561,
year = {2025},
author = {Fryer, E and Bishop, DT and Campbell, PT and Chan, AT and Le Marchand, L and Li, CI and Moreno, V and Gunter, MJ and Phipps, AI and Grant, RC and Schmit, SL and Martin, RM and Yarmolinsky, J and Haycock, P},
title = {Investigating the causal effect of potential therapeutic agents for colorectal cancer prevention: a Mendelian randomization analysis.},
journal = {Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology},
volume = {},
number = {},
pages = {},
doi = {10.1158/1055-9965.EPI-25-0875},
pmid = {41085561},
issn = {1538-7755},
abstract = {BACKGROUND: Conventional observational studies have identified several potential therapeutic agents that may lower risk of colorectal cancer development. However, these studies are susceptible to unmeasured and residual confounding and reverse causation, undermining robust causal inference.

METHODS: We used Mendelian randomization (MR), a genetic epidemiological method that can strengthen causal inference, to evaluate the effect of previously reported therapeutic agents on colorectal cancer risk, including medications, dietary micronutrients, and exogenous hormones. Genetic instruments were constructed using genome-wide association studies (GWASs) of molecular traits (e.g. circulating levels of protein drug targets, blood-based biomarkers of micronutrients, circulating levels of endogenous hormones). Using summary statistics from these GWASs and a colorectal cancer risk GWAS (cases=78,473, controls=107,143), we employed Wald ratios and inverse-variance weighted models to estimate causal effects.

RESULTS: We found evidence for associations of genetically-proxied elevated omega-3 fatty acids (OR 1.10; 95% CI 1.03, 1.18; p=6.20x10-3) and reduced plasma ACE levels (OR 1.08; 95% CI 1.03, 1.13; p=9.36x10-4) with colorectal cancer risk. Findings for ACE inhibition were consistent across sensitivity analyses.

CONCLUSIONS: Reduced plasma ACE levels were robustly linked to increased colorectal cancer risk. Further work is required to better understand the mechanism behind this finding and whether this translates to adverse effects via medication use (i.e. ACE inhibitors).

IMPACT: These findings provide updated evidence on the role of previously reported therapeutic agents in colorectal cancer risk, helping to prioritise further evaluation of those agents with potential aetiological roles in cancer development.},
}

@article {pmid41084890,
year = {2025},
author = {Fitzgerald, L and Ghosh, S and Bokun, A and Lax, A and Mu, F and Wu, E and Lin, Y and Shi, L and Qureshi, ZP and Graf, SA},
title = {Healthcare cost comparison between first-line ibrutinib and acalabrutinib in chronic lymphocytic leukemia patients in the Veterans Affairs.},
journal = {Journal of comparative effectiveness research},
volume = {},
number = {},
pages = {e250084},
doi = {10.57264/cer-2025-0084},
pmid = {41084890},
issn = {2042-6313},
abstract = {Aim: Bruton's tyrosine kinase inhibitors (BTKis), including ibrutinib and acalabrutinib, transformed the treatment landscape of chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) by improving outcomes compared with chemoimmunotherapy. Real-world economic comparisons between BTKis are needed in diverse populations. This study aimed to compare healthcare costs in the Veterans Health Administration (VHA) among patients with CLL/SLL treated with, and remaining persistent on, first-line (1L) ibrutinib versus acalabrutinib monotherapy for 12 months. Materials & methods: This retrospective study used VHA electronic medical record data from January 2006 to July 2024. Eligible patients initiated 1L ibrutinib or acalabrutinib monotherapy on or after November 2019 and remained on continuous treatment for ≥12 months. All-cause and CLL/SLL-related costs were assessed over 12 months of follow-up. Generalized linear models were used to estimate adjusted costs and compare differences between treatment cohorts. Results: A total of 1059 patients were included (ibrutinib: n = 732; acalabrutinib: n = 327). During the 12-month follow-up of continuous 1L treatment, the annual adjusted all-cause total healthcare cost difference between ibrutinib and acalabrutinib was -$2422 (p = 0.46) (adjusted medical cost difference: $5259, p = 0.03; adjusted pharmacy cost difference: -$5886, p = 0.02). The annual adjusted CLL/SLL-related total healthcare cost difference between ibrutinib and acalabrutinib was -$3793 (p = 0.15) (adjusted medical cost difference: $2085, p = 0.05; adjusted pharmacy cost difference: -$5860, p = 0.02). Conclusion: Among VHA patients with CLL/SLL who initiated and remained on treatment with 1L BTKi monotherapy for 12 months, annual all-cause and CLL/SLL-related total healthcare costs were similar between ibrutinib and acalabrutinib. Pharmacy costs were lower for ibrutinib, while medical costs were lower for acalabrutinib, resulting in overall comparable total costs.},
}

@article {pmid41084727,
year = {2025},
author = {Özcan, M and Cassaday, RD and Zarzycka, E and Vandendries, E and Zhang, F and Chen, Y and Nieto, A and Demirkan, F and Montesinos, P and Altuntas, F},
title = {Comparing two different doses of inotuzumab ozogamicin treatment in adult patients with acute lymphoblastic leukemia: a plain language summary of publication.},
journal = {Therapeutic advances in medical oncology},
volume = {17},
number = {},
pages = {17588359251370948},
doi = {10.1177/17588359251370948},
pmid = {41084727},
issn = {1758-8340},
abstract = {What is this summary about? This summary describes the results of a clinical study that compared two different doses of a treatment, called inotuzumab ozogamicin (inotuzumab for short), for acute lymphoblastic leukemia (ALL for short). This summary describes the results for people aged 18 years and older who took part in the study. Why was this study done? People who took part in the study had a higher risk of developing a side effect called sinusoidal obstruction syndrome (SOS for short), also known as veno-occlusive disease (VOD for short), which is a rare condition where some of the small blood vessels in the liver become blocked. Researchers wanted to find out if receiving a lower dose than the recommended dose of inotuzumab reduced the likelihood of people developing SOS after a stem cell transplant. Researchers wanted to find out if a lower dose of inotuzumab would also impact the efficacy (how well inotuzumab works to treat ALL) in people with ALL and what other side effects occurred.},
}

@article {pmid41083679,
year = {2025},
author = {Salit, RB and Hexner, EO and Gagelmann, N and Kröger, N and McLornan, DP and Jain, T and Gupta, V and Hobbs, GS and Tamari, R and Robin, M and Scott, B and Saber, W},
title = {Defining remission following hematopoietic cell transplant for myelofibrosis: an international expert panel consensus.},
journal = {Leukemia},
volume = {},
number = {},
pages = {},
pmid = {41083679},
issn = {1476-5551},
}

@article {pmid41082548,
year = {2025},
author = {Matsuno, A and Tollefson, D and Cover, J and Obong'o, C and Gamba, H and Chen, YQ and Duerr, A},
title = {What drives adolescent girls and young women's decisions to persist on PrEP? Results of a comparative qualitative study from a DREAMS program in western Kenya.},
journal = {AIDS care},
volume = {},
number = {},
pages = {1-11},
doi = {10.1080/09540121.2025.2570098},
pmid = {41082548},
issn = {1360-0451},
abstract = {Oral pre-exposure prophylaxis (PrEP) is a valuable tool to help end HIV, but persistent PrEP use is low amongst adolescent girls and young women (AGYW) in sub-Saharan Africa (SSA), who are at high risk for HIV. To improve persistent PrEP use in AGYW, more research is needed to understand what drives their decisions to continue with PrEP. We conducted a thematic, comparative qualitative analysis of in-depth interviews with 32 AGYW who participated in PEPFAR's DREAMS program in western Kenya: 16 were randomly sampled among those who persisted with PrEP and 16 among those who discontinued. We compared results between these groups to explore drivers for the decision to persist with PrEP. We interpreted findings using the Integrated Behavior Model, which posits that the decision to persist is influenced by attitudes, social norms and personal agency. Three themes emerged that illuminated AGYW's decision to persist with PrEP. First, having positive attitudes towards PrEP was insufficient to ensure persistence in absence of correct knowledge. All AGYW were positive about PrEP, but those who discontinued often had insufficient/misinformation about PrEP, specifically on its appropriate use during pregnancy/breastfeeding. Second, support from family and friends was critical to overcome societal stigma and could counter lack of support from romantic partners. Third, strong mentors supported PrEP persistence by increasing self-agency, but this was secondary in importance to the need for robust knowledge and social support. To improve PrEP persistence amongst AGYW in SSA, PrEP programs may benefit from increasing education delivered to AGYWs and their communities, specifically family and friends. In particular, messages that PrEP may be used when pregnant/breastfeeding should be reinforced. Other health programs for AGYWs may also benefit from an increased focus on educational messaging to program recipients and people in their existing social networks.},
}

@article {pmid41081510,
year = {2025},
author = {Dadonaite, B and Harari, S and Larsen, BB and Kampman, L and Harteloo, A and Elias-Warren, A and Chu, HY and Bloom, JD},
title = {Spike mutations that affect the function and antigenicity of recent KP.3.1.1-like SARS-CoV-2 variants.},
journal = {Journal of virology},
volume = {},
number = {},
pages = {e0142325},
doi = {10.1128/jvi.01423-25},
pmid = {41081510},
issn = {1098-5514},
abstract = {SARS-CoV-2 is under strong evolutionary selection to acquire mutations in its spike protein that reduce neutralization by human polyclonal antibodies. Here, we use pseudovirus-based deep mutational scanning to measure how mutations to the spike from the recent KP.3.1.1 SARS-CoV-2 strain affect cell entry, binding to the ACE2 receptor, RBD up/down motion, and neutralization by human sera and clinically relevant antibodies. The spike mutations that most affect serum antibody neutralization sometimes differ between sera collected before versus after recent vaccination or infection, indicating that these exposures shift the neutralization immunodominance hierarchy. The sites where mutations cause the greatest reduction in neutralization by post-vaccination or infection sera include receptor-binding domain (RBD) sites 475, 478, and 487, all of which have mutated in recent SARS-CoV-2 variants. Multiple mutations outside the RBD affect sera neutralization as strongly as any RBD mutations by modulating the RBD up/down movement. Some sites that affect RBD up/down movement have mutated in recent SARS-CoV-2 variants. Finally, we measure how spike mutations affect neutralization by three clinically relevant SARS-CoV-2 antibodies: VYD222, BD55-1205, and SA55. Overall, these results illuminate the current constraints and pressures shaping SARS-CoV-2 evolution and can help with efforts to forecast possible future antigenic changes that may impact vaccines or clinical antibodies.IMPORTANCEThis study measures how mutations to the spike of a SARS-CoV-2 variant that circulated in early 2025 affect its function and recognition by both the polyclonal antibodies produced by the human immune system and monoclonal antibodies used as prophylactics. These measurements are made with a pseudovirus system that enables safe study of viral protein mutations using virions that can only infect cells once. The study identifies mutations that decrease recognition by current human antibody immunity; many of these mutations are increasingly being observed in new viral variants. It also shows the importance of mutations that move the spike's receptor-binding domain up or down. Overall, these results are useful for forecasting viral evolution and assessing which newly emerging variants have reduced recognition by immunity and antibody prophylactics.},
}

@article {pmid41081432,
year = {2025},
author = {Avanessian, SC and van den Bijgaart, RJE and Chew, NW and Supper, VM and Tang, TT and Zhang, Y and Zhao, YQ and Abe, K and Gauthier, J and Barry, KC},
title = {IL-2/IL-15 signaling induces NK cell production of FLT3LG augmenting anti-PD-1 immunotherapy.},
journal = {Cancer immunology research},
volume = {},
number = {},
pages = {},
doi = {10.1158/2326-6066.CIR-24-1259},
pmid = {41081432},
issn = {2326-6074},
abstract = {Natural killer (NK) cells play a critical role in anti-cancer immunity through their direct cytotoxicity and production of cytokines, such as Flt3L. NK cell production of Flt3L controls conventional type I dendritic cell (cDC1) abundance in the tumor and promotes protective immune responses. Here, we show that NK cell production of Flt3l in the tumor is regulated by activation, and that activation by IL-2 and IL-15 uniquely induced Flt3L expression in NK cells. In melanoma, IL-2 signaling in NK cells led to increased Flt3L production, which boosted cDC1 abundance in the tumor and improved anti-PD-1 immunotherapy response. Further, NK cell subsets differentially regulated Flt3L in the tumor, with CD11b-CD27+ NK cells in mouse tumors enriched for IL-2-family signaling and upregulated Flt3l upon activation. Consistently, human CD56brightCD16- NK cells more strongly correlated with cDC1 and FLT3LG expression than other NK cell subsets across multiple human melanoma datasets and cancer indications. This mechanistic study of NK cell regulation of FLT3LG and control of the NK cell-cDC1 axis provides insights and strategies for the development of more effective cancer immunotherapies.},
}

@article {pmid41077138,
year = {2025},
author = {Akaike, T and Thakuria, M and Silk, AW and Hippe, DS and Ch'en, PY and Park, SY and Urman, NM and Chiu, MW and Kim, H and Kim, EY and Hall, ET and Bhatia, S and Reddy, S and Krainock, M and Aleshin, A and Choi, JS and Tsai, K and Yom, SS and Yu, SS and Choi, J and Chandra, S and Nghiem, PT and Zaba, LC},
title = {Circulating tumor DNA level is associated with time to clinical recurrence in Merkel cell carcinoma: Implications for patient management.},
journal = {Journal of the American Academy of Dermatology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jaad.2025.10.032},
pmid = {41077138},
issn = {1097-6787},
abstract = {BACKGROUND: Merkel cell carcinoma (MCC) recurs in 40% of patients. Circulating tumor DNA (ctDNA) is an emerging blood-based biomarker for early MCC recurrence detection.

OBJECTIVE: To evaluate the timing and prognostic significance of ctDNA levels relative to clinical recurrence.

METHODS: This multicenter prospective study analyzed 669 tumor-informed ctDNA tests from 215 MCC patients (stage I-IV) without clinically evident disease after treatment.

RESULTS: Patients with at least one positive ctDNA test were more likely to experience recurrence compared to ctDNA-negative patients (hazard ratio: 18.1, 95% CI: 8.9-36.7), with 77% developing clinically evident disease by one year. The median interval between the first positive ctDNA and clinical recurrence was 2.7 months. Clinical recurrences usually occurred within 3 months for ctDNA levels above 10 molecules/mL, within 6 months for levels between 1-10 molecules/mL, and within 9 months for levels below 1 molecule/mL.

LIMITATIONS: In this real-world study, there was variability in timing and frequency of follow-up examinations, imaging, and ctDNA testing, although most patients were followed with both ctDNA and imaging.

CONCLUSIONS: A positive ctDNA test detects MCC recurrence approximately 3 months earlier than imaging. Negative ctDNA can help reduce imaging frequency through serial ctDNA monitoring, while positive ctDNA warrants closer patient follow-up.},
}

@article {pmid41076992,
year = {2025},
author = {Bouras, E and Yu, R and Kim, AE and Markozannes, G and Murphy, N and Albanes, D and Anderson, LN and Barry, EL and Berndt, SI and Bishop, DT and Brenner, H and Burnett-Hartman, A and Campbell, PT and Carreras-Torres, R and Chan, AT and Cheng, I and Devall, MA and Diez-Obrero, V and Dimou, N and Drew, DA and Gruber, SB and Gsur, A and Hoffmeister, M and Hsu, L and Huyghe, JR and Kawaguchi, E and Keku, TO and Kundaje, A and Küry, S and Le Marchand, L and Lewinger, JP and Li, L and Lynch, BM and Moreno, V and Morrison, JL and Newton, CC and Obón-Santacana, M and Palmer, JR and Papadimitriou, N and Pellatt, AJ and Peoples, AR and Pharoah, PDP and Platz, EA and Qu, C and Ruiz-Narvaez, E and Mendez, JS and Schoen, RE and Stern, MC and Thomas, CE and Tian, Y and Um, CY and Visvanathan, K and Vodicka, P and Vymetalkova, V and White, E and Wolk, A and Woods, MO and Wu, AH and Gunter, MJ and Gauderman, WJ and Peters, U and Evangelou, M and Tsilidis, KK},
title = {Using gene-environment interactions to explore pathways for colorectal cancer risk.},
journal = {EBioMedicine},
volume = {121},
number = {},
pages = {105964},
doi = {10.1016/j.ebiom.2025.105964},
pmid = {41076992},
issn = {2352-3964},
abstract = {BACKGROUND: Colorectal cancer (CRC) is a significant public health concern, highlighting the critical need for identifying novel intervention targets for its prevention.

METHODS: We conducted genome-wide interaction analyses for 15 exposures with established or putative CRC risk [body mass index (BMI), height, physical activity, smoking, type 2 diabetes, use of menopausal hormone therapy, non-steroidal anti-inflammatory drugs, and intake of alcohol, calcium, fibre, folate, fruits, processed meat, red meat, and vegetables], and used interaction estimates to explore pathways and genes underlying CRC risk. The adaptive combination of Bayes Factors (ADABF), and over-representation analysis (ORA) were used for pathway analyses, and findings were further investigated using publicly available resources [hallmarks of cancer, Open Targets Platform (OTP)].

FINDINGS: A total of 1973 pathways using ADABF, and 840 pathways using ORA, out of the 2950 analysed, were enriched (P < 0.05) for at least one exposure, as well as 1227 genes within the enriched pathways. Data were available for 811/1227 coding genes in the OTP, 241 of which were supported by strong relative abundance of prior evidence (overall OTP score > 0.05). Fifty percent of the genes (617/1227) mapped to at least one hallmark of cancer, most of which (388/617) pertained to the Sustaining Proliferative Signalling hallmark. Our findings reflect previously established pathways for CRC risk and highlight the emerging importance of several less studied genes. Common pathways were found for several combinations of exposures, potentially suggesting common underlying mechanisms.

INTERPRETATION: The results of the present analysis provide a basis for further functional research. If confirmed, they may help elucidate the etiological associations between risk factors and CRC risk and ultimately inform personalized prevention strategies.

FUNDING: This study was funded by Cancer Research UK (CRUK; grant number:PPRCPJT∖100005) and World Cancer Research Fund International (WCRF; IIG_FULL_2020_022). Funding for grant IIG_FULL_2020_022 was obtained from Wereld Kanker Onderzoek Fonds (WKOF) as part of the World Cancer Research Fund International grant programme. Full funding details for the individual consortia are provided in the acknowledgements.},
}

@article {pmid41076366,
year = {2025},
author = {Li, R and Hensley, PJ and Babjuk, M and Bukavina, L and Psutka, SP and Lerner, SP and O'Donnell, MA and Lotan, Y and Bree, KK and Redorta, JP and McConkey, DJ and Lee, BH and Mariappan, P and Mertens, LS and Soloway, MS and Svatek, RS and Tan, WS and Williams, SB and Gupta, S and Buckley, R and Kamat, AM},
title = {Intermediate-risk Non-muscle-invasive Bladder Cancer: Recommendations for Definitions, Risk Stratification, Management Strategies, and Clinical Trial Design from the International Bladder Cancer Group.},
journal = {European urology oncology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.euo.2025.08.003},
pmid = {41076366},
issn = {2588-9311},
abstract = {BACKGROUND AND OBJECTIVE: Intermediate-risk (IR) non-muscle-invasive bladder cancer (NMIBC) is a heterogeneous disease, and standardized definitions and risk-guided management are critical for appropriate patient care and clinical trial development.

METHODS: A global committee of bladder cancer experts developed IR-NMIBC recommendations. Working groups reviewed literature and drafted recommendations, which were voted on by International Bladder Cancer Group (IBCG) members using a modified Delphi process. During an August 2024 meeting, voting results and evidence were presented, and recommendations were refined. Final recommendations achieved >75% agreement.

KEY FINDINGS AND LIMITATIONS: The IBCG recommends inclusion of only low-grade (LG; G1 and G2) tumors in the IR-NMIBC category, risk stratified using the IBCG IR-NMIBC risk scoring system. Given the relatively indolent course and treatment burden of IR-NMIBC, therapeutic deintensification with active surveillance or office-based ablation is appropriate for select patients. Morbidity related to transurethral resection of a bladder tumor can be mitigated by forgoing restaging resection in completely resected LG tumors and not mandating muscularis propria sampling. Perioperative chemotherapy reduces recurrences, and additional adjuvant intravesical treatment should be risk stratified. Clinical trials evaluating novel IR-NMIBC therapies, including adjuvant and ablative designs, should incorporate patient-reported outcomes and risk-stratified controls. Ablative trials, as proof-of-concept studies for efficacy, require randomized controlled studies in the adjuvant setting to confirm superiority over the standard of care.

The IBCG consensus recommendations provide practical guidance for clinical care and clinical trial design for patients with IR-NMIBC.},
}

@article {pmid41076116,
year = {2025},
author = {Louie, T and Snidarich, M and Hippe, DS and Wernli, KJ and Palazzo, L and Hansell, L and Brown, M and Coronado, GD and Lodhi, S and Leone, R and DeCell, K and Mardesich, K and Wysham, N and Triplette, M},
title = {A pragmatic pre-post intervention trial to address adherence to lung cancer screening follow-up in community settings (the ACCELL trial): Study protocol.},
journal = {Contemporary clinical trials},
volume = {},
number = {},
pages = {108106},
doi = {10.1016/j.cct.2025.108106},
pmid = {41076116},
issn = {1559-2030},
abstract = {BACKGROUND: Lung cancer remains the leading cause of cancer death in the United States. Annual lung cancer screening (LCS) with low-dose chest CT (LDCT) can prevent lung cancer deaths in high-risk individuals; However, these benefits are tempered by low adherence to annual screening and low rates of follow-up for those with abnormal findings.

OBJECTIVE: To evaluate the impact of centralized approaches to care coordination on LCS follow-up in community settings through a hybrid implementation-effectiveness trial.

METHODS: This is a pre-post intervention trial of a pragmatic and flexible approach to LCS care coordination delivered at the system-level at two community LCS programs based at regional hospitals in Washington state. Care coordination approaches include standardized LCS follow-up workflows incorporating universal tracking of LCS results, universal results delivery to patients, stepped approaches to follow-up reminders and personalized approaches to positive findings. Participants who are eligible for and undergo LCS during either period (n ~ 6750) will be included. Primary outcomes include adjusted changes in screening adherence to annual follow-up and follow-up for positive findings between the pre- (August 2022-January 2025) and post- (January 2025-July 2027) intervention period. Secondary outcomes include assessing the impact of interventions by community site, patient ethnicity, socioeconomic status, and rurality. We will also assess the implementation of the intervention with attention to adaptation, sustainability and equity.

DISCUSSION: Implementing centralizing care coordination models may decrease barriers and improve adherence to LCS in community settings and serve as a model to improve LCS follow-up in clinical care settings.

REGISTRATION: ClinicalTrials.gov ID NCT06324110.},
}

@article {pmid41075386,
year = {2025},
author = {Minnie, SA and Berrien-Elliott, MM and Smith, M and Biernacki, MA and Bleakley, M},
title = {Optimizing post-transplantation cell therapies to enhance graft-versus-leukemia effects in hematological malignancies.},
journal = {Current opinion in immunology},
volume = {97},
number = {},
pages = {102675},
doi = {10.1016/j.coi.2025.102675},
pmid = {41075386},
issn = {1879-0372},
abstract = {Allogeneic hematopoietic cell transplantation (HCT) can cure patients with high-risk hematologic malignancies. Donor T and natural killer (NK) cells contribute to graft-versus-leukemia (GVL) effects that provide relapse protection. Post-HCT relapses often represent inadequate GVL, but alloreactive lymphocytes that confer GVL may also cause graft-versus-host-disease (GVHD). Here, we review recent developments to selectively augment GVL while minimizing GVHD. Insights into the unique mechanisms of post-HCT T cell dysfunction highlight interventions to enhance GVL-mediating T cells. Early clinical data suggest that adoptive transfer of engineered donor T cells, expressing either transgenic T cell receptors specific for minor histocompatibility antigens presented exclusively on recipient hematopoietic cells or chimeric antigen receptors binding surface proteins on malignant cells, can mitigate post-HCT relapse. NK cells, key GVL mediators after haploidentical HCT, can be induced into a highly functional memory-like state and administered to HCT recipients to enhance GVL. These innovations promise much-needed improvements in post-HCT outcomes.},
}

@article {pmid41074700,
year = {2025},
author = {Aldoss, I and Ali, A and Cassaday, RD and Curran, EK and Luskin, MR and Maese, LD and Orgel, E and Douer, D},
title = {Optimizing Asparaginase Treatment for Adolescent and Young Adult (AYA) Patients With Acute Lymphoblastic Leukemia: US Consensus Panel Recommendations.},
journal = {American journal of hematology},
volume = {},
number = {},
pages = {},
doi = {10.1002/ajh.70103},
pmid = {41074700},
issn = {1096-8652},
support = {//Jazz Pharmaceuticals/ ; },
abstract = {Asparaginase is an integral component of therapy for pediatric patients with acute lymphoblastic leukemia/lymphoblastic lymphoma. The success of asparaginase-containing regimens has led to trials of pediatric/pediatric-inspired regimens incorporating asparaginase for treating adolescent and young adult (AYA) and adult populations with acute lymphoblastic leukemia/lymphoblastic lymphoma. While treatment of AYA patients with these regimens is associated with improved clinical outcomes compared with adult-specific protocols, AYA patients face unique challenges with these treatments, further complicated by a rapidly evolving therapeutic landscape. In this article, we identify barriers and other feasibility issues associated with administering asparaginase-based treatment to AYA patients and provide recommendations from a consensus panel of experts to optimize AYA patient outcomes and experiences. Barriers identified include the limited access to clinical trials and specialized expertise in pediatric-inspired regimens for AYA patients compared with pediatric patients, the complex management of asparaginase toxicities, limited medical facilities and experienced staff to administer and manage pediatric-inspired regimens, and reduced AYA patient access/adherence to treatment due to lifestyle-related or psychosocial challenges. Recommendations are provided on addressing and managing these challenges to improve asparaginase-based treatment accessibility and safety in AYA patients, including specific recommendations for high-risk populations. Trial Registration: ClinicalTrials.gov: NCT04817761.},
}

@article {pmid41074685,
year = {2025},
author = {Banerjee, R and Kaur, G and Razzo, BM and Portuguese, AJ and Sidana, S and Richards, T and Grajales-Cruz, A and Richard, S and Shune, L and Khouri, J and Dima, D and Lee, HC and Patel, KK and Pasvolsky, O and Vazquez-Martinez, M and Hansen, DK and Afrough, A and Davis, JA and Hashmi, H and Atrash, S and Ferreri, CJ and Julian, KL and Herr, MM and Midha, S and Costello, P and Forsberg, P and de Menezes Silva Corraes, A and Lin, Y and Cowan, AJ and Anderson, LD and Garfall, AL},
title = {Predictors of Delayed Responses to Teclistamab in Multiple Myeloma After Initial Non-Response.},
journal = {American journal of hematology},
volume = {},
number = {},
pages = {},
doi = {10.1002/ajh.70108},
pmid = {41074685},
issn = {1096-8652},
support = {//Leukemia and Lymphoma Society (Blood Cancer United)/ ; },
}

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

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

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

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

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

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

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

@article {pmid41072416,
year = {2025},
author = {Di Meo, F and Albano, F and Cesarano, A and Wang, Y and Kale, B and Shain, K and Silva, A and Kurihara, N and Tenshin, H and Jellyman, D and Song, X and Ghaffari, S and Mesa, H and Creelan, B and Freeman, C and Zhao, X and Meads, MB and Rodriguez, PC and Marino, S and Locke, F and Hwu, P and Roodman, D and Mansilla-Soto, J and Perna, F},
title = {Developing SEMA4A-directed CAR T cells to overcome low BCMA antigen density in multiple myeloma.},
journal = {Cancer cell},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.ccell.2025.09.007},
pmid = {41072416},
issn = {1878-3686},
abstract = {Chimeric antigen receptor (CAR) T cell therapy targeting B cell maturation antigen (BCMA) for multiple myeloma (MM) is effective, but relapses associated with low-to-negative BCMA expression are common, indicating the need for additional targets. We quantitatively profile antigen density in a cohort of patients relapsed after BCMA CAR T therapy, showing high number of SEMA4A molecules/cell where BCMA density is low. SEMA4A deletion limits MM cell growth, migration, tissue infiltration, and osteoclast formation, while extending mouse survival. We generate monoclonal antibodies targeting SEMA4A-extracellular domain for CAR construction, screen engineered T cells for expansion, cytokine release, and cytotoxicity against MM cells. Lead constructs lack reactivity against normal non-hematopoietic tissues. SEMA4A CAR T cells show superior efficacy than BCMA CAR T cells eliminating patient-derived BCMA[low] tumors and MM cells progressing under suboptimal doses of BCMA CAR T cells. This study prepares for a phase 1 clinical trial with SEMA4A-directed CAR T cells for MM.},
}

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

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

@article {pmid41071741,
year = {2025},
author = {Dionne, JA and Campbell, JD and Salim, J and Atmar, RL and Healy, CM and Posavad, CM and Flach, B and Brown, ER and Farley, MM and Stephens, DS},
title = {Baptism in a Pandemic: Infectious Diseases Clinical Research Consortium Network Design for Readiness and Response.},
journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America},
volume = {81},
number = {Supplement_2},
pages = {S109-S116},
doi = {10.1093/cid/ciaf419},
pmid = {41071741},
issn = {1537-6591},
}

@article {pmid41071598,
year = {2025},
author = {Corvera, S and Rajan, A and Townsend, KL and Shamsi, F and Wu, J and Svensson, KJ and Zeltser, LM and Collins, S and Reis, T and Tseng, YH and Goodyear, LJ},
title = {Advances in Adipose Tissue Biology.},
journal = {Endocrine reviews},
volume = {},
number = {},
pages = {},
doi = {10.1210/endrev/bnaf032},
pmid = {41071598},
issn = {1945-7189},
abstract = {Adipose tissue has emerged as a central regulator of human physiology, with its dysfunction driving the global rise in obesity-associated diseases, such as type 2 diabetes, cardiovascular and liver diseases, and several cancers. Once thought to be inert, adipocytes are now recognized as dynamic, responsive cells essential for energy homeostasis and interorgan communication, including the brain. Distinct adipose depots support specialized functions across development, sex, and aging. Technologies like single-cell RNA sequencing are unraveling depot-specific mechanisms, with the potential of identifying new therapeutic targets. This review highlights major scientific advancements leading to our current appreciation of the pivotal role of adipose tissue in health and disease. Many key discoveries in this field have been catalyzed by National Institutes of Health funding, particularly through the National Institute of Diabetes, Digestive and Kidney Diseases, now celebrating its 75th anniversary.},
}

@article {pmid38978671,
year = {2025},
author = {Blechter, B and Wang, X and Dai, J and Karsonaki, C and Shi, J and Shiraishi, K and Choi, J and Matsuo, K and Chen, TY and Hung, RJ and Chen, K and Shu, XO and Kim, YT and Choudhury, PP and Williams, J and Landi, MT and Lin, D and Zheng, W and Yin, Z and Zhou, B and Wang, J and Seow, WJ and Song, L and Chang, IS and Hu, W and Chien, LH and Cai, Q and Hong, YC and Kim, HN and Wu, YL and Wong, MP and Richardson, BD and Li, S and Zhang, T and Breeze, C and Wang, Z and Bassig, BA and Kim, JH and Albanes, D and Wong, JY and Shin, MH and Chung, LP and Yang, Y and Zheng, H and Dai, H and Yatabe, Y and Zhang, XC and Kim, YC and Caporaso, NE and Chang, J and Man Ho, JC and Daigo, Y and Momozawa, Y and Kamatani, Y and Kobayashi, M and Okubo, K and Honda, T and Hosgood, HD and Kunitoh, H and Watanabe, SI and Miyagi, Y and Matsumoto, S and Horinouchi, H and Tsuboi, M and Hamamoto, R and Goto, K and Takahashi, A and Goto, A and Minamiya, Y and Hara, M and Nishida, Y and Takeuchi, K and Wakai, K and Matsuda, K and Murakami, Y and Shimizu, K and Suzuki, H and Saito, M and Ohtaki, Y and Tanaka, K and Wu, T and Wei, F and Machiela, MJ and Kim, YH and Oh, IJ and Fun Lee, VH and Chang, GC and Chen, KY and Su, WC and Chen, YM and Seow, A and Park, JY and Kweon, SS and Gao, YT and Liu, J and Schwartz, AG and Houlston, R and Gorlov, IP and Wu, X and Yang, P and Lam, S and Tardon, A and Chen, C and Bojesen, SE and Johansson, M and Risch, A and Bickeböller, H and Ji, BT and Wichmann, HE and Christiani, DC and Rennert, G and Arnold, SM and Brennan, P and McKay, J and Field, JK and Davies, MPA and Shete, SS and Le Marchand, L and Liu, G and Andrew, AS and Kiemeney, LA and Zienolddiny-Narui, S and Grankvist, K and Cox, A and Taylor, F and Yuan, JM and Lazarus, P and Schabath, MB and Aldrich, MC and Jeon, HS and Jiang, SS and Chen, CH and Hsiao, CF and Hu, Z and Burdett, L and Yeager, M and Hutchinson, A and Hicks, B and Liu, J and Berndt, SI and Wu, W and Wang, J and Li, Y and Choi, JE and Park, KH and Sung, SW and Kang, CH and Wang, WC and Xu, J and Guan, P and Tan, W and Yu, CJ and Yang, G and Loon Sihoe, AD and Choi, YY and Park, IK and Hung, HH and Vermeulen, RCH and Cheng, I and Wu, J and Tsai, FY and Chan, JKC and Li, J and Lin, HC and Liu, J and Song, B and Sawada, N and Yamaji, T and Wyatt, K and Ma, H and Zhu, M and Wang, Y and Qi, T and Li, X and Ren, Y and Chao, A and Iwasaki, M and Zhu, J and Wu, G and Chen, CY and Chen, CJ and Yang, PC and Stevens, VL and Fraumeni, JF and Lin, K and Walters, RG and Chen, Z and Chatterjee, N and Gorlova, OY and Amos, CI and Shen, H and Hsiung, CA and Chanock, SJ and Rothman, N and Kohno, T and Lan, Q and Zhang, H},
title = {Stratifying Lung Adenocarcinoma Risk with Multi-ancestry Polygenic Risk Scores in East Asian Never-Smokers.},
journal = {medRxiv : the preprint server for health sciences},
volume = {},
number = {},
pages = {},
pmid = {38978671},
abstract = {BACKGROUND: Lung adenocarcinoma (LUAD) in never-smokers is a major public health burden, especially among East Asian women. Polygenic risk scores (PRSs) are promising for risk stratification but are primarily developed in European-ancestry populations. We aimed to develop and validate single- and multi-ancestry PRSs for East Asian never-smokers to improve LUAD risk prediction.

METHODS: PRSs were developed using genome-wide association study summary statistics from East Asian (8,002 cases; 20,782 controls) and European (2,058 cases; 5,575 controls) populations. Single-ancestry models included PRS-25, PRS-CT, and LDpred2; multi-ancestry models included LDpred2+PRS-EUR128, PRS-CSx, and CT-SLEB. Performance was evaluated in independent East Asian data from the Female Lung Cancer Consortium (FLCCA) and externally validated in the Nanjing Lung Cancer Cohort (NJLCC). We assessed predictive accuracy via AUC, with 10-year and (age 30-80) absolute risks estimates.

RESULTS: The best multi-ancestry PRS, using East Asian and European data via CT-SLEB (clumping and thresholding, super learning, empirical Bayes), outperformed the best East Asian-only PRS (LDpred2; AUC=0.629, 95% CI:0.618,0.641), achieving an AUC of 0.640 (95% CI:0.629,0.653) and odds ratio of 1.71 (95% CI:1.61,1.82) per SD increase. NJLCC Validation confirmed robust performance (AUC =0.649, 95% CI: 0.623, 0.676). The top 20% PRS group had a 3.92-fold higher LUAD risk than the bottom 20%. Further, the top 5% PRS group reached a 6.69% lifetime absolute risk. Notably, this group reached the average population 10-year LUAD risk at age 50 (0.42%) by age 41, nine years earlier.

CONCLUSIONS: Multi-ancestry PRS approaches enhance LUAD risk stratification in East Asian never-smokers, with consistent external validation, suggesting future clinical utility.},
}

@article {pmid41071311,
year = {2025},
author = {Carballo, EV and Gonzalez-Ericsson, P and Lehmann, BD and Taylor, BC and Wulfkuhle, JD and Ocampo, A and Gallagher, RI and Huang, DS and Maxey, C and Steele, JA and Kleinberg, K and Sun, X and Marshall, JL and Sanchez, V and Opalenik, SR and Petricoin, E and Rimel, BJ and Balko, JM and Penn, CA},
title = {The impact of JAK1 pathogenic variants and MHC-I expression on response to immune checkpoint inhibition in endometrial cancer.},
journal = {Clinical cancer research : an official journal of the American Association for Cancer Research},
volume = {},
number = {},
pages = {},
doi = {10.1158/1078-0432.CCR-25-1442},
pmid = {41071311},
issn = {1557-3265},
abstract = {PURPOSE: Immune checkpoint inhibitors (ICI) have increasing application in endometrial cancer, underscoring the need for robust biomarkers for patient selection. JAK1 pathogenic variants (PV) have previously been implicated in immune evasion. Here, we identify biomarkers predictive of ICI response in endometrial cancer and the implications of JAK1 PV in this context.

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

RESULTS: MHC-I expression correlated with improved progression-free survival (p = 0.035), validated in orthogonal approaches. Notably, a subset of patients harboring JAK1 PVs demonstrated exceptional survival on ICI. In TCGA cohort of microsatellite instability-high (MSI-H) and DNA polymerase epsilon (POLE)-mutated tumors, homozygous loss of JAK1 (JAK1Hom) trended toward decreased survival, whereas heterozygous loss of JAK1 (JAK1Het) was associated with significantly improved survival (p = 0.026), suggesting partial retention of antigen presentation pathways. Among our ICI-treated MSI-H tumor samples, NK cell marker NCAM1 was associated with improved survival (p=0.02).

CONCLUSIONS: These data support MHC-I as a potential predictive biomarker for ICI response in endometrial cancer. Additionally, we show that partial retention of JAK1 signaling in JAK1Het tumors is associated with improved survival, potentially attributable to enhanced NK cell activity in tumors with low MHC-I expression.},
}

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

@article {pmid41066089,
year = {2025},
author = {O'Brien, KM and Keil, AP and Taylor, JA and Weinberg, CR and Polley, EC and Yadav, S and Boddicker, NJ and Hu, C and Ambrosone, CB and Anton-Culver, H and Auer, PL and Bodelon, C and Brantley, K and Burnside, ES and Chen, F and Domchek, SM and Eliassen, AH and Haiman, CA and Hodge, JM and Kraft, P and Lacey, JV and Lindstroem, S and Martinez, ME and Nathanson, KL and Neuhausen, SL and Olson, JE and Palmer, JR and Patel, AV and Penney, KL and Ruddy, KJ and Scott, CG and Teras, LR and Trentham-Dietz, A and Vachon, CM and Weitzel, JN and Yao, S and Zirpoli, G and Couch, FJ and Sandler, DP},
title = {Pathogenic Variants, Family History, and Cumulative Risk of Breast Cancer in US Women.},
journal = {JAMA oncology},
volume = {},
number = {},
pages = {},
pmid = {41066089},
issn = {2374-2445},
abstract = {IMPORTANCE: Inherited pathogenic variants (PVs) in known predisposition genes can greatly increase breast cancer risk, but the combined impact of PV status, family history, and other factors on breast cancer risk in the general US population has not been well described.

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

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

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

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

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

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

@article {pmid41065373,
year = {2025},
author = {Pradere, B and Schuit, M and Guerrero-Ramos, F and Shariat, SF and Kitamura, H and Jacob, JM and Bao, Y and Heesakkers, J and Peters, KM and Cahn, DJ and De Troyer, B and Herrera Imbroda, B and Morris, DS and Pieczonka, CM and Wei, Q and Bhanvadia, S and Somer, R and Jessner, W and Triantos, S and Sánchez de Llano, C and Maffeo, JC and Sweiti, H and Psutka, SP},
title = {Side effect management and procedural best practices with indwelling intravesical drug-releasing systems in the treatment of bladder cancer: recommendations from expert panels.},
journal = {Current opinion in urology},
volume = {},
number = {},
pages = {},
pmid = {41065373},
issn = {1473-6586},
abstract = {PURPOSE OF REVIEW: To provide expert recommendations for side effect management in patients with bladder cancer receiving intravesical-drug releasing system (iDRS) treatment and for optimizing iDRS insertion procedure success.

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

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

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

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

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

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

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

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

@article {pmid41063661,
year = {2025},
author = {Sesay, FA and Oware, K and Violette, LR and Donnell, D and Odoyo, JB and Omollo, V and Mogaka, FO and McClelland, RS and Balkus, JE and Bukusi, EA and Baeten, JM and Stewart, J},
title = {Trichomonas vaginalis Among Cisgender Women Taking Doxycycline Postexposure Prophylaxis.},
journal = {The Journal of infectious diseases},
volume = {},
number = {},
pages = {},
doi = {10.1093/infdis/jiaf519},
pmid = {41063661},
issn = {1537-6613},
abstract = {Doxycycline treats and prevents several bacterial and parasitic infections and has been proposed as a possible treatment for Trichomonas vaginalis. Nested in a trial of doxycycline postexposure prophylaxis among cisgender women in Kenya, we conducted a secondary analysis of incident T. vaginalis infections. Among 224 cisgender women randomized to doxycycline postexposure prophylaxis and 225 to standard-of-care, there were 27 T. vaginalis diagnoses in the doxycycline postexposure prophylaxis group and 29 in the standard-of-care group (RR: 0.96, 95% CI: 0.54-1.73, p=0.9)). Understanding doxycycline postexposure prophylaxis's impact on T. vaginalis remains an important public health question that warrants further investigation.},
}

@article {pmid41063387,
year = {2025},
author = {Chari, ST and Feng, Z and Wu, B and Fisher, W and Kambadakone, A and Zhao, YQ and Maitra, A and Kenner, B and Matrisian, LM},
title = {Heuriskance: a novel paradigm for systematic earlier detection of sporadic pancreatic cancer.},
journal = {Journal of the National Cancer Institute},
volume = {},
number = {},
pages = {},
doi = {10.1093/jnci/djaf291},
pmid = {41063387},
issn = {1460-2105},
abstract = {Early detection is key to improving survival and mortality from pancreatic cancer. Traditional periodic screening for cancer in an asymptomatic population is infeasible and not recommended for this low-incidence disease. We describe a novel approach we call "heuriskance" (hyou-ris-kance) wherein a systematic search for and onetime workup of a "heurisk" (hyou-risk) leads to earlier detection of cancer. A heurisk is an early warning sign with three defining characteristics: i) indicates higher-than-threshold-probability of having prevalent invasive cancer, ii) is associated with a meaningful lead time to diagnosis, and iii) is identifiable by a systematic and scalable process in the population. Heuriskance aims to systematically detect cancer with clinically meaningful lead time to clinical diagnosis, minimize proportion of patients with advanced disease, and maximize treatment options leading to increases in lead time-adjusted 1-, 3- and eventually 5- year survival. A specific example of a heurisk for pancreatic cancer is glycemically defined new onset diabetes (GNOD) and the Early Detection Initiative (NCT04662879) an example of GNOD-based heuriskance. As heuriskance has no precedent, we provide i) a tiered risk stratification approach (Define-Enrich-Find), ii) metrics for choosing a heurisk, iii) success metrics for strategy and iv) Phases 1-5 for evaluating the strategy in retrospective and prospective studies. Like all current cancer therapies, heuriskance aims to iteratively improve survival from a fatal disease using a pragmatic, evidence-based systematic approach to its earlier detection. The concept of heuriskance is applied to pancreatic cancer but could be extended to other cancer types.},
}

@article {pmid41030929,
year = {2025},
author = {Bents, SJ and Martin, ET and Steven-Ayers, T and Andrews, C and Adler, A and Perofsky, A and Krantz, EM and Blazevic, R and Kimball, L and Prentice, R and Hansen, C and Starita, L and Han, P and Englund, JA and Wolter, N and von Gottberg, A and Maake, L and Moyes, J and Cohen, C and Boeckh, M and Hay, JA and Waghmare, A and Viboud, C},
title = {Multiplex serology reveals age-specific immunodynamics of endemic respiratory pathogens in the wake of the COVID-19 pandemic.},
journal = {medRxiv : the preprint server for health sciences},
volume = {},
number = {},
pages = {},
pmid = {41030929},
support = {/WT_/Wellcome Trust/United Kingdom ; 75N93021C00015/AI/NIAID NIH HHS/United States ; },
abstract = {The rebound of endemic respiratory viruses following the COVID-19 pandemic was marked by atypical transmission dynamics, with children experiencing increased disease burden and out-of-season epidemics as restrictions relaxed. Here we used serology from a newly developed quantitative multiplex assay to assess the post-pandemic immunity debt, a drop in immunity due to a lack of endemic virus circulation during COVID-19. We assessed age-specific antibody dynamics in Seattle, Washington, US, across a broad range of respiratory viruses, including influenza, respiratory syncytial virus, seasonal coronaviruses, and SARS-CoV-2. We found that respiratory virus immunodynamics differed between individuals <5 years of age and older individuals, with young children experiencing both larger boosts and quicker waning of antibodies across pathogens. We confirmed that these patterns are upheld in a non-pandemic setting by analyzing influenza serological data from South Africa. We incorporated our serological insights into an influenza transmission model calibrated to epidemiological data from Seattle and show that consideration of age-specific immunodynamics may be important to anticipate the effects of pandemic perturbations.},
}

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

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

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

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

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

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

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

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

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

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

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

@article {pmid41061233,
year = {2025},
author = {Dean, NE and Crisp, AM and Che-Mendoza, A and Kirstein, OD and Barrera-Fuentes, GA and Earnest, JT and Puerta-Guardo, HN and Collins, MH and Pavia-Ruz, N and Ayora-Talavera, G and González-Olvera, G and Medina-Barreiro, A and Bibiano-Marín, W and Jabbarzadeh, S and Halloran, ME and Longini, IM and Lenhart, A and Waller, LA and Correa-Morales, F and Palacio-Vargas, J and Gomez-Dantes, H and Manrique-Saide, P and Vazquez-Prokopec, GM},
title = {Randomized Trial of Targeted Indoor Spraying to Prevent Aedes-Borne Diseases.},
journal = {The New England journal of medicine},
volume = {393},
number = {14},
pages = {1387-1398},
doi = {10.1056/NEJMoa2501069},
pmid = {41061233},
issn = {1533-4406},
support = {U54 GM111274/GM/NIGMS NIH HHS/United States ; R37 AI032042/AI/NIAID NIH HHS/United States ; U01 AI148069/AI/NIAID NIH HHS/United States ; DFID: 30041-105//Bill and Melinda Gates Foundation/ ; },
mesh = {Humans ; Animals ; *Aedes ; Child ; Child, Preschool ; *Insecticides/administration & dosage ; *Mosquito Control/methods ; *Dengue/prevention & control/epidemiology ; Mexico/epidemiology ; *Zika Virus Infection/prevention & control/epidemiology ; Adolescent ; *Chikungunya Fever/prevention & control/epidemiology ; Female ; Male ; *Mosquito Vectors ; Housing ; Seasons ; Mosquito-Borne Diseases ; },
abstract = {BACKGROUND: Targeted indoor residual spraying focuses insecticide applications on common resting surfaces of Aedes aegypti mosquitoes (an arboviral disease vector) in houses, such as exposed lower sections of walls and under furniture.

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

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

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

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

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

@article {pmid41061155,
year = {2025},
author = {Banerjee, R and Raje, NS},
title = {Vaccination during bispecific antibody treatment for myeloma.},
journal = {Blood advances},
volume = {},
number = {},
pages = {},
doi = {10.1182/bloodadvances.2025018225},
pmid = {41061155},
issn = {2473-9537},
}

@article {pmid41060772,
year = {2025},
author = {Sedovy, MW and Renton, MC and Roberts, K and Leng, X and Dennison, CL and Toler, CO and Leaf, M and Lampe, PD and Best, AK and Isakson, BE and Johnstone, SR},
title = {Injury-Induced Connexin 43 Expression Regulates Endothelial Wound Healing.},
journal = {American journal of physiology. Heart and circulatory physiology},
volume = {},
number = {},
pages = {},
doi = {10.1152/ajpheart.00153.2025},
pmid = {41060772},
issn = {1522-1539},
support = {AHA23PRE1010870//American Heart Association (AHA)/ ; NIH-F31HL170721//HHS | NIH | National Heart, Lung, and Blood Institute (NHLBI)/ ; AHA25POST1410066//American Heart Association (AHA)/ ; AHA19CDA34630036//American Heart Association (AHA)/ ; NIH-R215R21HL168614-02//HHS | NIH | National Heart, Lung, and Blood Institute (NHLBI)/ ; NIH-HL120840//HHS | NIH | National Heart, Lung, and Blood Institute (NHLBI)/ ; NIH-HL137112//HHS | NIH | National Heart, Lung, and Blood Institute (NHLBI)/ ; },
abstract = {Endothelial cell (EC) injury is a major contributing factor to vascular surgical failure. As such, understanding the mechanisms of endothelial healing is essential to the development of vascular therapeutics and procedures. Gap junctions formed by connexin 43 (Cx43) are implicated in regulating skin wound healing, but their role in endothelial healing is unknown. Secondary analysis of RNAseq data from in vivo injured mouse aortas (GEO: GSE115618), identified significant Cx43 upregulation in EC post-injury. We developed a novel in vivo model of EC injury using mouse carotid artery ligation to test the role of Cx43. We identified that EC immediately adjacent to the wound edge upregulate Cx43 protein expression, predominantly at cell-cell junctions. We show significantly delayed EC healing in a mouse model of inducible EC-specific Cx43 deletion (EC-Cx43 KO) at 24 hr post ligation. Single cell RNAseq analysis of 10,829 cells from 18 hr injured EC-WT and EC-Cx43 KO carotids revealed a Cx43-associated reduction in enrichment of EC pathways associated with migration, proliferation, and ERK/MAPK signaling pathways. Finally, the importance of Cx43 phosphorylation on EC healing was tested in mice with single-point alanine mutations (phospho-null) in known phosphorylation sites that alter Cx43 channel assembly and opening. Mice containing alanine mutations at ERK phosphorylated Cx43 serines (Cx43[S255/262/279/282A]) have reduced healing rates similar to EC-Cx43 KO mice. These data suggest that EC injury-induced Cx43 upregulation, and subsequent Cx43 gap junction-mediated cell-to-cell communication are required for normal EC migration during wound healing after vascular injury.},
}

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

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

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

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

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

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

@article {pmid41058545,
year = {2025},
author = {Haneda, E and Peters, N and Zhang, J and Karageorgos, G and Xia, W and Paganetti, H and Wang, G and Guo, Y and Ma, J and Park, HS and Jeon, K and Fan, F and Thies, M and De Man, B},
title = {AAPM CT metal artifact reduction grand challenge.},
journal = {Medical physics},
volume = {52},
number = {10},
pages = {e70050},
doi = {10.1002/mp.70050},
pmid = {41058545},
issn = {2473-4209},
mesh = {*Artifacts ; *Metals ; *Tomography, X-Ray Computed ; *Image Processing, Computer-Assisted/methods ; Humans ; Algorithms ; },
abstract = {BACKGROUND: Metal artifact reduction (MAR) is a long-standing challenge in CT imaging. The presence of highly attenuating objects, such as dental fillings, hip prostheses, spinal screws/rods, and gold fiducial markers, can introduce severe streak artifacts in CT images, often reducing their diagnostic value. Existing CT MAR studies typically define their own test cases and evaluation metrics, making it difficult to objectively and comprehensively compare the performance of different MAR methods. There is a widespread need for a universal CT MAR image quality benchmark to evaluate the clinical impact of new MAR methods and compare them to state-of-the-art techniques.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

@article {pmid41056445,
year = {2025},
author = {Jiang, CY and Hwang, H and Epstein, IY and Bakaloudi, DR and Talukder, R and Taylor, AK and Nizam, A and Jindal, T and Glover, MJ and Khaki, AR and Barata, PC and Nguyen, CB and Oh, E and Davis, NB and Mabey, H and Hoimes, CJ and Evans, ST and Abuqayas, B and Lemke, E and Tsung, I and Qiao, W and Kilari, D and Zakharia, Y and Bilen, MA and Milowsky, MI and Shah, SA and Gupta, S and Emamekhoo, H and Bellmunt, J and Alva, AS and Grivas, P and Msaouel, P and Koshkin, VS and Campbell, MT and Alhalabi, O},
title = {Efficacy of erdafitinib before or after enfortumab vedotin in FGFR3-altered advanced urothelial cancer: analysis of the UNITE collaborative study.},
journal = {The oncologist},
volume = {},
number = {},
pages = {},
doi = {10.1093/oncolo/oyaf342},
pmid = {41056445},
issn = {1549-490X},
abstract = {BACKGROUND: Erdafitinib is approved for locally advanced/metastatic urothelial cancer (LA/mUC). As enfortumab vedotin (EV) plus pembrolizumab enters frontline management, outcomes with erdafitinib pre- and post-EV are clinically relevant but not specifically evaluated in clinical trials.

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

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

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

IMPLICATIONS FOR PRACTICE: Non-trial outcomes of erdafitinib in FGFR3-altered locally advanced/metastatic urothelial cancer are consistent with reported clinical trial data. Erdafitinib therapy is effective in the pre- and post- EV setting.},
}

@article {pmid41056200,
year = {2025},
author = {Lee, T and Buchanan, AL and Katenka, N and Forastiere, L and Halloran, ME and Nikolopoulos, G},
title = {Assessing spillover effects: Handling missing outcomes in network-based studies.},
journal = {Statistical methods in medical research},
volume = {},
number = {},
pages = {9622802251382586},
doi = {10.1177/09622802251382586},
pmid = {41056200},
issn = {1477-0334},
abstract = {Estimating causal effects in the presence of spillover among individuals within a social network poses challenges due to missing information. Spillover effects refer to the impact of an intervention on individuals not directly exposed themselves but connected to intervention recipients within the network. In network-based studies, outcomes may be missing due to study termination or participant dropout, termed censoring. We introduce an inverse probability censoring weighted estimator which extends the inverse probability weighted estimator for network-based observational studies to handle possible outcome censoring. We prove the consistency and asymptotic normality of the proposed estimator and derive a closed-form estimator for its asymptotic variance. Applying the inverse probability censoring weighted estimator, we assess spillover effects in a network-based study of a nonrandomized intervention with outcome censoring. A simulation study evaluates the finite-sample performance of the inverse probability censoring weighted estimator, demonstrating its effectiveness with sufficiently large sample sizes and number of connected subnetworks. We then employ the method to assess spillover effects of community alerts on self-reported human immunodeficiency virus risk behavior among people who inject drugs and their contacts in the Transmission Reduction Intervention Project (TRIP), from 2013 to 2015, Athens, Greece. Results suggest that community alerts may help reduce human immunodeficiency virus risk behavior for both the individuals who receive them and others in their network, possibly through shared information. In this study, we found that the risk of human immunodeficiency virus behavior was reduced by increasing the proportion of a participant's immediate contacts exposed to community alerts.},
}

@article {pmid41040260,
year = {2025},
author = {Bhattacharya, T and Freeman, TS and Alleman, EM and Wang, F and Chechik, L and Emerman, M and Myles, KM and Malik, HS},
title = {The Sindbis virus nsP3 opal codon protects viral RNA and fitness by maintaining replication spherule integrity.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {41040260},
issn = {2692-8205},
abstract = {Most alphaviruses encode an in-frame opal stop codon between nsP3 and nsP4 in their nsP ORF. This opal stop codon mediates a temperature-dependent balance between viral polymerase production and proteolytic processing in vertebrate hosts. Yet, why this opal codon is maintained in insect hosts is unknown. Here, we show that the nsP3 opal stop codon confers a replicative advantage to Sindbis virus (SINV) in RNAi-competent mosquito cells, but not in cells lacking RNAi. Through delays in nsP processing, the lack of opal stop codon disrupts viral replication spherule integrity and increases Dicer 2-dependent cleavage of viral RNA, resulting in higher antiviral siRNA responses to the virus. Moreover, in mammalian cells, the opal codon-mediated spherule integrity also blocks MDA5-dependent viral RNA detection and interferon signaling. Thus, the highly conserved alphavirus opal codon mediates a multipotent viral defensive strategy.},
}

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

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

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

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

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

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

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

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

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

@article {pmid41055541,
year = {2025},
author = {Salerno, S and Roberts, EK and Needham, BL and McCormick, TH and Li, F and Mukherjee, B and Shi, X},
title = {What's the Weight? Estimating Controlled Outcome Differences in Complex Surveys for Health Disparities Research.},
journal = {Statistics in medicine},
volume = {44},
number = {23-24},
pages = {e70289},
doi = {10.1002/sim.70289},
pmid = {41055541},
issn = {1097-0258},
support = {R35 GM144128/GM/NIGMS NIH HHS/United States ; R01 GM139926/GM/NIGMS NIH HHS/United States ; DP2 MH122405/MH/NIMH NIH HHS/United States ; R01 HD107015/MH/NIMH NIH HHS/United States ; P2C HD042828/MH/NIMH NIH HHS/United States ; 1712933//Division of Mathematical Sciences/ ; UG3 CA267907/CA/NCI NIH HHS/United States ; //Fred Hutchinson Cancer Center/ ; },
mesh = {Humans ; Nutrition Surveys/statistics & numerical data ; *Health Status Disparities ; White People/statistics & numerical data/genetics ; Propensity Score ; Black or African American/statistics & numerical data/genetics ; Female ; Male ; Computer Simulation ; Bias ; Telomere/genetics ; Middle Aged ; Socioeconomic Factors ; United States ; White ; },
abstract = {In this work, we are motivated by the problem of estimating racial disparities in health outcomes, specifically the average controlled difference (ACD) in telomere length between Black and White individuals, using data from the National Health and Nutrition Examination Survey (NHANES). To do so, we build a propensity for race to properly adjust for other social determinants while characterizing the controlled effect of race on telomere length. Propensity score methods are broadly employed with observational data as a tool to achieve covariate balance, but how to implement them in complex surveys is less studied-in particular, when the survey weights depend on the group variable under comparison (as the NHANES sampling scheme depends on self-reported race). We propose identification formulas to properly estimate the ACD in outcomes between Black and White individuals, with appropriate weighting for both covariate imbalance across the two racial groups and generalizability. Via extensive simulation, we show that our proposed methods outperform traditional analytic approaches in terms of bias, mean squared error, and coverage when estimating the ACD for our setting of interest. In our data, we find that evidence of racial differences in telomere length between Black and White individuals attenuates after accounting for confounding by socioeconomic factors and utilizing appropriate propensity score and survey weighting techniques. Software to implement these methods and code to reproduce our results can be found in the R package svycdiff, available through the Comprehensive R Archive Network (CRAN) at cran.r-project.org/web/packages/svycdiff/, or in a development version on GitHub at github.com/salernos/svycdiff.},
}

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

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

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

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

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

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

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

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

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

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

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

@article {pmid39896535,
year = {2025},
author = {Verwimp, S and Wagoner, J and Arenas, EG and De Coninck, L and Abdelnabi, R and Hyde, JL and Schiffer, JT and White, JM and Matthijnssens, J and Neyts, J and Polyak, SJ and Delang, L},
title = {Combinations of approved oral nucleoside analogues confer potent suppression of alphaviruses in vitro and in vivo.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {39896535},
issn = {2692-8205},
support = {R01 AI121129/AI/NIAID NIH HHS/United States ; },
abstract = {BACKGROUND: Alphaviruses, including chikungunya virus (CHIKV), pose a significant global health threat, yet specific antiviral therapies remain unavailable.

METHODS: We evaluated combinations of three oral directly acting antiviral drugs (sofosbuvir (SOF), molnupiravir (MPV), and favipiravir (FAV)), which are approved for other indications, against CHIKV, Semliki Forest virus (SFV), Sindbis virus (SINV), and Venezuelan Equine Encephalitis virus (VEEV) in vitro and in vivo. We assessed antiviral efficacy in human skin fibroblasts and liver cells, as well as in a mouse model of CHIKV-induced arthritis.

FINDINGS: In human skin fibroblasts, synergistic antiviral effects were observed for combinations of MPV + SOF and FAV + SOF against CHIKV, and for FAV + SOF against SFV. In human liver cells, FAV + MPV conferred additive to synergistic activity against VEEV and SINV, while SOF synergized with FAV against SINV. In mice, MPV improved CHIKV-induced foot swelling and reduced systemic infectious virus titres. Combination treatment with MPV and SOF significantly reduced swelling and infectious virus titres compared to monotherapies of each drug. Sequencing of CHIKV RNA from joint tissue revealed that MPV caused dose-dependent increases in mutations in the CHIKV genome. Upon combination therapy of MPV with SOF, the number of mutations was significantly lower compared to monotherapy with several higher doses of MPV.

INTERPRETATION: Combining these approved oral nucleoside analogues confers potent suppression of multiple alphaviruses in vitro and in vivo with enhanced control of viral genetic evolution in face of antiviral pressure. These drug combinations may ultimately lead to the development of potent combinations of pan-family alphavirus inhibitors.

FUNDING: This work was supported by a PhD fellowship granted to S.V. by the Research Foundation - Flanders (FWO) (11D5923N). L.D.C. was also supported by Research Foundation - Flanders (FWO) PhD fellowship (11L1325N). Dr. Polyak and Schiffer are partially supported by R01AI121129.},
}

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

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

@article {pmid41052457,
year = {2025},
author = {Balogh, EP and Levit, LA and Unger, JM and Accordino, MK and Chism, DD and Kirkwood, MK and Parsons, HM and Patel, MI and Peppercorn, JM and Polite, BN and Sedrak, MS and Sharma, P and Subbiah, IM and Temel, JS and Yabroff, KR and Osarogiagbon, RU},
title = {ASCO State of Cancer Care in America Special Report 2025: Access to Cancer Clinical Trials in the United States.},
journal = {JCO oncology practice},
volume = {},
number = {},
pages = {OP2500233},
doi = {10.1200/OP-25-00233},
pmid = {41052457},
issn = {2688-1535},
abstract = {Improving patient access to cancer clinical trials is a fundamental ASCO priority because clinical cancer research is the essential link transforming biomedical discoveries into meaningful progress in cancer care and patient outcomes. Today's standard of care emerged from yesterday's clinical trials. However, numerous barriers continue to threaten patient access to cancer clinical trials. This Special Report describes the essential role clinical trials play in improving cancer care and patient outcomes, current challenges in the design and conduct of clinical trials, and steps taken by ASCO to make clinical trials more accessible, patient-centered, and embedded within the communities where people live.},
}

@article {pmid41052403,
year = {2025},
author = {Modi, D and Aljawai, YM and DeFor, TE and Bupp, C and Al Malki, MM and Bolaños-Meade, J and Gooptu, M and Jimenez Jimenez, AM and Liu, H and Mensah, F and Mielcarek, M and Shaffer, BC and Shaw, BE and Spellman, SR and Stefanski, HE and Auletta, JJ and Devine, SM and Khimani, F and Abboud, R},
title = {Matched Unrelated vs Haploidentical Donor Hematopoietic Cell Transplantation Using Post-Transplant Cyclophosphamide.},
journal = {Blood advances},
volume = {},
number = {},
pages = {},
doi = {10.1182/bloodadvances.2025017194},
pmid = {41052403},
issn = {2473-9537},
abstract = {Post-transplant cyclophosphamide (PTCy)-based graft-vs-host disease (GVHD) prophylaxis is the new standard for matched unrelated donor (MUD) hematopoietic cell transplantation (HCT). Prior studies comparing MUD and haploidentical donor HCT using PTCy were limited by size and short follow-up. We therefore performed a registry-based analysis examining the impact of donor type on HCT with PTCy. Adult patients (n=5,873) who received MUD (n=1,973) or haploidentical (n=3900) HCT with PTCy for acute leukemia (74.2%) or myelodysplastic syndrome (25.8%) reported to the CIBMTR between 2017- 2021 were included. Primary endpoints were three-year overall survival (OS) and GVHD-free, relapse-free survival (GRFS). Cox regression and sensitivity analyses were performed through adjustment of propensity scores. Haploidentical HCT had worse OS (Hazard ratio [HR] 1.15, 95% confidence interval [CI] 1.04-1.27, p=0.005) and GRFS (HR 1.19, 95% CI 1.10-1.29, p<0.001) compared to MUD HCT. Donor age was the only other consistent donor-related factor associated with survival. Results were confirmed in a sensitivity analysis adjusted for propensity scores. When the cohort was restricted to reduced intensity conditioning only or donors <30 years-old, OS did not differ between groups. Haploidentical HCT was associated with higher primary graft failure (HR 1.67; p=0.002), increased grade III-IV acute GVHD (HR 1.28; p=0.039), higher moderate/severe chronic GVHD (HR 1.47; p<0.001) and non-relapse mortality (HR 1.34; p<0.001). Grade II-IV aGVHD and relapse risk did not differ between the donor types. This large analysis showed that in adults with acute leukemia or MDS, MUD HCT was associated with improved outcomes compared to haplo HCT with PTCy-based GVHD prophylaxis.},
}

@article {pmid41052219,
year = {2025},
author = {Brokaw, A and Wallen, G and Orvis, A and Kwon, HJ and Seepersaud, R and Nguyen, S and Sharma, K and Coleman, M and Quach, P and Twentyman, J and Vornhagen, J and Jones, LA and Lin, C and Gafken, PR and Rajagopal, L},
title = {The serine protease HtrA regulates Group B Streptococcus virulence and affects the host response to infection.},
journal = {PLoS pathogens},
volume = {21},
number = {10},
pages = {e1013562},
doi = {10.1371/journal.ppat.1013562},
pmid = {41052219},
issn = {1553-7374},
abstract = {Group B Streptococcus (GBS) rectovaginally colonizes up to 20% of women worldwide and is a leading cause of invasive infections during pregnancy, contributing annually to a significant proportion of preterm births, neonatal infections, and stillbirths. Despite its reputation as a perinatal pathogen, GBS infection rates in non-pregnant adults are also increasing. While much progress has been made to understand transcriptional regulation of virulence by two-component systems, many aspects of GBS virulence regulation remain understudied. Although many bacterial pathogens utilize high temperature response A (HtrA) family serine proteases to regulate virulence and stress responses through varied mechanisms, the function of HtrA in GBS was unknown. Here, we demonstrate that HtrA is localized to the GBS membrane and regulates the abundance of endogenous surface and secreted proteins, including a subset of virulence factors. Although deletion of htrA (ΔhtrA) increased dissemination to placentas and fetuses, this strain caused significantly fewer adverse pregnancy outcomes compared to isogenic wild-type (WT). Placentas from ΔhtrA-infected dams contained more chemokines, pro-inflammatory IL-1β, and neutrophil myeloperoxidase than isogenic WT-infected placentas, suggesting that ΔhtrA GBS induces potent neutrophil chemotaxis. However, immunosuppressive IL-10 was present at increased concentration, which may in part explain the attenuation of adverse pregnancy outcomes during ΔhtrA infection. Finally, we note that recombinant GBS HtrA directly cleaves human fibronectin in vitro, highlighting that this protease may also target host substrates during infection. Together, these findings support a role for HtrA as a post-translational regulator of GBS virulence and suggest that inhibiting HtrA activity may hold therapeutic promise against GBS induced adverse pregnancy outcomes.},
}

@article {pmid41051932,
year = {2025},
author = {Jones, SMW and Aoki, RF and Alexeeff, SE and Carrell, D and Cronkite, D and Kushi, LH and Mosen, D and Strayhorn, S and Tuzzio, L and Mogk, J and Mammini, L and Kroenke, CH},
title = {Evaluation of the Electronic Health Record-Support Social Support Score in Breast Cancer: Comparison of Count and Item Response Theory Scores.},
journal = {Population health management},
volume = {},
number = {},
pages = {},
doi = {10.1177/19427891251383539},
pmid = {41051932},
issn = {1942-7905},
abstract = {In breast cancer, clinicians add data on social support to patient electronic health records (EHRs) often in free text notes, but those data may be challenging to use for population health initiatives or research purposes. We evaluated the EHR-Support score designed to summarize need for social support using data from the EHR. This study included 996 women from the Pathways study, a Kaiser Permanente Northern California cohort of women diagnosed in 2005-2013 with breast cancer. This unique data resource included both EHR data and questionnaire data on patient-reported social support. Using unstructured EHR data and natural language processing, we developed 11 concept groups (items) characterizing social support. We also used structured data to create two additional concept groups. EHR-Support scores reflecting the lack of social support were generated three ways: counting the number of negative concept groups (count score), using item response theory (IRT), and converting counts to the IRT metric (converted count scores). The count scores were only associated with two of six patient-reported measures (r's: -0.004 to -0.073). The IRT score (r's: -0.038 to -0.179) and converted count score (r's: -0.032 to -0.195) were associated with five of six patient-reported measures, indicating more need for support was associated with less patient-reported social support. The EHR-Support score is a valid and feasible measure of social support that can be used for health services research and managing population health. The converted count score may provide the best balance of validity, precision from IRT and feasibility.},
}

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

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

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

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

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

@article {pmid41047130,
year = {2025},
author = {Johnson, JJ and Ghosh, S and Shaw, PA and Neuhouser, ML and Lampe, JW and Tinker, LF and Prentice, RL and Tasevska, N and Freedman, LS and Boyer, BB and Hopkins, SE and Nash, SH and Votruba, SB and Krakoff, J and O'Brien, DM},
title = {The carbon isotope ratio of alanine is a biomarker of added sugar and sugar-sweetened beverage intakes: a pooled analysis of four studies.},
journal = {The American journal of clinical nutrition},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.ajcnut.2025.09.049},
pmid = {41047130},
issn = {1938-3207},
abstract = {BACKGROUND: The alanine carbon isotope ratio (Ala CIR) biomarker was positively associated with added sugar (AS) and sugar-sweetened beverage (SSB) intake in multiple studies from the USA. Association strengths varied, and Ala CIR was also correlated with protein source in certain studies.

OBJECTIVE: To examine Ala CIR associations with AS and SSB intake and animal protein ratio (animal protein/total protein, APR), and adjustment for APR, by pooling data from 4 previous studies.

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

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

CONCLUSIONS: The Ala CIR is a robust biomarker of AS/SSB intake. Potential associations with APR can be adjusted for using a simultaneously-measured biomarker.

(DBD study) clinicaltrials.gov/NCT01237093; (NPAAS) clinicaltrials.gov/NCT00000611.},
}

@article {pmid41046201,
year = {2025},
author = {Robesti, D and Micheli, F and Rai, SN and Fallara, G and Gallina, A and Montorsi, F and Briganti, A and Fossati, N and Grivas, P and van der Heijden, AG and Ploussard, G and Malavaud, B and Martini, A},
title = {Addressing Uneven Treatment Discontinuation Rate in the Chemotherapy Arm of the EV-302 Phase 3 Randomized Clinical Trial: Implications for Outcome Interpretation.},
journal = {Clinical genitourinary cancer},
volume = {},
number = {},
pages = {102423},
doi = {10.1016/j.clgc.2025.102423},
pmid = {41046201},
issn = {1938-0682},
abstract = {INTRODUCTION: The EV-302 trial demonstrated a very significant overall survival (OS) benefit for Enfortumab Vedotin plus Pembrolizumab (EVP) relative to standard chemotherapy (CHT) for patients with metastatic urothelial carcinoma. However, questions have been raised regarding the high rate of treatment discontinuation in the CHT arm for reasons unrelated to adverse events or progression (33% vs. 10% with EVP, P < .01), potentially resulting in loss of unaccounted information, or informative censoring, and affecting survival results interpretation.

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

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

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

@article {pmid41046057,
year = {2025},
author = {Arnold, DE and Leiding, JW and Logan, B and Marsh, RA and Griffith, LM and Grunebaum, E and Murguía-Favela, L and Mallhi, K and Chellapandian, D and Deal, CL and Lim, SS and Prasad, V and Heimall, J and Chandrakasan, S and Chen, K and Yu, LC and Seroogy, CM and Gillio, A and Bednarski, JJ and Kapoor, N and Moore, TB and Cuvelier, GDE and Touzot, F and Rayes, A and Ebens, CL and Schaefer, E and Bauchat, A and Chopek, A and Burroughs, L and Cowan, MJ and Dvorak, CC and Haddad, E and Kohn, DB and Notarangelo, LD and Pai, SY and Puck, JM and Pulsipher, MA and Torgerson, T and Malech, HL and Kang, EM and Parikh, S},
title = {Umbilical Cord Blood Transplantation Provides an Alternative for Patients with Chronic Granulomatous Disease Lacking HLA-Matched Donors: a PIDTC Report.},
journal = {Transplantation and cellular therapy},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jtct.2025.05.020},
pmid = {41046057},
issn = {2666-6367},
abstract = {BACKGROUND: Allogeneic hematopoietic cell transplantation corrects the phagocytic defect in patients with chronic granulomatous disease (CGD) and resolve infection risk and immune dysregulation. Umbilical cord blood transplantation (UCBT) is an option for patients lacking suitable HLA-matched bone marrow or peripheral blood stem cell donors. However, information related to UCBT for CGD is limited to a few small case series and limited subsets of larger cohorts where detailed information is lacking.

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

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

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

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

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

@article {pmid41001449,
year = {2025},
author = {Ssemambo, PK and Burton, M and Mirembe, BG and Nakabiito, C and Donnell, D and Beauchamp, G and Delany-Moretlwe, S and Celum, C and Velloza, J},
title = {Correlates of long-acting reversible contraceptive (LARC) use among young women in Southern Africa: a secondary analysis from HPTN 082.},
journal = {medRxiv : the preprint server for health sciences},
volume = {},
number = {},
pages = {},
pmid = {41001449},
abstract = {BACKGROUND: Long-acting reversible contraception (LARCs), including intrauterine devices (IUDs), injectables, and implants, are highly effective in preventing unintended pregnancies but LARC use rates are low among African adolescents and young women (AGYW). Understanding factors associated with LARC uptake and continuation among African AGYW may provide insights into strategies to promote LARC use.

METHODS: We conducted a secondary data analysis from the HIV Prevention Trials Network (HPTN 082) pre-exposure prophylaxis (PrEP) study, which enrolled 451 AGYW in Zimbabwe and South Africa ages 16-25 years, who reported vaginal or anal sex in the prior month, and reported PrEP interest (ClinicalTrials.gov, NCT02732730). Contraception and contraceptive counseling were offered at enrollment and visits at 4, 8, 13, 26, and 39 weeks post enrollment, with follow-up through 52 weeks. The outcome variable was any LARC use, defined as copper or hormonal IUDs, injectable contraceptives, and implants. We performed descriptive analyses and regression models to assess contraceptive use patterns and characteristics associated with LARC use and condomless sex.

RESULTS: Overall, 60% (299/499) of AGYW adopted a LARC method at enrollment and 78% (234/299) persisted on a LARC method during follow up. Among the 449 women who used contraception at enrollment and/or during follow-up, 38 (8.4%) switched between non-LARC to LARC and 34 (7.5%) discontinued contraception at some point during the study. AGYW not using a LARC at enrollment were more likely to switch contraceptive method through week 39 compared to those already using a LARC (32.7% vs. 14.7%, respectively; p-value<0.001). Factors significantly associated with choosing a LARC method were prior pregnancy [adjusted odds ratio [aOR]:2.46; 95% confidence interval [CI]: 1.59-3.79; p<0.01], and comfort talking to close friends about sexual relationships [aOR:1.82; 95% CI:1.02-3.23; p=0.04]. Consistent condom users were less likely to choose a LARC method [aOR:0.27; 95% CI:0.19-0.39; p<0.01].

CONCLUSION: Contraceptive counseling and offering LARC methods with HIV PrEP was associated with a majority of African AGYW selecting a LARC method. Peer support is important in facilitating LARC use and the high contraceptive efficacy of LARC should be discussed with AGYW using condoms for contraception. Contraceptive counseling and promotion of LARCs should be integrated with PrEP delivery for African AGYW.},
}