@article {pmid41400994,
year = {2025},
author = {Holland, M and Ahmed, M and Young, JM and Drurey, JR and McFadyen, S and Ostrowski, EA and Levin, TC},
title = {Hypermutable hotspot enables the rapid evolution of self/non-self recognition genes in Dictyostelium.},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
volume = {122},
number = {51},
pages = {e2520843122},
doi = {10.1073/pnas.2520843122},
pmid = {41400994},
issn = {1091-6490},
support = {R35-GM150681//HHS | NIH | National Institute of General Medical Sciences (NIGMS)/ ; R01-GM74108//HHS | NIH | National Institute of General Medical Sciences (NIGMS)/ ; 1176659//Burroughs Wellcome Fund (BWF)/ ; },
mesh = {*Dictyostelium/genetics ; *Evolution, Molecular ; *Protozoan Proteins/genetics ; Phylogeny ; Genome, Protozoan ; Mutation ; Haplotypes ; },
abstract = {Cells require highly polymorphic receptors to perform accurate self/non-self recognition. In the amoeba Dictyostelium discoideum, polymorphic TgrB1 and TgrC1 proteins are used to bind sister cells and exclude cheaters, but it remains unknown how cells continually generate their extreme genetic diversity. Here, we created a collection of chromosome-length, whole genome sequences from 10 D. discoideum isolates and sister species to understand the evolution of the large tgr gene family. Our dataset includes AX2-214, a widely used D. discoideum lab strain, as well as complete genomes for two Chlamydia-like endosymbionts harbored within amoebae. We find that tgrB1 and C1 lie in a hypermutational hotspot, with haplotypes that undergo repeated intralocus recombination, duplications, transpositions, and inversions. These structural dynamics are highly localized adjacent to tgrB and C, resulting in the gain and loss of dozens of genes. The tgrBC genes themselves frequently duplicate and recombine, leading to the rapid generation of unique tgrBC repertoires. In the broader tgr gene family, some genes (e.g., tgrN) are single copy and syntenic across all the genomes, whereas others (e.g., tgrA) prolifically duplicate at similar rates to Dictyostelium transposons. Thus, the tgr genes are among the most rapidly evolving families genome-wide. We propose that the intense diversification within the tgrBC locus can help explain how these genes acquire such extreme levels of polymorphism, with parallels to the MHC immune genes in mammals and other allorecognition systems. This collection of amoeba genomes is also a useful resource for future comparative genomics and molecular evolution studies in Amoebozoa.},
}

*Dictyostelium/genetics
*Evolution, Molecular
*Protozoan Proteins/genetics
Phylogeny
Genome, Protozoan
Mutation
Haplotypes

@article {pmid41398395,
year = {2025},
author = {Zhou, X and Sevilla-Gonzalez, M and Phipps, AI and Udler, M and Castellví-Bel, S and Chan, AT and Pellatt, AJ and Schoen, RE and Giovannucci, E and Gunter, MJ and Florez, JC and Peters, U and Song, M and Merino, J},
title = {Diabetogenic processes for insulin resistance-linked hyperinsulinaemia are associated with colorectal cancer.},
journal = {Diabetologia},
volume = {},
number = {},
pages = {},
pmid = {41398395},
issn = {1432-0428},
support = {U01 CA137088/CA/NCI NIH HHS/United States ; R01 CA201407/CA/NCI NIH HHS/United States ; R01 CA273198/CA/NCI NIH HHS/United States ; },
abstract = {AIMS/HYPOTHESIS: Type 2 diabetes has been associated with increased risk of colorectal cancer (CRC), but the specific diabetogenic pathways contributing to this risk remain unclear.

METHODS: We analysed individual-level data from 129,420 participants of European ancestry in the Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO) and the Colon Cancer Family Registry (CCFR), comprising 58,531 patients with CRC and 70,889 control participants. We applied eight validated partitioned polygenic scores (PPSs) representing distinct diabetogenic processes: two related to relative insulin secretion insufficiency and six to insulin resistance with varying degrees of preserved insulin secretion. Adjusted ORs and 95% CIs for CRC and early-onset CRC were estimated using conditional logistic regression.

RESULTS: PPSs reflecting insulin resistance-linked hyperinsulinaemia, particularly those related to lipodystrophy, body fat and obesity, were associated with higher odds of CRC (p<0.001 for each). Compared with individuals in the lowest decile, those in the highest decile had ORs of 1.09 (95% CI 1.05, 1.14), 1.13 (1.09, 1.18) and 1.15 (1.10, 1.20) for lipodystrophy, body fat and obesity, respectively. In contrast, PPSs for insulin secretion insufficiency or insulin resistance without hyperinsulinaemia were not associated with CRC. The obesity-related hyperinsulinaemic insulin resistance PPS was also associated with higher odds of early-onset CRC (OR for top vs bottom decile=1.26; 95% CI 1.13, 1.41), with the strongest association among those with obesity (OR 1.75; 95% CI 1.46, 2.11; p value for interaction with BMI <0.001).

CONCLUSIONS/INTERPRETATION: Diabetogenic processes characterised by insulin resistance-linked hyperinsulinaemia were associated with increased odds of CRC, including early-onset disease. These findings offer new insights into diabetes-CRC pathogenesis, and may inform targeted prevention strategies.},
}

@article {pmid41358287,
year = {2025},
author = {Sevilla-González, M and Wang, N and Hanson, PA and Bebo, A and Hitchcock, D and Hsu, S and Westerman, KE and Cromer, SJ and Barry, VG and Borns-Weil, Y and Zhang, Y and Ben-Yossef, O and Patel, CJ and Franceschini, N and Taylor, KD and Ávila-Pacheco, J and Clish, CB and Gertzen, RE and Raffield, LM and Kooperberg, C and Rich, SS and Dupuis, J and Rotter, JI and Liu, CT and Meigs, JB and Manning, AK},
title = {Dissecting Genetic and Environmental Determinants of Plasma Molecular Signatures and Their Link to Type 2 Diabetes Risk.},
journal = {medRxiv : the preprint server for health sciences},
volume = {},
number = {},
pages = {},
pmid = {41358287},
support = {75N92021D00005/WH/WHI NIH HHS/United States ; 75N92020D00001/HL/NHLBI NIH HHS/United States ; U01 HL120393/HL/NHLBI NIH HHS/United States ; 75N98025D00025/OD/NIH HHS/United States ; N01 HC095167/HL/NHLBI NIH HHS/United States ; P30 DK063491/DK/NIDDK NIH HHS/United States ; HHSN268201800001C/HL/NHLBI NIH HHS/United States ; 75N92021D00003/WH/WHI NIH HHS/United States ; HHSN268201500003I/HL/NHLBI NIH HHS/United States ; 75N98025D00027/OD/NIH HHS/United States ; UL1 TR000040/TR/NCATS NIH HHS/United States ; 75N92021D00004/WH/WHI NIH HHS/United States ; 75N98025D00026/OD/NIH HHS/United States ; N01 HC095160/HL/NHLBI NIH HHS/United States ; 75N92020D00002/HL/NHLBI NIH HHS/United States ; 75N98025D00028/OD/NIH HHS/United States ; 75N92021D00002/HL/NHLBI NIH HHS/United States ; HHSN268201500003C/HL/NHLBI NIH HHS/United States ; N01 HC095161/HL/NHLBI NIH HHS/United States ; 75N92020D00005/HL/NHLBI NIH HHS/United States ; N01 HC095168/HL/NHLBI NIH HHS/United States ; R01 HL120393/HL/NHLBI NIH HHS/United States ; 75N98025D00024/OD/NIH HHS/United States ; UL1 TR001079/TR/NCATS NIH HHS/United States ; N01 HC095169/HL/NHLBI NIH HHS/United States ; K99 DK139461/DK/NIDDK NIH HHS/United States ; N01 HC095159/HL/NHLBI NIH HHS/United States ; 75N92020D00003/HL/NHLBI NIH HHS/United States ; R01 HL105756/HL/NHLBI NIH HHS/United States ; 75N92021D00001/HL/NHLBI NIH HHS/United States ; UL1 TR001420/TR/NCATS NIH HHS/United States ; 75N92020D00004/HL/NHLBI NIH HHS/United States ; 75N98025D00022/OD/NIH HHS/United States ; N01 HC095163/HL/NHLBI NIH HHS/United States ; 75N92020D00007/HL/NHLBI NIH HHS/United States ; N01 HC095166/HL/NHLBI NIH HHS/United States ; UM1 DK078616/DK/NIDDK NIH HHS/United States ; 75N92020D00006/HL/NHLBI NIH HHS/United States ; R01 HL117626/HL/NHLBI NIH HHS/United States ; N01 HC095162/HL/NHLBI NIH HHS/United States ; UL1 TR001881/TR/NCATS NIH HHS/United States ; N01 HC095165/HL/NHLBI NIH HHS/United States ; N01 HC095164/HL/NHLBI NIH HHS/United States ; },
abstract = {BACKGROUND: Type 2 diabetes (T2D) is a heterogeneous disease shaped by both genetic, environmental, cultural, and socioeconomic factors, with well-documented disparities in incidence across populations. The molecular pathways underlying these disparities, however, remain poorly understood. Plasma metabolites and proteins integrate both genetic and environmental influences on type 2 diabetes (T2D) risk, providing insight into disease mechanisms. We aimed to quantify the variance in these molecular profiles explained by environmental and genetic ancestry domains and to apply causal inference approaches to identify environmentally and genetic ancestry influenced pathways contributing to T2D risk.

METHODS: We analyzed plasma proteomic and metabolomic profiles from 3,360 MESA participants (51.6% female), and in 1,333 participants from the Women's Health Initiative. To characterize the sources of variance in plasma proteomic and metabolomic profiles, we performed variance decomposition partitioning into four domains: biological (age, sex, BMI), genetic ancestry (principal components), lifestyle (smoking, alcohol intake, diet), and social determinants (self-reported race and ethnicity, income, education). To assess causal pathways towards T2D risk, we applied two-sample Mendelian Randomization to disentangle environmental and genetic contributors to T2D risk.

RESULTS: The largest share of variance in proteomic and metabolomic profiles was explained by biological and lifestyle factors, while race and ethnicity and genetic ancestry accounted for smaller but non-redundant contributions. Genetic ancestry was primarily associated with lipid and apolipoprotein variation, whereas race and ethnicity and socioeconomic factors were associated with immune and inflammatory signatures. Environmentally influenced metabolites (e.g., diacylglycerols, phosphatidylethanolamines, lysophosphatidylcholines) and vascular-inflammatory proteins were consistently linked to higher T2D risk, while genetic ancestry influenced triglycerides and IGFBP3 reflected inherited risk pathways. Mediation analyses showed that selected lipids and proteins (e.g., IGFBP2, HGF, SSC4D) explained 10-25% of racial/ethnic disparities in T2D. Mendelian randomization identified causal roles for seven lipid species and IGFBP3 in T2D risk.

CONCLUSIONS: Our results reveal both genetic and non-genetic sources of variation in proteomic and metabolomic profiles, uncovering environmental and genetic pathways contributing to T2D risk. These findings advance precision medicine by identifying modifiable molecular mediators of disparities and potential causal targets for prevention.},
}

@article {pmid41333381,
year = {2025},
author = {Vasavada, A and Palazzo, L and Luce, C and Sanchez, M and Triplette, M and Ralston, JD and Carter-Bawa, L and Green, BB and Gao, H and Li, CI and Anderson, ML and Su, YR and Rogers, K and Wernli, KJ},
title = {"It's coming whether we want it to or not": A qualitative exploration of older adults' comfort with and perceptions of technology and digital health.},
journal = {Research square},
volume = {},
number = {},
pages = {},
pmid = {41333381},
issn = {2693-5015},
support = {R01 CA262015/CA/NCI NIH HHS/United States ; },
abstract = {BACKGROUND: Older adults bear a disproportionate cancer burden but remain underrepresented in digital health intervention trials compared to younger counterparts. Since the COVID-19 pandemic, engagement with telemedicine and patient portals through the electronic health record (EHR) has grown for all age groups, suggesting readiness to adopt digital health tools. This qualitative study primarily sought to understand how adults eligible for lung cancer screening (LCS) engage with technology and digital health in their daily lives. The secondary objective was to assess acceptability and compatibility of a video-based LCS health communication as a digital health tool.

METHODS: Semi-structured interviews were conducted with 15 participants aged 51-80 through videoconferencing or telephone. Transcripts were analyzed using a rapid team-based analysis approach. The Consolidated Framework for Implementation Research (CFIR) was used as a guiding framework from throughout the study, with constructs of interest informing interview guide questions in data collection, and CFIR-mapping to generate a code list in the analysis.

RESULTS: Our findings generated four CFIR-informed themes, with 8 subthemes: 1) Internal facilitators: comfort with technology, self-efficacy in troubleshooting; 2) External facilitators: leveraging internet for health information, use of wearable devices, patient portal functionalities; 3) Internal barriers: emotional response, social isolation; 4) External barriers: scamming and data privacy. When shown the LCS video-based health communication, participants described general approval of the content and delivery but expressed concerns about safety related to accessing the video due to its delivery via weblink.

CONCLUSIONS: Broadly, we found that older adults had high levels of technology use and leveraged various digital tools (such as wearable devices, mobile applications, and EHR patient portals) to manage their health care needs. Our findings underscore that older adults are active users of digital tools, yet persistent concerns about privacy, social isolation, and emotional burden must be addressed for digital health interventions to be acceptable and sustainable in this population.

TRIAL REGISTRATION: ClinicalTrials.gov: NCT05747443; 2023-02-17.},
}

@article {pmid41332752,
year = {2025},
author = {Hsieh, HC and Gao, G and Han, Q and Brenes, D and Baraznenok, E and Yan, R and Serafin, R and Bishop, KW and Wang, R and Konnick, EQ and Pritchard, CC and Figiel, S and Hamdy, FC and Mills, IG and Reder, NP and Reddi, DM and Paulson, TG and Grady, WM and Valk, JE and True, LD and Haffner, MC and Rao, SR and Woodcock, DJ and Liu, JTC},
title = {3D pathology-guided microdissection.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {41332752},
issn = {2692-8205},
support = {R01 CA268207/CA/NCI NIH HHS/United States ; P50 CA097186/CA/NCI NIH HHS/United States ; U01 CA182940/CA/NCI NIH HHS/United States ; U2C CA271902/CA/NCI NIH HHS/United States ; R01 CA220004/CA/NCI NIH HHS/United States ; R01 DK138948/DK/NIDDK NIH HHS/United States ; U54 DK137328/DK/NIDDK NIH HHS/United States ; R01 EB031002/EB/NIBIB NIH HHS/United States ; U01 CA152756/CA/NCI NIH HHS/United States ; U54 CA163060/CA/NCI NIH HHS/United States ; },
abstract = {Traditional micro- and macro-dissection techniques enable the extraction of localized regions in thin tissue sections for molecular analysis. Despite the growing use of 3D microscopy, analogous methods for volumetric microdissection are lacking. We have developed a 3D microdissection method based on computer numerical controlled (CNC) milling integrated with open-top light-sheet microscopy. We demonstrate the ability to study tumor evolution along convoluted 3D branching architectures, which is inaccessible to 2D methods.},
}

@article {pmid41332638,
year = {2025},
author = {McCutcheon, KR and Wu, J and Ozdemir, YC and McKinney, BJ and Srinivasan, S and Itokawa, A and Newsom, OJ and Vigil, A and Fox, DB and Sullivan, LB and Alvarez, JV},
title = {Recurrent Breast Cancer Cells Depend on De novo Pyrimidine Biosynthesis to Suppress Ferroptosis.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {41332638},
issn = {2692-8205},
support = {P30 CA015704/CA/NCI NIH HHS/United States ; R01 CA285322/CA/NCI NIH HHS/United States ; R01 CA292658/CA/NCI NIH HHS/United States ; },
abstract = {Breast cancer recurrence remains a major clinical challenge, often associated with therapy resistance and altered metabolic states. To define metabolic vulnerabilities of recurrent disease, we performed a CRISPR knockout screen targeting 421 metabolic genes in paired primary and recurrent HER2-driven breast cancer cell lines. While both primary and recurrent tumors shared dependencies on core metabolic pathways, recurrent tumors exhibited selective essentiality for the de novo pyrimidine synthesis pathway, including Cad, Dhodh, and Ctps. Pharmacologic inhibition of the rate-limiting enzyme DHODH with BAY-2402234 selectively impaired the growth of recurrent tumor cells, while primary tumor cells were relatively resistant. BAY treatment robustly inhibited pyrimidine synthesis in all lines, but only recurrent cells underwent iron-dependent lipid peroxidation and ferroptotic cell death. Lipidomic profiling revealed enrichment of polyunsaturated ether phospholipids in recurrent cells, which may predispose them to ferroptosis. A sensitizer CRISPR screen in primary cells further identified nucleotide salvage and lipid metabolic pathways as modifiers of DHODH inhibitor sensitivity. Stable isotope tracing and nutrient depletion experiments showed that primary cells can compensate for DHODH inhibition through nucleotide salvage, whereas recurrent cells exhibit impaired salvage capacity, likely due to reduced expression of Slc28/Slc29 nucleoside transporters. Together, these findings reveal that breast cancer recurrence is associated with increased dependence on de novo pyrimidine synthesis to suppress ferroptosis, highlighting a therapeutically actionable metabolic vulnerability in recurrent disease.},
}

@article {pmid41397550,
year = {2025},
author = {Saultz, JN and Bolon, YT and Wang, T and Spellman, S and Lee, S and He, M and Camacho-Bydume, C and Krishna, C and Chowell, D and Shaffer, BC and Hsu, KC and Paczesny, S and Gadalla, SM and Marsh, SGE and Betts, BC and Arrieta-Bolaños, E},
title = {HIGHER HLA-DRB1 EVOLUTIONARY DIVERGENCE (HED) IS ASSOCIATED WITH REDUCED RELAPSE AND IMPROVED SURVIVAL AFTER MATCHED UNRELATED HEMATOPOIETIC CELL TRANSPLANTATION.},
journal = {Transplantation and cellular therapy},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jtct.2025.12.949},
pmid = {41397550},
issn = {2666-6367},
abstract = {BACKGROUND: HLA evolutionary divergence (HED) can be used as a surrogate for the degree of immunopeptidome diversity of HLA phenotypes. Different degrees of HED in the patient-donor pair may influence the presentation of peptides relevant for alloreactive responses involved in graft-versus-host and graft-versus-leukemia (GvL) effects, potentially impacting outcomes after hematopoietic cell transplantation (HCT).

OBJECTIVE(S): To test whether higher HED scores (both class I and class II) correlate with improved GvL and survival after HLA-matched HCT.

STUDY DESIGN: Pediatric and adult patients (N=9,231) reported to the Center for International Blood and Marrow Transplant Research (CIBMTR) database who underwent a first HCT from 8/8 matched unrelated donors between 2008 and 2018 for the treatment of acute myeloid leukemia, acute lymphoblastic leukemia, myelodysplastic syndrome, chronic myeloid leukemia, or lymphoma were included. HED was calculated on the amino acid sequences at HLA-A, HLA-B, HLA-C, and HLA-DRB1, and class I (HLA-A, HLA-B, HLA-C), and HLA-DRB1 HED scores were assigned to each patient-donor pair. The association between increasing HED (top quartile vs lower three quartiles) and HCT outcome was evaluated with malignant disease relapse and disease-free (DFS) and overall survival (OS) as primary endpoints. Secondary enpoints were transplant-related mortality (TRM), acute and chronic graft-versus-host disease (GvHD), and engraftment.

RESULTS: Greater HLA-DRB1 HED was associated with significantly decreased malignant disease relapse [HR 0.86; 95% CI, 0.79-0.94; P=0.0014], better disease free survival [HR 0.92; 95% CI, 0.86-0.98; P=0.0067] and improved OS [HR 0.91; 95% CI, 0.85-0.96; p=0.0019] in the total population after adjustment for other significant clinical variables. There was no significant association between HLA-DRB1 HED and TRM, or risk of acute or chronic GVHD. Conversely, higher (upper quartile) HLA class I HED did not significantly impact OS, DFS, TRM, relapse, or acute and chronic GVHD, compared with the lower three quartiles. In addition, neither class I nor HLA-DRB1 HED significantly impact neutrophil or platelet engraftment post transplant.

CONCLUSION(S): Higher HLA-DRB1 HED scores are associated with reduced relapse, improved DFS and OS in patients undergoing matched unrelated donor transplantation for hematological malignancies. These findings contribute to the growing evidence supporting the importance of HED in post-transplant outcomes. However, further refinement and validation are required before incorporating HED into clinical transplant risk assessment.},
}

@article {pmid41397238,
year = {2025},
author = {Cloos, J and Valk, PJM and Thiede, C and Döhner, K and Roboz, GJ and Wood, BL and Walter, RB and Wang, SA and Wierzbowska, A and Wei, AH and Wu, D and Vergez, F and Venditti, A and van der Reijden, BA and van de Loosdrecht, AA and Tiong, IS and Thol, FR and Subklewe, M and Roumier, C and Reuvekamp, T and Ravandi, F and Preudhomme, C and Plesa, A and Othman, J and Ossenkoppele, GJ and Ofran, Y and Mimoun, A and Maurillo, L and Majchrzak, A and de Leeuw, DC and Kern, W and Kim, DDHDH and Ikoma-Colturato, MRV and Haaksma, LH and Guzman, ML and Feuring, M and Depreter, B and Czyz, A and Bücklein, VL and Baer, C and Bachas, C and Freeman, SD and Buccisano, F and Hourigan, CS and Dillon, RJ and Heuser, M},
title = {2025 Update on MRD in Acute Myeloid Leukemia: A Consensus Document from the ELN-DAVID MRD Working Party.},
journal = {Blood},
volume = {},
number = {},
pages = {},
doi = {10.1182/blood.2025031480},
pmid = {41397238},
issn = {1528-0020},
abstract = {Measurable residual disease (MRD) monitoring has become a critical component in the management of acute myeloid leukemia (AML), to inform prognosis, guide therapy, and serve as a key endpoint in clinical trials. The 2025 update of the MRD guideline provides a comprehensive and refined framework for MRD assessment, aligned with the ELN 2022 genetic risk classification. Developed by members of the ELN-DAVID consortium, the guidelines incorporate expert consensus determined through a two-stage Delphi round. They address the clinical implementation of MRD methodologies, technical considerations, integration into clinical trials, and future directions. Importantly, MRD recommendations are tailored to individual prognostic and genetic subgroups. A new qualitative MRD response category, designated as optimal, warning, or high risk of treatment failure, has been introduced to facilitate contextual interpretation of the MRD burden and its clinical relevance. Notably, ultrahigh-sensitivity (UHS) NGS-based MRD assessment is now recommended for FLT3-ITD-mutated AML following intensive chemotherapy and prior to allogeneic hematopoietic cell transplantation. A total of 56 recommendations were formulated, with 53 achieving a high level of consensus (≥90%). These updated guidelines represent a major step forward toward harmonizing MRD assessments in AML and enhancing its clinical utility across diverse treatment settings.},
}

@article {pmid41397203,
year = {2025},
author = {Kouadio, C and Selukar, S and Othus, M and Chevret, S},
title = {Detecting the Cure Model Appropriateness in Randomized Clinical Trials With Long-Term Survivors.},
journal = {JCO clinical cancer informatics},
volume = {9},
number = {},
pages = {e2500084},
doi = {10.1200/CCI-25-00084},
pmid = {41397203},
issn = {2473-4276},
mesh = {Humans ; *Randomized Controlled Trials as Topic/methods ; *COVID-19/virology/mortality/epidemiology/therapy ; SARS-CoV-2/isolation & purification ; *Cancer Survivors/statistics & numerical data ; Computer Simulation ; *Models, Statistical ; },
abstract = {PURPOSE: To evaluate the appropriateness of a cure model when analyzing right-censored end points of a randomized clinical trial (RCT) in malignancy in the presence of long-term survivors. We aim to derive how the ratio estimation of censored cured subjects (RECeUS), previously proposed for a homogeneous population, could be extended for use in RCTs.

METHODS: Based on the RECeUS method, four decision rules were considered to assess the appropriateness of a cure model. They considered the eligibility conditions to be met: in both arms, in at least one randomized arm, in the entire sample, or when only considering an average of the conditions, respectively. A simulation study was performed to evaluate their performance and the impact of the link function when considering the appropriateness of cure models. We also illustrate the method using two real data examples from two RCTs conducted in patients with acute leukemia and COVID-19 disease.

RESULTS: Simulation results show that the best decision rule that can be applied in all considered treatment effect scenarios might be to check the criteria in at least one randomized arm. Regardless of the rules, the cure model appeared to be appropriate in both RCT data.

CONCLUSION: When analyzing survival data from RCTs, the appropriateness of a cure model could be considered in the face of a plateau shape of the survival curves. To ensure that the presence of such a plateau in the survival curves is a reliable indicator of the presence of cured patients in the population, the RECeUS method should be used in each randomized arm separately, with criteria met in at least one randomized arm.},
}

Humans
*Randomized Controlled Trials as Topic/methods
*COVID-19/virology/mortality/epidemiology/therapy
SARS-CoV-2/isolation & purification
*Cancer Survivors/statistics & numerical data
Computer Simulation
*Models, Statistical

@article {pmid41397186,
year = {2025},
author = {Huang, AH and Lee, GY and Lu, CA and Sahin, IH and King, GT and Safyan, RA and Cohen, SA and Zhen, DB and Shankaran, V and Harris, WP and Coveler, AL and Malhotra, J and Forbes, VE and Gold, PJ and Chiorean, EG and Hsieh, RW},
title = {Rechallenge With an Epidermal Growth Factor Receptor Inhibitor in Metastatic Colorectal Cancer: A Systematic Review and Meta-Analysis.},
journal = {JCO oncology practice},
volume = {},
number = {},
pages = {OP2500646},
doi = {10.1200/OP-25-00646},
pmid = {41397186},
issn = {2688-1535},
abstract = {PURPOSE: Clonal evolution is a mechanism of treatment resistance against epidermal growth factor receptor inhibitors (EGFRi) in metastatic colorectal cancer (mCRC). When EGFRi is discontinued, EGFRi-resistant tumor subclones decay with time, allowing for EGFRi rechallenge at later time. We conducted a meta-analysis to investigate the efficacy of EGFRi rechallenge in mCRC.

METHODS: Clinical trials and observational studies investigating the efficacy of EGFRi rechallenge in mCRC were included from PubMed and Embase from inception to December 8, 2024. Hazard ratios (HRs) of overall survival (OS) and progression-free survival (PFS) were aggregated using Bayesian random-effects models. Objective response rates (ORRs) were aggregated using meta-random-effects models.

RESULTS: Twenty-nine studies were included. The pooled median PFS, median OS, and ORR were 3.83 months (95% CI, 3.25 to 4.50), 10.43 months (95% CI, 8.14 to 13.36), and 14.61% (95% CI, 8.70 to 23.51), respectively. EGFRi rechallenge was associated with significantly longer pooled PFS (HR, 0.54 [95% CI, 0.31 to 0.93]) and numerically longer pooled OS (HR, 0.71 [95% CI, 0.46 to 1.09]) than non-EGFRi systemic therapy. Patients without detectable RAS/RAF mutations by circulating tumor DNA (ctDNA) at the time of EGFRi rechallenge had significantly longer OS (HR, 0.43 [95% CI, 0.24 to 0.75]) and PFS (HR, 0.40 [95% CI, 0.26 to 0.62]) than those with ctDNA RAS/RAF mutations. Studies with EGFRi-free intervals ≥4 months before rechallenge (18.77%) had a numerically greater pooled ORR than those with EGFRi-free intervals <4 months (6.60%). No unexpected adverse events were reported, and treatment discontinuation because of adverse events was 2.7%.

CONCLUSION: EGFRi rechallenge is associated with significantly longer PFS, numerically longer OS, and clinically meaningful ORR as compared with non-EGFRi systemic therapy in mCRC, particularly for ctDNA RAS/RAF wild-type mCRC.},
}

@article {pmid41396068,
year = {2025},
author = {Lee, P and Nelson, PS},
title = {The Multifaceted Role of Androgen Receptor Signaling in Immunity: Implications for Oncology.},
journal = {Molecular cancer research : MCR},
volume = {},
number = {},
pages = {},
doi = {10.1158/1541-7786.MCR-25-0802},
pmid = {41396068},
issn = {1557-3125},
abstract = {While the androgen receptor (AR) is canonically known for its role in the prostate and testis, AR signaling exerts broad immunomodulatory effects through direct and indirect signaling in multiple immune cell compartments and contributes significantly to sex differences in autoimmunity, infection, and cancer. Mouse model perturbations of androgen signaling through castration, testicular feminization, and cell type-specific AR knockout have provided important insights into cell-intrinsic and -extrinsic mechanisms by which AR signaling affects innate and adaptive immunity. However, the precise molecular underpinnings of these effects remain largely unknown. Moreover, despite convincing epidemiological and correlative observations that highlight the importance of AR signaling in human immune function, it remains unclear how reliably findings in mice will translate to humans. A better understanding of how to augment immune function through androgen signaling modulation could have significant clinical relevance for the treatment of cancer, as well as other disease states involving immune dysregulation. In this review, we discuss the current evidence for the functional effects of AR signaling within the major immune cell compartments of the innate and adaptive immune systems. We also review ongoing clinical efforts that modify AR signaling for the purpose of enhancing antitumor immunity.},
}

@article {pmid41391604,
year = {2025},
author = {Greenlee, H and Santiago-Torres, M and Contento, I and Koch, PA and Rillamas-Sun, E and Gray, HL and Brickman, AM and Ogden Gaffney, A and Thomson, CA and Crane, TE and Dominguez, N and Sepulveda, J and Marín-Chollom, AM and Paul, R and Shi, Z and Ulanday, KT and Accordino, M and Camacho, FJ and Crew, KD and Kalinsky, K and Taback, B and Trivedi, MS and Hale, C and Reaves, B and Beauchemin, MP and Castellano, M and Fuentes, Y and Eddy, M and Bella, AL and Meisner, A and Hershman, DL},
title = {¡Mi Vida Saludable!: Results of a Randomized, Controlled, 2x2 Factorial Trial of an In-Person and eHealth Diet and Physical Activity Intervention in Latina Breast Cancer Survivors.},
journal = {Journal of the Academy of Nutrition and Dietetics},
volume = {},
number = {},
pages = {156260},
doi = {10.1016/j.jand.2025.156260},
pmid = {41391604},
issn = {2212-2672},
abstract = {BACKGROUND: Latina breast cancer (BC) survivors experience health disparities. Effective lifestyle interventions are sparse.

OBJECTIVE: This trial tested the effectiveness of a culturally-tailored diet and physical activity (PA) intervention in Latina BC survivors.

DESIGN: Using a 2x2 factorial design, women were randomized to receive: 1) 4 weekly in-person group sessions, 2) 11 months of eHealth communications, 3) in-person sessions and eHealth, or 4) control. Follow-up data were collected at months 6 and 12.

PARTICIPANTS/SETTING: Eligibility criteria were self-identification as Latina, post-treatment for early-stage BC, and consuming <5 daily servings of fruits and vegetables (F/V) and/or engaging in <150 minutes/week of moderate-to-vigorous PA (MVPA). A total 167 women from New York City were enrolled from July 2016 to October 2018 with 93.4% retention at 12-month follow-up (n=156).

INTERVENTION: All participants received a Fitbit and one 1:1 health coaching session. In-person group sessions included nutrition and PA education, cooking classes, fitness classes or grocery store visit, and social activities. The eHealth communications included motivational text messaging, emailed newsletters, and study website access. Activities were conducted in Spanish and English.

MAIN OUTCOME MEASURES: Primary outcomes were 12-month change in F/V servings/day and energy density of food. Secondary outcomes were 12-month change in MVPA and anthropometry.

STATISTICAL ANALYSIS: Outcomes comparing intervention arms with the control were examined using generalized estimating equations.

RESULTS: At baseline (n=167), mean age was 56.7 years; 82.3% had overweight/obesity. At month 12, daily F/V intake for women in the in-person sessions increased by 10% and decreased by 44% for women in the control, a +96% group difference (p=0.01); no other between-group differences were observed. At month 12, women in the control had a 53% increase in minutes/week of MVPA while women in the in-person plus eHealth group had a 34% decrease, a -57% group difference (p=0.01); no other between-group differences were noted. No changes in energy density or weight between groups were observed.

CONCLUSION: Women randomized to the in-person ¡Mi Vida Saludable! classes modestly increased F/V intake at 12 months relative to control. Those receiving eHealth communication did not have diet, MVPA, or weight change. More research is needed to understand how to support Latina BC survivors make sustained diet and PA changes.},
}

@article {pmid41390763,
year = {2025},
author = {Singh, S and Islam, SMS and Liu, R and Adeniji, OS and Simons, LM and Saini, P and Tateno, H and Danesh, A and Denton, PW and Giron, LB and Jones, RB and Hultquist, JF and Xiao, H and Abdel-Mohsen, M},
title = {HIV-induced sialoglycans on infected CD4+ T cells promote immune evasion from myeloid cell-mediated killing.},
journal = {Nature communications},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41467-025-66540-y},
pmid = {41390763},
issn = {2041-1723},
support = {R01AI165079//U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (NIAID)/ ; },
abstract = {Sialic acid-containing glycans (sialoglycans) on pathological cells interact with Siglecs, glyco-immune checkpoint receptors expressed on myeloid cells, suppressing the cytotoxic functions of these immune cells. Using targeted glycomic analyses and gene editing, we show that HIV infection reprograms the glycosylation machinery of infected cells to increase the expression of the sialoglycan ligands for Siglec-3, -7, and -9. These ligands engage Siglecs on myeloid cells, impairing their ability to target HIV-infected cells. Selective disruption of these interactions using 10-1074-SiaD, an HIV-specific antibody conjugated to sialidase, an enzyme that removes sialic acids, significantly enhances monocyte- and neutrophil-mediated killing of HIV-infected cells in autologous assays. Treatment with 10-1074-SiaD in female humanized mice infected with HIV reduces viral load and decreases inflammation. These findings reveal an immune evasion mechanism exploited by HIV to evade myeloid cell immune surveillance and highlight the potential of targeting sialoglycan-Siglec interactions to improve immune clearance of HIV-infected cells.},
}

@article {pmid41390126,
year = {2025},
author = {Dickey, AK and Bonkovsky, HL and Balwani, M and Anderson, KE and Levy, C and Thapar, M and Wang, B and Chin, M and Savage, W and Desnick, R and Keel, S},
title = {Bitopertin Shows Efficacy in Patients with Erythropoietic Protoporphyria: Results from the Randomized, Double-Blind, Placebo-Controlled AURORA Trial.},
journal = {Journal of the American Academy of Dermatology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jaad.2025.12.024},
pmid = {41390126},
issn = {1097-6787},
abstract = {BACKGROUND: Erythropoietic protoporphyria is a rare genetic disorder of heme biosynthesis characterized by protoporphyrin-IX accumulation, painful phototoxic reactions, and hepatobiliary disease, for which no disease-modifying therapies are approved.

OBJECTIVE: To evaluate efficacy and safety of bitopertin, an inhibitor of glycine transporter 1, in adults with erythropoietic protoporphyria.

METHODS: In this randomized, double-blind, phase 2 study, patients received once-daily oral bitopertin 20 mg, bitopertin 60 mg, or placebo for 17 weeks. The primary endpoint was percentage change from baseline in whole-blood metal-free protoporphyrin-IX levels at day 121.

RESULTS: Patients received bitopertin 20 mg (n = 26), 60 mg (n = 25), or placebo (n = 24). At day 121, the percentage change from baseline in whole-blood metal-free protoporphyrin-IX versus placebo was -29.6% (P = .004) with bitopertin 20 mg and -49.8% (P < .001) with bitopertin 60 mg. Bitopertin was associated with a reduced incidence of phototoxic reactions. Bitopertin was well tolerated with no notable safety concerns identified.

LIMITATIONS: Small sample size, short follow-up period, and no formal adjustments for between-group multiple-pairwise comparisons.

CONCLUSIONS: Bitopertin significantly reduced protoporphyrin-IX levels, showed improved measures of sunlight tolerance, and had a favorable safety profile in patients with erythropoietic protoporphyria.},
}

@article {pmid41389316,
year = {2026},
author = {McKay, RR and Pal, S and Xie, W and Aggen, D and Albiges, L and Apolo, A and Atkins, MB and Bangs, R and Beckermann, KE and Bellmunt, J and Berg, SA and Bilen, MA and Braun, D and Carlo, MI and Efstathiou, J and Galsky, M and Grivas, P and Gupta, S and Haas, N and Hakimi, AA and Hammers, H and Heng, DYC and Hirsch, M and Iyer, G and Jonasch, E and Koshkin, VS and Kryvenko, O and Lewis, B and Li, R and Matin, S and Maughan, B and McDermott, DF and McGregor, B and Meeks, J and Milowsky, M and Motzer, R and Necchi, A and Petrylak, D and Porten, S and Powles, T and Rini, B and Shuch, B and Siefker-Radtke, A and Sonpavde, G and Sridhar, SS and Suarez, C and Tang, C and Tripathi, A and Van Der Heijden, MS and Voss, M and Xu, W and Zhang, T and Rosenberg, J and Choueiri, TK},
title = {Advanced Urologic Cancer Consensus Conference (AUC3) 2025: Expert consensus on the management of renal cell and urinary tract cancers.},
journal = {CA: a cancer journal for clinicians},
volume = {76},
number = {1},
pages = {e70052},
pmid = {41389316},
issn = {1542-4863},
mesh = {Humans ; *Carcinoma, Renal Cell/therapy/pathology ; *Kidney Neoplasms/therapy/pathology ; *Urologic Neoplasms/therapy/pathology ; Consensus ; Neoadjuvant Therapy/methods ; Antibodies, Monoclonal, Humanized/therapeutic use ; },
abstract = {The therapeutic landscape for renal cell carcinoma (RCC) and urinary tract cancer (UTC) has transformed dramatically, creating complexity in treatment selection and sequencing. The 2025 Advanced Urologic Cancer Consensus Conference was convened to establish evidence-based expert consensus recommendations for optimal management. A multidisciplinary panel of 51 experts participated in a modified Delphi process addressing questions developed through iterative consensus-building covering RCC and UTC management. Voting occurred before and after the conference, and analyses focused on postmeeting responses. Consensus was defined as ≥75% agreement, with strong consensus as >90%. Strong consensus was found on the use of adjuvant pembrolizumab for higher risk RCC (pathologic T2 [pT2], grade 4; pT3-pT4, any grade; pTXN1; or fully resected metastatic disease) and on neoadjuvant therapy before cystectomy for localized UTC. There was strong consensus on the use of enfortumab vedotin plus pembrolizumab as frontline therapy for metastatic UTC and the use of platinum-based chemotherapy postprogression in biomarker-negative UTC. For RCC, there was consensus on the role of single-agent vascular endothelial growth factor receptor-tyrosine kinase inhibitor therapy after progression on frontline immune checkpoint inhibitor/vascular endothelial growth factor receptor-tyrosine kinase inhibitor therapy or dual immune checkpoint inhibitor therapy. However, there was a lack of consensus on other critical areas in the management of RCC and UTC. The 2025 Advanced Urologic Cancer Consensus Conference provides evidence-informed guidance for complex clinical scenarios while identifying critical research priorities. The group recognizes that the lack of consensus across multiple areas highlights the need for improved patient selection and prospective studies enabling optimal combination and sequencing approaches. This iterative annual process will address evolving treatment paradigms to optimize outcomes.},
}

Humans
*Carcinoma, Renal Cell/therapy/pathology
*Kidney Neoplasms/therapy/pathology
*Urologic Neoplasms/therapy/pathology
Consensus
Neoadjuvant Therapy/methods
Antibodies, Monoclonal, Humanized/therapeutic use

@article {pmid41388301,
year = {2025},
author = {Caceres-Palomo, L and Sanchez-Mejias, E and Trujillo-Estrada, L and Perez-Moreno, JJ and Lopez-Oliva, E and Lim, TE and DeFlitch, L and Chang, SH and Kampman, L and Corces, MR and Blurton-Jones, M and Moreno-Gonzalez, I and Pascual, A and Vitorica, J and Garcia-Leon, JA and Gutierrez, A},
title = {Human iPSC-derived APOE4/4 Alzheimer´s disease astrocytes exhibit a senescent and pro-inflammatory state that compromises neuronal support.},
journal = {Journal of neuroinflammation},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12974-025-03607-z},
pmid = {41388301},
issn = {1742-2094},
support = {UMA20-FEDERJA-048 (to JAGL), PY18-RT-2233 (to AG), SNGJ4-11 (to LCP)//Consejería de Economía, Innovación, Ciencia y Empleo, Junta de Andalucía/ ; UMA20-FEDERJA-048 (to JAGL), PY18-RT-2233 (to AG), SNGJ4-11 (to LCP)//Consejería de Economía, Innovación, Ciencia y Empleo, Junta de Andalucía/ ; UMA20-FEDERJA-048 (to JAGL), PY18-RT-2233 (to AG), SNGJ4-11 (to LCP)//Consejería de Economía, Innovación, Ciencia y Empleo, Junta de Andalucía/ ; P30 AG066519/NH/NIH HHS/United States ; P01AG073082, U01AG072573, and UM1HG012076 to MRC./NH/NIH HHS/United States ; P30 AG066519/NH/NIH HHS/United States ; PI21/00915 and PI24/00274 (to AG) and PI21/00914 and PI24/00308 (to JV)//Instituto de Salud Carlos III/ ; PI21/00915 and PI24/00274 (to AG) and PI21/00914 and PI24/00308 (to JV)//Instituto de Salud Carlos III/ ; PI-0276-2018 (to JAGL)//Consejería de Salud y Familias, Junta de Andalucía/ ; B1-2020_04 (to JAGL)//Universidad de Málaga/ ; },
}

@article {pmid41388019,
year = {2025},
author = {Chac, D and Heller, FJ and Banna, HA and Kaisar, MH and Markiewicz, SM and Pruitt, EL and Chowdhury, F and Bhuiyan, TR and Akter, A and Khan, AI and Dumayas, MG and Rice, A and Karmakar, PC and Dash, P and LaRocque, RC and Ryan, ET and Xu, L and Minot, SS and Harris, JB and Qadri, F and Weil, AA},
title = {Gut bacteria-derived sphingolipids alter innate immune responses to oral cholera vaccine antigens.},
journal = {Nature communications},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41467-025-67388-y},
pmid = {41388019},
issn = {2041-1723},
support = {K08 AI123494/AI/NIAID NIH HHS/United States ; T32HD007233//Division of Intramural Research, National Institute of Allergy and Infectious Diseases (Division of Intramural Research of the NIAID)/ ; R01 106878//Division of Intramural Research, National Institute of Allergy and Infectious Diseases (Division of Intramural Research of the NIAID)/ ; R01 AI AI136979//Division of Intramural Research, National Institute of Allergy and Infectious Diseases (Division of Intramural Research of the NIAID)/ ; R01 AI103055/AI/NIAID NIH HHS/United States ; R01 AI099243/AI/NIAID NIH HHS/United States ; D43 TW005572/TW/FIC NIH HHS/United States ; K43 TW010362/TW/FIC NIH HHS/United States ; R35 GM133420/GM/NIGMS NIH HHS/United States ; },
abstract = {The degree of protection conferred after receiving an oral cholera vaccine (OCV) varies based on age, prior exposure to Vibrio cholerae, and unknown factors. Recent evidence suggests that the microbiota may mediate some of the unexplained differences in oral vaccine responses. Here, we use metagenomic sequencing of the fecal microbiota at the time of vaccination and relate microbial features to immune responses after OCV using a reference-independent gene-level method. We find that the presence of sphingolipid-producing bacteria is associated with the development of protective immune responses after OCV. We test these associations by stimulating human macrophages with Bacteroides xylanisolvens metabolites and find that sphingolipid-containing extracts increase innate immune responses to OCV antigens. Our findings demonstrate a new analytic method for translating metagenomic sequencing data into strain-specific results associated with a biological outcome, and in validating this tool, we identify that microbe-derived sphingolipids impact immune responses to OCV antigens.},
}

@article {pmid41387075,
year = {2025},
author = {Beydoun, MA and Beydoun, HA and Tsai, J and Tinker, LF and Gradidge, PJ and Maldonado, AI and Le Kennedy, J and Allison, M and Jung, SY and Zonderman, AB and Evans, MK and Manson, JE},
title = {Anthropometric indices of obesity and their relationships with diabetes risk by race and ethnicity among postmenopausal women.},
journal = {Nutrition, metabolism, and cardiovascular diseases : NMCD},
volume = {},
number = {},
pages = {104430},
doi = {10.1016/j.numecd.2025.104430},
pmid = {41387075},
issn = {1590-3729},
abstract = {BACKGROUND AND AIMS: Traditional measures of obesity such as body mass index (BMI) and waist circumference (WC) have shown inconsistent predictive utility for diabetes across diverse populations. Novel anthropometric measures that focus on abdominal adiposity and body shape may offer better risk assessment for diabetes. Yet, the utility of traditional and novel anthropometric measures in postmenopausal women and in different racial and ethnic groups remains unclear. The predictive utilities of traditional and novel anthropometric measures for diabetes risk were comprehensively assessed, among postmenopausal women, overall, and across racial and ethnic groups.

METHODS AND RESULTS: Using data from 91,392 diabetes-free Women's Health Initiative participants, predictive values of anthropometric measures were examined using Receiver Operating Characteristic (ROC) and Cox regression with Harrell's c-statistics. ROC analyses suggested that novel anthropometric measures with best predictive abilities were 'a Body Shape Index' (ABSI), 'Abdominal Volume Index', and 'Body Roundness Index', although WC and novel anthropometric measures had similarly modest predictive abilities to BMI (Areas Under the Curve <0.6). Cut-off points for anthropometric measures varied by race/ethnicity. Multivariable Cox regression modeling suggested that 'Clinica Universidad de Navarra-Body Adiposity Estimator', WC, ABSI, and BMI had the strongest associations with diabetes risk (adjusted hazard ratios [HRs]: 1.27, 1.26, 1.23, and 1.22 per 1-SD increase, respectively), although predictive accuracies involving any measure were modest (Harrell's c-statistics∼0.58-0.59).

CONCLUSIONS: In this comprehensive evaluation, anthropometric measures were marginally predictive of diabetes risk, and novel measures did not outperform traditional measures among postmenopausal women, irrespective of race/ethnicity.},
}

@article {pmid41332722,
year = {2025},
author = {Motmaen, A and Jude, KM and Wang, N and Minervina, A and Feldman, D and Lichtenstein, MA and Ebenezer, A and Correnti, C and Thomas, PG and Garcia, KC and Baker, D and Bradley, P},
title = {Targeting peptide-MHC complexes with designed T cell receptors and antibodies.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {41332722},
issn = {2692-8205},
abstract = {Class I major histocompatibility complexes (MHCs), expressed on the surface of all nucleated cells, present peptides derived from intracellular proteins for surveillance by T cells. The precise recognition of foreign or mutated peptide-MHC (pMHC) complexes by T cell receptors (TCRs) is central to immune defense against pathogens and tumors. Although patient-derived TCRs specific for cancer-associated antigens have been used to engineer tumor-targeting therapies, their reactivity toward self- or near-self antigens may be constrained by negative selection in the thymus. Here, we introduce a structure-based deep learning framework, ADAPT (Antigen-receptor Design Against Peptide-MHC Targets), for the design of TCRs and antibodies that bind to pMHC targets of interest. We evaluate the ADAPT pipeline by designing and characterizing TCRs and antibodies against a diverse panel of pMHCs. Cryogenic electron microscopy structures of two designed antibodies bound to their respective pMHC targets demonstrate atomic-level accuracy at the recognition interface, supporting the robustness of our structure-based approach. Computationally designed TCRs and antibodies targeting pMHC complexes could enable a broad range of therapeutic applications, from cancer immunotherapy to autoimmune disease treatment, and insights gained from TCR-pMHC design should advance predictive understanding of TCR specificity with implications for basic immunology and clinical diagnostics.},
}

@article {pmid41332714,
year = {2025},
author = {Isaac, KJ and Cox, KEL and Ho, KY and Humphries, EM and Kucher, N and Leek, JT and Mosher, S and Schatz, MC and Tan, FJ and Hoffman, AM},
title = {Insights into the Datasets, Tools, and Training Needs of the AnVIL Community: 2024.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {41332714},
issn = {2692-8205},
abstract = {The NHGRI Genomic Data Science Analysis, Visualization, and Informatics Lab-space (AnVIL) provides a secure cloud-based environment where research and education communities can analyze genomic and biomedical data. The platform supports a wide range of data analysis as well as the ability to safely store and access data in compliance with NIH policies. Work on the AnVIL platform can be easily shared to promote reproducible science and collaboration. The purpose of this study is to better understand the current user base of the AnVIL platform. The AnVIL Community Poll aimed to collect baseline information, identify development opportunities, guide the prioritization of user support strategies, and succinctly but comprehensively describe the current AnVIL Community. The AnVIL Team disseminated the inaugural AnVIL Community Poll by sharing it broadly on social media and through AnVIL and related consortia mailing lists. We categorized respondents as either returning or potential users of the AnVIL platform (based on their provided usage description) and examined user experiences: specifically user backgrounds, technological comfort, research interests, computational needs, and preferences for training and support. Our sample of the AnVIL community found opportunities for platform adoption beyond the current user base and identified areas where training should be enhanced, training preferences, and user computational needs. Specifically, while most respondents were involved in human genomics research, there may be potential for growth in adoption of the platform by prioritizing materials to support clinical researchers. All respondents felt availability of specific tools or datasets was a key feature of the platform. The broader community may also benefit from further development or showcasing of resources to facilitate cost management, finding and incorporating analysis tools, and data import. Our sample greatly preferred virtual training opportunities and returning users of the platform foresaw needing large amounts of storage. This poll provided an insightful snapshot of the current state of the AnVIL and demonstrated areas where the AnVIL Team can take specific steps to address barriers related to platform adoption and further support the existing and varied AnVIL Community. This work can be built upon through user interviews, community discussion, and coordinating a recurring poll.},
}

@article {pmid41332620,
year = {2025},
author = {Crowell, HL and Dong, Y and Billato, I and Cai, P and Emons, M and Gunz, S and Guo, B and Li, M and Mahmoud, A and Manukyan, A and Pagès, H and Panwar, P and Rao, S and Sargeant, CJ and Kern, LS and Ramos, M and Sun, J and Totty, M and Carey, VJ and Chen, Y and Collado-Torres, L and Ghazanfar, S and Hansen, KD and Martinowich, K and Maynard, KR and Patrick, E and Righelli, D and Risso, D and Tiberi, S and Waldron, L and Gottardo, R and Robinson, MD and Hicks, SC and Weber, LM},
title = {Orchestrating Spatial Transcriptomics Analysis with Bioconductor.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {41332620},
issn = {2692-8205},
abstract = {Spatial transcriptomics technologies provide spatially-resolved measurements of gene expression through assays that can either target selected genes or capture transcriptome-wide expression profiles. The complexity and variability of these technologies and their associated data necessitate multi-step workflows integrating diverse computational methods and software packages. We provide a freely accessible, open-source, continuously updated and tested online book containing reproducible code examples, datasets, and discussion about data analysis workflows for spatial omics data using Bioconductor in R, including interoperability with Python.},
}

@article {pmid41292945,
year = {2025},
author = {Salisbury, N and Amonkar, S and Roman, A and Galloway, DA},
title = {E2F1-3 activate polyomavirus early transcription and replication.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {41292945},
issn = {2692-8205},
abstract = {Polyomaviruses (PyVs) are small, circular double-stranded DNA viruses that establish lifelong persistent infections. PyV infections are typically asymptomatic, but they can cause severe disease particularly in immunosuppressed individuals, including BKPyV-associated nephropathy, and Merkel cell carcinoma (MCC) caused by Merkel cell polyomavirus (MCPyV). While most individuals are infected with PyVs during childhood, it is unclear how these viruses persist in the host and what cellular signals prompt their reactivation. The early regions of PyV genomes encode regulatory proteins that control viral replication and host cell transformation in the case of MCPyV, SV40 and murine polyomavirus (MuPyV). All PyV early regions encode Large and Small Tumor antigens (LT, ST), which are splice variants of a common transcript. PyV LTs bind and inhibit RB1 via a conserved LxCxE motif, deregulating E2F transcriptional activity and cell cycle control to promote viral replication and tumorigenesis. The existing paradigm in the field is during normal PyV infection, LT is expressed and drives the host cell into S phase. However, a recent study revealed that cells infected with BKPyV only express LT and replicate the viral genome when already in S phase, but the mechanisms activating LT expression during S phase are unknown. The Non-Coding Control Region (NCCR), found in all PyVs, contains the viral origin of replication and predicted transcription factor (TF) binding sites, yet only a handful have been experimentally validated and shown to regulate PyV early transcription. Here, we set out to identify host TFs that bind the MCPyV NCCR to regulate early transcription in both MCC cells and in an in vitro model of MCPyV infection. We identified E2F1-3 as critical regulators of MCPyV early transcription, which bind to the MCPyV NCCR via a consensus E2 site just upstream of LT/ST transcriptional start site. We discovered E2 sites in the NCCRs of several other polyomaviruses, including MuPyV but not BKPyV. Deletion of the E2 sites in PyV NCCRs downregulates early transcription in luciferase assays. Despite not containing a consensus E2 site, we detected weak E2F binding to the NCCRs of BKPyV and SV40, suggesting that E2Fs also contribute to transcription of their early genes. Overall, our findings challenge the existing paradigm of PyV infection, that LT expression activates E2F signaling via RB1 inhibition, and suggest that E2Fs must already be active in the PyV-infected host cell for LT/ST expression and viral replication.},
}

@article {pmid41292719,
year = {2025},
author = {Masaki, N and Bedford, T},
title = {Hidden Markov Models Detect Recombination and Ancestry of SARS-CoV-2.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {41292719},
issn = {2692-8205},
abstract = {When individuals are co-infected with distinct SARS-CoV-2 lineages, homologous recombination can generate mosaic genomes carrying mutations from both parental lineages. A variety of methods exist to detect recombinant sequences and their parental lineages in surveillance-scale datasets comprised of millions of SARS-CoV-2 genomes. However, these methods often rely on user-defined settings, such as the probability that a recombination breakpoint occurs between adjacent positions on the query sequence. In this study, we devise a hidden Markov model that detects recombinant SARS-CoV-2 sequences and identifies their parental lineages within a test set of sequences. Our method does not depend on user-defined parameters and can accommodate de novo mutations on the query sequence that are not present in the predicted parental lineages. To achieve this, we use maximum likelihood to estimate parameters that characterize the transition and emission probabilities in our hidden Markov model. Applying our method to 440,307 SARS-CoV-2 sequences sampled in England between September 2020 and March 2024, we detect 7,619 recombinant sequences corresponding to 1.73% (95% CI: [1.69%, 1.77%]) of all sampled sequences. We show a positive association between the proportion of query sequences detected as recombinant in each week and community SARS-CoV-2 prevalence. This is consistent with higher prevalence increasing co-infection risk and promoting the emergence of recombinant sequences. We further observe localized clusters of recombination breakpoints within spike and in intergenic regions.},
}

@article {pmid41385397,
year = {2025},
author = {Yazzie, D and Pete, D and Briscoe, C and Jim, MA and Meisner, A and Wiggins, C and Doyle, D and Yee, G and Goldtooth, C and Sanderson, PR and Keene, CN and Smith, M and Sehn, H and Damon, S and Kettering, CL and Emerson, M and Curley, C and Bea, J and Yazzie, S and Joe, N and Doherty, J and Dirk de Heer, H and , },
title = {Cancer incidence, stage at diagnosis, and trends across the Navajo Nation, 2014-2018.},
journal = {Cancer},
volume = {131},
number = {24},
pages = {e70202},
pmid = {41385397},
issn = {1097-0142},
support = {HHSN2612018000014I/CA/NCI NIH HHS/United States ; K00CA253685/CA/NCI NIH HHS/United States ; U54CA143924/CA/NCI NIH HHS/United States ; U54CA143925/CA/NCI NIH HHS/United States ; U1B1IHS0011-12-00//Indian Health Service/ ; Cancer Health Research Centers//American Cancer Society/ ; },
mesh = {Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; *American Indian or Alaska Native/statistics & numerical data ; Incidence ; Neoplasm Staging ; *Neoplasms/epidemiology/pathology/diagnosis/ethnology ; Registries ; SEER Program ; United States/epidemiology ; },
abstract = {BACKGROUND: American Indian/Alaska Native (AI/AN) people in the United States experience cancer disparities, but little is known about cancer patterns specific to each Tribal Nation. This study describes cancer incidence (2014-2018), trends (1998-2018), and stage of diagnosis across the Navajo Nation, one of the largest sovereign tribal nations worldwide.

METHODS: Cases from six Arizona, New Mexico, and Utah counties covering most of the Navajo Nation were identified by population-based cancer registries and linked with Indian Health Services patient registrations. Cancer incidence and stage at diagnosis were compared between Navajo and non-Hispanic White persons in the same counties. Trends from 1998 through 2018 were analyzed using Joinpoint regression.

RESULTS: Navajo people had significantly higher incidence than non-Hispanic White people of gallbladder (incidence rate ratio [RR] = 6.25), stomach (RR = 3.19), kidney (RR = 1.89), myeloma (RR = 1.80), and liver cancers (RR = 1.79) and a lower incidence of cancers of the lung (RR = 0.16), female breast (RR = 0.49), leukemia (RR = 0.49), prostate (RR = 0.62), pancreas (RR = 0.79), and non-Hodgkin lymphoma (RR = 0.79). Diagnostic stage was not different for breast, cervical, and colorectal cancers, but two thirds of patients with cervical and colorectal cancer were diagnosed in later/unknown stages. Although all-site cancer rates did not change significantly from 1998 through 2018 among Navajo people, a significant decrease was found from 2010 through 2018 (-2.1% annual percentage change, p < .01).

CONCLUSIONS: Navajo people experience a higher incidence of kidney, stomach, liver, myeloma, and gallbladder cancers and a lower incidence of cancers of the breast, prostate, lung, non-Hodgkin lymphoma, and leukemia. Tailored and targeted prevention efforts may help reduce cancer disparities in the Navajo Nation.},
}

Adult
Aged
Female
Humans
Male
Middle Aged
*American Indian or Alaska Native/statistics & numerical data
Incidence
Neoplasm Staging
*Neoplasms/epidemiology/pathology/diagnosis/ethnology
Registries
SEER Program
United States/epidemiology

@article {pmid41385388,
year = {2025},
author = {Amundsen, SK and Zhu, Y and Smith, GR},
title = {Chi hotspot control of RecBCD enzyme requires a RecB tether-RecC groove crosspoint interaction.},
journal = {Genetics},
volume = {},
number = {},
pages = {},
doi = {10.1093/genetics/iyaf240},
pmid = {41385388},
issn = {1943-2631},
support = {//G.R.S. from the National Institute of General Medical Sciences of the United States of America/ ; P30 CA015704/NH/NIH HHS/United States ; //Fred Hutch/University of Washington/Seattle Children's Cancer Consortium/ ; RRID:SCR_022606//Genomics & Bioinformatics Shared Resource/ ; },
abstract = {Homologous genetic recombination is required for the faithful repair of broken DNA to continue life and for genetic diversification to propel evolution. The bacterial RecBCD enzyme promotes these processes through coordinated DNA helicase and nuclease activities, which are regulated by a Chi recombination hotspot sequence (5'-GCTGGTGG-3' in enteric bacteria) and the loading of the RecA DNA strand-exchange protein onto the newly generated 3' single-stranded DNA end. Chi's control of RecBCD requires a complex interaction of all three subunits at widely dispersed points in the 330 kDa three-subunit protein. Here, we describe an additional point that is critical for Chi's site-specific stimulation of recombination in Escherichia coli. This point, on the surface of RecBCD, is where the middle of the 19-amino-acid tether connecting the RecB helicase and nuclease domains fits into a groove on the surface of RecC. Deleting or changing even a single amino acid in this crosspoint dramatically reduces Chi hotspot activity. Surprisingly, severing the tether at the RecB helicase junction leaves Chi and RecBCD fully active, but severing the tether at the RecB nuclease junction abolishes Chi activity and strongly reduces recombination proficiency. This difference is accounted for by the critical role of the tether-groove interaction described here. We discuss how Chi controls RecBCD via the coordinated interaction of the tether-groove crosspoint and 13 other widely spaced points throughout RecBCD.},
}

@article {pmid41292772,
year = {2025},
author = {Rajendran, A and Haldipur, P and Arora, S and Grama, K and Subramanian, SS and Galan, LM and Johnson, D and Aldinger, KA and Shendure, J and Millen, KJ and Gennari, JH and Pattwell, SS},
title = {Elucidating Neurodevelopmental Trajectories in Cancer with Topic Modeling: Revealing Persistent External Granule Layer Lineages in Medulloblastoma.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {41292772},
issn = {2692-8205},
abstract = {The cerebellar rhombic lip generates cerebellar progenitors and neurons that ultimately differentiate to comprise over half of all neurons in the adult human brain. Standard clustering approaches often fragment or miss rhombic lip progenitor populations entirely due to their transient nature, small size, and rapid state transitions, leaving fundamental questions unanswered about normal cerebellar development and how such processes may be hijacked in pediatric brain cancer. Medulloblastoma, the most common malignant pediatric brain tumor, affects approximately 500 children annually in the United States with overall survival rates varying dramatically by subgroup. Sonic hedgehog (SHH) medulloblastoma, comprising 25-30% of cases, arises from rhombic lip-derived granule neuron precursors (GNP) within the external granule layer (EGL) and has particularly poor outcomes in several subtypes (5-year survival ~41%). Using our topic modeling framework on over one million fetal cerebellar nuclei, we identify proliferative rhombic lip and EGL states that bifurcate into distinct glial and neuronal lineages through intermediate progenitors and capture a portion of the developmental spectrum form outer EGL (oEGL) proliferation through inner EGL (iEGL) differentiation. These developmental signatures (topics) persist in medulloblastoma, validating GNP origins of SHH tumors and revealing age-specific molecular programs that correspond to distinct stages of EGL development within SHH subtypes. Our transferable framework enables systematic comparison of developmental and disease states across technologies without data integration, solving a fundamental challenge as genomic atlases expand.},
}

@article {pmid41292664,
year = {2025},
author = {Ercan, C and Pan, X and Paulson, TG and Stachler, MD and Akarca, FG and Grady, WM and Maley, CC and Yuan, Y},
title = {Histopathology-based Spatial Profiling of Immune and Molecular Features Predicts Cancer risk in Barrett's Esophagus.},
journal = {medRxiv : the preprint server for health sciences},
volume = {},
number = {},
pages = {},
pmid = {41292664},
abstract = {BACKGROUND: Improved cancer risk stratification is needed to differentiate high-risk individuals with Barrett's esophagus (BE) from low-risk populations to reduce overtreatment and improve outcome. The evolution of BE towards adenocarcinoma is likely driven by a combination of genomic and microenvironmental factors, yet existing predictive models rarely integrate both using routine specimens.

METHOD: We developed BEACON (Barrett Esophagus DNA content Abnormality and immune ecology for Cancer Outcome), a spatially aware framework predicting DNA content abnormalities and characterizing immune spatial ecology from routine histopathology. First, using 777 BE biopsies with flow cytometry-based DNA content data scanned at two institutions, we trained and tested DACOR (DNA content abnormality recognition), a multi-instance learning model that predicts DNA content abnormalities from histopathology. Next, complementary models for cell classification and tissue segmentation enabled spatial immune ecology metric computations. Lastly, a logistic regression model integrated molecular immune ecological features and epithelial morphology for cancer risk stratification.

RESULTS: DACOR achieved 0.825 AUC in the test cohort for DNA content abnormality prediction. DNA content abnormal regions exhibited increased lymphoplasma cellular inflammation versus normal regions (p=0.006). Patients classified as DNA content abnormal by DACOR demonstrated increased cancer progression (p=0.0001). Among patients with DNA content abnormality, cancer progressors exhibited increased plasma cell clustering adjacent to abnormal epithelium compared to non-progressors. The integrated risk classification model stratified DNA content abnormal patients into high- and low-risk groups with 0.817 AUC.

CONCLUSION: BEACON spatially integrates molecular abnormality with immune spatial ecology to stratify BE patients by cancer progression risk using routine pathology images. This scalable, explainable approach could improve clinical decision-making and reduce unnecessary surveillance in low-risk patients.},
}

@article {pmid41385339,
year = {2025},
author = {Nishitani, M and Graham, RT and Wang, T and DeVos, JD and Lee, SJ and Spellman, SR and Kitko, CL and MacMillan, ML and DeFilipp, Z and Gray, AN and Williams, KM and Takahashi, T and Schoettler, ML and Hashem, H and Rangarajan, HG and Prestidge, T and Ringden, O and Hamilton, BK and Sharma, A and Nusrat, R and El Jurdi, N and Bhatt, NS and Duncan, CN and Qayed, M},
title = {Impact of Age on Graft-vs-Host Disease and Overall Survival in Pediatric Hematopoietic Cell Transplant Recipients.},
journal = {Blood advances},
volume = {},
number = {},
pages = {},
doi = {10.1182/bloodadvances.2025017393},
pmid = {41385339},
issn = {2473-9537},
abstract = {Advances in graft-versus-host disease (GVHD) prevention and treatment have resulted in expanded donor options and improvement in treatment-related mortality (TRM). This analysis aimed to compare the incidence of acute and chronic GVHD (aGVHD and cGVHD) in pediatric patients by recipient age and to evaluate the impact of GVHD on overall survival (OS) and TRM. We included 14,099 patients ≤21 years who received their first allogeneic hematopoietic cell transplantation from 2002-2020, categorizing recipient age as: 0-2y (infants/toddlers), 3-12y (school-aged), and 13-21y (adolescent/young adult). There was no difference in grade II-IV and III-IV aGVHD by Day 100 among age groups, except in patients with nonmalignant disease, where there was a small increase in incidence of severe aGVHD in older patients. Incidence of moderate/severe cGVHD by 1y was higher with age. A similar impact of age was observed after adjusting for patient, donor and transplant characteristics. Risk of severe aGVHD was higher in older children with NMD. Severe aGVHD and moderate/severe cGVHD were independently associated with inferior OS. In patients with malignant disease, both severe aGVHD and moderate/severe cGVHD were associated with increased risk of TRM. In conclusion, risk of moderate/severe cGVHD increases with recipient age, and risk of severe aGVHD is increased among older patients with nonmalignant conditions. Despite the low overall incidence of aGVHD and cGVHD in children, both are associated with significantly worse survival. These data highlight the need to consider GVHD outcomes at time of consultation and for improved prevention and treatment approaches.},
}

@article {pmid41384688,
year = {2026},
author = {Dsouza, JM and Sayar, E and Schweizer, MT and Harmon, S and Morrissey, C and Beltran, H and Nelson, PS and Cheng, L and Ding, CC and Haffner, MC},
title = {Molecular subtypes of metastatic prostate cancer: from pathophysiology to diagnosis.},
journal = {Histopathology},
volume = {88},
number = {1},
pages = {24-39},
doi = {10.1111/his.70033},
pmid = {41384688},
issn = {1365-2559},
support = {R37CA286450//NIH/NCI/ ; P30CA15704//NIH/NCI/ ; P50CA097186//NIH/NCI/ ; P01CA163227-06A1//NIH/NCI/ ; R01CA234715-03//NIH/NCI/ ; R01CA266452//NIH/NCI/ ; R01CA280056//NIH/NCI/ ; R50CA221836//NIH/NCI/ ; PO1CA163227//NIH/NCI/ ; CA282978//NIH/NCI/ ; R37CA241486-01A1//NIH/NCI/ ; P50 CA272390-01//NIH/NCI/ ; W81XWH-20-1-0111//U.S. Department of Defence Prostate Cancer Research Program/ ; W81XWH-21-1-0229//U.S. Department of Defence Prostate Cancer Research Program/ ; W81XWH-22-1-0278//U.S. Department of Defence Prostate Cancer Research Program/ ; W81XWH-18-1-0347//U.S. Department of Defence Prostate Cancer Research Program/ ; W81XWH-18-1-0689//U.S. Department of Defence Prostate Cancer Research Program/ ; W81XWH-17-1-0653//U.S. Department of Defence Prostate Cancer Research Program/ ; W81XWH-21-1-0264//U.S. Department of Defence Prostate Cancer Research Program/ ; W81XWH-14-2-0183//U.S. Department of Defence Prostate Cancer Research Program/ ; W81XWH-17-2-0043//U.S. Department of Defence Prostate Cancer Research Program/ ; PC230420//U.S. Department of Defence Prostate Cancer Research Program/ ; PC230582//U.S. Department of Defence Prostate Cancer Research Program/ ; 2021184/DDCF/Doris Duke Charitable Foundation/United States ; //V Foundation/ ; //Prostate Cancer Foundation Felix Feng PC-SYNERGY award/ ; //UCSF Benioff Initiative for Prostate Cancer Research/ ; //Safeway Foundation/ ; //Fred Hutch/UW Cancer Consortium/ ; //Brotman Baty Institute for Precision Medicine/ ; //UW/FHCC Institute for Prostate Cancer Research/ ; /RC/CCR NIH HHS/United States ; /CA/NCI NIH HHS/United States ; //National Institutes of Health Intramural Research Program project number ZIABC012163/ ; },
mesh = {Humans ; Male ; *Prostatic Neoplasms/pathology/diagnosis/genetics ; Neoplasm Metastasis/pathology/diagnosis ; Biomarkers, Tumor ; },
abstract = {Metastatic prostate cancer (mPC) is characterized by molecular and phenotypic heterogeneity. With increasing guideline-driven use of metastatic biopsies, more mPC specimens are being evaluated in surgical pathology. However, unlike localized prostate cancer, no standardized framework currently exists to guide the diagnostic workup of metastatic biopsies or reliably determine phenotypic subtypes. While many mPCs retain conventional acinar features, a growing subset exhibits phenotypic plasticity - including loss of prostate epithelial identity and emergence of neuroendocrine or other divergent lineages. This phenotypic diversity often occurs in castration-resistant prostate cancer as a mechanism of resistance to chronic androgen receptor pathway inhibition and is characterized by genomic alterations and epigenetic reprogramming. This review outlines the histologic and molecular spectrum of mPC and proposes a practical, pathology-informed diagnostic approach integrating morphologic assessment and immunohistochemistry. Adoption of a standardized diagnostic framework and multidisciplinary integration will be useful for employing precision oncology in advanced mPC.},
}

Humans
Male
*Prostatic Neoplasms/pathology/diagnosis/genetics
Neoplasm Metastasis/pathology/diagnosis
Biomarkers, Tumor

@article {pmid41384541,
year = {2025},
author = {Meissner, HC and Gilbert, PB and Eisnor, D and Wolfe, DN},
title = {Viral correlates of protection and the multifarious interactions of B and T cells.},
journal = {Human vaccines & immunotherapeutics},
volume = {21},
number = {1},
pages = {2598695},
doi = {10.1080/21645515.2025.2598695},
pmid = {41384541},
issn = {2164-554X},
mesh = {Humans ; *T-Lymphocytes/immunology ; Antibodies, Neutralizing/blood/immunology ; *B-Lymphocytes/immunology ; *Virus Diseases/immunology/prevention & control ; Antibodies, Viral/blood/immunology ; Adaptive Immunity ; Animals ; Immunity, Innate ; Immunity, Cellular ; Immunity, Humoral ; },
abstract = {Validated, reproducible methods to assess immunity to a specific virus following either infection or vaccination are important for understanding susceptibility to existing and emerging infectious diseases. Correlates of protection for a specific viral illness involve humoral and cellular responses that differ by pathogen and by the portal of entry into the host. Contemporary understanding of a correlate of protection primarily is based on serum neutralizing antibody concentrations because of difficulty in assaying the complex interactions of T cells. A more comprehensive understanding of susceptibility and protection is needed. The goal of this paper is to enumerate the multiple variables that complicate understanding of cellular contributions to the innate and adaptive immune responses.},
}

Humans
*T-Lymphocytes/immunology
Antibodies, Neutralizing/blood/immunology
*B-Lymphocytes/immunology
*Virus Diseases/immunology/prevention & control
Antibodies, Viral/blood/immunology
Adaptive Immunity
Animals
Immunity, Innate
Immunity, Cellular
Immunity, Humoral

@article {pmid41380698,
year = {2025},
author = {Kater, AP and Janssens, A and Eradat, H and Offner, F and Sandoval-Sus, JD and Shadman, M and Poulsen, CB and Christensen, JH and Thompson, MC and Guan, M and Steele, AJ and Rios, M and Holst Mørch, M and Oki, T and Valentin, R and Bellido, M and Eichhorst, B},
title = {Epcoritamab monotherapy for Richter transformation (EPCORE CLL-1): findings from a single-arm, multicentre, open-label, phase 1b/2 trial.},
journal = {The Lancet. Haematology},
volume = {},
number = {},
pages = {},
doi = {10.1016/S2352-3026(25)00327-8},
pmid = {41380698},
issn = {2352-3026},
abstract = {BACKGROUND: Richter transformation is one of the most challenging B-cell lymphomas to treat, particularly in patients with high-risk chronic lymphocytic leukaemia features or who have had previous therapy for chronic lymphocytic leukaemia. Median survival remains 6-12 months across various therapeutic approaches. We evaluated the safety and preliminary activity of epcoritamab monotherapy, a subcutaneous CD3×CD20 bispecific antibody, in patients with Richter transformation.

METHODS: This multicentre, open-label, phase 1b/2 trial was conducted at 24 centres in nine countries (Australia, Belgium, Denmark, Germany, Israel, Italy, Spain, The Netherlands, and USA). Eligible patients were aged 18 years or older and had histologically confirmed Richter transformation (diffuse large B-cell lymphoma [DLBCL]), an Eastern Cooperative Oncology Group performance status of 0-2, and up to two previous lines of Richter transformation-directed therapy. The trial includes dose-escalation and dose-expansion phases. The expansion groups evaluate epcoritamab monotherapy (group 2A), epcoritamab plus lenalidomide (group 2B), and epcoritamab plus the combination of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP; group 2C). The current report describes results from group 2A. Epcoritamab was administered subcutaneously in step-up doses followed by 48 mg every week for cycles 1-3, every 2 weeks for cycles 4-9, and every 4 weeks thereafter until disease progression or unacceptable toxicity. The primary endpoint was investigator-assessed overall response rate per Lugano 2014 criteria in the full analysis set (all patients who received ≥1 dose of epcoritamab). It was evaluated against a null hypothesis of 30% versus an alternative of 50%. Prespecified subgroup analyses by line of therapy for Richter transformation and TP53 aberration and/or del(17p) status were performed. Safety was assessed in all treated patients. This trial is ongoing and registered with ClinicalTrials.gov, NCT04623541.

FINDINGS: Between Oct 18, 2021, and March 21, 2025, we enrolled 42 patients with Richter transformation. The median age was 69 years (range 50-80); and 32 (76%) of 42 patients were male and ten (24%) were female. Race or ethnicity data were available for 40 patients (37 [88%] identified as White, two [5%] as Asian, and one [2%] as Black or African American; ethnicity was not reported for two patients). The median time from diagnosis of chronic lymphocytic leukaemia or small lymphocytic lymphoma to Richter transformation was 7·6 years (range 0-23·9). 21 (50%) of 42 patients received epcoritamab as first-line Richter transformation-directed therapy. At a median follow-up of 22·9 months (range 0·5-39·9), 20 of 42 patients had a response with an investigator-assessed overall response rate of 47·6% (95% CI 32·0-63·6), which did not meet the prespecified alternative hypothesis (50%). Overall response occurred in 12 of 21 patients in the first-line population (overall response rate 57·1%, 34·0-78·2), in eight of 21 patients in the second-line or later-line population (38·1%, 18·1-61·6), and in eight of 20 patients with TP53 aberration and/or del(17p) alteration at baseline (40%, 19·1-63·9). The most common grade 3-4 adverse events were neutropenia in 19 (45%) of 42 patients, anaemia in 16 (38%) patients, thrombocytopenia in 16 (38%) patients, infection in nine (21%) patients, pneumonia in four (10%) patients, and COVID-19 in two (5%) patients. Cytokine release syndrome occurred in 36 (86%) patients with three (7%) being grade 3, immune effector cell-associated neurotoxicity syndrome in five (12%; all grade 1-2) patients and clinical tumour lysis syndrome in two (5%; all grade 1-2) patients. Three fatal adverse events were reported, one each due to general physical health deterioration in the context of progressive disease, sepsis, and cerebrovascular accident; none were considered by the investigator to be related to study treatment.

INTERPRETATION: In patients with Richter transformation, epcoritamab monotherapy showed clinically meaningful antitumour activity, although the investigator-assessed overall response rate was below the alternative hypothesis of 50%, with a safety profile consistent with previous studies. These findings support further investigation of epcoritamab as a potential treatment option for patients with Richter transformation.

FUNDING: Genmab A/S and AbbVie.},
}

@article {pmid41380171,
year = {2026},
author = {Doshi, S and Richardson, BA and Nazzinda, R and Mugerwa, H and Bittencourt, MS and Erem, G and Narendrula, A and Farquhar, C and Kityo, C and Longenecker, CT},
title = {The Association of Mild Kidney Disease With Coronary Artery Disease Is Stronger for People Living With HIV.},
journal = {Journal of acquired immune deficiency syndromes (1999)},
volume = {101},
number = {1},
pages = {95-102},
pmid = {41380171},
issn = {1944-7884},
support = {K23 HL123341/HL/NHLBI NIH HHS/United States ; D43 TW011596/TW/FIC NIH HHS/United States ; },
mesh = {Humans ; Female ; Male ; *HIV Infections/complications ; Middle Aged ; *Coronary Artery Disease/complications/epidemiology ; Cross-Sectional Studies ; Uganda/epidemiology ; Glomerular Filtration Rate ; *Kidney Diseases/complications ; Risk Factors ; },
abstract = {OBJECTIVE: To examine the association between mild kidney disease and coronary plaque parameters using coronary computed tomography angiography in people living with HIV (PWH) compared with people without HIV in Uganda.

DESIGN: Cross-sectional secondary analysis.

METHODS: We studied 165 participants aged >45 years with ≥1 cardiovascular risk factor (78 PWH on stable antiretroviral therapy, 87 HIV-negative). Kidney function was assessed using estimated glomerular filtration rate (eGFR) and albumin-creatinine ratio (ACR). Coronary artery disease (CAD) was characterized by segment involvement score (SIS), segment stenosis score (SSS), and coronary artery calcium score. Multivariable Tobit regression assessed associations of kidney function measures with CAD parameters, testing for differences by HIV status.

RESULTS: The median (interquartile range) age was 57.0 (53-62) years, 62.4% of subjects were female, and 87.3% had hypertension. Among PWH, mildly impaired eGFR (<90 mL/min/1.73 m2) was associated with higher SIS [β 3.31, 95% confidence interval (CI): 0.41 to 6.21, P = 0.03] and SSS (β 5.95, 95% CI: 0.54 to 11.36, P = 0.03). The association with SIS remained significant after adjusting for age, gender, and 10-year ASCVD score (β 2.58, 95% CI: 0.10 to 5.06, P = 0.04). Associations of ACR with coronary plaque were not statistically significant for participants with or without HIV (all P > 0.07).

CONCLUSION: In PWH, mildly reduced eGFR was associated with greater coronary plaque burden (SIS, SSS) but not coronary artery calcium; ACR showed no associations with any CAD measures. Incorporating kidney function measures into cardiovascular risk assessment may be valuable in HIV care.},
}

Humans
Female
Male
*HIV Infections/complications
Middle Aged
*Coronary Artery Disease/complications/epidemiology
Cross-Sectional Studies
Uganda/epidemiology
Glomerular Filtration Rate
*Kidney Diseases/complications
Risk Factors

@article {pmid41255967,
year = {2025},
author = {Garsed, D and Zwimpfer, T and Fereday, S and Pandey, A and Ariyaratne, D and Jayawardana, M and Twomey, L and Laumont, C and Kennedy, C and Bolithon, A and Meagher, N and Milne, K and Hamilton, P and Alsop, J and Antoniou, A and Au-Yeung, G and Beckmann, M and de Gonzalez, AB and Bisinotto, C and Blome, F and Bodelon, C and Boros, J and Brand, A and Carney, M and Cazorla-Jimenez, A and Chiu, D and Christie, E and Chudecka-Glaz, A and Coulson, P and Cushing-Haugen, K and Cybulski, C and Darcy, K and David, C and Davidson, T and Ekici, A and Elishaev, E and Emons, J and Engler, T and Farrell, R and Fischer, A and Garcia-Closas, M and Gentry-Maharaj, A and Ghatage, P and Glasspool, R and Harter, P and Hartkopf, A and Hartmann, A and Heikaus, S and Hernandez, B and Hettiaratchi, A and Heublein, S and Huntsman, D and Jimenez-Linan, M and Jones, M and Kang, E and Kaznowska, E and Kluz, T and Kommoss, F and Konecny, GE and Kruitwagen, R and Kwon, J and Lambrechts, D and Lee, CH and Lester, J and Leung, S and Leung, Y and Linder, A and Lissowska, J and Loverix, L and Lubiński, J and Mateoiu, C and McNeish, L and Moubarak, M and Nelson, G and Nevins, N and Olawaiye, A and Olbrecht, S and Orsulic, S and Osorio, A and Quinn, C and Mohan, GR and Ray-Coquard, I and Rodriguez-Antona, C and Roxburgh, P and Rübner, M and Salfinger, S and Samra, S and Schoemaker, M and Sinn, HP and Sonke, G and Steele, L and Stewart, C and Talhouk, A and Tan, A and Tarney, C and Taylor, S and Van de Vijver, K and der Aa, MA and Van Gorp, T and Van Nieuwenhuysen, E and van Wagensveld, L and Wahner-Hendrickson, A and Walter, C and Wang, C and Welz, J and Wentzensen, N and Wilkens, L and Winham, S and Winterhoff, B and Anglesio, M and Berchuck, A and do Reis, FC and Cohen, P and Conrads, T and Crowe, P and Doherty, J and Fasching, P and Fortner, R and Garcia, M and Gayther, S and Goodman, M and Gronwald, J and Harris, H and Heitz, F and Horlings, H and Karlan, B and Kelemen, L and Maxwell, G and Menon, U and Modugno, F and Neuhausen, S and Schildkraut, J and Staebler, A and Sundfeldt, K and Swedlow, A and Vergote, I and Wu, A and Brenton, J and Pharoah, P and Pearce, C and Pike, M and Goode, E and Ramus, S and Köbel, M and Nelson, B and DeFazio, A and Friedlander, M and Bowtell, D},
title = {Beyond BRCA deficiency: Clinical and molecular predictors of survival in patients with BRCA-deficient tubo-ovarian high-grade serous carcinoma.},
journal = {Research square},
volume = {},
number = {},
pages = {},
pmid = {41255967},
issn = {2693-5015},
support = {R21 CA267050/CA/NCI NIH HHS/United States ; R01 CA172404/CA/NCI NIH HHS/United States ; K07 CA080668/CA/NCI NIH HHS/United States ; P30 CA015083/CA/NCI NIH HHS/United States ; R01 CA248288/CA/NCI NIH HHS/United States ; M01 RR000056/RR/NCRR NIH HHS/United States ; R01 CA095023/CA/NCI NIH HHS/United States ; R01 CA168758/CA/NCI NIH HHS/United States ; P50 CA136393/CA/NCI NIH HHS/United States ; },
abstract = {BRCA-associated homologous recombination deficiency (HRD) is present in ~ 50% of high-grade serous carcinomas (HGSC) and predicts sensitivity to platinum-based therapy. However, there is little understanding of why some patients with BRCA-deficient tumors experience unexpectedly poor outcomes. We profiled 154 tumors, enriched for patients with BRCA-deficient tumors that experienced short overall survival (≤ 3 years, n = 42), using whole-genome, transcriptome, and methylation analyses. All but one BRCA-deficient tumor exceeded an accepted HRD genomic scarring threshold. However, patients with BRCA1-deficient HGSC with a more elevated HRD score survived significantly longer. Patients with BRCA2-deficient HGSC and loss of NF1 survived twice as long as those without NF1 loss, whereas PIK3CA or RAD21 amplification defined BRCA2-deficient HGSC with exceptionally short survival. BRCA1-deficient tumors in short survivors had evidence of immunosuppressive c-kit signaling and EMT. In a large HGSC cohort (n = 1,389) including 282 individuals with pathogenic germline BRCA variants (gBRCApv), the location of the mutation within functional domains stratified clinical outcomes. Notably, residual disease after primary surgery had limited prognostic effect in gBRCApv-carriers compared to non-carriers. Our findings indicate that tumor HR proficiency in the context of therapy response and survival is not a binary property, and highlight genomic and immune modifiers of outcomes in BRCA-deficient HGSC.},
}

@article {pmid41379459,
year = {2025},
author = {Kang, IM and Forschmiedt, JK and Loch, MM and Lew, DL and Barlow, WE and Gralow, JR and Meric-Bernstam, F and Albain, KS and Hayes, DF and Lin, NU and Perez, EA and Goldstein, LJ and Rastogi, P and Schott, AF and Baehner, R and Sharma, P and Tripathy, D and Pusztai, L and Hortobagyi, GN and Kalinsky, K and Henry, NL},
title = {Cognitive Impairment and Chemoendocrine vs Endocrine Therapy in Pre- and Postmenopausal Women: A Secondary Analysis of the RxPONDER Randomized Clinical Trial.},
journal = {JAMA oncology},
volume = {},
number = {},
pages = {},
pmid = {41379459},
issn = {2374-2445},
abstract = {IMPORTANCE: Breast cancer treatment is associated with cancer-related cognitive impairment (CRCI). However, the association of endocrine therapy (ET) vs chemotherapy plus endocrine therapy (CET) with CRCI is poorly understood.

OBJECTIVE: To compare patient-reported CRCI between women with breast cancer treated with ET vs CET and to consider whether menopausal status may be associated.

This was a prespecified secondary analysis of RxPONDER (SWOG S1007), a multinational phase 3 randomized clinical trial of more than 5000 women with hormone receptor-positive ERBB2-negative (formerly HER2-negative) breast cancer with 1 to 3 involved lymph nodes and Oncotype DX (21-gene recurrence score) of 25 or less. Participants were enrolled from February 2011 to September 2017, with results first reported in December 2020. Participants were randomly assigned to CET or ET, with ongoing follow-up. This secondary analysis assessed cognitive function using the Patient-Reported Outcomes Measurement Information System Perceived Cognitive Function Concerns (PCF) questionnaire at baseline, 6, 12, and 36 months. Data were analyzed from July 2022 to August 2025.

INTERVENTION: Random assignment to CET or ET.

MAIN OUTCOMES AND MEASURES: Mean PCF standardized (T) scores by menopausal status over time using generalized estimating equations analysis for continuous outcomes.

RESULTS: Of the 568 patients who completed the baseline questionnaire and were included in the analysis, 139 (24%) were premenopausal (median [range] age, 47.8 [28.0-56.3] years) and 429 (76%) were postmenopausal (median [range] age, 62.3 [37.3-87.6] years). Among the 274 (48%) who received CET and the 294 (52%) who received ET alone, CET was determined to have a greater negative association with patient-reported CRCI in both the pre- and postmenopausal participants during the 36-month follow-up. In the ET alone group, PCF scores for premenopausal participants decreased from baseline to 6 and 12 months (53.53, 51.51, and 51.72, respectively) but recovered to baseline (54.36) at 36 months. For postmenopausal participants, mean PCF scores were essentially stable (51.72, 51.13, 51.11, and 51.70, respectively); however, in the CET group, PCF scores for both pre- and postmenopausal participants decreased from baseline to 6 and 12 months (premenopausal, 52.84, 49.27, 48.04; postmenopausal, 50.65, 48.39, 47.13, respectively) and did not return to baseline at 36 months (premenopausal, 49.25; postmenopausal, 48.44). The difference in longitudinal mean PCF scores over time between CET and ET groups was -3.02 (95% CI, -5.33 to -0.72; P = .01) for premenopausal and -2.37 (95% CI, -3.92 to -0.82; P = .003) for postmenopausal participants.

CONCLUSIONS AND RELEVANCE: This secondary analysis of the RxPONDER found that CET had a greater negative association with patient-reported CRCI compared to ET alone in both pre- and postmenopausal participants over a 36-month follow-up period. Interventions to prevent or treat CRCI are needed to improve the long-term quality of life of these patients treated with chemotherapy.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01272037.},
}

@article {pmid41379444,
year = {2025},
author = {Bowers, DC and Cooney, T and Chen, Y and Yuan, Y and Galvin, R and Im, C and Leisenring, W and Brady, SW and Smith, SA and Howell, RM and Arnold, MA and Conces, M and Yasui, Y and Diller, LR and Armstrong, GT and Neglia, JP and Turcotte, LM},
title = {Subsequent Meningiomas Among Survivors of Childhood Cancer.},
journal = {JAMA network open},
volume = {8},
number = {12},
pages = {e2548715},
pmid = {41379444},
issn = {2574-3805},
mesh = {Humans ; *Meningioma/epidemiology/mortality/etiology ; Female ; Male ; *Cancer Survivors/statistics & numerical data ; Adult ; Child ; Retrospective Studies ; Canada/epidemiology ; Incidence ; Adolescent ; *Meningeal Neoplasms/epidemiology/mortality ; Young Adult ; Middle Aged ; Risk Factors ; Child, Preschool ; United States/epidemiology ; *Neoplasms, Second Primary/epidemiology ; Infant ; Aged ; Longitudinal Studies ; },
abstract = {IMPORTANCE: Associations with chemotherapy, occurrence of multiple meningiomas, and mortality after subsequent meningioma diagnosis among survivors of childhood cancer remain unclear.

OBJECTIVES: To report the incidence of meningioma among childhood cancer survivors, identify novel risk factors for meningiomas, characterize survivors with multiple meningiomas, and describe cause-specific mortality following meningioma occurrence.

The Childhood Cancer Survivor Study is a retrospective cohort study with longitudinal prospective follow-up of childhood cancer survivors diagnosed between 1970 to 1999 in the US and Canada. Eligibility included diagnosis of cancer before age 21 years and surviving more than 5 years after diagnosis. Meningiomas were self-reported and confirmed by review of pathology reports. Childhood cancer diagnosis, chemotherapy details, and radiation therapy exposures from up to 5 years from diagnosis were abstracted from medical records.

MAIN OUTCOMES AND MEASURES: Cumulative incidence of meningioma was calculated starting from 5 years from the diagnosis. Overall survival (OS) from diagnosis of the first subsequent meningioma was estimated using Kaplan-Meier methods.

RESULTS: The CCSS cohort included 24 886 survivors initially diagnosed from 1970 to 1999, including 471 survivors (263 female [56%]; median [range] age at last follow-up, 42.5 [19.7-66.3] years; median [range] age at primary cancer diagnosis, 5.6 [0-20.9] years) who were diagnosed with 710 meningiomas. Thirty-five years after primary cancer diagnosis, the cumulative incidence of a subsequent meningioma was 2.3% (95% CI, 2.1%-2.6%). Of the 471 survivors who developed meningioma, 137 (29.0%) had at least 2 meningiomas, and 80 (16%) met criteria for meningiomatosis. An increased risk of meningioma was associated with higher doses of cranial radiation therapy (eg, HR, 125.3 [95% CI, 58.1-270.5]), younger age at primary cancer diagnosis (eg, 0 to 4 years: HR, 4.0 [95% CI, 2.4-6.1]), female sex (HR, 1.6 [95% CI, 1.3-1.9]), and exposure to platinum, 6-mercaptopurine, and intrathecal chemotherapy, and a lower risk was associated with non-Hispanic Black race (HR, 0.5 [95% CI, 0.3-1.0]) and exposure to alkylating agents (HR, 0.6 [95% CI, 0.5-0.8]). The all-cause cumulative mortality was 4.9%, 10.5% and 18.4% at 5, 10, and 15 years from the first subsequent meningioma diagnosis.

CONCLUSIONS AND RELEVANCE: Meningiomas have a relatively high incidence and mortality for childhood cancer survivors. Results from this study could justify screening for meningiomas in high-risk populations.},
}

Humans
*Meningioma/epidemiology/mortality/etiology
Female
Male
*Cancer Survivors/statistics & numerical data
Adult
Child
Retrospective Studies
Canada/epidemiology
Incidence
Adolescent
*Meningeal Neoplasms/epidemiology/mortality
Young Adult
Middle Aged
Risk Factors
Child, Preschool
United States/epidemiology
*Neoplasms, Second Primary/epidemiology
Infant
Aged
Longitudinal Studies

@article {pmid41378983,
year = {2025},
author = {Ahluwalia, MS and Solomon, S and Patel, SP and Sarfraz, Z and Othus, M and Chae, YK and Kurzrock, R},
title = {Efficacy and CNS Toxicity of Nivolumab and Ipilimumab in Rare Cancer Brain Metastases: A Multi-Center Basket Trial Analysis (NCI/SWOG S1609).},
journal = {Clinical cancer research : an official journal of the American Association for Cancer Research},
volume = {},
number = {},
pages = {},
doi = {10.1158/1078-0432.CCR-25-2900},
pmid = {41378983},
issn = {1557-3265},
abstract = {PURPOSE: To evaluate the efficacy and safety of dual immune checkpoint inhibitors (ICI) in patients with brain metastases (BM) from rare cancers.

PATIENTS AND METHODS: Patients with and without BM received nivolumab (240 mg every two weeks) and ipilimumab (1 mg/kg every six weeks) (NCI/SWOG S1609 DART trial, NCT02834013) across >1,000 sites. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method; hazard ratios (HR) with 95% confidence intervals (CI) were derived from Cox models. Systemic ORR was assessed by RECIST v1.1, and adverse events were graded using CTCAE v5.0. Intracranial outcomes were assessed in a subset of patients with BM to evaluate best intracranial response.

RESULTS: Among 727 patients, the systemic ORR was 11.5% in those without BM (n=707) and 10% in those with BM (n=20) (p=0.76). PFS and OS were similar between groups (PFS: HR=1.29, 95% CI 0.81-2.07, p=0.28; OS: HR=1.36, 95% CI 0.81-2.27, p=0.24). Intracranial response was evaluable in 12 patients with BM (60%). No intracranial complete or partial responses were observed, and six patients (50%) achieved intracranial stable disease as their best intracranial response. Grade ≥3 CNS toxicities occurred in 3% of patients without BM and 5% of those with BM (p=0.43).

CONCLUSIONS: Dual-ICI therapy showed comparable efficacy and safety in patients with and without BM.},
}

@article {pmid41378902,
year = {2025},
author = {Mandrycky, CJ and Ishida, T and Merkel, T and Rayner, SG and Heck, A and Hadland, B and Zheng, Y},
title = {Under pressure: integrated endothelial cell response to hydrostatic and shear stresses.},
journal = {Vascular biology (Bristol, England)},
volume = {},
number = {},
pages = {},
doi = {10.1530/VB-25-0015},
pmid = {41378902},
issn = {2516-5658},
abstract = {Blood flow within the vasculature is a critical determinant of endothelial cell (EC) identity and functionality, yet the intricate interplay of various hemodynamic forces and their collective impact on endothelial and vascular responses are not fully understood. Specifically, the role of hydrostatic pressure in the EC flow response is understudied, despite its known significance in vascular development and disease. To address this gap, we developed in vitro models to investigate how pressure influences EC responses to flow. Our study demonstrates that elevated pressure conditions significantly modify shear-induced flow alignment and increase endothelial cell density. Bulk and single-cell RNA sequencing analyses revealed that, while shear stress remains the primary driver of flow-induced transcriptional changes, pressure modulates shear-induced signaling in a dose-dependent manner. These pressure-responsive transcriptional signatures identified in human ECs were conserved during the onset of circulation in early mouse embryonic vascular development, where pressure was notably associated with transcriptional programs essential to arterial and hemogenic EC fates. Our findings suggest that pressure plays a synergistic role with shear stress on ECs and emphasizes the need for an integrative approach to endothelial cell mechanotransduction, one that encompasses the effects induced by pressure alongside other hemodynamic forces.},
}

@article {pmid41374977,
year = {2025},
author = {Chen, X and Fang, H and Wu, Y and Meshinchi, S and Naresh, KN and Reister, E and Langford, K and Eacker, SM and Liu, YJ},
title = {Comprehensive Detection of Chromosomal and Genomic Abnormalities via Next-Generation Sequencing-Based Genomic Proximity Mapping Improves Diagnostic Classification of Hematologic Neoplasms.},
journal = {Cancers},
volume = {17},
number = {23},
pages = {},
pmid = {41374977},
issn = {2072-6694},
support = {R44CA281528 and R44CA278140/CA/NCI NIH HHS/United States ; },
abstract = {Background/Objectives: Accurate detection of all classes of genomic structural variants (SVs), including chromosomal rearrangements and copy number alterations (CNAs), is essential for the diagnosis and classification of hematologic neoplasms. Conventional cytogenetic methods currently serve as routine clinical tools for detecting SVs. However, each commonly used cytogenetic test has specific limitations, and sequential application of these different tests may delay timely diagnosis and treatment. Methods: In this study, we evaluated the feasibility and utility of genomic proximity mapping (GPM), a novel high-throughput chromosome conformation capture (Hi-C)-based next-generation sequencing (NGS) method, to identify chromosomal and genetic aberrations in hematologic neoplasms in the clinical setting. GPM was performed on 18 cases of hematologic neoplasms (fresh/frozen cells or formalin-fixed paraffin-embedded tissue), and concordance with other methodologies was assessed, including karyotyping, FISH, RT-PCR, chromosomal microarray analysis (CMA), and/or RNA sequencing. Results: GPM reliably detected balanced and unbalanced chromosomal rearrangements, including chimeric gene fusions and gene juxtapositions, with 95.2% concordance with previously applied methods in cases with >10% tumor burden. Additionally, GPM can detect CNAs and copy-neutral loss of heterozygosity (cnLOH) simultaneously in a single assay. Furthermore, detection of genomic rearrangements not identified by other methods improved the accuracy of disease classification. Conclusions: These findings demonstrate that GPM is a powerful method for identifying clinically actionable variants in hematologic neoplasms, overcoming some limitations of current cytogenetic technologies and improving the diagnostic accuracy and classification in challenging cases.},
}

@article {pmid41374973,
year = {2025},
author = {Surento, W and Fischer, R and Biswas, D and Hippe, DS and Kazerouni, AS and Kim, JY and Li, I and Gennari, JH and Rahbar, H and Partridge, SC},
title = {Multiparametric MRI Markers Associated with Breast Cancer Risk in Women with Dense Breasts.},
journal = {Cancers},
volume = {17},
number = {23},
pages = {},
pmid = {41374973},
issn = {2072-6694},
support = {U01CA152637//NIH/NCI/ ; R01CA207290//NIH/NCI/ ; R01CA190299//NIH/NCI/ ; },
abstract = {Background/Objectives: This study explored the associations of normal breast tissue characteristics on multiparametric MRI with clinical assessments of breast cancer risk in women with dense breasts. Methods: Women with dense breasts who underwent multiparametric MRI were included. Breast cancer risk was determined based on Tyrer-Cuzick (TC) lifetime risk scores, categorized as high (TC ≥ 20%) or low risk. Qualitative background parenchymal enhancement (BPE) assessment was obtained from imaging reports. Quantitative imaging markers were calculated, including median BPE, median apparent diffusion coefficient, and volume measures of the whole breast, fibroglandular tissue (FGT), blood vessels, and BPE regions. The associations between imaging markers and TC risk groups were evaluated using age-adjusted logistic regression and summarized by area under the receiver operating characteristic curve (AUC). Results: Seventy-seven women were evaluated; a total of 20 (26%) were low risk, and 57 (74%) were high risk. After adjusting for age and multiple testing, BPE:breast ratio (adj. p = 0.037), FGT:breast ratio (adj. p = 0.046), and BPE:vessel ratio (adj. p = 0.037) were positively associated with risk, while qualitative BPE was not (adj. p = 0.11). Overall, risk categorizations based on imaging markers were concordant with TC score in up to 70% of women. Conclusions: In women with dense breasts, quantitative measures from multiparametric MRI (BPE:breast, FGT:breast, and BPE:vessel ratios) moderately discriminated high- and low-risk groups, warranting further investigation of their value to supplement conventional breast cancer risk assessment tools.},
}

@article {pmid41292998,
year = {2025},
author = {Kuppers, DA and Arora, S and Wladyka, CL and Ge, R and Liu, S and Peng, Y and Su, R and Wilhite, A and Chen, J and He, C and Hsieh, AC and Paddison, PJ},
title = {N6-methyladenosine regulation of mRNA translation is essential for early human erythropoiesis.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {41292998},
issn = {2692-8205},
support = {R01 GM135362/GM/NIGMS NIH HHS/United States ; P30 CA015704/CA/NCI NIH HHS/United States ; R01 CA280389/CA/NCI NIH HHS/United States ; R01 DK119270/DK/NIDDK NIH HHS/United States ; P30 DK056465/DK/NIDDK NIH HHS/United States ; R37 CA230617/CA/NCI NIH HHS/United States ; U54 DK106829/DK/NIDDK NIH HHS/United States ; R01 CA276308/CA/NCI NIH HHS/United States ; },
abstract = {N6-methyladenosine (m[6]A) is an abundant modification of mRNA with important regulatory roles in normal and malignant hematopoiesis. We previously reported that in human erythroid leukemia (HEL) cells, m[6]A mRNA marking selectively regulates translation of essential erythropoiesis genes required for in vitro differentiation and human erythroid colony formation. Here, we further investigated the timing and nature of requirement for m[6]A-methyltransferase (MTase) activity during human erythropoiesis, using a standardized in vitro erythroid differentiation assay for hHSPCs. We identified two critical m[6]A regulated developmental windows in BFU-E and during the transition from CFU-E to proerythroblasts. These windows of m[6]A-MTase requirement coincide with rising global m[6]A levels, which peak in proerythroblasts. After proerythroblast formation, however, m[6]A -MTase activity is dispensable for differentiation, proliferation, and survival. In BFU-E, m[6]A-MTase promotes proliferation but is dispensable for differentiation, while, in CFU-E, both m[6]A -MTase and the YTHDF family of m[6]A readers are essential for differentiation to proerythroblasts. Mechanistically, in CFU-E, m[6]A - MTase activity enhances translation of ribosomal and oxidative phosphorylation (OXPHOS) genes, thereby elevating global protein synthesis rates and enabling efficient erythroblast formation. We propose that this form of translational regulation by m[6]A emerged as an evolutionary adaptation to meet the high translational demands of human erythropoiesis.},
}

@article {pmid41279072,
year = {2025},
author = {Williamson, C and Curry, L and Mkhize, NN and Giorgi, EE and Magaret, CA and Lambson, BE and Hons, SB and Kaldine, H and Moyo-Gwete, T and Rolland, M and Rossenkhan, R and Garcia, NMG and Moodley, C and Yssel, A and Huang, Y and Marsden, AA and Reeves, DB and Mayer, BT and Bumgarner, RE and Beaume, N and Westfall, DH and Juraska, M and DeCamp, AC and Murrell, H and Bai, H and Deng, W and Pankow, AP and Bhattacharya, T and York, T and Ndabambi, N and Chen, L and Zhao, H and Gwashu-Nyangiri, A and Thebus, R and Cohen, P and Murrell, B and Karuna, S and Hural, J and Mgodi, N and Edupuganti, S and Morris, L and Montefiori, D and McElrath, MJ and Cohen, MS and Corey, L and Edlefsen, PT and Gilbert, PB and Moore, PL and Mullins, JI},
title = {VRC01 Selects Rare HIV Escape Mutations After Acquisition in Antibody-Mediated Prevention Trials.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {41279072},
issn = {2692-8205},
support = {K25 AI155224/AI/NIAID NIH HHS/United States ; UM1 AI068614/AI/NIAID NIH HHS/United States ; R01 AI152115/AI/NIAID NIH HHS/United States ; UM1 AI068635/AI/NIAID NIH HHS/United States ; UM1 AI068619/AI/NIAID NIH HHS/United States ; UM1 AI068613/AI/NIAID NIH HHS/United States ; R01 AI157854/AI/NIAID NIH HHS/United States ; INV-016189/GATES/Gates Foundation/United States ; UM1 AI068617/AI/NIAID NIH HHS/United States ; UM1 AI068618/AI/NIAID NIH HHS/United States ; R01 AI186721/AI/NIAID NIH HHS/United States ; },
abstract = {Broadly neutralizing antibodies (bnAbs) show promise in HIV prevention, yet viral escape remains a challenge. In the Antibody Mediated Prevention (AMP) trials, the CD4 binding site (CD4bs) bNAb VRC01 blocked acquisition by VRC01-sensitive strains. However, its influence on viral evolution post-acquisition is not fully understood. Here we analyzed >12,000 HIV env sequences from 47 participants from the AMP trials, identifying VRC01-mediated de novo escape mutations in 8 of 26 VRC01-treated participants but none in 21 placebo participants. These mutations were found at very low frequency (<1%) in global viruses. Escape mutations, primarily located in the Loop-D and β23/V5 regions of Env, conferred cross-resistance to several CD4bs bnAbs, while more potent CD4bs bnAbs like N6 and 1-18 largely retained their activity. Our findings demonstrate that prophylactic VRC01 can select for viral escape after infection, underscoring the need for next-generation bnAbs with improved breadth and potency to enhance durability and efficacy of antibody-based HIV prevention.},
}

@article {pmid41256406,
year = {2025},
author = {Soysa, R and Abideen, S and Reyes, VZ and Headley, MB},
title = {Ontogeny and functional potential of founding dendritic cells in the developing lung.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {41256406},
issn = {2692-8205},
support = {R21 AI173825/AI/NIAID NIH HHS/United States ; },
abstract = {Lung development begins in utero and reaches full maturity post birth. Dendritic cells (DC) play a key role in immune regulation in lungs. However, comprehensive exploration of DCs in these immature lungs has not been performed. Here we explored DCs from fetal to newborn mouse lungs phenotypically, ontogenetically, transcriptomically and functionally and found two DC subsets, resembling adult cDC1 and cDC2, but with key differences. Phenotypically, fetal-cDC1 lacks the classical-DC1 (cDC1) marker XCR1, while the fetal-cDC2 express both cDCassociated genes as well as monocyte-derived DC genes. Both DC subsets wane as lungs enter the alveolar stage, giving way to the more familiar adult cDC1 and cDC2. Both fetal-cDC1 and fetal-cDC2 derive from ED14.5 fetal liver Macrophage Dendritic Progenitors, not from monocytes or classic Precursor-cDC (Pre-cDC), indicating a unique ontogeny of first DCs in developing mouse lungs. Together we provide the first in depth exploration of first DCs in developing lungs.},
}

@article {pmid41372729,
year = {2025},
author = {Sarfraz, Z and Ranjan, T and Mustafayev, FNA and Jaramillo, M and Odia, Y and Venur, VA and Ahluwalia, MS},
title = {Emerging therapies for glioblastoma.},
journal = {Journal of neuro-oncology},
volume = {176},
number = {1},
pages = {116},
pmid = {41372729},
issn = {1573-7373},
mesh = {Humans ; *Glioblastoma/therapy ; *Brain Neoplasms/therapy ; *Immunotherapy/methods ; *Molecular Targeted Therapy/methods ; *Antineoplastic Agents/therapeutic use ; },
abstract = {Glioblastoma (GBM) remains associated with poor outcomes, with a median survival of 15-18 months despite maximal safe resection, radiotherapy, and temozolomide. Therapeutic development has increasingly centered on overcoming drug resistance, intratumoral diversity, and restricted delivery across the blood-brain barrier. Progress in targeted therapy includes evaluation of EGFR inhibitors, multitarget tyrosine kinase inhibitors, and FGFR-directed agents, while rare molecularly defined subsets such as BRAF V600E and NTRK fusions offer tumor-agnostic precision approaches. JAK/STAT inhibition, PARP blockade, and PI3K/AKT/mTOR pathway modulation remain under investigation, although clinical benefit has been inconsistent. In parallel, precision oncology platforms incorporating multi-omic profiling, patient-derived organoids, and functional drug testing are refining therapy selection and supporting rational drug combinations. Adaptive clinical trial frameworks such as GBM AGILE and INSIGhT are accelerating the evaluation of novel agents within stratified cohorts,while emerging approaches including ChemoID-guided therapy, radiogenomic profiling, and digital modeling are beginning to influence translational endpoints. Immunotherapy continues to be an active area of research, though efficacy has thus far been limited. Immune checkpoint inhibitors have not yet demonstrated significant survival benefits as monotherapy, but combination strategies with vaccines, oncolytic viruses, and engineered cellular therapies are under evaluation. CAR T-cell therapies are advancing toward bispecific and armored constructs with locoregional delivery, while oncolytic viruses such as DNX-2401 and PVSRIPO demonstrate potential for durable responses in select patients. Looking ahead, progress is likely to arise from biomarker-informed, multimodal regimens that integrate targeted agents, next-generation immunotherapies, and precision-guided strategies, while embedding translational endpoints into trial design to address the complex biology and therapeutic resistance of GBM.},
}

Humans
*Glioblastoma/therapy
*Brain Neoplasms/therapy
*Immunotherapy/methods
*Molecular Targeted Therapy/methods
*Antineoplastic Agents/therapeutic use

@article {pmid41372159,
year = {2025},
author = {Pan, R and Ren, J and Chen, X and Flores, LF and Gonzalez, RVL and Adonnino, AA and Lofts, B and Waldo, J and Halmai, J and Devinsky, O and Fink, K and Liu, XS},
title = {Editing DNA methylation in vivo.},
journal = {Nature communications},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41467-025-67222-5},
pmid = {41372159},
issn = {2041-1723},
support = {R01MH134519//U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (NIMH)/ ; R01NS126185//U.S. Department of Health & Human Services | NIH | National Institute of Neurological Disorders and Stroke (NINDS)/ ; },
abstract = {DNA methylation is a crucial epigenetic mechanism that regulates gene expression. Precise editing of DNA methylation has emerged as a promising tool for dissecting its biological function. However, challenges in delivery have limited most applications of DNA methylation editing to in vitro systems. Here, we develop two transgenic mouse lines harboring an inducible dCas9-DNMT3A or dCas9-TET1 editor to enable tissue-specific DNA methylation editing in vivo. We demonstrate that targeted methylation of the Psck9 promoter in the liver of dCas9-DNMT3A mice results in decreased Pcsk9 expression and a subsequent reduction in serum low-density lipoprotein cholesterol level. Targeted demethylation of the Mecp2 promoter in dCas9-TET1 mice reactivates Mecp2 expression from the inactive X chromosome and rescues neuronal nuclear size in Mecp2[+/-] mice. Genome-wide sequencing analyses reveal minimal transcriptional off-targets, demonstrating the specificity of the system. These results demonstrate the feasibility and versatility of methylation editing, to functionally interrogate DNA methylation in vivo.},
}

@article {pmid41372127,
year = {2025},
author = {Bents, SJ and Martin, ET and Stevens-Ayers, T and Andrews, C and Adler, A and Perofsky, AC 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 respiratory pathogens in the wake of the COVID-19 pandemic.},
journal = {Nature communications},
volume = {16},
number = {1},
pages = {11015},
pmid = {41372127},
issn = {2041-1723},
mesh = {Humans ; *COVID-19/immunology/epidemiology/virology/transmission ; Child, Preschool ; SARS-CoV-2/immunology ; Child ; *Antibodies, Viral/blood/immunology ; Adult ; Influenza, Human/immunology/epidemiology/virology ; Middle Aged ; Adolescent ; Age Factors ; Infant ; Young Adult ; Male ; Female ; Aged ; Pandemics ; Washington/epidemiology ; South Africa/epidemiology ; },
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. We assessed age-specific antibody dynamics across a broad range of respiratory viruses, including influenza, respiratory syncytial virus, seasonal coronaviruses, and SARS-CoV-2 using serology collected in King County, Washington, US, from 2020-2022 (n = 1508). We found that respiratory virus immunodynamics differed between individuals <5 years of age and older individuals, with young children experiencing larger boosts and quicker waning of antibodies across pathogens. We confirmed that these patterns are upheld in a non-pandemic setting by analyzing influenza serology collected in South Africa between 2016-2018 (n = 1028). We incorporated our serological insights into an influenza transmission model calibrated to epidemiological data from King County and show that consideration of age-specific immunodynamics may be important to anticipate the effects of pandemic perturbations.},
}

Humans
*COVID-19/immunology/epidemiology/virology/transmission
Child, Preschool
SARS-CoV-2/immunology
Child
*Antibodies, Viral/blood/immunology
Adult
Influenza, Human/immunology/epidemiology/virology
Middle Aged
Adolescent
Age Factors
Infant
Young Adult
Male
Female
Aged
Pandemics
Washington/epidemiology
South Africa/epidemiology

@article {pmid41371208,
year = {2025},
author = {Huckestein, BR and Thomas, PG},
title = {Memories are I(F)N-credibly protective.},
journal = {Immunity},
volume = {58},
number = {12},
pages = {2923-2925},
doi = {10.1016/j.immuni.2025.11.016},
pmid = {41371208},
issn = {1097-4180},
mesh = {Humans ; *Immunologic Memory/immunology ; *CD8-Positive T-Lymphocytes/immunology ; *Interferon-gamma/immunology/metabolism ; Animals ; *Lung/immunology/virology ; *Memory T Cells/immunology ; Virus Replication ; },
abstract = {Lung-resident memory CD8[+] T cells coordinate rapid antiviral defense mechanisms across lung compartments to quicky limit viral replication and spread. In this issue of Immunity, Mattingly et al. demonstrate the importance of CD8[+] Trm cell-derived interferon-γ in epithelial reprogramming for barrier defense in humans.},
}

Humans
*Immunologic Memory/immunology
*CD8-Positive T-Lymphocytes/immunology
*Interferon-gamma/immunology/metabolism
Animals
*Lung/immunology/virology
*Memory T Cells/immunology
Virus Replication

@article {pmid41370081,
year = {2025},
author = {Shin, MB and Axeen, S and Cole, AM and Guo, XM and Islam, JY and Ko, LK and Volpi, CR and Winer, RL and Tsui, J},
title = {Nonadherence to Cervical Cancer Screening Guidelines in Commercially Insured US Adults, 2013-2021.},
journal = {JAMA network open},
volume = {8},
number = {12},
pages = {e2548512},
pmid = {41370081},
issn = {2574-3805},
}

@article {pmid41369938,
year = {2025},
author = {Konstantopoulos, A and de Virgilio, C and Childers, CP},
title = {The Cost of Prolonged Surgical Training-Time Is Money.},
journal = {JAMA surgery},
volume = {},
number = {},
pages = {},
doi = {10.1001/jamasurg.2025.5363},
pmid = {41369938},
issn = {2168-6262},
}

@article {pmid41369932,
year = {2025},
author = {Childers, CP and Selzer, DJ and Mabry, CD},
title = {Refining CPT Codes to Reflect the Complexity of Pediatric Appendicitis-Reply.},
journal = {JAMA surgery},
volume = {},
number = {},
pages = {},
doi = {10.1001/jamasurg.2025.5369},
pmid = {41369932},
issn = {2168-6262},
}

@article {pmid41369553,
year = {2025},
author = {Tsuji, T and Hirose, H and Sugiyama, D and Shindo, M and Hartantyo, RY and Saito, Y and Tatematsu, T and Sugio, S and Sanbo, M and Hirabayashi, M and Kojima, Y and Koseki, J and Hosoya, K and Yoshida, H and Ogimoto, T and Yasuda, Y and Hashimoto, K and Ajimizu, H and Sakamori, Y and Yoshida, H and Sano, N and Tanji, M and Ito, H and Terada, K and Hamaji, M and Menju, T and Konishi, H and Kumagai, S and Ghajar, CM and Kato, D and Date, H and Yoshizawa, A and Arakawa, Y and Ozasa, H and Moorhouse, AJ and Shimamura, T and Nishikawa, H and Hirai, T and Wake, H},
title = {Microglia Display Heterogeneous Initial Responses to Disseminated Tumor Cells.},
journal = {Cancer research},
volume = {},
number = {},
pages = {},
doi = {10.1158/0008-5472.CAN-25-3425},
pmid = {41369553},
issn = {1538-7445},
abstract = {Brain metastases are frequent and often lethal complications of advanced cancers. Microglia, resident immune cells of the brain, are known to exert both anti-tumor and pro-tumor functions in late-stage metastases; however, their response during the initial outgrowth of metastatic lesions is not well characterized. Understanding how heterogeneous microglial subgroups are regulated in the developing tumor microenvironment could pave the way for therapeutic strategies to eliminate metastatic tumors at an early stage. In this study, we used a combination of in vivo fate map imaging, single-cell RNA sequencing, and a holographic photoconversion-based technique (Opto-omics) to track tumor fate and early microglial responses over time in the same animals during colonization of disseminated tumor cells. The microglial population was transcriptionally and morphologically heterogeneous, comprising both pro- and anti-tumor subsets. Genetic and pharmacological perturbations revealed that microglial phenotypes could be shifted by inhibiting TGF-β signaling or by deleting the tumor cell surface antigens CD24a and CD47. These findings reveal targetable plasticity in early-stage microglial responses to brain metastasis and suggest that harnessing pro-phagocytic microglial states may offer a therapeutic window before systemic immunosuppression becomes dominant.},
}

@article {pmid41369537,
year = {2025},
author = {Atuluru, P and Kwendakwema, CN and Bell-Brown, A and Hopkins, T and Simianu, VV and Shankaran, V and Issaka, RB},
title = {Patient Perspectives on Barriers and Facilitators to 1-year Surveillance Colonoscopy Completion in Survivors of Colorectal Cancer: A Multi-Method Analysis.},
journal = {Diseases of the colon and rectum},
volume = {},
number = {},
pages = {},
doi = {10.1097/DCR.0000000000004067},
pmid = {41369537},
issn = {1530-0358},
abstract = {BACKGROUND: Patients treated for stage I-III colorectal cancer are at high risk for developing new and recurrent colon cancers. Therefore, professional organizations recommend a surveillance colonoscopy approximately 1-year post-surgical resection to ensure early detection. Despite these guidelines, surveillance colonoscopy completion rates remain suboptimal.

OBJECTIVE: This multi-methods study aimed to explore patient-identified barriers and facilitators affecting the completion of 1-year surveillance colonoscopies among stage I-III colorectal cancer survivors.

DESIGN: Multi-methods study.

SETTINGS: The study was conducted within the Hutchinson Institute for Cancer Outcomes Research Value in Cancer Care Network, comprising 46 clinics across 13 counties in Washington State.

PATIENTS: We enrolled stage I-III colorectal cancer survivors who had not completed surveillance colonoscopy within 18 months of surgery. Participants completed questionnaires and semi-structured interviews between December 2023 and June 2024.

MAIN OUTCOME MEASURES: Questionnaire data and interview transcripts were independently coded and analyzed by two coders to identify key themes and subthemes related to barriers and facilitators of surveillance colonoscopy completion.

RESULTS: The study included nineteen patients. The median (interquartile range) participant age was 73 (17.8) years, 9 (47.4%) were male and 8 (42.1%) had stage I cancer. All participants reported cognitive and environmental factors as barriers or facilitators to surveillance colonoscopy completion. The most reported barriers were fear of the colonoscopy results and cancer recurrence (cognitive) and challenges with the bowel preparation (environmental). The most frequently reported facilitators were patient's motivation to receive reassurance (cognitive) and clinic assistance in scheduling appointments (environmental).

LIMITATIONS: Results may not be generalizable due to population and selection bias of participants.

CONCLUSIONS: This study identified barriers and facilitators to completing a 1-year surveillance colonoscopy to guide future interventions. Addressing both psychological concerns and improving communication between patients and clinics could be key strategies to enhance adherence rates and improve long-term outcomes for colorectal cancer survivors. See Video Abstract.},
}

@article {pmid41369204,
year = {2025},
author = {Kenny, A and van der Laan, L and Gilbert, P and Carone, M},
title = {Inference on Controlled Effects for Assessing Immune Correlates of Protection Based on a Cox Model.},
journal = {Statistics in medicine},
volume = {44},
number = {28-30},
pages = {e70347},
doi = {10.1002/sim.70347},
pmid = {41369204},
issn = {1097-0258},
support = {R37AI054165//National Institute Of Allergy And Infectious Diseases of the National Institutes of Health under Award Number/ ; },
mesh = {Humans ; Biomarkers ; Clinical Trials, Phase III as Topic ; Computer Simulation ; COVID-19/prevention & control/immunology ; Proportional Hazards Models ; *Vaccine Efficacy ; *2019-nCoV Vaccine mRNA-1273/immunology ; },
abstract = {In vaccine research, it is important to identify biomarkers that can reliably predict vaccine efficacy against a clinical endpoint. Such biomarkers are known as immune correlates of protection (CoP) and can serve as surrogate endpoints in vaccine efficacy trials to accelerate the approval process. CoPs must be rigorously validated, and one method of doing so is through the controlled risk (CR) curve, a function that represents the causal effect of the biomarker on population-level risk of experiencing the endpoint of interest by a certain time post-vaccination. The CR curve can be estimated by leveraging a Cox proportional hazards model, but researchers currently rely on the bootstrap for inference, which can be computationally demanding. In this article, we analytically derive the asymptotic variance of this estimator, providing an analytic approach for constructing both pointwise and uniform confidence bands. We evaluate the finite sample performance of these methods in a simulation study and illustrate their use on data from the Coronavirus Efficacy (COVE) placebo-controlled phase 3 trial (NCT04470427) of the mRNA-1273 COVID-19 vaccine.},
}

Humans
Biomarkers
Clinical Trials, Phase III as Topic
Computer Simulation
COVID-19/prevention & control/immunology
Proportional Hazards Models
*Vaccine Efficacy
*2019-nCoV Vaccine mRNA-1273/immunology

@article {pmid41368947,
year = {2025},
author = {Gong, IY and Soto, MJ and Rafinejad-Farahani, B and Unger, JM and Conti, RM and Guerra, CE and Oza, A and Rosenthal, M and Rodin, D},
title = {Disparities in clinical trial participation among older adult Medicare beneficiaries with hematologic malignancies from 2006 to 2019: A SEER-Medicare analysis.},
journal = {Cancer},
volume = {131},
number = {24},
pages = {e70204},
pmid = {41368947},
issn = {1097-0142},
support = {HSR9020-23//Leukemia and Lymphoma Society/ ; },
mesh = {Humans ; Aged ; Female ; United States/epidemiology ; Male ; *Medicare/statistics & numerical data ; SEER Program/statistics & numerical data ; *Hematologic Neoplasms/therapy/epidemiology ; Aged, 80 and over ; Retrospective Studies ; *Clinical Trials as Topic/statistics & numerical data ; *Healthcare Disparities/statistics & numerical data ; *Patient Participation/statistics & numerical data ; },
abstract = {BACKGROUND: Clinical trials (CTs) are essential for expanding treatment options across hematologic malignancies (HM) and providing access to novel treatments. However, older adults with HM are often underrepresented in CTs, and a national-level evaluation of factors influencing their participation is lacking.

METHODS: The authors conducted a retrospective cohort study using the Surveillance, Epidemiology, and End Results (SEER)-Medicare database, identifying patients ≥66 years old diagnosed with HM between 2006 and 2018 (follow-up to December 2019). CT participation was defined by Medicare claims for CT services. Cumulative incidence and Fine-Gray models were used to estimate participation rates and adjusted hazard ratios (aHRs) assessed the association between participation and sociodemographic factors.

RESULTS: The cohort (n = 53,919) was 50% female, median age 78 years old, and 86% White. Cumulative incidence of CT participation was low at 2.7% at 1 year after diagnosis, increasing to 4.3% at 5 years. After adjustment for the competing risk of death, significantly lower CT participation was observed for older age (vs. 66-69 years: aHR for 70-74 years, 0.79 [95% CI, 0.71-0.88]; aHR for 75-79 years, 0.63 [95% CI, 0.56-0.70]; aHR for 80-84 years, 0.41 [95% CI, 0.36-0.46]; aHR for ≥85 years, 0.21 [95% CI, 0.18-0.24]), female sex (aHR, 0.79 [95% CI, 0.73-0.86]), Black race (aHR, 0.73 [95% CI, 0.59-0.90]), certain comorbidities (aHR for pulmonary disease, 0.76 [95% CI, 0.68-0.85]; aHR for renal disease, 0.67 [95% CI, 0.59-0.76]), dual Medicare-Medicaid eligibility (aHR, 0.66 [95% CI, 0.56-0.77]), and distance to National Cancer Institute centers from the patient's ZIP code (aHR for ≥250 miles, 0.64 [95% CI, 0.48-0.86]).

CONCLUSIONS: These results highlight the need for targeted interventions, such as CT navigator programs and decentralized trials, to increase older adult participation in HM CTs.},
}

Humans
Aged
Female
United States/epidemiology
Male
*Medicare/statistics & numerical data
SEER Program/statistics & numerical data
*Hematologic Neoplasms/therapy/epidemiology
Aged, 80 and over
Retrospective Studies
*Clinical Trials as Topic/statistics & numerical data
*Healthcare Disparities/statistics & numerical data
*Patient Participation/statistics & numerical data

@article {pmid41368258,
year = {2025},
author = {Tachiki, LM and Tykodi, SS},
title = {From surgery to systemic therapy in von Hippel-Lindau disease: insights from extended follow-up of LITESPARK-004.},
journal = {Translational andrology and urology},
volume = {14},
number = {11},
pages = {3446-3452},
pmid = {41368258},
issn = {2223-4691},
}

@article {pmid41279707,
year = {2025},
author = {Barker, M and Milanov, O and Dumm, W and Rich, D and Turakhia, Y and Matsen, FA},
title = {larch: mapping the parsimony-optimal landscape of trees for directed exploration.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {41279707},
issn = {2692-8205},
abstract = {Phylogenetic inference algorithms for large data sets typically return a single tree. However, there are often many optimal trees, especially when sequence data is closely related. We develop a compact representation of large collections of maximally parsimonious histories-trees with mutations mapped onto tree edges. Our C++ implementation, larch, leverages this representation for a highly parallel search algorithm. The storage component uses our history DAG structure to compactly represent large families of optimal trees. The search algorithm integrates this storage with matOptimize for rapid tree optimization; the DAG structure allows us to accept thousands of conflicting tree rearrangements in parallel. The integration enables a new type of tree search: one that systematically maps out the collection of good trees, enabling moves that are directed away from the current set of optimal trees to cross valleys and increase the diversity of the set of optimal trees. It is able to identify more parsimonious trees than are found by other methods. We find diverse optimality landscapes for viral datasets, including many distinct plateaux. We also find that our implementation produces similar results whether using a variety of single starting trees or an ensemble of starting trees, indicating effective global optimization.},
}

@article {pmid41365774,
year = {2025},
author = {Su, CT and Banerjee, R and Li, L and Fedorenko, C and Cowan, A and Ramsey, SD and Shankaran, V},
title = {Association of Personal Credit Data With Financial Hardship and Treatment Outcomes in Patients With Multiple Myeloma.},
journal = {Clinical lymphoma, myeloma & leukemia},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.clml.2025.11.006},
pmid = {41365774},
issn = {2152-2669},
abstract = {INTRODUCTION: Financial difficulty among patients with multiple myeloma (MM) is linked to reduced treatment adherence and worse outcomes. However, it is usually measured through patient questionnaires, which may be inconsistently offered or poorly completed. We hypothesized that credit data could detect financial difficulty and assessed its relationship with treatment outcomes.

METHODS: We conducted retrospective analyses using an integrated database with cancer registry data, insurance claims, and credit data for Western Washington State patients with MM diagnosed between 2012 to 2020. Financial difficulty was categorized into 4 tiers using credit attributes at diagnosis ("financial fragility") and during 2-year follow-up ("financial hardship"). We examined associations between financial fragility and suboptimal treatment, and identified predictors of financial hardship.

RESULTS: Among 396 MM patients, 35%, 38%, 5%, and 20% had no, mild, moderate, and severe financial fragility at diagnosis. Those with moderate/severe fragility were more likely to have delayed treatment initiation or interruptions (OR 1.67, 95% CI, 0.99-2.81, P = .06). Among 290 patients with 2-year follow-up, 69% showed no change in financial hardship from baseline. Financial fragility at diagnosis strongly predicted higher levels of future hardship (OR: 25.0, 95% CI, 11.17-56.13, P < .001). Patients receiving autologous transplant within the first year had lower odds of future hardship (OR 0.33, 95% CI, 0.12-0.90, P = .03).

DISCUSSION: Financial fragility at diagnosis is associated with suboptimal MM treatment and predict future hardship. Credit data could offer an alternative method to identify patients at risk.},
}

@article {pmid41364805,
year = {2025},
author = {Ohlstrom, DJ and Pilcher, WC and Michaud, ME and Acharya, C and Satpathy, S and Gonzalez-Kozlova, E and Jayasinghe, RG and Ferguson, K and Mumme, HL and Nanda, S and Song, Y and Mantrala, S and Karagkouni, D and Schulman, J and Pabustan, N and Vieira Dos Santos, J and Sherbenou, DW and Keats, JJ and Gout, AM and Foltz, S and Lagana, A and Kourelis, T and Vij, R and Dhodapkar, MV and Avigan, D and Cho, HJ and Baughn, LB and Nooka, AK and Lonial, S and Kumar, S and Samur, MK and Vlachos, IS and Ding, L and Gnjatic, S and Mulligan, G and Bhasin, MK},
title = {Longitudinal profiling of tumor and immune compartments uncovers patterns of dysregulation and associations with response in multiple myeloma.},
journal = {Blood cancer discovery},
volume = {},
number = {},
pages = {},
doi = {10.1158/2643-3230.BCD-25-0205},
pmid = {41364805},
issn = {2643-3249},
abstract = {Multiple myeloma (MM) is a malignancy of clonally expanded plasma cells shaped by complex interactions with the immune microenvironment. To investigate immune correlates of treatment response and disease progression, we conducted multi-omics profiling including CD138neg single-cell RNA sequencing of 243 bone marrow samples from 102 patients (631,226 cells) and CD138pos bulk RNA and whole-genome sequencing from 209 samples. In longitudinal analyses, interferon-γ signaling associated with markers of impaired T cell memory after autologous stem cell transplant, while naïve B cell abundance and immunoglobulin diversity correlated with improved progression-free survival (HR = 0.48, p = 2.3e-4). At disease progression, MM cells upregulated cancer-testis antigens and immune effector genes, with concurrent B cell depletion, enrichment of myeloid-derived suppressor cell expression, and phenotypic T-cell exhaustion. These findings highlight dynamic immune-tumor interactions, identifying naïve B cell reconstitution as a biomarker of durable response, and cancer-testis antigens as potential targets for high-risk disease at progression.},
}

@article {pmid41364763,
year = {2025},
author = {Lanzar, ZR and Aldridge, DL and Cruz-Morales, E and Howard, CA and Conway, IO and Zhong, Z and Eberhard, JN and Pereira, JA and Phan, AT and Ring, AM and Parker, M and Kanellopoulou, C and Min, B and Kedl, RM and Christian, DA and Hunter, CA},
title = {IL-27 promotes Treg cell expression of CD122 and fitness at homeostasis.},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
volume = {122},
number = {50},
pages = {e2519141122},
doi = {10.1073/pnas.2519141122},
pmid = {41364763},
issn = {1091-6490},
support = {F31 AI179240/AI/NIAID NIH HHS/United States ; U01 AI160664/AI/NIAID NIH HHS/United States ; R01 AI125247/AI/NIAID NIH HHS/United States ; R01 AI157247/AI/NIAID NIH HHS/United States ; R01 AI148249/AI/NIAID NIH HHS/United States ; },
mesh = {Animals ; *T-Lymphocytes, Regulatory/immunology/metabolism ; *Homeostasis/immunology ; Mice ; *Interleukin-2 Receptor beta Subunit/metabolism/genetics/immunology ; *Interleukin-27/metabolism ; *Interleukins/metabolism ; Mice, Inbred C57BL ; Interleukin-2 ; Mice, Knockout ; },
abstract = {Regulatory T (Treg) cells express high levels of the IL-27R, and in the setting of infection and autoimmunity, the cytokine IL-27 promotes Treg cell activities that mitigate tissue pathology. However, IL-27 appears dispensable for Treg cell development and maintenance as lineage-specific depletion of the IL-27R on Treg cells does not impact these populations at steady state. In contrast, when mice were generated in which the Treg compartment comprised a mix of IL-27R-sufficient and -deficient Treg cells, those that lacked IL-27R were at a competitive disadvantage. Aging experiments illustrate that IL-27R-deficient Treg cells are preferentially eroded, and this defect was associated with reduced expression of CD122, the β chain of the IL-2/15R. Moreover, blockade of CD122 led to a similar loss of Treg cells, and in vitro and in vivo studies highlight that IL-27 promotes Treg cell expression of CD122 and improves responsiveness to IL-2/15. These datasets reveal that homeostatic IL-27 signals provide a competitive advantage that shapes the composition of the Treg cell pool by modulating responsiveness to growth factors.},
}

Animals
*T-Lymphocytes, Regulatory/immunology/metabolism
*Homeostasis/immunology
Mice
*Interleukin-2 Receptor beta Subunit/metabolism/genetics/immunology
*Interleukin-27/metabolism
*Interleukins/metabolism
Mice, Inbred C57BL
Interleukin-2
Mice, Knockout

@article {pmid41364481,
year = {2025},
author = {Cheng, KK and Copeland, V and Liu, A and Vijapurapu, S and Jao, M},
title = {Safety evaluation of outpatient ifosfamide regimens in adult sarcoma patients.},
journal = {Journal of oncology pharmacy practice : official publication of the International Society of Oncology Pharmacy Practitioners},
volume = {},
number = {},
pages = {10781552251399903},
doi = {10.1177/10781552251399903},
pmid = {41364481},
issn = {1477-092X},
abstract = {INTRODUCTION: Transitioning historically inpatient chemotherapy regimens to outpatient administration can reduce hospital stays, resource use, and healthcare expenditures while improving patient quality of life. However, agents like ifosfamide, commonly used in sarcoma, often necessitate inpatient administration for close monitoring of adverse effects. The Fred Hutchinson Cancer Center (FHCC) sarcoma group has developed criteria for outpatient ifosfamide administration after one successful inpatient administration. Nevertheless, there remains a paucity of literature characterizing the safety profile of outpatient ifosfamide administration.

METHODS: This was a single-center, retrospective, observational study that included adults 18 years and older with a diagnosis of sarcoma receiving an ifosfamide-based regimen in the outpatient setting at FHCC between March 2021 and September 2024. The primary outcome was a composite proportion of grade 3 or higher ifosfamide-related neurotoxicity, hemorrhagic cystitis, febrile neutropenia, and uncontrolled nausea or vomiting. Secondary outcomes included days of hospitalization saved with outpatient administration.

RESULTS: A total of 12 patients met the inclusion criteria. The most common outpatient treatment regimen was AIM (42%) followed by IE (25%) and VDC-IE (25%). Out of a total of 53 outpatient cycles, 15 cycles (28.3%) across 4 patients (33.3%) had at least 1 grade 3 or higher adverse effect of interest included in the primary outcome. A total of 257 hospitalization days were saved with outpatient administration, resulting in an estimated cost savings of $987,651.

CONCLUSION: Overall, among sarcoma patients meeting the FHCC outpatient ifosfamide criteria, administration of ifosfamide in the outpatient setting is safe with considerable cost savings to the institution.},
}

@article {pmid41364449,
year = {2025},
author = {Lynch, RC and Gopal, AK},
title = {Pharma steps back from Hodgkin lymphoma: now what?.},
journal = {Blood advances},
volume = {9},
number = {23},
pages = {6218-6219},
doi = {10.1182/bloodadvances.2025017650},
pmid = {41364449},
issn = {2473-9537},
}

@article {pmid41364082,
year = {2025},
author = {Beck, ML and Supiano, KP and Clayton, MF and Shannon Dorcy, K and Cloyes, KG},
title = {Oncology Nurses' Perceptions of Barriers and Facilitators to Conducting Spiritual Histories.},
journal = {Journal of hospice and palliative nursing : JHPN : the official journal of the Hospice and Palliative Nurses Association},
volume = {},
number = {},
pages = {},
doi = {10.1097/NJH.0000000000001194},
pmid = {41364082},
issn = {1539-0705},
abstract = {Nurses can relieve spiritual suffering experienced by advanced cancer patients through meaningful spiritual conversations (eg, spiritual histories), but may be reticent to do so, citing lack of knowledge, skills, and time as primary barriers. The Lift the Spirit (LtS), a novel online educational communication intervention targeting these barriers, was tested using a pilot quasi-experimental concurrent mixed-methods design. The LtS pilot integrated online education, simulated spiritual history assessment using the Faith, Importance, Community, Action tool, and post-test debriefing with nurse participants (n = 17) to elicit their perceptions of the facilitators and barriers of the LtS and conducting spiritual histories in clinical practice. Debrief interview data were deductively then inductively coded, and content analyzed to describe patterns of response. Participants described barriers and facilitators at the levels of institution/profession (lack of education and training), self (vulnerability and perceived riskiness), and patient (cultural difference) that were similar to barriers noted in the literature. Facilitators included feeling equipped and supported, and having external cues as reminders. No new barriers were uncovered, but the degree of negative affect (eg, angst, fear, and vulnerability) in the responses was discovered. The LtS, primarily the Faith, Importance, Community, Action tool and role-play components, demonstrated clinical utility in equipping nurses to overcome barriers to spiritual care in clinical practice.},
}

@article {pmid41279840,
year = {2025},
author = {Billato, I and Pages, H and Carey, V and Waldron, L and Sales, G and Romualdi, C and Risso, D},
title = {Benchmarking large-scale single-cell RNA-seq analysis.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {41279840},
issn = {2692-8205},
abstract = {The increasing size of single-cell RNA sequencing (scRNA-seq) datasets poses major computational challenges. This work benchmarks the scalability, efficiency, and accuracy of five widely used analysis frameworks (Seurat, OSCA, scrapper, Scanpy, and rapids_singlecell), focusing on the impact of algorithmic and infrastructural choices on performance. We performed a systematic comparison of these workflows using representative datasets, including a 1.3 million mouse brain cell dataset for scalability and three smaller datasets (BE1, scMixology, and cord blood CITE-seq) with ground truth labels to assess clustering accuracy. Principal Component Analysis (PCA) was used as a paradigmatic step to evaluate the computational performance of six SVD algorithms (exact, ARPACK, IRLBA, randomized, Jacobi, and incremental PCA) across multiple data representations (dense, sparse, HDF5) and hardware configurations (CPU vs GPU). All methods showed high concordance in PCA results, with negligible loss of accuracy in truncated approaches. GPU-based computation using rapids_singlecell provided a 15× speed-up over the best CPU methods, with moderate memory usage. On CPU, ARPACK and IRLBA were the most efficient for sparse matrices, while randomized SVD performed best for HDF5-backed data. Among full pipelines, rapids_singlecell was the fastest, whereas OSCA and scrapper achieved the highest clustering accuracy (ARI up to 0.97) in datasets with known cell identities. Performance differences were largely driven by the choice of highly variable genes (HVGs) and PCA implementation. The study highlights that scalability in scRNA-seq analysis depends critically on both algorithmic and infrastructural factors. GPU acceleration and optimized BLAS/LAPACK configurations markedly enhance performance, while Bioconductor-based pipelines remain robust in accuracy. The provided benchmarks offer practical guidelines for efficient and reliable analysis of large-scale single-cell datasets.},
}

@article {pmid41056518,
year = {2025},
author = {Cassaday, RD},
title = {Challenges and opportunities for improvement in the practical management of adults with acute lymphoblastic leukemia.},
journal = {Blood advances},
volume = {9},
number = {24},
pages = {6345-6353},
doi = {10.1182/bloodadvances.2025017584},
pmid = {41056518},
issn = {2473-9537},
mesh = {Humans ; *Precursor Cell Lymphoblastic Leukemia-Lymphoma/therapy/diagnosis ; Adult ; Disease Management ; },
abstract = {As our approaches to the management of adults with acute lymphoblastic leukemia (ALL) have become more effective, they have introduced new administrative complexities. These include challenges pertaining to medication administration and financial implications of treatment choices. Because approximately half of these patients are typically treated outside of larger referral centers, these difficulties are being passed on to clinicians in settings that rarely encounter this complex disease. Instead of an evidence-focused review on contemporary management of ALL in adults, this article seeks to highlight how some of these important medical advances may be difficult to operationalize outside of high-volume centers. It will also attempt to identify areas in which clinicians and investigators might consider modifying their respective approaches to mitigate how the realities of modern medical care may affect our ability to optimally manage these patients now and in the future.},
}

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

@article {pmid41363715,
year = {2025},
author = {Wassertheil-Smoller, S and Larson, JC and Xue, X and Greywoode, R and Bohm, M and Liu, L and Wallace, R and Wactawski-Wende, J and Haring, B and LaMonte, M},
title = {Low Diastolic Blood Pressure and Risk of Ischemic Colitis in the Women's Health Initiative Cohort.},
journal = {The American journal of gastroenterology},
volume = {},
number = {},
pages = {},
doi = {10.14309/ajg.0000000000003878},
pmid = {41363715},
issn = {1572-0241},
abstract = {OBJECTIVES: To identify risk and protective factors in older women for incidence of ischemic colitis (IC) and 30-day mortality.

METHODS: We conducted a prospective study of 100,825 women in the Women's Health Initiative, with average of 13.1 years follow-up and extensive phenotypic and outcomes data in diverse race and ethnic groups. Lasso Cox regression selected variables related to incidence of ischemic colitis from multiple domains (demographic, comorbidities, risk factors, biomarkers, psychosocial factors, dietary factors). Cox regressions modelled the selected variables to obtain adjusted hazard ratios and 95% confidence limits.

RESULTS: Incidence rate of IC was twice as high among those with history of cardiovascular disease (55.7 per 10,000 person-years (py)) compared to those with no such history (27.3 per 10,000 py). After adjustment for multiple covariates, higher risk was associated with diastolic blood pressure below 90mmHg, using two or more types of antihypertensive medication compared to none (aHR =1.62, 95%CI: 1.47, 1.78), having gastrointestinal symptoms (aHR = 1.31, 95%CI: 1.20, 1.42 highest versus lowest quartile). Higher fiber intake was associated with lower risk, (aHR per increase of 10 grams per day = 0.93, 95%CI: 0.89, 0.97) Black women had lower adjusted risk of IC than White women (aHR = 0.73, 95%CI: 0.63, 0.83). Post IC 30-day all-cause mortality was 10.6% sepsis was an important cause of death.

CONCLUSIONS: Incidence rate of IC in older women was twice as high in those with a history of cardiovascular disease and was associated with low diastolic blood pressure and multi-class antihypertensive treatment. Dietary fiber intake was associated with lower risk. Black women had lower risk of IC compared to White women.},
}

@article {pmid41363134,
year = {2025},
author = {Murphy, NR and Snidarich, M and Budak, JZ and Brown, MC and Weiner, BJ and Giustini, N and Caverly, TJ and Ross, K and DeCell, K and Crothers, K and Triplette, M},
title = {Tensions in Implementation: A Mixed-Methods Evaluation of a Lung Cancer Screening Shared Decision-Making Aid for People With HIV.},
journal = {Health promotion practice},
volume = {},
number = {},
pages = {15248399251388644},
doi = {10.1177/15248399251388644},
pmid = {41363134},
issn = {1552-6372},
abstract = {People with HIV (PWH) are at increased risk for lung cancer, but lung cancer screening (LCS) is understudied in this population. We previously adapted a shared decision-making (SDM) aid for PWH and demonstrated its efficacy in improving LCS knowledge. In this study, we conducted a mixed-methods evaluation of the implementation of this aid. Participants were LCS-eligible PWH. Forty participants reviewed HIV-adapted and individually tailored decision aids at SDM visits and completed pre-/post-visit surveys. Fifteen completed semi-structured interviews. Interviews were analyzed using thematic analysis guided by the Health Equity Implementation Framework and triangulated with surveys through joint displays. Participants generally approved of the SDM aid as it explained the risks and benefits of screening, but six key implementation tensions emerged: (1) Participants generally trusted clinician recommendations but highlighted how their lived experience with HIV informed some medical skepticism and desire for autonomy. (2) There was appreciation for HIV-focused material, but emphasis on individuality and the variable experiences of PWH. (3) Participants were interested and motivated regarding LCS but highlighted systemic barriers. (4) The aid improved comfort for many, but increased anxiety or confusion for others. (5) Some preferred SDM with their primary care clinician, while others prioritized the opinion of an LCS-focused clinician. (6) Several were motivated to quit smoking after SDM, while others were reassured to continue smoking by lower-than-expected risk estimates. This adapted decision aid was well-received, but interviews highlighted tensions in implementation. Iterative adaptation of the decision aid and communication strategies is needed to optimize SDM for PWH.},
}

@article {pmid41361127,
year = {2025},
author = {Zvolensky, MJ and Shepherd, JM and Bevers, LM and Redmond, BY and Garey, L and Jo, D and Asfar, T and Castillo-Avilés, R and Santiago-Torres, M and Bricker, JB},
title = {Quit behavior among Hispanic persons who smoke: evaluating differences in nicotine replacement therapy.},
journal = {Journal of behavioral medicine},
volume = {},
number = {},
pages = {},
pmid = {41361127},
issn = {1573-3521},
support = {U54MD015946/MD/NIMHD NIH HHS/United States ; },
abstract = {Hispanic individuals experience significant health disparities related to smoking. Research focused on the methods employed to quit smoking among the Hispanic population is needed to better understand how to increase engagement with evidence-based smoking cessation guidelines and mitigate smoking-related health disparities. The present investigation sought to: (1) document smoking cessation methods used in previous quit attempts, including Nicotine Replacement Therapy (NRT), and (2) test group differences (NRT use vs not) in smoking-related vulnerability processes (i.e., cigarette dependence, perceived barriers for smoking cessation, severity of problems when trying to quit, and number of prior failed quit attempts). Participants were recruited nationally throughout the United States via Qualtrics Panels and were 302 Hispanic adults (38.1% female, Mage = 35.70, SD = 8.63) who endorsed daily cigarette smoking and a prior quit attempt. Results indicated that the most common method of quitting was 'cold turkey' (65.6%), but other methods were also employed (e.g., gradual reduction of cigarettes, enlisting social support). Moreover, there was a substantial number (57.9%) who used NRT in the form of nicotine gum or patch. Additionally, across each of the criterion variables studied, those who had used NRT demonstrated greater cigarette dependence, perceived barriers for smoking cessation, severity of problems when trying to quit, and number of prior failed quit attempts when compared to persons with no such history of NRT use. Overall, these data suggest that history of NRT use may identify a subgroup of Hispanic persons in need of more intensive smoking cessation treatment.},
}

@article {pmid41360798,
year = {2025},
author = {Birukov, A and Lin, N and Mongiovi, J and Razquin, C and Wang, F and Semnani-Azad, Z and Tessier, AJ and Guasch-Ferré, M and Ley, SH and Manson, JE and Sinkey, RG and Haring, B and Shadyab, AH and Balasubramanian, R and Martínez-González, MA and Rexrode, KM and Hu, FB and Zhang, C and Zeleznik, OA and Sasamoto, N},
title = {Plasma metabolomic signature of breastfeeding and risk of cardiometabolic diseases.},
journal = {Nature communications},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41467-025-65977-5},
pmid = {41360798},
issn = {2041-1723},
support = {R03CA259659//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; R01CA49449//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; R01HL034594//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; U01CA176726//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; R01CA67262//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; },
abstract = {Breastfeeding is inversely associated with cardiometabolic disease incidence in prospective studies; however, the metabolic pathways underlying these associations remain largely unknown. Here, we derive a plasma metabolomic score of lifetime total duration of breastfeeding using elastic net regularized regression in Nurses' Health Studies (n = 4349) and replicate in the Women's Health Initiative (n = 2088). Data include 181 untargeted plasma metabolites profiled by liquid chromatography mass spectrometry using blood samples collected in mid-life, and self-reported lifetime total duration of breastfeeding. We then examine the associations between the metabolite-based breastfeeding score and risk of T2D and CVD using multivariable Cox regression models and replicated in two external cohorts. The metabolite-based breastfeeding score comprised of 5 metabolites (i.e., C54:2 triglyceride, C56:2 triglyceride, C56:3 triglyceride, cotinine, indole-3-propionate), which show a modest but statistically significant correlation with lifetime total duration of breastfeeding. The metabolite-based breastfeeding score significantly inversely associate with T2D incidence (HR = 0.76, 95%CI = 0.71-0.82) and with CVD incidence (HR = 0.88, 95%CI = 0.84-0.93) independent of T2D and CVD risk factors. We identify plasma metabolite profiles in mid-life associated with breastfeeding duration, which is also linked to CVD and T2D risk.},
}

@article {pmid41360064,
year = {2025},
author = {Sehn, LH and Hübel, K and Luminari, S and Scholz, CW and Salar, A and Paneesha, S and Wahlin, BE and Panayiotidis, P and Lee, HP and Jiménez-Ubieto, A and Sancho, JM and Kim, TM and Domingo Domenech, E and Kumode, T and Poh, C and Thieblemont, C and Deeren, D and de Wit, E and Arbushites, M and Vassallo, I and Trneny, M and , },
title = {Tafasitamab, lenalidomide, and rituximab in relapsed or refractory follicular lymphoma (inMIND): a global, phase 3, randomised controlled trial.},
journal = {Lancet (London, England)},
volume = {},
number = {},
pages = {},
doi = {10.1016/S0140-6736(25)01778-7},
pmid = {41360064},
issn = {1474-547X},
abstract = {BACKGROUND: Follicular lymphoma is characterised by episodes of remission and relapse, with patients requiring multiple lines of therapy. Lenalidomide plus rituximab is a commonly used immunotherapy combination in patients with relapsed or refractory follicular lymphoma. We aimed to assess the efficacy and safety of adding tafasitamab, a CD19-targeted Fc-enhanced monoclonal antibody, to lenalidomide and rituximab in this setting.

METHODS: This phase 3, double-blind, randomised, placebo-controlled trial (inMIND) was done in 210 centres (including community-based haematology clinics, major hospitals, and academic institutions) in North America, Europe, and the Asia-Pacific region. Adults with relapsed or refractory follicular lymphoma, who had received at least one previous line of systemic therapy, were eligible for enrolment and randomly assigned (1:1) to receive treatment with up to 12 cycles (28-day cycle length) of tafasitamab (12 mg/kg by intravenous infusion on days 1, 8, 15, and 22 of cycles 1-3 and days 1 and 15 of cycles 4-12) or placebo, both with lenalidomide (20 mg/day orally on days 1-21 of cycles 1-12) and rituximab (375 mg/m[2] by intravenous infusion on days 1, 8, 15, and 22 of cycle 1 and day 1 of cycles 2-5). Treatment assignment was achieved via an interactive voice or web response system; patients, investigators, and the funder were masked until the primary analysis. Study endpoints were investigator assessed unless otherwise specified. The primary endpoint was progression-free survival in the intention-to-treat population of all randomised patients; safety was assessed in all randomised patients who received at least one dose of study drug. The trial is registered with ClinicalTrials.gov (NCT04680052) and EUDRA-CT (2020-004407-13) and is active but no longer enrolling.

FINDINGS: Between April 16, 2021, and Aug 10, 2023, a total of 817 patients were assessed for eligibility; 548 patients with relapsed or refractory follicular lymphoma were enrolled and randomly assigned to treatment with either tafasitamab (n=273) or placebo (n=275). 299 (55%) of all randomised patients were male and 249 (45%) were female. The addition of tafasitamab to lenalidomide and rituximab resulted in significantly lower risk of progression, relapse, or death versus placebo (median progression-free survival by investigator 22·4 months [95% CI 19·2 to not evaluable] in the tafasitamab group vs 13·9 months [11·5-16·4] in the placebo group; hazard ratio 0·43 [95% CI 0·32-0·58]; p<0·0001) in the planned primary analysis. Improvement in progression-free survival was confirmed by independent review committee. Adverse events were reported in 272 (99%) of 274 patients in the tafasitamab group and 270 (99%) of 272 patients in the placebo group. Most common adverse events occurring in either the tafasitamab group or placebo group were neutropenia (133 [49%] vs 123 [45%]) and diarrhoea (103 [38%] vs 77 [28%]). There were no deaths due to treatment-related adverse events in the tafasitamab group; two (1%) patients had fatal adverse events related to treatment in the placebo group.

INTERPRETATION: The addition of tafasitamab to lenalidomide and rituximab resulted in a statistically significant and clinically meaningful improvement in progression-free survival, with an acceptable safety profile in patients with relapsed or refractory follicular lymphoma. This combination represents a potential new standard-of-care treatment.

FUNDING: Incyte.},
}

@article {pmid41359796,
year = {2025},
author = {Leaf, RK and Mones, JV and Shenoy, T and Warsame, M and Beltrami-Moreira, M and Panch, S and Leavitt, AD and Zon, RL and Kendall, EK and Shahamatdar, S and Lim, TL and Cui, C and Jiang, D and Kaunfer, SA and Durai, L and Hoge, ST and Dias, JA and Sha, C and Holmes, A and Easton, N and Corley, E and Zhao, E and Li, X and Spelman, A and Amos, CB and Soebbing, DR and Shabih, M and Jamison, T and Liu, B and Hussein, G and Yadav, SK and Elsaid, MI and Owen, DH and Mera, A and Juras, PK and Suresh, A and Heskel, MJ and Huang, JJ and Glezerman, I and Go, RS and Reynolds, K and Al-Samkari, H and Kroll, MH and Leaf, DE},
title = {Immune thrombocytopenia in patients treated with immune checkpoint inhibitors.},
journal = {Blood},
volume = {},
number = {},
pages = {},
doi = {10.1182/blood.2025031449},
pmid = {41359796},
issn = {1528-0020},
abstract = {Immune checkpoint inhibitor-associated immune thrombocytopenia (ICI-ITP) has been described in case reports and small case series, but comprehensive data on its incidence, risk factors, clinical features, treatment, and outcomes are lacking. We reviewed medical records of all adults initiating ICI therapy between 2016-2023 at 29 U.S. hospitals across seven major cancer centers to identify cases of ICI-ITP. Multivariable logistic regression was used to identify risk factors, and Cox modeling was performed to assess the association between ICI-ITP, its severity, and mortality. Among 86,467 patients, ICI-ITP occurred in 214 (0.25%). Independent risk factors included lower baseline platelet count, combination ICI therapy, stage 4 cancer, and additional immune-related adverse events. ICI-ITP occurred at a median of 8 weeks (IQR, 4-18) after ICI initiation, with a median nadir platelet count of 41 x109/L (IQR, 17-64). Patients were treated with glucocorticoids (n=106, [49.5%]), immune globulin (n=39 [18.2%]), and thrombopoietin receptor agonists (n=29 [13.6%]). Recovery occurred in 161 patients (75.2%) at a median of 2.3 weeks (IQR, 1.0-5.3). Of 76 patients rechallenged with ICIs, 23 (30.3%) developed recurrent ICI-ITP. ICI-ITP and its severity were associated with higher all-cause mortality, with a nearly threefold increase in risk among patients with severe ICI-ITP compared with those without ICI-ITP (adjusted HR 2.96 [95% CI, 2.14-4.08]). These findings establish ICI-ITP as a rare but clinically significant complication of ICI therapy, provide the first large-scale description of its risk factors and clinical course, and underscore the importance of timely recognition and management.},
}

@article {pmid41358143,
year = {2025},
author = {Othus, M and Patel, SP and Chae, YK and Dietrich, E and Ahluwalia, MS and Kurzrock, R},
title = {Outcomes of Patients with Rare Cancers Treated with Combination Immune Checkpoint Inhibitors With and Without Prior anti-PD-1/L1 Exposure (NCI/SWOG S1609).},
journal = {JCO oncology advances},
volume = {2},
number = {1},
pages = {},
pmid = {41358143},
issn = {2994-9750},
support = {U10 CA180819/CA/NCI NIH HHS/United States ; U10 CA180888/CA/NCI NIH HHS/United States ; UG1 CA233198/CA/NCI NIH HHS/United States ; },
abstract = {BACKGROUND: There are limited data on response and survival outcomes for patients who receive the combination of anti-PD-1 and anti-CLTA-4 after prior failure of an anti-PD-1/L1, in particular among patients with less common cancers. We analyzed a unique trial resource, an NCI-sponsored basket trial for participants with rare solid tumors conducted by SWOG that was open at over 1,000 sites across the USA (S1609/DART). Participants received Ipilimumab (1mg/kg every six weeks) plus nivolumab (240 mg every two weeks) (both intravenously). The trial eligibility allowed prior exposure to anti-PD-1/L1, and our objective was to compare response and survival outcomes for patients with and without prior anti-PD-1/PDL-1.

METHODS: Logistic and Cox regression models were used to evaluate associations between prior anti-PD-1/PDL-1 exposure and the endpoints of clinical benefit rate (CBR) (includes stable disease of at least six months and objective response by RECISTv1.1), progression-free survival (PFS), and overall survival (OS).

RESULTS: CBR was not significantly different between those with and without prior anti-PD-1/L1 exposure, 26% in both groups. There were no significant differences in PFS and OS between patients with and without prior anti-PD-1/L1 exposure on either univariate and multivariable analysis (multivariable hazard ratio, 95% confidence interval and p-value: PFS: 1.18, 0.83-1.68, p=0.36; OS: 1.11, 0.76-1.63, p=0.58).

CONCLUSIONS: There were no statistically or clinically significant differences in outcomes with and without prior anti-PD-1/L1 exposure for patients with a variety of rare cancers treated with nivolumab and ipilimumab. Patients with prior anti-PD-1/L1 exposure should be eligible for clinical trials evaluating combination immunotherapy.},
}

@article {pmid41356727,
year = {2025},
author = {Mohty, M and Ye, Y and Banerjee, R},
title = {Skills, attitude and knowledge for early-career hematologists: a pragmatic, scientific framework.},
journal = {Clinical hematology international},
volume = {7},
number = {4},
pages = {37-40},
pmid = {41356727},
issn = {2590-0048},
}

@article {pmid41354605,
year = {2025},
author = {Cheng, HH and Callis, S and Yu, EY and Delacroix, SE and Sokolova, AO and Tangen, CM and Lerner, SP and Dorff, TB and Lin, DW},
title = {Clinical Trial in Progress: SWOG S2210, a Phase 2 Study of Neoadjuvant Carboplatin for Localized High-risk Prostate Cancer with Germline BRCA1/2 Mutations.},
journal = {European urology focus},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.euf.2025.11.011},
pmid = {41354605},
issn = {2405-4569},
abstract = {SWOG S2210 is a phase 2 trial testing the use of biomarker-guided neoadjuvant carboplatin, a safe and accessible chemotherapy agent, for patients with localized high-risk prostate cancer and inherited BRCA1/2 mutations. The endpoints are pathologic complete response rates and survival outcomes.},
}

@article {pmid41354273,
year = {2025},
author = {Merkel, EC and Gooley, T and Thakar, MS and Furlan, SN and Summers, C and Kirkey, DC and Hadland, B and Burroughs, LM and Carpenter, PA and Petrovic, A and Goshorn, R and Irwin, R and Bleakley, M and Cooper, T and Tarlock, K and Dahlberg, A},
title = {Post Hematopoietic Cell Transplantation Maintenance Therapy with Low-Dose Azacitidine in a Pediatric Population with High-Risk Myeloid Malignancies.},
journal = {Transplantation and cellular therapy},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jtct.2025.12.003},
pmid = {41354273},
issn = {2666-6367},
abstract = {BACKGROUND: Patients with acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) with high-risk features undergoing hematopoietic cell transplantation (HCT) experience high rates of relapse. Hypomethylating agent azacitidine (AZA) has been explored as post-HCT maintenance therapy at low-doses to prevent relapse based on its potential for clinical efficacy and enhancing the graft-versus-leukemia effect.

OBJECTIVE: To better understand the feasibility, tolerability, and efficacy of post-HCT maintenance AZA in the pediatric population with high-risk myeloid malignancies who underwent allogeneic HCT.

STUDY DESIGN: A retrospective analysis was conducted of 24 pediatric patients (median age 12.4 years) with high-risk myeloid malignancies who received post-HCT AZA at a single institution. Descriptive measures were used to summarize participant characteristics. Point estimates of overall survival (OS) and relapse-free survival (RFS) were obtained using the method of Kaplan and Meier. Point estimates of relapse and non-relapse mortality were summarized using cumulative incidence estimates.

RESULTS: AZA began at a median of 81 days post-HCT. The AZA dose ranged between 32-50 mg/m[2] x 5 days and AZA continued for a median of 9 cycles. No significant myelosuppression or hospitalizations attributed to AZA were observed. Eighteen patients (75%) were diagnosed with grade II acute graft-versus-host disease (GVHD) before AZA initiation; 3 (16.7%) experienced ≤ grade II acute GVHD flares while tapering immunosuppressive treatment (IST) and receiving AZA. Of the 20 patients in remission at 1-year post-HCT, 18 (90%) had completed or were tapering IST. Six patients relapsed and the 3-year point estimate of relapse was 27%. There were 3 deaths due to relapsed disease. The 3-year point estimate of OS was 91% (one of the 3 deaths occurred beyond 3 years, at 3.2 years) and the 3-year estimate of RFS was 73%. The median follow-up among the 21 surviving patients was 29 months (range 12-80).

CONCLUSIONS: This is the largest reported pediatric cohort receiving post-HCT prophylaxis with AZA. Our findings suggest AZA is tolerable with limited toxicity post-HCT and can be administered to pediatric patients with myeloid malignancies as maintenance therapy. Outcomes were favorable warranting further study.},
}

@article {pmid41352870,
year = {2025},
author = {Nagana Gowda, GA and Zhu, W and Raftery, D},
title = {NMR-based metabolomics: Where are we now and where are we going?.},
journal = {Progress in nuclear magnetic resonance spectroscopy},
volume = {150-151},
number = {},
pages = {101564},
pmid = {41352870},
issn = {1873-3301},
support = {P30 CA015704/CA/NCI NIH HHS/United States ; P30 AR074990/AR/NIAMS NIH HHS/United States ; R01 GM138465/GM/NIGMS NIH HHS/United States ; R01 CA119171/CA/NCI NIH HHS/United States ; P30 DK035816/DK/NIDDK NIH HHS/United States ; R01 GM131491/GM/NIGMS NIH HHS/United States ; },
mesh = {*Metabolomics/methods ; Humans ; Magnetic Resonance Spectroscopy/methods ; Mass Spectrometry/methods ; Biomarkers/analysis/metabolism ; Animals ; },
abstract = {The fast-growing field of metabolomics focuses on the analyses of complicated mixtures of small molecules present in biological samples. To date, metabolomics has provided a wealth of information on biological systems and impacted numerous areas of basic and life sciences. A major focus of metabolomics has been on biomedicine with the goal of biomarker discovery, drug discovery and improved mechanistic understanding of the pathogenesis of many human diseases. Analytical methods play a pivotal role in metabolomics, with the two most widely used platforms being nuclear magnetic resonance (NMR) spectroscopy and mass spectrometry (MS). Among their many complementary capabilities, NMR is generally more reproducible and quantitative, whereas MS is more sensitive. Recent technological advances in NMR have resulted in multifaceted developments, including improvements in sensitivity, resolution and speed, along with expanded metabolite identification and quantitation, which together provide exciting potential for future studies. In addition to NMR developments, the combination of NMR with MS provides numerous benefits that are becoming more evident over time. Hence, the metabolomics field has witnessed an increased number of studies and applications that combine NMR with MS in numerous areas, including new methods development for unknown identification, metabolite quantitation, disease biomarker discovery, mechanistic understanding of disease pathogenesis, and dietary risk factors of diseases among others. This report describes the current status of state-of-the-art methods in NMR-based metabolomics, along with recent advances and future prospects, with an emphasis on the benefits of combining NMR with MS.},
}

*Metabolomics/methods
Humans
Magnetic Resonance Spectroscopy/methods
Mass Spectrometry/methods
Biomarkers/analysis/metabolism
Animals

@article {pmid41351880,
year = {2025},
author = {Wang, K and Saniei, S and Poddar, N and Martinez, IG and Chao, C and Autar, S and Fiore, P and Carcamo, S and Sreenath, M and Peplinski, JH and Ries, RE and Mei, AH and Rahman, NA and Mekerishvili, L and Quijada-Álamo, M and Freed, G and Zhang, M and Lachman, K and Diaz, Z and Gonzalez, MM and Zhang, J and Pham, G and Filipescu, D and Berisa, M and Balestra, T and Wheeler, N and Reisz, JA and D'Alessandro, A and Puleston, DJ and Bernstein, E and Chipuk, JE and Wunderlich, M and Tasian, SK and Marcellino, BK and Glass, IA and , and Sturgeon, CM and Landau, DA and Chen, Z and Papapetrou, EP and Izzo, F and Meshinchi, S and Hasson, D and Wagenblast, E and , },
title = {Ontogeny Dictates Oncogenic Potential, Lineage Hierarchy, and Therapy Response in Pediatric Leukemia.},
journal = {Cancer discovery},
volume = {},
number = {},
pages = {OF1-OF30},
doi = {10.1158/2159-8290.CD-25-0556},
pmid = {41351880},
issn = {2159-8290},
support = {R01CA292503//National Institutes of Health (NIH)/ ; R01CA290681//National Institutes of Health (NIH)/ ; S10OD026880//National Institutes of Health (NIH)/ ; S10OD030463//National Institutes of Health (NIH)/ ; //CureSearch for Children's Cancer (CSCC)/ ; //Edward P. Evans Foundation/ ; V2024-015//V Foundation for Cancer Research (VFCR)/ ; //Pew Charitable Trusts (Pew)/ ; 77-23//Damon Runyon Cancer Research Foundation (DRCRF)/ ; 7039-25//Leukemia and Lymphoma Society (LLS)/ ; 22-25847//Alex's Lemonade Stand Foundation for Childhood Cancer (ALSF)/ ; //Rally Foundation (Rally)/ ; R24HD000836//National Institutes of Health (NIH)/ ; //Leukemia and Lymphoma Society (LLS)/ ; //Andrew McDonough B+ Foundation (AMBF)/ ; P30CA196521//National Institutes of Health (NIH)/ ; UL1TR004419//National Center for Advancing Translational Sciences (NCATS)/ ; },
abstract = {UNLABELLED: Accumulating evidence links pediatric cancers to prenatal transformation events, yet the influence of the developmental stage on oncogenesis remains elusive. We investigated how hematopoietic stem cell developmental stages affect leukemic transformation, disease progression, and therapy response using a novel, humanized model of NUP98::NSD1-driven pediatric acute myeloid leukemia that is particularly aggressive with WT1 comutations. Fetal-derived hematopoietic stem cells readily transform into leukemia, and WT1 mutations further enhance stemness and alter lineage hierarchy. In contrast, stem cells from later developmental stages become progressively resistant to transformation. Single-cell analyses revealed that fetal-origin leukemia stem cells exhibit greater quiescence and reliance on oxidative phosphorylation than their postnatal counterparts. These differences drive distinct therapeutic responses despite identical oncogenic mutations. In patients, onco-fetal transcriptional programs correlate with worse outcomes. By targeting key vulnerabilities of fetal-origin leukemia cells, we identified combination therapies that significantly reduce aggressiveness, highlighting the critical role of ontogeny in pediatric cancer treatment.

SIGNIFICANCE: This study signifies the critical consequences of developmental timing in cancer initiation, revealing that identical driver mutations in fetal- versus postnatal-origin leukemias exhibit fundamentally distinct biology and treatment responses. Recognizing these developmental differences opens avenues for personalized therapeutic strategies, improving outcomes for pediatric patients with aggressive disease subtypes in leukemia.},
}

@article {pmid41351263,
year = {2025},
author = {Ferrier, K and Graff, M and Konigsberg, IR and Stanislawski, M and Highland, HM and Raffield, LM and Carson, AP and Boerwinkle, E and Norris, JM and Gignoux, CR and Hendricks, AE and Raghavan, S and North, KE and Young, KL and Justice, AE and Allison, MA and Budoff, MJ and Kasela, S and Aguet, F and Joseph, JJ and Kooperberg, C and Rich, SS and Rotter, JI and Lange, EM and Lange, LA},
title = {Epigenome-wide association study meta-analysis of BMI in African Americans.},
journal = {HGG advances},
volume = {},
number = {},
pages = {100552},
doi = {10.1016/j.xhgg.2025.100552},
pmid = {41351263},
issn = {2666-2477},
abstract = {Despite considerable advances in identifying risk factors for obesity, gaps remain in our understanding about its etiology. Genetic variants explain only a small portion of variation in obesity-related traits such as body mass index (BMI). Epigenetic regulation, which controls gene expression and is influenced by environmental and genetic factors, may account for additional variability in BMI. Epigenetic studies of BMI have largely been conducted in European ancestry populations, despite the disproportionate burden of obesity in African Americans (AAs). We conducted a sex-stratified BMI epigenome-wide association study (EWAS) meta-analysis in AA participants from the Jackson Heart Study (JHS, n=1604) and the Multi-Ethnic Study of Atherosclerosis (MESA, n=179) with Illumina EPIC (850k) array data. Linear regression models with methylation as the outcome and continuous BMI as the predictor were stratified by study and sex and meta-analyzed. We identified 208 methylation sites (CpGs, p< 8.72x10[-8]) significantly associated with BMI; 151 not been previously reported in literature. Replication was performed in a separate sample of AA participants with 450k array data, which lacks many CpGs present in the 850k array. Replication testing was possible for only 29 of the 151 CpGs; 19 were statistically significant (p<1.72×10[-3]). Sex-specific results showed 4 female-only and 3 male-only BMI-CpGs not identified in the sex-combined results. Differentially methylated region (DMR) analysis resulted in 66 DMRs, including several regions near genes previously implicated for obesity (e.g., SOCS3 and TGFB1). Further analyses showed enrichment of genes and traits related to the immune system and inflammation-related pathways (e.g., the IL-6/JAK/STAT pathway).},
}

@article {pmid41350402,
year = {2025},
author = {Robertson, AJ and Kerr, B and Feder, AF},
title = {Intracellular interactions shape antiviral resistance outcomes in poliovirus via eco-evolutionary feedback.},
journal = {Nature ecology & evolution},
volume = {},
number = {},
pages = {},
pmid = {41350402},
issn = {2397-334X},
support = {T32-GM136534-02//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; 2142718//National Science Foundation (NSF)/ ; },
abstract = {Resistance evolution can undermine antiviral treatment. However, targeting antivirals to shared viral proteins could inhibit resistance evolution if susceptible viruses sensitize resistant ones during cellular coinfection. Pocapavir, a poliovirus capsid inhibitor, uses this sociovirological interference strategy. While susceptible viruses substantially suppress pocapavir resistance in cell culture, a pocapavir clinical trial found widespread resistance and limited clearance time improvements in treated participants. Here, to reconcile these findings, we present an intrahost eco-evolutionary model of pocapavir-treated poliovirus, which reproduces both in vitro interference and clinical resistance evolution. In the short term, high densities of susceptible viruses sensitize resistant ones, mirroring cell culture results. However, over multiple replication cycles, pocapavir's high potency collapses viral density, reducing coinfection and enabling resistance evolution, as observed clinically. Because resistance suppression relies on coinfection, enhancing susceptible virus survival could offer therapeutic advantages. Counterintuitively, we demonstrate that lessening antiviral potency can increase coinfection, limiting resistance while also maintaining low viral load. These findings suggest that antivirals relying on viral intracellular interactions must balance immediate neutralization with preserving future coinfection for sustained inhibition. Explicitly considering the eco-evolutionary feedback encompassing viral density, shared phenotypes and absolute fitness provides new insights for effective therapy design and illuminates viral evolutionary dynamics more broadly.},
}

@article {pmid41348987,
year = {2025},
author = {Kilari, D and Henderson, NC and Yamamoto, K and Yao, Y and Hwang, C and Barata, PC and Bilen, MA and Graham, L and Garje, R and Rothstein, S and Haider, S and Park, JJ and Raychaudhuri, R and Pilling, A and Chin, E and Koshkin, VS and Tripathi, A and Cackowski, FC and Nauseef, JT and Sokolova, A and Ayanambakkam, A and Zakharia, Y and Schweizer, MT and Armstrong, AJ and Dorff, TB and Reichert, ZR and McKay, RR},
title = {Impact of SPOP Mutations on Clinical Outcomes in Metastatic Prostate Cancer.},
journal = {JCO precision oncology},
volume = {9},
number = {},
pages = {e2500590},
doi = {10.1200/PO-25-00590},
pmid = {41348987},
issn = {2473-4284},
mesh = {Humans ; Male ; *Repressor Proteins/genetics ; *Prostatic Neoplasms/genetics/pathology/mortality/drug therapy ; Aged ; Middle Aged ; *Mutation ; *Nuclear Proteins/genetics ; Neoplasm Metastasis ; },
abstract = {PURPOSE: Previous studies suggest that SPOP mutations result in increased sensitivity to androgen receptor pathway inhibitors (ARPIs) but are limited by lack of granular data. We hypothesize that SPOP mutations are associated with improved outcomes across the spectrum of advanced prostate cancer (PC).

METHODS: Using the real-world clinicogenomic Prostate Cancer Precision Medicine Multi-Institutional Collaborative Effort database, we analyzed outcomes based on SPOP mutation status. The primary end point was overall survival (OS) from the diagnosis of metastatic disease. Secondary end points included real-world progression-free survival (PFS) and PSA90 response.

RESULTS: Among 2,097 patients with metastatic PC, 5.5% (N = 115) had SPOP-mutated tumors. Compared with SPOP wild-type, patients with SPOP mutations were older at diagnosis (median 65 v 63 years; P = .001) and had higher (≥8) Gleason sum (68% v 54%; P = .02), higher incidence of lung metastasis (17% v 6%; P = .001), and increased frequency of intraductal features (13% v 5%; P < .001). SPOP mutations were associated with improved PSA90 response with first ARPI exposure in the castrate-resistant setting (60% v 40.6%; OR, 2.20 [95% CI, 1.15 to 4.19]; P = .02) but not in the castrate-sensitive setting (78.9% v 71.5%; OR, 1.49 [95% CI, 0.66 to 3.37]; P = .43). Median PFS with first ARPI did not differ in SPOP-mutated versus wild-type group in both the castrate-sensitive (24.2 v 19.2 months; hazard ratio [HR], 0.80 [95% CI, 0.49 to 1.32]; P = .39) and castrate-resistant settings (15.0 v 12.4 months; HR, 0.81 [95% CI, 0.58 to 1.12]; P = .20). In multivariable analysis, SPOP mutations were associated with improved OS (HR, 0.65, P = .02).

CONCLUSION: SPOP mutations were associated with longer OS despite the presence of aggressive clinical features. The distinct clinical and molecular features of SPOP-mutated PC support its consideration as a unique molecular subtype with prognostic implications.},
}

Humans
Male
*Repressor Proteins/genetics
*Prostatic Neoplasms/genetics/pathology/mortality/drug therapy
Aged
Middle Aged
*Mutation
*Nuclear Proteins/genetics
Neoplasm Metastasis

@article {pmid41348052,
year = {2025},
author = {Dima, D and Banerjee, R and Hansen, DK},
title = {CAR T-cell therapy and bispecific antibodies in the management of multiple myeloma.},
journal = {Hematology. American Society of Hematology. Education Program},
volume = {2025},
number = {1},
pages = {324-333},
doi = {10.1182/hematology.2025000721},
pmid = {41348052},
issn = {1520-4383},
mesh = {Humans ; *Multiple Myeloma/therapy/immunology ; *Antibodies, Bispecific/therapeutic use ; *Immunotherapy, Adoptive/methods ; *Receptors, Chimeric Antigen/therapeutic use/immunology ; B-Cell Maturation Antigen/immunology ; },
abstract = {The introduction of CAR (chimeric antigen receptor) T-cell therapy and bispecific antibodies into clinical practice has revolutionized the treatment landscape of relapsed/refractory multiple myeloma (RRMM). Both modalities have shown impressive clinical efficacy with slightly different but overall manageable toxicity profiles. At present, two B-cell maturation antigen (BCMA)-targeted CAR T-cell therapies, idecabtagene vicleucel and ciltacabtagene autoleucel, are approved for standard use in the United States. There are currently 4 commercially approved bispecific antibodies: teclistamab, elranatamab, and linvoseltamab, which target BCMA, as well as talquetamab, which targets the GPRC5D antigen on the surface of plasma cells. In this review, we explore (a) the advantages and challenges of integrating CAR T-cell therapy earlier in the RRMM treatment course; (b) the safety and efficacy of bispecific antibodies and their evolving role in the current RRMM treatment paradigm; (c) practical considerations for both modalities, focusing on patient selection and supportive care strategies; and (d) recommendations for sequencing of T-cell redirecting therapies to maximize long-term outcomes.},
}

Humans
*Multiple Myeloma/therapy/immunology
*Antibodies, Bispecific/therapeutic use
*Immunotherapy, Adoptive/methods
*Receptors, Chimeric Antigen/therapeutic use/immunology
B-Cell Maturation Antigen/immunology

@article {pmid41348047,
year = {2025},
author = {Raychaudhuri, S and Cassaday, RD and Percival, MM},
title = {Peri-transplant conundrums: optimizing maintenance therapy using MRD-directed approaches.},
journal = {Hematology. American Society of Hematology. Education Program},
volume = {2025},
number = {1},
pages = {523-530},
doi = {10.1182/hematology.2025000745},
pmid = {41348047},
issn = {1520-4383},
mesh = {Humans ; Neoplasm, Residual ; *Hematopoietic Stem Cell Transplantation ; *Leukemia, Myeloid, Acute/therapy/genetics ; *Precursor Cell Lymphoblastic Leukemia-Lymphoma/therapy/genetics ; Antibodies, Bispecific/therapeutic use ; Sorafenib/therapeutic use ; Azacitidine/therapeutic use ; Aniline Compounds/therapeutic use ; *Maintenance Chemotherapy/methods ; Pyrazines ; },
abstract = {Improved understanding of the molecular underpinnings of acute leukemia has led to advances in the detection of very low levels of leukemia-specific abnormalities, known as measurable residual disease (MRD). The limit of detection for modern next-generation sequencing and polymerase chain reaction-based assays is as low as 10-6, allowing for quantitative and longitudinal monitoring in both acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL). In the period surrounding allogeneic hematopoietic cell transplantation (HCT), detectable MRD is clearly associated with poor outcomes, primarily due to an increased risk of morphologic relapse. In this review, we address the use of maintenance therapy for patients with acute leukemia, including those who are MRD-positive prior to and following HCT. Post-HCT azacitidine may have a role for MRD-positive AML. In AML with FLT3-internal tandem duplication mutation, post-HCT gilteritinib and sorafenib can be evidence-based strategies to target MRD. In ALL, blinatumomab is a powerful tool to eradicate MRD in patients with Philadelphia (Ph)-positive or Ph-negative ALL; tyrosine kinase inhibitors are indicated for post-HCT management of Ph+ ALL. Despite these advances, the optimal duration and type of intervention still remain unknown for many patients with acute leukemia who have peri-HCT MRD.},
}

Humans
Neoplasm, Residual
*Hematopoietic Stem Cell Transplantation
*Leukemia, Myeloid, Acute/therapy/genetics
*Precursor Cell Lymphoblastic Leukemia-Lymphoma/therapy/genetics
Antibodies, Bispecific/therapeutic use
Sorafenib/therapeutic use
Azacitidine/therapeutic use
Aniline Compounds/therapeutic use
*Maintenance Chemotherapy/methods
Pyrazines

@article {pmid41348027,
year = {2025},
author = {Wang'ondu, RW and Loh, ML},
title = {Revisiting novel genomic classifiers in the era of immunotherapy for pediatric B-ALL.},
journal = {Hematology. American Society of Hematology. Education Program},
volume = {2025},
number = {1},
pages = {252-261},
doi = {10.1182/hematology.2025000712},
pmid = {41348027},
issn = {1520-4383},
mesh = {Humans ; Child ; *Immunotherapy/methods ; *Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/therapy/genetics ; *Genomics ; Antibodies, Bispecific/therapeutic use ; Neoplasm, Residual ; Inotuzumab Ozogamicin/therapeutic use ; Algorithms ; Male ; },
abstract = {While recent improvements in survival for pediatric patients with newly diagnosed B-cell precursor acute lymphoblastic leukemia (B-ALL) have been attributed to risk stratification algorithms incorporating somatic genetics and early response dictating therapeutic intensity, recent antibody-based immunotherapeutic agents are changing the therapeutic landscape. Blinatumomab, inotuzumab ozogamicin, and chimeric antigen T-cell receptor therapies are approved by the US Food and Drug Administration for the treatment of relapsed and refractory B-ALL in children, and some have been incorporated into frontline therapies. Studies in both pediatric and adult patients have recently demonstrated superiority of adding blinatumomab to the consolidation phase of treatment in the frontline setting. Revisiting genomic classifiers of B-ALL in the era of antibody-based immunotherapeutic agents may be necessary to maximize the benefits of current risk stratification algorithms in combination with immunotherapy. Available data suggest the efficacy of these agents across genomic subtypes. Here we consider the impact of immunotherapeutic agents within the context of minimal residual disease and molecular classification-based risk stratification.},
}

Humans
Child
*Immunotherapy/methods
*Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/therapy/genetics
*Genomics
Antibodies, Bispecific/therapeutic use
Neoplasm, Residual
Inotuzumab Ozogamicin/therapeutic use
Algorithms
Male

@article {pmid41348023,
year = {2025},
author = {Ali, N and Sandmaier, BM},
title = {New age HCT conditioning regimens: what works and why?.},
journal = {Hematology. American Society of Hematology. Education Program},
volume = {2025},
number = {1},
pages = {465-475},
doi = {10.1182/hematology.2025000738},
pmid = {41348023},
issn = {1520-4383},
mesh = {Humans ; *Transplantation Conditioning/methods ; *Hematopoietic Stem Cell Transplantation/methods ; Busulfan/analogs & derivatives/therapeutic use ; Radioimmunotherapy/methods ; },
abstract = {Conditioning regimens play an essential role in allogeneic transplantation by facilitating engraftment and eradicating malignancies. The landscape of conditioning regimens has undergone an evolution in the concept of intensity. Novel conditioning strategies aim to provide highly efficacious regimens with improved toxicity profiles. Integrating disease- specific chemotherapy and targeted agents into conditioning regimens provides enhanced disease elimination and relapse prevention. Agents like treosulfan provide safer conditioning with a favorable toxicity profile for patients with older age or medical comorbidities and can lower the incidence of long-term complications for younger patients. Additionally, methodologies for precise and targeted radiation delivery with minimal off-target effects are emerging. A promising development is radioimmunotherapy-based regimens that preferentially deplete hematopoietic cells and spare nonhematopoietic tissues. These advancements necessitate reexamination and harmonization of conditioning intensity stratification schemes for a more personalized and selective approach.},
}

Humans
*Transplantation Conditioning/methods
*Hematopoietic Stem Cell Transplantation/methods
Busulfan/analogs & derivatives/therapeutic use
Radioimmunotherapy/methods

@article {pmid40135838,
year = {2025},
author = {Iravani, A},
title = {Beyond the AJR: When Nonmetastatic Disease Is No Longer Nonmetastatic.},
journal = {AJR. American journal of roentgenology},
volume = {225},
number = {5},
pages = {e2532975},
doi = {10.2214/AJR.25.32975},
pmid = {40135838},
issn = {1546-3141},
}

@article {pmid41348020,
year = {2025},
author = {Pigazzi, M and Meshinchi, S and Locatelli, F},
title = {Using genomics to refine pediatric AML risk stratification.},
journal = {Hematology. American Society of Hematology. Education Program},
volume = {2025},
number = {1},
pages = {270-278},
doi = {10.1182/hematology.2025000714},
pmid = {41348020},
issn = {1520-4383},
mesh = {Humans ; *Leukemia, Myeloid, Acute/genetics/diagnosis/metabolism/therapy ; Nucleophosmin ; *Genomics/methods ; Child ; Mutation ; Risk Assessment ; Male ; Female ; },
abstract = {In the past 20 years, advances in genomic technologies have greatly improved our understanding of pediatric acute myeloid leukemia (AML). Today, cytogenetic tests can detect structural changes in approximately 75% of cases and remain a main tool for assessing risk. Recent technologies, such as next-generation sequencing, are revealing additional structural alterations (cryptic fusions) and mutations that often cooperate to influence disease biology and treatment response. This evolving genetic landscape has identified unique childhood subtypes of AML defined by specific fusions, such as NUP98::NSD1, CBFA2T3::GLIS2, and varied KMT2A rearrangements, which are linked to distinct clinical outcomes. Emerging data also point to the poor prognosis associated with certain subtypes of NPM1, like the NPM1-D isoform. Additionally, mutations in genes like WT1, DNMT3A, and TP53, the latter of which are rare in childhood AML, may influence patients' outcomes, particularly when occurring in combination. Targeted therapies, including FLT3, BCL2, and menin inhibitors, are beginning to reshape treatment, offering more personalized approaches. However, integrating these drugs effectively into the patient's treatment strategy remains challenging due to the genetic complexity and rarity of pediatric AML. Key issues ahead include identifying which genetic features truly affect outcomes, using this information to personalize therapy, predicting who will benefit from targeted drugs, and choosing the best markers to track disease response over time. Looking forward, collaborative efforts are urgently needed to validate pediatric-specific biomarkers, test novel drug combinations, and link genetic data to clinical outcomes to design trials and future treatment strategies.},
}

Humans
*Leukemia, Myeloid, Acute/genetics/diagnosis/metabolism/therapy
Nucleophosmin
*Genomics/methods
Child
Mutation
Risk Assessment
Male
Female

@article {pmid41347997,
year = {2025},
author = {Panch, SR and Raman, G and Bussel, JB},
title = {Refractory ITP: revisiting definitions, diagnostics, and management paradigms.},
journal = {Hematology. American Society of Hematology. Education Program},
volume = {2025},
number = {1},
pages = {312-323},
doi = {10.1182/hematology.2025000720},
pmid = {41347997},
issn = {1520-4383},
mesh = {Humans ; *Purpura, Thrombocytopenic, Idiopathic/diagnosis/therapy/physiopathology/blood ; Hemorrhage/therapy ; Platelet Count ; Disease Management ; },
abstract = {Immune thrombocytopenia (ITP) is a heterogeneous autoimmune disorder characterized by decreased platelet counts and a variable propensity for bleeding. Significant strides have delineated the pathophysiologic mechanisms of ITP and led to new therapeutics. Despite these advances, 5% to 30% of patients persist with low platelet counts and/or ongoing bleeding. This review summarizes the current definitions and pathophysiology of refractory ITP, revisiting diagnostic realms and management strategies for these difficult-to-treat patients.},
}

Humans
*Purpura, Thrombocytopenic, Idiopathic/diagnosis/therapy/physiopathology/blood
Hemorrhage/therapy
Platelet Count
Disease Management

@article {pmid41347988,
year = {2025},
author = {Gupta, S and McNeer, J and O'Brien, M and Rau, R and Teachey, D},
title = {The challenge of deintensifying chemotherapy for children and adolescents with B-ALL in the immunotherapy era.},
journal = {Hematology. American Society of Hematology. Education Program},
volume = {2025},
number = {1},
pages = {229-235},
doi = {10.1182/hematology.2025000709},
pmid = {41347988},
issn = {1520-4383},
mesh = {Humans ; Adolescent ; Child ; *Immunotherapy/methods ; *Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/therapy/drug therapy/immunology ; Female ; Male ; },
abstract = {Recent clinical trials have shown that the addition of immunotherapy has substantially improved cure rates for children and adolescents newly diagnosed with B-acute lymphoblastic leukemia. Most of these patients now have outcomes similar to those previously seen in only the most favorable subgroups. As such, efforts are underway to study whether the incorporation of immunotherapy can allow for elements of traditional toxic chemotherapy to be removed while maintaining excellent outcomes. In this article, we discuss important considerations for such studies, including those related to which patients are appropriate targets of deintensification efforts and which elements of therapy are or are not appropriate candidates for omission.},
}

Humans
Adolescent
Child
*Immunotherapy/methods
*Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/therapy/drug therapy/immunology
Female
Male

@article {pmid41347976,
year = {2025},
author = {Cassaday, RD},
title = {Sanctuary sites and extramedullary relapses in the chemo-free world: insights from immunotherapies in B-ALL.},
journal = {Hematology. American Society of Hematology. Education Program},
volume = {2025},
number = {1},
pages = {245-251},
doi = {10.1182/hematology.2025000711},
pmid = {41347976},
issn = {1520-4383},
mesh = {Humans ; *Immunotherapy/methods ; *Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/therapy/pathology/immunology ; Recurrence ; Tumor Microenvironment ; },
abstract = {When acute lymphoblastic leukemia (ALL) involves extramedullary sites, the appropriate pathologic term for this is lymphoblastic lymphoma. The biological mechanisms underpinning this process are not clear, but they are presumed to involve a multifactorial interplay between tumor cells and the microenvironment of the tissue in which they develop (eg, lymph nodes, thymus, leptomeninges). Importantly for clinicians, these factors may impair the efficacy of systemic therapy given to treat ALL. This gives rise to "sanctuary sites," so named because of the relative protection they provide to malignant blasts that may possess these characteristics. This has become increasingly relevant in the era of "chemotherapy-free" approaches for B-cell ALL, where the potency of antigen-targeted immunotherapies (eg, blinatumomab, inotuzumab ozogamicin, and chimeric antigen receptor-modified T cells) has been leveraged to reduce or eliminate the reliance on cytotoxic chemotherapy. Such approaches are appealing for their high response rates and favorable toxicity profiles compared to chemotherapy. However, extramedullary relapses have been observed with increased frequency: an outcome historically seen in around 10% of such cases, this can represent over 50% of relapses in some series. This review provides an overview of this emerging issue and what clinicians and investigators can do to address it.},
}

Humans
*Immunotherapy/methods
*Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/therapy/pathology/immunology
Recurrence
Tumor Microenvironment

@article {pmid41346295,
year = {2025},
author = {Alexander, JL and Dávila Saldaña, BJ and Brazauskas, R and Dammalapati, SG and Griffith, LM and Shah, AJ and Shimano, KA and Ochs, HD and Bleesing, J and Ebens, CL and Kapadia, M and Bauchat, A and Kapoor, N and Oved, JH and Eissa, H and Lust, H and Keller, MD and Haines, H and Chandrakasan, S and Talano, JM and Rayes, A and Madden, LM and Shereck, EB and Miller, HK and Forbes Satter, LR and Martinez, CA and Rozmus, J and Bednarski, JJ and Yu, LC and Chellapandian, D and Aquino, VM and Knutsen, AP and Chong, H and Chopek, A and Gillio, AP and Joshi, A and Rangarajan, HG and Moore, TB and Andolina, JR and DeSantes, K and Vander Lugt, MT and Prockop, SE and Shyr, D and Sullivan, KE and Parikh, SH and Weinacht, KG and Torgerson, TR and Marsh, RA and Dvorak, CC and Chan, AY and Haddad, E and Heimall, J and Pulsipher, MA and Leiding, JW and Kohn, DB and Puck, JM and Notarangelo, LD and Rawlings, DJ and Cowan, MJ and Petrovic, A and Pai, SY and Burroughs, LM},
title = {Hematopoietic Cell Transplantation for Wiskott-Aldrich syndrome: A PIDTC Report.},
journal = {Blood advances},
volume = {},
number = {},
pages = {},
doi = {10.1182/bloodadvances.2025017662},
pmid = {41346295},
issn = {2473-9537},
abstract = {Wiskott-Aldrich syndrome (WAS), an X-linked disorder characterized by immunodeficiency, thrombocytopenia, autoimmunity, and malignancy, can be effectively treated with allogeneic hematopoietic cell transplantation (HCT). Older age at HCT and mismatched donors are known to impact overall survival (OS). The influence of specific clinical manifestations or WAS variant class on OS and factors associated with event-free survival (EFS) remain incompletely defined. We analyzed outcomes of 308 patients with WAS who underwent HCT at 37 institutions of the Primary Immune Deficiency Treatment Consortium (PIDTC) from 1990-2018. With a median follow-up of 5.3 years, the 5-year OS and EFS were 87.2% and 79.7%, respectively. Age ≥5 years, donor type, and a pre-HCT history of severe infection had a negative impact on OS and EFS, whereas pre-HCT autoimmunity had no impact. Reduced intensity regimens were associated with lower T cell and myeloid donor chimerism, particularly when non-busulfan-based regimens were used. Low myeloid donor chimerism was associated with lower platelet counts. Mixed chimerism was not consistently associated with post-HCT autoimmunity. Patients with class I (exon 1-2 missense and intron 5 hotspot variants) and class II variants (all others) had similar pre-HCT clinical symptom severity and no difference in OS, EFS or platelet recovery post-HCT. In conclusion, our study showed excellent long-term OS and EFS following HCT for WAS, highlighting the importance of early HCT, before the development of severe infections. We confirmed that HCT using busulfan-based conditioning was associated with improved donor chimerism and platelet recovery. This study was registered at www.clinicaltrials.gov as #NCT02064933.},
}

@article {pmid41279816,
year = {2025},
author = {Giorgi, EE and Gillespie, K and Domin, E and Fouda, G and Permar, SR and Montefiori, DC and Janes, H},
title = {Differences in neutralization susceptibility between clade C HIV viruses from breastmilk versus contemporaneous circulating viruses from sexually acquired infections.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {41279816},
issn = {2692-8205},
support = {INV-036842/GATES/Gates Foundation/United States ; INV-007368/GATES/Gates Foundation/United States ; UM1 AI068635/AI/NIAID NIH HHS/United States ; R01 AI162245/AI/NIAID NIH HHS/United States ; P01 AI117915/AI/NIAID NIH HHS/United States ; },
abstract = {HIV viruses that establish infection possess phenotypic and genotypic characteristics that have been selected for and that differ across transmission routes, including their susceptibility to broadly neutralizing antibodies (bnAbs). While sexually transmitted viruses have been well characterized, studies of vertically transmitted viruses are sparse and from cohorts that are often small in size and more than a decade old. To investigate whether viruses transmitted vertically during lactation possess distinct neutralization profiles compared to viruses transmitted sexually, we compared the neutralization sensitivity of 25 clade C breastmilk viruses to that of 99 contemporaneous clade C viruses from sera of adults with sexual acquisition against three bnAbs in clinical development. Three out of 7 breastmilk donors (43%) had one or more viruses resistant to 2 or more bnAbs, compared to 8 out of 99 (8%) contemporaneous adult viruses (p=0.02). Breastmilk viruses were more resistant to PGT121 and VRC07.523 (median IC80 >50 compared to 1.16 for PGT121, and 12.75 vs. 0.38 for VRC07.523; p=0.013 and <0.001 respectively), and more breastmilk viruses than adult viruses were resistant to VRC07.523 (94% vs. 43%, p=0.001). Interestingly, the breastmilk viruses most resistant to VRC07.523 had on average one or more glycans in V3 compared to adult transmitted viruses (median 3 vs. 2 glycosylation sites, including flanking position 295; p=0.009), and the number of V3 glycans was negatively correlated with VRC07.523 sensitivity (p=0.007). These findings highlight potential differences in bnAb susceptibility of vertically transmitted viruses and emphasize the need to increase sequencing efforts and screening of infant viruses to better inform the efficacy of candidate bnAbs to prevent vertical transmission of HIV.},
}

@article {pmid41347212,
year = {2022},
author = {Ak, Ç and Chitsazan, AD and Gönen, M and Etzioni, R and Grossberg, AJ},
title = {Spatial prediction of COVID-19 pandemic dynamics in the United States.},
journal = {ISPRS international journal of geo-information},
volume = {11},
number = {9},
pages = {},
pmid = {41347212},
issn = {2220-9964},
support = {K08 CA245188/CA/NCI NIH HHS/United States ; },
abstract = {The impact of COVID-19 across the United States has been heterogeneous, with rapid spread and greater mortality in some areas compared with others. We used geographically-linked data to test the hypothesis that the risk for COVID-19 is defined by location and sought to define which demographic features are most closely associated with elevated COVID-19 spread and mortality. We leveraged geographically-restricted social, economic, political, and demographic information from US counties, to develop a computational framework using structured Gaussian processing to predict county-level case and death counts during the pandemic's initial and nationwide phases. After identifying the most predictive information sources by location, we applied an unsupervised clustering algorithm and topic modelling to identify groups of features most closely associated with COVID-19 spread. Our model successfully predicted COVID-19 case counts of unseen locations, after examining case counts and demographic information of neighboring locations, with overall Pearson's correlation coefficient and the proportion of variance explained of 0.96 and 0.84 during the initial phase and 0.95 and 0.87, respectively, during the nationwide phase. Aside from population metrics, presidential vote margin was the most consistently selected spatial feature in our COVID-19 prediction models. Urbanicity and 2020 presidential vote margins were more predictive than other demographic features. Models trained using death counts showed similar performance metrics. Topic modeling showed that counties with similar socioeconomic and demographic features tended to group together, and some of these grouped feature sets were associated with COVID-19 dynamics. Clustering of counties based on these feature groups found by topic modeling revealed groups of counties that experienced markedly different COVID-19 spread. We conclude that topic modeling can be used to group similar features and identify counties with similar features in epidemiologic research.},
}

@article {pmid41346251,
year = {2025},
author = {Hershman, DL and Till, C and Leblanc, M and Ramsey, S and Unger, JM},
title = {Development and validation of a risk prediction model for acute care use among older advanced cancer patients on clinical trials.},
journal = {Journal of the National Cancer Institute},
volume = {},
number = {},
pages = {},
doi = {10.1093/jnci/djaf342},
pmid = {41346251},
issn = {1460-2105},
abstract = {BACKGROUND: patients with advanced cancer are at risk for unplanned Emergency Department (ED) visits and hospital stays (HS). The purpose was to develop and validate a risk prediction model to identify patients at the highest risk for acute care use.

METHODS: We identified advanced cancer patients ≥65 years treated on SWOG trials from 1999-2014 using data linked to Medicare claims. The primary outcome was acute care use (ED visits or HS). A 60% random sample training set was used to identify candidate variables. An adverse risk model was built by summing adverse factors and creating high vs low-risk groups by splitting at the median. This risk model was tested in the 40% validation set.

RESULTS: Among N = 1397 patients from 6 trials, 839 comprised the training set. The proportion of patients with ≥1 HS/ED visit was 67.5%. Adverse risk factors were performance status (0 vs.≥1), coronary artery disease, hypertension, and liver disease. Patients with ≥2 factors (high-risk; 57.3%) vs. 0/1 risk factor (low-risk; 42.7%) were more likely to experience acute care (79.6% vs. 51.1%), corresponding to a > 3-fold increase in odds (OR = 3.38, 95%CI , 2.48-4.62). Results were similar in the test set, indicating successful validation. Among all patients, quartile-level proportions were 48.9% for zero risk factors vs. 84.0% for 3/4 risk factors. The C-statistic was 0.703.

CONCLUSIONS: A limited set of 4 variables predicted a threefold increased risk of acute care use in older patients with advanced cancer. Personalized interventions aimed at preventing acute care use could improve the quality of cancer care.},
}

@article {pmid41345384,
year = {2025},
author = {Shadman, M and Harper, JS and Bokun, A and Xu, C and Lin, P and Graf, G and Lu, X},
title = {Real-world treatment patterns and clinical outcomes among patients with diffuse large B-cell lymphoma in a US healthcare claims database.},
journal = {Blood cancer journal},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41408-025-01412-8},
pmid = {41345384},
issn = {2044-5385},
abstract = {Treatment options for diffuse large B-cell lymphoma (DLBCL) have expanded, but real-world data on treatment patterns and outcomes remain limited. This study examined real-world outcomes in DLBCL patients treated between 10/1/2015 and 6/30/2024. Patients were stratified by lines of therapy (LOT) and treatments (1L rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone [R-CHOP]; 2L stem cell transplant [SCT]; and chimeric antigen receptor T-cell [CAR T] therapy (any LOT). Variables were reported descriptively. Time-to-event outcomes were assessed using the Kaplan-Meier method. LOT data from 9875 patients were included. R-CHOP-based regimens were the most common 1L treatment (61.7%-67.3% in 2016-2023; 49.4% in 2024). Conventional chemoimmunotherapy use decreased in 2L (81.6% in 2016 to 41.9% in 2024) and 3L (47.6% in 2016 to 22.1% in 2024), while novel therapies increased (43.0% in 2L and 55.9% in 3L in 2024). Median overall survival declined across LOT (1L: 58.1 months; 2L: 30.0 months), as did median time to next treatment (1L: 36.1 months; 2L: 10.6 months). Twelve-month treatment failure rates were 36.0% after 1L, 51.8% after 2L, and 42.2% after CAR T. Among CAR T recipients, 93 received one of 36 distinct subsequent regimens, indicating no standard of care. These findings highlight the unmet needs in DLBCL.},
}

@article {pmid41344861,
year = {2025},
author = {Specht, JM and van Geel, JJL and Song, S and Liu, C and Hippe, DS and DiGregorio, NA and Brand, CJ and Linden, HM},
title = {The Role of Estrogen Receptor-Targeted PET with 16α-[18]F-Fluoro-17β-Estradiol in Predicting Response to Endocrine Therapies in Metastatic Breast Cancer: A Metaanalysis.},
journal = {Journal of nuclear medicine : official publication, Society of Nuclear Medicine},
volume = {},
number = {},
pages = {},
doi = {10.2967/jnumed.125.270763},
pmid = {41344861},
issn = {1535-5667},
abstract = {[[18]F]16α-fluoro-17β-fluoroestradiol ([[18]F]FES) PET/CT imaging enables whole-body assessment of functional estrogen receptor (ER) expression in metastatic breast cancer (mBC). Identifying imaging biomarkers that predict endocrine therapy (ET) response remains a critical need in optimizing treatment selection. Our objective was to assess the predictive utility of [[18]F]FES PET/CT imaging in determining response to ET, with a focus on interlesional heterogeneity and individual patient outcomes. Methods: A systematic literature review and metaanalysis were conducted using 6 major databases through April 2024. Ten studies met inclusion criteria based on quantitative SUV reporting, use of FES PET/CT in mBC, and correlation with clinical outcomes. All patients had ER-positive mBC and received ET. Primary endpoints included progression-free survival (PFS) and response to ET. Patients were stratified by baseline [[18]F]FES PET/CT SUVmean or SUVmax thresholds (including 1.8) and by interlesional [[18]F]FES heterogeneity (presence of both [[18]F]FES-positive and [[18]F]FES-negative lesions). Results: Responders had a significantly higher baseline SUVmean than nonresponders (standardized mean difference, 0.91; 95% CI, 0.49-1.34; P < 0.001). Patients with a baseline SUVmax below 1.5 were significantly less likely to respond (odds ratio, 0.11; 95% CI, 0.02-0.72; P = 0.02). Across 5 studies, patients with heterogeneous [[18]F]FES uptake had a shorter median PFS (2.4-12.4 mo) than did those with all [[18]F]FES-positive lesions (14.6-23.6 mo), a statistically significant difference (ratio of median PFS, 0.25; 95% CI, 0.17-0.36; P < 0.001). In an individual-level analysis (n = 101), lesion-level [[18]F]FES-heterogeneous uptake was associated with a PFS of 5.5 versus 21.6 mo and a hazard ratio of 5.4 (95% CI, 3.2-9.4; P < 0.001). An [[18]F]FES SUVmax threshold of at least 1.8 was more prognostic of PFS than were higher SUVmax thresholds. Conclusion: [[18]F]FES PET/CT imaging provides prognostic insight beyond static ER testing by identifying functional heterogeneity in mBC. Lesion-level FES heterogeneity based on an SUVmax threshold of 1.8 may help stratify patients unlikely to benefit from ET, guiding more personalized treatment strategies.},
}

@article {pmid41344792,
year = {2026},
author = {, },
title = {Quantifying the fatal and non-fatal burden of disease associated with child growth failure, 2000-2023: a systematic analysis from the Global Burden of Disease Study 2023.},
journal = {The Lancet. Child & adolescent health},
volume = {10},
number = {1},
pages = {22-38},
pmid = {41344792},
issn = {2352-4650},
mesh = {Humans ; Child, Preschool ; *Global Burden of Disease/trends ; *Growth Disorders/epidemiology/mortality ; Infant ; Male ; Disability-Adjusted Life Years ; Female ; Thinness/epidemiology ; Prevalence ; Cost of Illness ; Child Mortality ; },
abstract = {BACKGROUND: Child growth failure (CGF), which includes underweight, wasting, and stunting, is among the factors most strongly associated with mortality and morbidity in children younger than 5 years worldwide. Poor height and bodyweight gain arise from a variety of biological and sociodemographic factors and are associated with increased vulnerability to infectious diseases. We used data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2023 to estimate CGF prevalence, the risk of infectious diseases associated with CGF, and the disease mortality, morbidity, and overall burden associated with CGF.

METHODS: In this analysis we estimated the all-cause and cause-specific (diarrhoea, lower respiratory tract infections, malaria, and measles) disability-adjusted life-years (DALYs) lost and mortality associated with stunting, wasting, underweight, and CGF in aggregate. We combined the burden associated with mild, moderate, and severe forms of CGF: stunting was defined as height-for-age Z scores (HAZ) less than -1, underweight was defined as weight-for-age Z scores (WAZ) less than -1, and wasting was defined as weight-for-height Z scores (WHZ) less than -1, according to WHO Child Growth Standards. Population-level continuous distributions of HAZ, WAZ, and WHZ were estimated for 2000 to 2023 using data from surveys, literature, and individual-level study data. The risk of incidence of, and mortality due to, diarrhoea, lower respiratory infections, malaria, and measles was separately estimated in a meta-regression framework from longitudinal cohort data for Z scores less than -1. Finally, fatal outcomes associated with these diseases were estimated with vital registration, verbal autopsy, and case-fatality data, while non-fatal outcomes were estimated with surveys as well as health-care utilisation and case reporting data. The exposure prevalence and relative risk estimates were from continuous distributions, allowing for direct assessment of the attributable fractions for mild, moderate, and severe stunting, underweight, wasting, and the combined impact of child growth failure within populations. All estimates were age-specific, sex-specific, geography-specific, and year-specific.

FINDINGS: We estimated that, in children younger than 5 years in 2023, CGF was associated with 79·4 million (95% uncertainty interval [UI] 47·0-106) DALYs lost and 880 000 (517 000-1 170 000) deaths. This represented 17·9% (10·6-23·8) of 444 million (434-457) total under-5 DALYs and 18·8% (11·1-25·0) of all 4·67 million (4·59-4·75) under-5 deaths. Compared to stunting (33·0 million [24·1-42·2] DALYs, 373 000 [272 000-477 000] deaths) and wasting (39·2 million [23·8-53·0] DALYs, 428 000 [256 000-583 000] deaths), childhood underweight was associated with the largest share of CGF-related disease burden: 52·2 million (21·9-75·1) DALYs and 573 000 (236 000-824 000) deaths in children younger than 5 years in 2023.

INTERPRETATION: CGF remains a leading factor associated with death and disability in children younger than 5 years, despite global attention and focused interventions to reduce the prevalence of associated CGF indicators. Our findings underscore the need for policies, strategies, and interventions that focus on all indicators of CGF to reduce its associated health burden.

FUNDING: Gates Foundation.},
}

Humans
Child, Preschool
*Global Burden of Disease/trends
*Growth Disorders/epidemiology/mortality
Infant
Male
Disability-Adjusted Life Years
Female
Thinness/epidemiology
Prevalence
Cost of Illness
Child Mortality

@article {pmid41344516,
year = {2025},
author = {Alongi, F and Cuccia, F and Kotecha, R and Campione, M and Louie, AV and Ma, L and Minniti, G and Tree, AC and Dahele, M and Lo, S and Af Rosenschold, PM and Suh, JH and Niyazi, M and Sheehan, J and Guckenberger, M and Sahgal, A},
title = {ESTRO-ISRS clinical practice recommendations for re-irradiation of spinal mestastases with Stereotactic body radiotherapy: delphi consensus supported by a systematic review and meta-analysis.},
journal = {Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology},
volume = {},
number = {},
pages = {111304},
doi = {10.1016/j.radonc.2025.111304},
pmid = {41344516},
issn = {1879-0887},
abstract = {BACKGROUND: Stereotactic body radiotherapy (SBRT) is an established treatment for previously unirradiated spinal metastases; however, the literature is limited with respect to SBRT as a re-irradiation salvage therapy. We performed a systematic review and meta-analysis as basis for joint ESTRO-ISRS clinical practice recommendations of salvage SBRT for spinal metastases.

METHODS: A systematic review and meta-analysis were performed using PRISMA methodology, including publications from January 2006 to September 2024, reporting on the clinical outcomes of ≥ 5 patients treated with spine SBRT re-irradiation (≥5 Gy per fraction) for vertebral metastases. These data served as basis for joint ESTRO-ISRS clinical practice recommendations.

RESULTS: After the initial article screen, 20 studies (5 prospective, 15 retrospective) met the inclusion criteria for analysis. A total of 1538 spine metastases were treated in 1284 patients. The median re-irradiation dose was 24 Gy in 2 fractions (range: 16-30 Gy in 1-5 fractions) after a median 30 Gy in 10 fractions of prior conventional radiotherapy. Vertebral compression fracture, nerve root damage, and myelopathy events were observed in a pooled proportion of 5.0 %, 5.6 %, and 1.7 %, respectively. With a median follow-up of 12 months, the pooled 1- and 2-year LC rates were 81 % (95 % CI: 77-86 %) and 70 % (95 % CI: 61-79 %), respectively. Despite the low level of evidence, a consensus was reached after the first round of voting for 11 practice recommendations, suggesting a substantial level of agreement among the experts.

CONCLUSIONS: Re-irradiation with SBRT for spine metastases following prior conventional radiation or SBRT was efficacious, safe, and is a recommended treatment option in appropriately selected patients. Joint practice recommendations are provided on behalf of ESTRO and ISRS to guide clinical practice.},
}

@article {pmid41343677,
year = {2025},
author = {Ersoy-Fazlioglu, B and Lingadahalli, S and Altintas, UB and Cingoz, A and Tekoglu, E and Lok Yu, IP and Dikbas, M and Missaghimamaghani, O and Yavuz, K and Adomat, H and Kulac, I and Morova, T and Xiao, K and Gleave, M and Fazli, L and Cejas, P and Cherkasov, A and Zwart, W and Haffner, MC and Long, HW and Collins, C and Bagci-Onder, T and Lack, NA},
title = {Distinct transcription factor interactions drive HOXB13 activity in different stages of prostate cancer.},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
volume = {122},
number = {49},
pages = {e2500327122},
doi = {10.1073/pnas.2500327122},
pmid = {41343677},
issn = {1091-6490},
support = {PJT-173331//CIHR | Canadian Institutes of Health Research - Antimicrobial Resistance Research Initiative (AMR)/ ; NIH P50 CA097186//North Spore/ ; 221Z116//TUBITAK | Ulusal Metroloji Enstitüsü, Türkiye Bilimsel ve Teknolojik Araştirma Kurumu (TÜBİTAK UME)/ ; PDF//Prostate Cancer Fight Foundation (PCFF)/ ; },
mesh = {Male ; *Homeodomain Proteins/metabolism/genetics ; Humans ; *Prostatic Neoplasms/metabolism/pathology/genetics ; Receptors, Androgen/metabolism/genetics ; Cell Proliferation ; Gene Expression Regulation, Neoplastic ; Cell Line, Tumor ; *Transcription Factors/metabolism/genetics ; Animals ; Mice ; },
abstract = {HOXB13 is a lineage-specific transcription factor that plays a critical role in initiation and progression of prostate cancer (PCa). While most research has focused on the role of HOXB13 on androgen receptor (AR) activity, here we demonstrate that HOXB13 is frequently expressed in AR-negative tumors and is essential for the proliferation of both AR-positive and -negative PCa models. Strikingly, HOXB13 is remarkably selective and has almost no effect on nonprostatic tissues. Despite this common essentiality in PCa, HOXB13 activity is markedly different in AR-negative stem cell-like tumors, where interactions with the AP-1 change the HOXB13 cistrome and interactome. Yet despite these distinct activities, HOXB13 activity is commonly mediated by SMARCD2, a member of the mSWI/SNF chromatin remodeling complex. The HOXB13/SMARCD2 interaction alters chromatin accessibility at HOXB13-binding sites, causing increased proliferation in AR-negative PCa. Overall, this work demonstrates a distinct mechanism of action for HOXB13 and highlights its critical role in AR-negative castration-resistant PCa.},
}

Male
*Homeodomain Proteins/metabolism/genetics
Humans
*Prostatic Neoplasms/metabolism/pathology/genetics
Receptors, Androgen/metabolism/genetics
Cell Proliferation
Gene Expression Regulation, Neoplastic
Cell Line, Tumor
*Transcription Factors/metabolism/genetics
Animals
Mice

@article {pmid41343299,
year = {2025},
author = {Huddleston, J and Bedford, T},
title = {Timely vaccine strain selection and genomic surveillance improve evolutionary forecast accuracy of seasonal influenza A/H3N2.},
journal = {eLife},
volume = {14},
number = {},
pages = {},
pmid = {41343299},
issn = {2050-084X},
support = {R01 AI165821-01//National Institute of Allergy and Infectious Diseases/ ; },
mesh = {*Influenza A Virus, H3N2 Subtype/genetics/immunology ; Humans ; *Influenza, Human/prevention & control/virology/epidemiology ; *Influenza Vaccines/immunology ; *Evolution, Molecular ; Seasons ; Forecasting ; COVID-19/prevention & control ; SARS-CoV-2 ; Genomics ; Pandemics ; },
abstract = {Evolutionary forecasting models inform seasonal influenza vaccine design by predicting which current genetic variants will dominate in the influenza season 12 months later. Forecasting models depend on hemagglutinin sequences from global public health networks to identify current genetic variants (clades) and estimate clade fitnesses. The lag between collection of a clinical sample and public availability of its sequence averages ∼3 months, complicating the 12-month forecasting problem by reducing our understanding of current clade frequencies. Despite continued methodological improvements to forecasting models, these constraints of a 12-month forecast horizon and 3-month submission lags impose an upper bound on any model's accuracy. The SARS-CoV-2 pandemic revealed that modern vaccine technology reduces forecast horizons to 6 months and expanded sequencing support reduces submission lags to 1 month on average. We quantified the potential effects of these public health policy changes on forecast accuracy for A/H3N2 populations. Reducing forecast horizons to 6 months reduced average absolute forecasting errors to 25% of the 12-month average, while reducing submission lags decreased uncertainty in current clade frequencies by 50%. These results show the potential to improve the accuracy of existing forecasting models through realistic changes to public health policy.},
}

*Influenza A Virus, H3N2 Subtype/genetics/immunology
Humans
*Influenza, Human/prevention & control/virology/epidemiology
*Influenza Vaccines/immunology
*Evolution, Molecular
Seasons
Forecasting
COVID-19/prevention & control
SARS-CoV-2
Genomics
Pandemics

@article {pmid41342729,
year = {2026},
author = {Perkins, RB and Wolf, AMD and Church, TR and Elkin, EB and Skates, SJ and Etzioni, RD and Guerra, CE and Herzig, A and Hoffman, RM and Oeffinger, KC and Raoof, S and Shih, YT and Walter, LC and Zeigler-Johnson, C and Manassaram-Baptiste, D and Smith, RA},
title = {Self-collected vaginal specimens for human papillomavirus testing and guidance on screening exit: An update to the American Cancer Society cervical cancer screening guideline.},
journal = {CA: a cancer journal for clinicians},
volume = {76},
number = {1},
pages = {e70041},
pmid = {41342729},
issn = {1542-4863},
mesh = {Humans ; Female ; *Uterine Cervical Neoplasms/diagnosis/virology ; *Papillomavirus Infections/diagnosis/virology ; *Early Detection of Cancer/methods/standards ; *Specimen Handling/methods/standards ; United States ; Adult ; Middle Aged ; *Vaginal Smears/methods ; Aged ; American Cancer Society ; *Papillomaviridae/isolation & purification ; Mass Screening/methods/standards ; Practice Guidelines as Topic ; Vagina/virology ; Human Papillomavirus Viruses ; },
abstract = {This update expands the 2020 American Cancer Society (ACS) cervical cancer screening guideline for average-risk women and individuals with a cervix who are at average risk, to include self-collection for human papillomavirus (HPV) testing and revised guidance for exiting cervical cancer screening. Self-collected vaginal specimens, a method of primary HPV testing, align with the ACS cervical cancer screening guideline. When clinician-collected cervical specimens are used for HPV testing, repeat screening is recommended every 5 years for those with a negative test. For self-collected vaginal specimens, the ACS endorses the following recommendations of the Enduring Consensus Cervical Cancer Screening and Management Guidelines Committee (of which it is a member): (1) primary HPV screening using clinician-collected cervical specimens is preferred, and self-collected vaginal specimens are acceptable for average-risk individuals aged 25-65 years; and (2) repeat testing in 3 years is recommended after a negative result on a self-collected HPV screening test. These recommendations apply only to combinations of collection devices and HPV assays approved by the US Food and Drug Administration for HPV testing in a clinical setting or at home. The rationale notes that the use of self-collected vaginal specimens can overcome barriers to screening for many patients, but most patients who test HPV-positive will require extra follow-up steps, and data on long-term, real-world effectiveness are limited. For certain high-risk individuals, clinician-collected samples are still recommended. Furthermore, in response to high rates of cervical cancer among individuals older than 65 years and with poor implementation of current exiting screening criteria, ACS has amended the 2020 guideline to recommend HPV testing at ages 60 and 65 years, with the last HPV test at an age no younger than 65 years as a requisite to exiting screening. The revised recommendation states: To qualify for discontinuation of screening, the ACS recommends an average-risk woman or an individual with a cervix at average risk have negative primary HPV tests (preferred) or negative co-testing using HPV tests and cytology (acceptable) at ages 60 and 65 years. If primary HPV tests or co-testing are not available, three consecutive negative cytology (Papanicolaou) tests at the recommended screening interval with the last test at age 65 years are acceptable. If self-collected vaginal specimens are used for HPV testing, the 3-year testing interval should be followed. Additional screening exit stipulations relate to women at higher risk because of prior abnormal test results or current immune suppression.},
}

Humans
Female
*Uterine Cervical Neoplasms/diagnosis/virology
*Papillomavirus Infections/diagnosis/virology
*Early Detection of Cancer/methods/standards
*Specimen Handling/methods/standards
United States
Adult
Middle Aged
*Vaginal Smears/methods
Aged
American Cancer Society
*Papillomaviridae/isolation & purification
Mass Screening/methods/standards
Practice Guidelines as Topic
Vagina/virology
Human Papillomavirus Viruses

@article {pmid41340045,
year = {2025},
author = {Omame, A and Iyaniwura, SA and Ebenezer, A and Han, Q and Wang, X and Bragazzi, NL and Kong, JD and Woldegerima, WA},
title = {Pre-exposure vaccination in the high-risk population is crucial in controlling mpox resurgence in Canada.},
journal = {BMC infectious diseases},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12879-025-12172-y},
pmid = {41340045},
issn = {1471-2334},
abstract = {As mpox spread continues across several endemic and non-endemic countries around the world, vaccination has become an integral part of the global response to control the epidemic. Some vaccines have been recommended for use against mpox by the World Health Organization (WHO). As the roll-out of mpox vaccines continue across the globe, it is imperative to develop mathematical models to support public health officials and governments agencies in optimizing vaccination strategies to curtail the resurgence of mpox. In this article, we develop a compartmental mathematical model to investigate the impact of vaccination in controlling a potential mpox resurgence in Canada. The model categorizes individuals into high- and low-risk groups and incorporates pre-exposure vaccination in the high-risk group and post-exposure vaccination in the high- and low-risk groups. The vaccine-free version of the model was calibrated to the daily reported cases of mpox in Canada from April to October 2022, from which we estimated key model parameters, including the sexual and non-sexual transmission rates. Furthermore, we calibrated the full model to the daily reported cases of mpox in Canada in 2024, to estimate the current mpox vaccination rates in Canada. Our results highlight the importance of pre-exposure vaccination in the high-risk group on controlling a potential resurgence of mpox in Canada, and the minimal effects of post-exposure vaccination in the high- and low-risk groups on the outbreak. In addition, our model predicts the possibility of mpox becoming endemic in Canada, in the absence of pre-exposure vaccination in the high-risk group. Overall, our modeling result suggests that pre-exposure vaccination in the high-risk group is crucial in controlling mpox outbreak in Canada. Stepping up this vaccination is sufficient to avert a potential mpox resurgence in Canada.Clinical trial number Not applicable.},
}

@article {pmid41338864,
year = {2025},
author = {Scordo, M and Perales, MA and Mauguen, A and Lin, A and Kunvarjee, B and Paes Pena, M and Mcavoy, D and Nguyen, LK and Hogan, M and Chapman, N and Bieler, J and Cho, C and Gyurkocza, B and Harris, AC and Spitzer, B and O'Reilly, RJ and Jakubowski, AA and Lin, RJ and Papadopoulos, EB and Politikos, I and Ponce, DM and Shaffer, BC and Shah, GL and Tamari, R and Giralt, SA and Boelens, JJ and Curran, KJ},
title = {Model-based antithymocyte globulin dosing in ex vivo CD34+ selected allogeneic haematopoietic cell transplantation: a single-centre, single-arm, phase 2 study.},
journal = {The Lancet. Haematology},
volume = {12},
number = {12},
pages = {e956-e965},
doi = {10.1016/S2352-3026(25)00293-5},
pmid = {41338864},
issn = {2352-3026},
mesh = {Humans ; *Antilymphocyte Serum/administration & dosage/therapeutic use ; *Hematopoietic Stem Cell Transplantation/methods/adverse effects ; Male ; Female ; Middle Aged ; Adult ; Graft vs Host Disease/prevention & control/etiology ; *Antigens, CD34/metabolism ; *Transplantation Conditioning/methods ; Transplantation, Homologous ; *Hematologic Neoplasms/therapy/mortality ; Aged ; Melphalan/administration & dosage ; },
abstract = {BACKGROUND: Ex-vivo CD34+ selected allogeneic haematopoietic cell transplantation (HCT) provides favourable chronic graft-versus-host disease (GVHD)-free relapse-free survival but is limited by delayed immune reconstitution and early non-relapse mortality. High anti-thymocyte globulin (ATG) exposure after HCT has been associated with delayed CD4+ T-cell immune reconstitution, increased non-relapse mortality, and poor overall survival.

METHODS: We report the final analysis of a single-centre, phase 2 trial investigating pharmacokinetic model-based ATG (targeting <20 AU × d/mL post-HCT exposure) in participants of any age undergoing ex vivo CD34+ selected allogeneic HCT after myeloablative conditioning for haematological malignancies. Two myeloablative conditioning regimens were used at the discretion of the treating physician: the chemotherapy-based regimen (target cumulative exposure of 65 mg × h/L busulfan, 140 mg/m[2] melphalan, and 150 mg/m[2] fludarabine) and a high-dose total-body irradiation-based regimen (included total-body irradiation [1375 cGy], thiotepa [10 mg/kg], and cyclophosphamide [100 mg/kg]). The primary objective was an improvement in CD4+ immune reconstitution (>50 cells per μL at two consecutive timepoints by day +100) in at least 32% of the per protocol population. This study was registered with ClinicalTrials.gov (NCT04872595) and is completed.

FINDINGS: Between June 14, 2021, and Nov 28, 2023, we enrolled 59 participants with haematological malignancies. Among evaluable participants (n=56), the median age was 55 years (IQR 30-63), 34 (61%) were male, 22 (39%) were female, 44 (79%) had myeloid malignancies, and 44 (79%) had received chemotherapy-only myeloablative conditioning. The median estimated ATG exposure after HCT was 10 AU × d/mL (IQR 9-11). CD4+ immune reconstitution was reached in 39 (70%) of 56 participants, meeting the study's primary endpoint. The most common grade 3 or worse adverse events were infections (103 [40%] of 259 events) and oral or gastrointestinal events (44 [17%] of 259 events). Grade 5 adverse events occurred in three participants including secondary graft failure (n=1) and multi-organ failure (n=2), with a total of four treatment-related deaths among participants.

INTERPRETATION: These results demonstrate that model-based ATG dosing promotes robust CD4+ immune reconstitution after ex vivo CD34+ selected allogeneic HCT, underscoring the potential of pharmacokinetically guided ATG as a strategy to optimise immune recovery in myeloablative, calcineurin inhibitor-free transplantation for haematological malignancies.

FUNDING: US National Cancer Institute, Memorial Sloan Kettering Cancer Center.},
}

Humans
*Antilymphocyte Serum/administration & dosage/therapeutic use
*Hematopoietic Stem Cell Transplantation/methods/adverse effects
Male
Female
Middle Aged
Adult
Graft vs Host Disease/prevention & control/etiology
*Antigens, CD34/metabolism
*Transplantation Conditioning/methods
Transplantation, Homologous
*Hematologic Neoplasms/therapy/mortality
Aged
Melphalan/administration & dosage