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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

@article {pmid40291683,
year = {2025},
author = {Cimino, PJ and Keiser, DJ and Parrish, AG and Holland, EC and Szulzewsky, F},
title = {C-terminal fusion partner activity contributes to the oncogenic functions of YAP1::TFE3.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {40291683},
issn = {2692-8205},
support = {R35 CA253119/CA/NCI NIH HHS/United States ; },
abstract = {YAP1 gene fusions are found in a multitude of human tumors, are potent oncogenic drivers, and are the likely initiating tumorigenic events in these tumors. We and others have previously shown that a YAP1 fusion proteins exert TEAD-dependent oncogenic YAP1 activity that is resistant to inhibitory Hippo pathway signaling. However, the contributions of the C-terminal fusion partners to the oncogenic functions of YAP1 fusion proteins are understudied. Here, we used the RCAS/tv-a system to express eight different YAP1 gene fusions in vivo and observed significant differences in the latencies of tumors induced by the various YAP1 fusions. We observed that tumors induced by YAP1::TFE3 displayed a significantly different histomorphology compared to tumors induced by other YAP1 fusions or activated non-fusion YAP1. To assess the extent to which the functional TFE3 domains (DNA binding: leucine zipper (LZ) and basic-helix-loop-helix (bHLH); activation domain (AD)) contribute to the oncogenic functions of YAP1::TFE3, we generated several mutant variants and performed functional in vitro and in vivo assays. In vitro, mutation or deletion of the TFE3 DNA binding domains (LZ, bHLH) resulted in reduced TFE3 activity but increased YAP1 activity of YAP1::TFE3. In vivo, deletion of the LZ and bHLH domains did not result in a decrease in tumor incidence but induced the formation of more YAP1-like tumors that lacked prominent features of YAP1::TFE3-driven tumors. By contrast, loss of the TFE3 AD almost completely abrogated tumor formation. Our results suggest that the TFE3 domains significantly contribute to the oncogenic activity of YAP1::TFE3.},
}

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

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

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

@article {pmid41043776,
year = {2025},
author = {McCurdy, SR and Solomon, SR and Shaffer, BC and He, M and Bolon, YT and Blouin, AG and Keyzner, A and Socola, FA and Ibrahim, U and Zou, J and Safah, H and Saba, N and Gadalla, S and Perales, MA and Paczesny, S and Marsh, SGE and Petersdorf, EW and Wang, T and Lee, SJ and Fuchs, EJ},
title = {Post-Transplant Cyclophosphamide Improves Survival in HLA-DPB1 Mismatched Unrelated Donor Allogeneic Transplantation.},
journal = {Transplantation and cellular therapy},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jtct.2025.09.048},
pmid = {41043776},
issn = {2666-6367},
abstract = {BACKGROUND: HLA-DPB1 mismatching is common in unrelated donor (URD) hematopoietic cell transplantation (HCT) and increases graft-versus-host disease (GVHD) when using methotrexate and tacrolimus (MTX/Tac)-based GVHD prophylaxis. Historically, national and international guidelines recommended prioritizing HLA-DPB1 matching in URD selection. The impact of HLA-DPB1 matching in URD HCT when using post-transplantation cyclophosphamide (PTCy) has been understudied.

OBJECTIVES: Our primary endpoint was the association of GVHD-prophylaxis strategy with overall survival (OS) after T cell-replete 12/12 HLA-matched or permissive or non-permissive (NP) mismatch (MM) at HLA-DPB1 (defined by the T-cell-epitope groups model) URD HCT.GVHD-free, relapse-free survival (GRFS) was our key secondary endpoint.

STUDY DESIGN: This was a retrospective cohort study using the Center for International Blood and Marrow Transplant Research (CIBMTR) database. Recipients underwent a first HCT from 2015-2020 for acute leukemia or myelodysplastic syndrome using either HLA-DPB1 NP MM (n=329), permissive MM (n=992), or 12/12 HLA-matched (n=300) URD with PTCy ± mycophenolate mofetil and/or a calcineurin inhibitor, or HLA-DPB1 NP MM (n=709), permissive MM (n=2,395), or 12/12 HLA-matched (n=911) URD with MTX/Tac.

RESULTS: HLA-DPB1 NP MM with MTX/Tac was associated with higher treatment-related mortality (TRM) (hazard ratio [HR]: 1.64, 1.08-2.49, p=0.019), lower relapse (HR: 0.73, 0.59-0.92, p=0.0073), inferior OS (HR: 1.27, 1.03 -1.57, p=0.023), and worse GRFS (HR: 1.61, 1.34-1.94, p<0.0001) when compared with PTCy. Adjusted 1-yr estimates for GRFS were 54% (95% confidence interval [CI]: 49-60%) for PTCy and 40% (CI: 37-44%) for MTX/Tac. For permissive MM URD HCT, MTX/Tac was associated with inferior GRFS (HR 1.54, CI: 1.36-1.76, p<0.0001) when compared with PTCy. When using PTCy, there were no significant differences in these outcomes for HLA-DPB1 NP MM, HLA-DPB1 permissive MM, or 12/12 HLA-matched URD HCT.

CONCLUSIONS: PTCy should be the preferred GVHD prophylaxis strategy for HLA-DPB1 MM URD HCT. Furthermore, within PTCy platforms, survival is comparable across HLA-DPB1 match and thus NP mismatching at HLA-DPB1 should not be a determinant in URD selection.},
}

@article {pmid41043723,
year = {2025},
author = {El-Serag, HB and Lopez, C and Luster, M and Reddy, KR and Parikh, N and Singal, AG and Marrero, JA and Thrift, AP and Chhatwal, J and Feng, Z and Page-Lester, S and Jin, Q and Tayob, N and Kanwal, F},
title = {HES V2.0 validation and performance compared to GALAD and ASAP in the HEDS cohort.},
journal = {Journal of hepatology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jhep.2025.09.023},
pmid = {41043723},
issn = {1600-0641},
abstract = {BACKGROUND: We previously developed Hepatocellular Carcinoma Early Detection Screening (HES) V2.0, biomarker panel (age, ALT, platelets, etiology, AFP, AFP L3, DCP and their gradient over the past one year) for early detection of HCC among patients with cirrhosis. We externally validated HES V2.0 and compared its performance to HES V1.0, GALAD, and ASAP.

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

RESULTS: HES V2.0 and GALAD had same AUROC (0.79) but different TPR/FPRs. At the FPR of 10%, HES V2.0 had 2.0%, 6.7%, and 6.0% higher TPR (sensitivity) than GALAD within 6, 12, and 24 months before HCC diagnosis (one-sided p-values 0.24, 0.025, 0.078, respectively). At 18.1% FPR, GALAD had 6% and 2% higher sensitivity than HES V2.0 within 6 and 12 months before HCC and similar sensitivity within 24 months before HCC diagnosis (all p-values >0.05).The sensitivity for HES V2.0 was 11.9% higher than HES V1.0 at 12 months (p=0.007). The sensitivity for HES V2.0 was considerably (10.9-16.3%) higher than ASAP. For patients with available labs to calculate gradients over time, the sensitivity of HES V2.0 was 3.5-8.7% higher than GALAD at all time points of testing before HCC (8.7% to 24.0% relative increase) with p<0.05 for several comparisons.

CONCLUSIONS: In a phase 3 biomarker validation study, HES V2.0 had higher sensitivity than ASAP for HCC detection, and a similar or higher sensitivity than GALAD only at 12 months before HCC diagnosis at 10% FPR and when over time gradients in AFP, AFP L3, and DCP are available.

IMPACT AND IMPLICATIONS: Hepatocellular carcinoma (HCC) remains a leading cause of cancer-related mortality, with early detection being critical for improving survival outcomes. This study provides a rigorous phase 3 validation of the HES V2.0 biomarker panel, demonstrating its superior or comparable sensitivity to established models like GALAD and ASAP in a large, diverse U.S. cirrhosis cohort. The findings are particularly impactful for clinicians and researchers focused on liver cancer surveillance, as HES V2.0 offers enhanced detection performance, especially when longitudinal biomarker data are available. These results support the integration of HES V2.0 into clinical workflows and future trials, potentially improving early HCC detection and enabling timely curative interventions for at-risk patients.},
}

@article {pmid41043413,
year = {2025},
author = {Zhang, P and Haeseleer, F and Waltner, OG and Gartlan, KH and Bhise, SS and Minnie, SA and Adams, RC and Yeh, AC and Ensbey, KS and Legg, SRW and Sekiguchi, T and Atilla, E and Nemychenkov, NS and Nelson, EL and Joshi, T and Liang, EC and Hirayama, AV and Abe, K and Koyama, M and Clouston, AD and Gauthier, J and Furlan, SN and Hill, GR},
title = {Eomesodermin[+] CD4[+] T cells are critical for curative immunotherapy outcomes.},
journal = {Immunity},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.immuni.2025.09.004},
pmid = {41043413},
issn = {1097-4180},
abstract = {Interleukin 10 (IL-10)-producing CD4[+] type-1 regulatory T cells (Tr1) promote immune tolerance during chronic infection, autoimmunity, and transplantation. However, specific Eomesodermin (Eomes)-dependent stages of Tr1 differentiation and function remain unclear. Using preclinical models of bone marrow transplantation (BMT), we demonstrated a Tr1 differentiation trajectory in vivo from Eomes[+]IL-10[-] to Eomes[+]IL-10[+] subsets with the acquisition of cytokine, cytolytic, and exhaustion features. The Eomes[+]CD4[+] fraction represented the dominant cytotoxic subset after BMT, mediating graft-versus-leukemia effects while limiting inflammation. In CD19-targeted chimeric antigen receptor (CAR) T cell immunotherapy, Eomes drove the same CD4[+] Tr1 phenotype that controlled cytolysis, while mitigating immune toxicity and promoting persistence. In individuals with high-grade B cell lymphomas that had long-term disease control after receiving commercial CD19-targeted CAR T cells, Eomes[+] Tr1 cells represented a stable population comprising 40%-80% of the CD4[+] CAR T cell population. Hence, Eomes controls both regulatory and cytotoxic programs in CD4[+] T cells, essential for curative immunotherapy outcomes.},
}

@article {pmid41043390,
year = {2025},
author = {Keogh, MC and Almouzni, G and Andrews, AJ and Armache, KJ and Arrowsmith, CH and Baek, SH and Bedford, MT and Bernstein, E and Côté, J and David, Y and Denu, JM and Fierz, B and Garcia, BA and Glass, KC and Gozani, O and Helin, K and Henikoff, S and Jensen, ON and Josefowicz, SZ and Kelleher, NL and Kutateladze, TG and Lindner, HH and Lu, C and Luger, K and Mallick, P and Musselman, CA and Muir, TW and Paša-Tolić, L and Schneider, R and Shi, X and Shi, Y and Sidoli, S and Smith, LM and Tyler, JK and Wolberger, C and Workman, JL and Strahl, BD and Young, NL},
title = {A needed nomenclature for nucleosomes.},
journal = {Molecular cell},
volume = {85},
number = {19},
pages = {3554-3561},
doi = {10.1016/j.molcel.2025.08.029},
pmid = {41043390},
issn = {1097-4164},
mesh = {*Nucleosomes/metabolism/genetics/classification ; *Protein Processing, Post-Translational ; *Histones/metabolism/genetics/classification ; Humans ; *Terminology as Topic ; Animals ; Chromatin/metabolism/genetics ; Chromatin Assembly and Disassembly ; },
abstract = {Histone post-translational modifications (PTMs) are crucial to eukaryotic genome regulation, with a range of reported functions and mechanisms of action. Though often studied individually, it has long been recognized that the modifications function by combinatorial synergy or antagonism. Interplay may involve PTMs on the same histone, within the same nucleosome (containing a histone octamer), or between nucleosomes in higher-order chromatin. Given this, the field must distinguish ever greater complexity, and the context in which it is studied, with brevity and precision. The proteoform was introduced to define individual forms of a protein by sequence and PTMs, followed by the nucleoform to describe the particular gathering of histones within an individual nucleosome. There is now a need to define specific forms of these entities in prose while providing space for experimental nuance. To this end, we introduce a nomenclature that can express discrete PTMs, proteoforms, nucleoforms, or situations where defined PTMs exist in an uncertain context. Though specifically designed for the chromatin field, adaptions of the framework could be used to describe-and thus dissect-how proteoforms are configured in functionally distinct complexes across biology.},
}

*Nucleosomes/metabolism/genetics/classification
*Protein Processing, Post-Translational
*Histones/metabolism/genetics/classification
Humans
*Terminology as Topic
Animals
Chromatin/metabolism/genetics
Chromatin Assembly and Disassembly

@article {pmid41043162,
year = {2025},
author = {Chung, K and Sotak, N},
title = {Use of Trigger Point Injections in the Management of Myofascial Pain in Patients With Temporomandibular Disorders.},
journal = {Compendium of continuing education in dentistry (Jamesburg, N.J. : 1995)},
volume = {46},
number = {8},
pages = {376-379},
pmid = {41043162},
issn = {2158-1797},
mesh = {Humans ; Aged ; *Trigger Points ; *Temporomandibular Joint Disorders/complications/drug therapy ; *Myofascial Pain Syndromes/drug therapy ; Male ; Anesthetics, Local/administration & dosage ; Injections ; },
abstract = {Myofascial pain, a prevalent condition that often involves trigger points in the craniofacial region, can significantly impair function and quality of life. This article reports on the case of a 69-year-old patient with chronic head and neck myofascial pain and limited mouth opening, which hindered dental care and obstructive sleep apnea management. Following a series of trigger point injections (TPIs), combined with pharmacologic and physical therapy, the patient experienced substantial symptom relief and improved jaw function, and was subsequently able to receive successful dental and sleep apnea treatment. The case underscores the importance of accurate diagnosis and multidisciplinary management of myofascial pain, highlighting TPI therapy as an effective, minimally invasive treatment within a multimodal care approach.},
}

Humans
Aged
*Trigger Points
*Temporomandibular Joint Disorders/complications/drug therapy
*Myofascial Pain Syndromes/drug therapy
Male
Anesthetics, Local/administration & dosage
Injections

@article {pmid41043099,
year = {2025},
author = {Ueda Oshima, M and Vo, PT and Boeckh, M and Bouvier, ME and Carpenter, PA and Mielcarek, M and Petersdorf, EW and Storb, R and Gooley, T and Sandmaier, BM},
title = {Sirolimus and Cyclosporine With Post-Transplant Cyclophosphamide or Mycophenolate Mofetil as Graft-Versus-Host Disease Prophylaxis in Unrelated Donor Hematopoietic Cell Transplantation.},
journal = {Journal of clinical oncology : official journal of the American Society of Clinical Oncology},
volume = {},
number = {},
pages = {JCO2501238},
doi = {10.1200/JCO-25-01238},
pmid = {41043099},
issn = {1527-7755},
abstract = {PURPOSE: To determine whether sirolimus (SIR) and cyclosporine (CSP) combined with post-transplantation cyclophosphamide (PTCy), after nonmyeloablative or reduced-intensity conditioning unrelated donor hematopoietic cell transplantation (HCT), would be more effective than SIR, CSP, and mycophenolate mofetil (MMF) in reducing the risk of chronic graft-versus-host disease (cGVHD) without increasing risk of recurrent malignancy.

METHODS: In a Phase II trial of HLA-matched or mismatched unrelated donor mobilized blood HCT (ClinicalTrials.gov identifier: NCT03246906), adults with hematologic malignancies ineligible for myeloablative HCT were randomly assigned 1:1 to GVHD prophylaxis with SIR/CSP/PTCy (50 mg/kg once daily on days +3, +4) or SIR/CSP/MMF. The primary end point was 1-year chronic GVHD-free relapse-free survival (CRFS).

RESULTS: One hundred forty-five patients were randomly assigned and transplanted. Median follow-up among survivors was 3.0 (range, 0.6-7.0) years. Comparing PTCy-based with non-PTCy-based immunosuppression, estimated 1-year CRFS was 73% (95% CI, 61% to 82%) versus 48% (95% CI, 36% to 59%), translating into a hazard ratio (HR) for CRFS failure of 0.46 (95% CI, 0.26 to 0.79; P = .005) for PTCy. Probabilities of acute GVHD (aGVHD) grades II-IV and III-IV, respectively, were 40% versus 42% and 6% versus 10%. One-year estimates for secondary end points were as follows: moderate-to-severe cGVHD, 3% (95% CI, 1% to 9%) versus 33% (95% CI, 22% to 44%); relapse, 15% versus 15%; progression-free survival, 75% versus 78%; survival, 86% versus 86%; and nonrelapse mortality, 10% versus 7%. The HR of ≥grade 3 infections with PTCy versus non-PTCy was 2.65 (95% CI, 1.41 to 4.97; P = .003).

CONCLUSION: After HLA-matched or mismatched unrelated donor mobilized blood HCT, replacing MMF with PTCy, when used in combination with SIR and CSP, significantly reduced risk of cGVHD, without increasing risks of aGVHD or relapse. Thus, the combination of PTCy and SIR/CSP may have synergistic cGVHD-protective effects warranting further study.},
}

@article {pmid41042747,
year = {2025},
author = {Feldacker, C and Fabens, I and Dong, TQ and Moyo, K and Makhele, C and Phohole, M and Igaba, N and Hlongwane, S and Pienaar, J and Sardini, M and Ndebele, F and Tweya, H and Holec, M and Waweru, E and Setswe, G},
title = {Strengthening evidence for text-based telehealth in post-operative care: A pragmatic study of the reach and effectiveness of two-way, text-based follow-up after voluntary medical male circumcision in South Africa.},
journal = {PloS one},
volume = {20},
number = {10},
pages = {e0314436},
pmid = {41042747},
issn = {1932-6203},
mesh = {Humans ; Male ; *Circumcision, Male/adverse effects ; South Africa ; *Telemedicine ; *Text Messaging ; Adult ; Adolescent ; *Postoperative Care/methods ; Young Adult ; Follow-Up Studies ; Middle Aged ; },
abstract = {Building upon evidence of safety and efficiency gains from a randomized control trial (RCT) in South Africa, we further scaled implementation of two-way, short message service (SMS), text-based (2wT) follow-up after voluntary medical male circumcision (VMMC). We aimed to determine if gains in adverse event (AE) identification and reduced follow-up visits could be maintained when 2wT was implemented in routine VMMC settings. A pragmatic, stepped wedge design (SWD) study was implemented across three districts in South Africa. Men ages 15 and older could opt into the 2wT telehealth follow-up approach when their facility was in the intervention period. Men in routine periods were offered the standard of care (SoC): in-person post-operative visits on days 2 and 7 as per national VMMC guidelines. 2wT participants were not required to attend any postoperative visits but could return for care if desired or referred. Two quality of care markers, safety (AE ascertainment rate) and efficiency (# in-person follow-up visits), were compared between groups. We aimed for at least 200 men per step to have 80% power to detect a change in AE rate from before to after 2wT was implemented. Secondary analysis explored response rates; client and site uptake; and AE details. Among 6842 clients in the intervention period, 2856 opted into 2wT (37.8%) across three intervention waves and two platforms (SMS or WhatsApp). Among those with post-operative follow-up, the AE ascertainment rate was higher among 2wT (0.60%) than SoC (0.13%) clients (p = 0.0018), demonstrating safety gains. On average, 2wT participants had 2.1 fewer visits compared to SoC clients (p < 0.001), demonstrating gains in follow-up efficiency. Among 2wT men, 2069/2586 (80%) responded via 2wT over 14 days, demonstrating engagement in post-operative care. Of all intervention clients, 93 2wT (3.6%) and 342 (8.0%) SoC were considered lost to follow-up. In this expansion trial, we provided additional evidence that the 2wT approach maintains the quality of post-operative care for adult VMMC clients. 2wT should be scaled to augment in-person, post-operative visits after VMMC for eligible, interested males ages 15 and older. To achieve potential impact, effort is needed to improve access and uptake to 2wT among providers and sites, expanding the 2wT approach for other acute follow-up care especially among men.},
}

Humans
Male
*Circumcision, Male/adverse effects
South Africa
*Telemedicine
*Text Messaging
Adult
Adolescent
*Postoperative Care/methods
Young Adult
Follow-Up Studies
Middle Aged

@article {pmid41001472,
year = {2025},
author = {Kerrebijn, I and Bjornsdottir, G and Arbabi, K and Urpa, L and Haapaniemi, H and Thorleifsson, G and Stefansdottir, L and Frangakis, S and Valliere, J and Kunorozva, L and Abner, E and Ji, C and Aagaard, B and Bliddal, H and Brunak, S and Bruun, MT and Didriksen, M and Erikstrup, C and Geirsson, AJ and Gudbjartsson, DF and Hansen, TF and Jonsdottir, I and Knight, S and Knowlton, KU and Mikkelsen, C and Nadauld, LD and Olafsdottir, TA and Ostrowski, SR and Pedersen, OB and Saevarsdottir, S and Skuladottir, AT and Sørensen, E and Stefansson, H and Sulem, P and Sveinsson, OA and Thorlacius, GE and Thorsteinsdottir, U and Ullum, H and Vikingsson, A and Werge, TM and , and , and , and , and , and Saxena, R and Stefansson, K and Brummett, CM and Glintborg, B and Clauw, DJ and Thorgeirsson, TE and Williams, FM and Sinnott-Armstrong, N and Ollila, HM and Wainberg, M},
title = {The genetic architecture of fibromyalgia across 2.5 million individuals.},
journal = {medRxiv : the preprint server for health sciences},
volume = {},
number = {},
pages = {},
pmid = {41001472},
support = {K08 AR082454/AR/NIAMS NIH HHS/United States ; RM1 HG010461/HG/NHGRI NIH HHS/United States ; },
abstract = {Fibromyalgia is a common and debilitating chronic pain syndrome of poorly understood etiology. Here, we conduct a multi-ancestry genome-wide association study meta-analysis across 2,563,755 individuals (54,629 cases and 2,509,126 controls) from 11 cohorts, identifying the first 26 risk loci for fibromyalgia. The strongest association was with a coding variant in HTT, the causal gene for Huntington's disease. Gene prioritization implicated the HTT regulator GPR52, as well as diverse genes with neural roles, including CAMKV, DCC, DRD2/NCAM1, MDGA2, and CELF4. Fibromyalgia heritability was exclusively enriched within brain tissues and neural cell types. Fibromyalgia showed strong, positive genetic correlation with a wide range of chronic pain, psychiatric, and somatic disorders, including genetic correlations above 0.7 with low back pain, post-traumatic stress disorder and irritable bowel syndrome. Despite large sex differences in fibromyalgia prevalence, the genetic architecture of fibromyalgia was nearly identical between males and females. This work provides the first robust genetic evidence defining fibromyalgia as a central nervous system disorder, thereby establishing a biological framework for its complex pathophysiology and extensive clinical comorbidities.},
}

@article {pmid41000947,
year = {2025},
author = {Kanaan, SB and Underwood, JG and Gladden, RG and Fan, E and Bhise, SS and Thakar, MS and Jaeger-Ruckstuhl, CA and Stevens, J and Gray, AN and Riddell, SR and Bleakley, M and Meshinchi, S and Furlan, SN},
title = {Quantifying HLA transcripts by genotype in chimeric mixtures at single-cell resolution.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {41000947},
issn = {2692-8205},
abstract = {Gene products from the highly variable major histocompatibility locus, including HLA, are essential for self-recognition and immune surveillance of malignancy. Following allogeneic hematopoietic cell transplantation (alloHCT), genetic and epigenetic alterations in HLA can drive disease recurrence, making precise HLA assessment critical for determining future therapy. However, current methods lack the sensitivity to quantify HLA transcripts at the single-cell level, limiting their clinical utility. We introduce scrHLA-typing, a novel technique that accurately identifies and quantifies HLA transcripts in single cells using long-read sequencing. When applied to samples from patients with post-transplant relapse, scrHLA-typing successfully detected HLA allele-specific expression, across a range of levels of donor-recipient chimerism, at clinically actionable levels. By characterizing allele expression in residual leukemia cells, our assay identified differences in expression patterns among patients. This capability highlights scrHLA-typing's potential to improve risk stratification and guide the selection of appropriate salvage therapies, enhancing personalized treatment strategies after relapse.},
}

@article {pmid41000687,
year = {2025},
author = {Wick, BJ and Kluesner, MG and Slipek, NJ and Skeate, JG and Niemeyer, EM and Webber, BR and Moriarity, BS},
title = {Installation of Dominant-Negative Mutations in FAS and TGFβR2 via Base Editing in Primary T Cells.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {41000687},
issn = {2692-8205},
abstract = {Adoptive cell transfer (ACT) of engineered T cells is effective against B-cell malignancies but has faltered against solid tumors due to the immunosuppressive tumor microenvironment (TME). FASL and TGFβ are key mediators of T cell dysfunction in the TME and overexpressing dominant negative (dn) forms of their receptors in T cells increases anti-tumor efficacy in solid tumor models. However, an approach which directly targets the endogenous genes would be more amenable to multiplex editing and reduce competition with WT alleles. Here, we employ base editing (BE) in primary human T cells to install naturally occurring dominant negative FAS and TGFβR2 mutations. In vitro survival and proliferation assays demonstrate that BE T cells are resistant to pro-apoptotic and anti-proliferative effects of FAS and TGFβ signaling. CAR-T cells with BE-installed dn TGFβR2 or dn FAS exhibit improvements in cytotoxicity, while dn TGFβR2 CAR T demonstrate increased persistence and reduced expression of phenotypic markers of exhaustion compared to controls. Moreover, BE-engineered dn CAR T outperform lentiviral-engineered cDNA over expression counterparts in several functional assays. Considering the efficiency of BE and its amenability for multiplex editing, our novel approach lends itself to engineering strategies necessary to overcome T cell dysfunction in solid tumors.},
}

@article {pmid40291684,
year = {2025},
author = {Vick, SC and Domenjo-Vila, E and Frutoso, M and Glabman, RA and Warrier, LS and Hughes, SM and Kirby, AC and Fialkow, MF and Hladik, F and Prlic, M and Lund, JM},
title = {Mucosal tissue NK cells tune their function between optimal anti-pathogen activity and tissue protection.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {40291684},
issn = {2692-8205},
support = {K99 AI180649/AI/NIAID NIH HHS/United States ; R01 AI141435/AI/NIAID NIH HHS/United States ; },
abstract = {Preserving barrier integrity is of great importance in mucosal tissues while simultaneously defending against inflammatory threats and exposures to pathogens. NK cells at barrier sites are essential for viral control during infections such as herpes simplex virus 2 (HSV-2) but must also balance pathogen response with tissue protection. We have characterized human tissue NK cells in the vaginal tissue (VT) as having distinct effector and tissue protective functions. Using scRNA-seq and high-parameter flow cytometry, we uncovered a unique signature for VT NK cells, indicating a reduced effector phenotype with increased factors related to tissue residency and immunoregulation at steady state. Despite their functionally quiescent nature, these cells were able to respond robustly to inflammatory signals, suggesting they are poised for pathogen response. We found that the gene signatures between mouse and human NK cells were remarkably similar, demonstrating the feasibility of using a mouse model to probe distinct NK cell functions during mucosal infection. In mice, VT NK cells responded robustly to acute HSV-2 infection and retained an enhanced recall potential after viral clearance. They also secreted tissue repair factors and played a role in restricting tissue damage following viral infection. Our data, using both human tissues and a mouse model, reveal an unexpected role of mucosal tissue NK cells in the VT in balancing host protection with tissue repair in the context of localized mucosal tissue infection.},
}

@article {pmid41042680,
year = {2025},
author = {Srinivasan, S and Strenk, SM and Beamer, MA and Fiedler, TL and Proll, S and Acevedo-Oquendo, GR and Bonura, GM and Nagana Gowda, GA and Raftery, D and Hillier, SL and Fredricks, DN},
title = {Umbribacter vaginalis gen. nov., sp. nov.: novel bacterium isolated from the human vagina.},
journal = {International journal of systematic and evolutionary microbiology},
volume = {75},
number = {10},
pages = {},
pmid = {41042680},
issn = {1466-5034},
mesh = {*Phylogeny ; Female ; RNA, Ribosomal, 16S/genetics ; Humans ; *Vagina/microbiology ; Fatty Acids/analysis/chemistry ; DNA, Bacterial/genetics ; Bacterial Typing Techniques ; Base Composition ; *Vaginosis, Bacterial/microbiology ; Sequence Analysis, DNA ; Adult ; },
abstract = {Gram-variable obligately anaerobic novel bacteria DNF00809 and PR-HUZ-602407-17 were isolated from vaginal fluid samples from women with bacterial vaginosis (BV) in two independent studies conducted in different laboratories. They each displayed ≥99.9% 16S rRNA gene sequence identity to the uncultured bacterial clone sequence AY738656 designated as Eggerthella-like vaginal bacterium (ELVB) and shared 100% 16S rRNA gene sequence identity with each other. Studies using molecular bacterial identification have associated ELVB sequences with BV, higher risk for human immunodeficiency virus acquisition and development of pelvic inflammatory disease in women. Given the clinical significance of this bacterium, we characterized the novel bacterium designated DNF00809[T] using biochemical, genotypic and phylogenetic analyses. DNF00809[T] was a coccobacillus that was non-motile, non-spore forming, asaccharolytic, proteolytic and indole negative. Fatty acid methyl ester analysis for DNF00809[T] indicated C14 : 0, C16 : 0, C16 : 0 dimethyl acetal and C18 : 1 cis9 to be the major fatty acids. Whole genomic DNA G+C content was 46.1 mol%. Phylogenetic and phylogenomic analyses indicate that DNF00809[T] represents a novel genus and novel species within the Eggerthellaceae family. We propose the name Umbribacter vaginalis gen. nov., sp. nov. with DNF00809[T] representing the type strain of this species (=DSM 118866[T]=CCUG77988[T]).},
}

*Phylogeny
Female
RNA, Ribosomal, 16S/genetics
Humans
*Vagina/microbiology
Fatty Acids/analysis/chemistry
DNA, Bacterial/genetics
Bacterial Typing Techniques
Base Composition
*Vaginosis, Bacterial/microbiology
Sequence Analysis, DNA
Adult

@article {pmid41042528,
year = {2025},
author = {Boiko, JR and Cooke, KR},
title = {Moving the needle on chronic GVHD of the lung.},
journal = {Blood advances},
volume = {9},
number = {19},
pages = {5038-5039},
doi = {10.1182/bloodadvances.2025017297},
pmid = {41042528},
issn = {2473-9537},
}

@article {pmid41042026,
year = {2025},
author = {Rafati, M and Wang, Y and Koppayi, AL and Savage, SA and Godley, LA and Williams, KM and Porter, C and Jones, K and Hicks, B and Spellman, SR and He, M and Atshan, R and Iwuagwu, C and Bolon, YT and Arrieta-Bolaños, E and Saultz, JN and Benjamin, CL and Lee, SJ and Saber, W and Gadalla, SM},
title = {Germline Pathogenic Variants in MUTYH Are Associated With Inferior Survival After Hematopoietic Cell Transplantation in Patients With Hematologic Malignancies or Disorders.},
journal = {American journal of hematology},
volume = {},
number = {},
pages = {},
doi = {10.1002/ajh.70093},
pmid = {41042026},
issn = {1096-8652},
support = {W81XWH-19-1-0241/CP/NCI NIH HHS/United States ; 75N910D00024/CA/NCI NIH HHS/United States ; U24CA076518//U.S. Public Health Service/ ; //Congressionally Directed Medical Research Programs/ ; },
}

@article {pmid41039543,
year = {2025},
author = {Bouras, E and Papagiannopoulos, CK and Mustafa, R and Sobieski, D and Schmit, SL and Wu, AH and Brenner, H and Li, CI and Chan, AT and Pellatt, AJ and Zheng, W and Keku, TO and Moreno, V and Um, CY and Van Guelpen, B and Phipps, AI and Pai, RK and Lewis, SJ and Martin, RM and Gunter, MJ and Peters, U and Dehghan, A and Tsilidis, KK},
title = {Investigating the relationship of plasma microRNAs and colorectal cancer risk using genetic evidence.},
journal = {BMC medicine},
volume = {23},
number = {1},
pages = {532},
pmid = {41039543},
issn = {1741-7015},
support = {C18281/A29019/CRUK_/Cancer Research UK/United Kingdom ; C18281/A29019/CRUK_/Cancer Research UK/United Kingdom ; },
mesh = {Humans ; *Colorectal Neoplasms/genetics/blood ; *MicroRNAs/blood/genetics ; Mendelian Randomization Analysis ; Male ; Genetic Predisposition to Disease ; Risk Factors ; Female ; Case-Control Studies ; Middle Aged ; },
abstract = {BACKGROUND: MicroRNAs (miRNAs) are short, single-stranded RNAs that function as post-transcriptional regulators of gene expression. Although circulating miRNAs have been linked to carcinogenesis, they have not yet been systematically investigated in relation to risk of colorectal cancer (CRC).

METHODS: We used Mendelian randomization (MR) and colocalization analyses to investigate the association of genetically predicted plasma miRNA concentrations (2083 miRNAs in 710 individuals) with risk of CRC (58,221 cases and 67,694 controls). For miRNAs associated with CRC risk, we also investigated their association with circulating plasma proteins (4907 proteins in 35,559 participants), bidirectionally, using MR. We performed pathway enrichment analysis (PEA) to explore downstream molecular pathways.

RESULTS: Associations of five miRNAs with CRC were found in MR and supported in colocalization analyses. Specifically, miR-146a-5p, miR-21-5p, and miR-4707-3p were positively, and miR-1908-5p and miR-6810-3p were inversely associated with CRC risk. Several protein associations were found for these miRNAs (range of proteins with P < 0.05: 78-796; 211 with FDR < 5%), and 11 pathways were identified in PEA, including regulation of Erb-B2 receptor tyrosine kinase 4 (miR-6810-3p) and insulin-like growth factor pathways (miR-1908-5p).

CONCLUSIONS: Our results support a potential implication of miR-146a-5p, miR-21-5p, miR-4707-3p, miR-1908-5p, and miR-6810-3p to CRC risk. However, their downstream effects should be elucidated before they can be utilized as preventive targets.},
}

Humans
*Colorectal Neoplasms/genetics/blood
*MicroRNAs/blood/genetics
Mendelian Randomization Analysis
Male
Genetic Predisposition to Disease
Risk Factors
Female
Case-Control Studies
Middle Aged

@article {pmid41038991,
year = {2025},
author = {Termini, CM},
title = {SLAM passes the haematopoietic stem cell identity test.},
journal = {Nature reviews. Molecular cell biology},
volume = {},
number = {},
pages = {},
pmid = {41038991},
issn = {1471-0080},
}

@article {pmid41037133,
year = {2025},
author = {Garzia, NA and Fest, S and Cushing-Haugen, K and Kensler, TW and Chavarro, JE and Tamimi, RM and Harris, HR},
title = {Childhood and adolescent dietary patterns and incidence of benign breast disease.},
journal = {Cancer causes & control : CCC},
volume = {},
number = {},
pages = {},
pmid = {41037133},
issn = {1573-7225},
support = {T32 CA094880/NH/NIH HHS/United States ; U01 HL145386/NH/NIH HHS/United States ; },
abstract = {PURPOSE: Childhood and adolescence may represent critical time windows for shaping future breast cancer risk. The association between early-life diet and breast cancer risk has been investigated, but few studies have examined the relation between adolescent diet and benign breast disease (BBD), an established breast cancer risk factor.

METHODS: Among 11,422 female Growing Up Today Study participants followed from 1996 to 2016 who completed food frequency questionnaires, we investigated the associations between adherence to three dietary patterns (Alternative Healthy Eating Index [AHEI], the Empirical Dietary Inflammatory Pattern [EDIP], and the Empirical Dietary Index for Hyperinsulinemia [EDIH]) at ages 10 and 14 years and self-reported BBD diagnosis. Cox proportional hazards models were used to estimates hazard ratios (HRs) and 95% confidence intervals (CIs).

RESULTS: Over 20 years of follow-up, 554 BBD cases were ascertained, with 259 biopsy-confirmed cases. Non-significant inverse associations were observed between greater adherence to the AHEI at age 10 and BBD risk (HR for fourth vs. first quartile = 0.74; 95% CI = 0.50-1.10; ptrend = 0.09), and between AHEI at age 14 and biopsy-confirmed BBD (HR for fourth vs. first quartile = 0.70; 95% CI = 0.48-1.03; ptrend = 0.10). Non-significant positive associations were observed between adherence to the EDIH at age 10 and (HR for fourth vs. first quartile = 1.49; 95% CI = 0.91-2.43; ptrend = 0.09) age 14 (HR for fourth vs. first quartile = 1.33; 95% CI = 0.97-1.82; ptrend = 0.09) and BBD risk. No associations were observed for EDIP. In secondary analyses, the association between EDIH at age 10 and BBD became statistically significant after accounting for change in dietary pattern quartile from age 10 to 14 (HR for fourth vs. first quartile = 2.14; 95% CI = 1.04-4.41). Adjustment for adult diet also strengthened associations between EDIH at age 10 and BBD risk (HR = 1.94; 95% CI = 1.12-3.37; ptrend = 0.007), and showed a significant inverse trend for AHEI (ptrend = 0.04).

CONCLUSION: These findings may suggest that greater early-life adherence to a healthier dietary pattern (AHEI) is associated with lower BBD risk, while consuming a more insulinemic dietary pattern (EDIH) may be associated with increased risk. Associations for EDIH at age 10 were statistically significant in secondary analyses accounting for dietary change and adult diet. Further research is needed to confirm these findings and clarify potential mechanisms.},
}

@article {pmid41036248,
year = {2025},
author = {Wallace, B and Dimitrov, D and Hébert-Dufresne, L and Berdahl, AM},
title = {Hotspot model shows how location-based superspreading accelerates and reshapes epidemics.},
journal = {PNAS nexus},
volume = {4},
number = {9},
pages = {pgaf299},
pmid = {41036248},
issn = {2752-6542},
abstract = {During outbreaks of many diseases, a small number of infected individuals are responsible for a disproportionately large number of new infections in what are called superspreading events (SSEs). SSEs broadly fall into four categories: (i) a single individual is more infectious due to biological differences in their infection or (ii) their greater degree of social connection; or (iii) the disease spreads more readily in certain high-risk facilities or (iv) "opportunistic" situations such as large gatherings. Existing modeling approaches work well to understand the first two of these but are not well suited to describe the dynamics in the latter two. Here, we introduce a simple agent-based model which captures the essential features of disease spreading more readily at high-risk locations or gatherings, which we call "hotspots." In our model, disease spreads and people recover as in a standard Susceptible, Infected, Recovered model, but agents are also characterized by individual probability of visiting the hotspot where disease spreads much more readily, providing an additional risk structure to the population. We use this model to investigate how an outbreak's probability, peak, and final size all vary under different risk heterogeneity assumptions. We show how some particular distributions of risk-taking behavior across the population heighten these effects. We complement our simulations with analytic results that provide theoretical bases for all of our numerical results and allow for robust interpretation and prediction.},
}

@article {pmid41035891,
year = {2025},
author = {Lawore, DC and Jena, S and Berard, AR and Birse, K and Lamont, A and Mackelprang, RD and Noel-Romas, L and Perner, M and Hou, X and Irungu, E and Mugo, N and Knodel, S and Muwonge, TR and Katabira, E and Hughes, SM and Levy, C and Calienes, FL and Hladik, F and Lingappa, JR and Burgener, AD and Green, LN and Brubaker, DK},
title = {Computational microbiome pharmacology analysis elucidates the anti-cancer potential of vaginal microbes and metabolites.},
journal = {Frontiers in microbiology},
volume = {16},
number = {},
pages = {1602217},
pmid = {41035891},
issn = {1664-302X},
abstract = {The vaginal microbiome's role in risk, progression, and treatment of female cancers has been widely explored. Yet, there remains a need to develop methods to understand the interaction of microbiome factors with host cells and to characterize their potential therapeutic functions. To address this challenge, we developed a systems biology framework we term the Pharmacobiome for microbiome pharmacology analysis. The Pharmacobiome framework evaluates similarities between microbes, microbial byproducts, and known drugs based on their impact on host transcriptomic cellular signatures. Here, we apply our framework to characterization of the Anti-Gynecologic Cancer Vaginal Pharmacobiome. Using published vaginal microbiome multi-omics data from the Partners PrEP clinical trial, we constructed vaginal epithelial gene signatures associated with each profiled vaginal microbe and metabolite. We compared these microbiome-associated host gene signatures to post-drug perturbation host gene signatures related to 35 FDA-approved anti-cancer drugs from the Library of Integrated Network-based Cellular Signatures database to identify vaginal microbes and metabolites with high statistical and functional similarity to these drugs. We found that select lactobacilli particularly L. crispatus and their metabolites, such as taurine, can regulate host gene expression in ways similar to certain anti-cancer drugs. Additionally, we experimentally tested our model prediction that taurine, a metabolite produced by L. crispatus, kills cancerous breast and endometrial cancer cells. Our study shows that the Pharmacobiome is a robust framework for characterizing the anti-cancer therapeutic potential of vaginal microbiome factors with generalizability to other cancers, microbiomes, and diseases.},
}

@article {pmid41034423,
year = {2025},
author = {Setiawan, T and Muhammad, JA and Marcellina, N and Wirawan, LM and Jun, N and Sari, IN and Oehler, VG and Kim, DW and Kwon, HY},
title = {Regulation of metabolic adaptation and leukemia progression by MUSASHI2-DEPTOR-KIF11 axis.},
journal = {Leukemia},
volume = {},
number = {},
pages = {},
pmid = {41034423},
issn = {1476-5551},
support = {2023R1A2C1003952//National Research Foundation of Korea (NRF)/ ; RS-2024-00437643//Korea Health Industry Development Institute (KHIDI)/ ; },
abstract = {Amino acid homeostasis is critical for leukemic cell survival, with the mTOR pathway playing a central role in sensing and responding to nutrient availability. DEPTOR, a component and negative regulator of mTOR complexes, has been extensively studied in solid tumors and multiple myeloma, but its role in acute myeloid leukemia (AML) remains unclear. Here, we identify DEPTOR as a key regulator of leukemia progression through its interaction with KIF11. DEPTOR expression is transcriptionally induced by ATF4 and post-transcriptionally stabilized by MSI2, which binds to DEPTOR mRNA and prevents its degradation. DEPTOR is highly expressed in leukemia stem cells (LSCs) and is associated with poor clinical outcomes. Functionally, DEPTOR loss impairs leukemogenesis in both AML and blast phase chronic myeloid leukemia (bpCML) models, without affecting normal hematopoietic stem cells. Mechanistically, DEPTOR stabilizes KIF11 by preventing its ubiquitination and proteasomal degradation, thereby ensuring proper mTORC1 localization and metabolic adaptation during nutrient stress. Collectively, our findings establish the MSI2/DEPTOR/KIF11 axis as a critical driver of leukemogenesis and a promising therapeutic target for aggressive myeloid leukemias.},
}

@article {pmid41034193,
year = {2025},
author = {Guo, B and Cai, Y and Kim, D and Smit, RAJ and Wang, Z and Iyer, KR and Hilliard, AT and Haessler, J and Tao, R and Broadaway, KA and Wang, Y and Pozdeyev, N and Stæger, FF and Yang, C and Vanderwerff, B and Patki, AD and Stalbow, L and Lin, M and Rafaels, N and Shortt, J and Wiley, L and Stanislawski, M and Pattee, J and Davis, L and Straub, PS and Shuey, MM and Cox, NJ and Lee, NR and Jørgensen, ME and Bjerregaard, P and Larsen, C and Hansen, T and Moltke, I and Meigs, JB and Stram, DO and Yin, X and Zhou, X and Chang, KM and Clarke, SL and Guarischi-Sousa, R and Lankester, J and Tsao, PS and Buyske, S and Graff, M and Raffield, LM and Sun, Q and Wilkens, LR and Carlson, CS and Easton, CB and Liu, S and Manson, JE and Marchand, LL and Haiman, CA and Mohlke, KL and Gordon-Larsen, P and Albrechtsen, A and Boehnke, M and Rich, SS and Manichaikul, A and Rotter, JI and Yousri, NA and Irvin, RM and , and , and Gignoux, C and North, KE and Loos, RJF and Assimes, TL and Peters, U and Kooperberg, C and Raghavan, S and Highland, HM and Darst, BF},
title = {Polygenic risk score for type 2 diabetes shows context-dependent effects across populations.},
journal = {Nature communications},
volume = {16},
number = {1},
pages = {8632},
pmid = {41034193},
issn = {2041-1723},
support = {R01HL143885//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; R01HD30880//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; R01HL151152//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; R01DK139598//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; R01HL142302//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; R01HL143885//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; R01HL163262//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; R01DK122503//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; R01HL151152//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; R01HL156991//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; R01DK123019//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; UM1DK078616//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; R00CA246063//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; R03CA287235//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; U01CA261339//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; R01HL174378//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; U54HG013243//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; PPM2-0226-170020//Qatar National Research Fund (QNRF)/ ; NPRP11S-0114-180299//Qatar National Research Fund (QNRF)/ ; NNF20OC0059313//Novo Nordisk Fonden (Novo Nordisk Foundation)/ ; NNF18CC0034900//Novo Nordisk Fonden (Novo Nordisk Foundation)/ ; P50CA097186//U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)/ ; P30CA015704//U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)/ ; },
mesh = {Humans ; *Diabetes Mellitus, Type 2/genetics/epidemiology ; *Multifactorial Inheritance/genetics ; Male ; Female ; *Genetic Predisposition to Disease ; Middle Aged ; Genome-Wide Association Study ; Risk Factors ; Aged ; Adult ; Polymorphism, Single Nucleotide ; Case-Control Studies ; Genetic Risk Score ; },
abstract = {Polygenic risk scores hold prognostic value for identifying individuals at higher risk of type 2 diabetes. However, further characterization is needed to understand the generalizability of type 2 diabetes polygenic risk scores in diverse populations across various contexts. We systematically characterize a multi-ancestry type 2 diabetes polygenic risk score among 244,637 cases and 637,891 controls across diverse populations from the Population Architecture Genomics and Epidemiology Study and 13 additional biobanks and cohorts. Polygenic risk score performance is context dependent, with better performance in those who are younger, male, without hypertension, and not obese or overweight. Additionally, the polygenic risk score is associated with various diabetes-related cardiometabolic traits and type 2 diabetes complications, suggesting its utility for stratifying risk of complications and identifying shared genetic architecture between type 2 diabetes and other diseases. These findings highlight the need to account for context when evaluating polygenic risk score as a tool for type 2 diabetes risk prognostication and the potentially generalizable associations of type 2 diabetes polygenic risk score with diabetes-related traits, despite differential performance in type 2 diabetes prediction across diverse populations. Our study provides a comprehensive resource to characterize a type 2 diabetes polygenic risk score.},
}

Humans
*Diabetes Mellitus, Type 2/genetics/epidemiology
*Multifactorial Inheritance/genetics
Male
Female
*Genetic Predisposition to Disease
Middle Aged
Genome-Wide Association Study
Risk Factors
Aged
Adult
Polymorphism, Single Nucleotide
Case-Control Studies
Genetic Risk Score

@article {pmid41033921,
year = {2025},
author = {Kishan, AU and Juarez Casillas, JE and Sargos, P and Kalbasi, TR and Chabaud, S and Brihoum, M and Sachdeva, A and Nikitas, JN and Ma, TM and Karasik, D and Ballas, LK and Lock, D and Valle, L and Taparra, K and Reiter, RE and Saigal, C and Chamie, K and Donin, N and Chin, AI and Rettig, M and Nickols, NG and Sun, Y and Spratt, D and Lamb, JM and Cao, M and Pommier, P and Steinberg, ML},
title = {Stereotactic Intensity-modulated Radiotherapy After Radical Prostatectomy (SCIMITAR): 4-Year Outcomes of a Phase 2 Clinical Trial.},
journal = {European urology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.eururo.2025.09.4149},
pmid = {41033921},
issn = {1873-7560},
abstract = {In the phase 2 SCIMITAR trial, stereotactic body radiotherapy (SBRT; 30-34 Gy in 5 fractions) was delivered to the prostatic fossa after radical prostatectomy in 100 patients requiring postoperative RT, with or without nodal RT and androgen deprivation therapy (ADT). The primary endpoint was 4-yr biochemical recurrence (BCR)-free survival (BCR-FS), with events defined as BCR (prostate-specific antigen ≥0.2 ng/ml above nadir), salvage ADT, or death. Outcomes were compared to individual patient data (IPD) from a phase 3 trial of conventionally fractionated RT (CFRT) using inverse probability of treatment weighting and Fine-Gray models. At median follow-up of 53 mo, the 4-yr BCR-FS rate was 60% (95% confidence interval [CI] 50-70%). The IPD analysis revealed that for men not receiving ADT, the risk of BCR was lower with SBRT than with CFRT (subdistribution hazard ratio [sHR] 0.49, 95% CI 0.29-0.84; p = 0.008). For men receiving ADT, there was no significant difference in BCR risk between SBRT and CFRT (sHR 1.58, 95% CI 0.81-3.11; p = 0.18), although the asymmetrically broad 95%CI and directionality of the point estimate suggest that a higher BCR risk with SBRT cannot be ruled out. The 4-yr cumulative incidence rates for late grade ≥2 gastrointestinal and genitourinary toxicities were 6.6% and 32%, respectively. At 48 mo, the proportion of patients reporting a decline of more than two times the minimal clinically important difference in urinary incontinence, urinary irritative/obstructive, bowel, and sexual domains was 23%, 6.7%, 13%, and 9.7%, respectively. SBRT to the prostatic fossa appears to be safe and effective through 4 yr.},
}

@article {pmid41032739,
year = {2025},
author = {Owens, CA and Ludmir, EB and Liu, Q and Qiu, W and Gupta, AC and Smith, SA and Rigaud, B and Brock, KK and Bates, JE and Meyers, TG and Paulino, AC and Peterson, CB and Kry, SF and Teepen, JC and Ronckers, CM and Neglia, JP and Leisenring, WM and Oeffinger, KC and Nathan, PC and Turcotte, LM and Hodgson, DC and Hudson, MM and Robison, LL and Moskowitz, CS and Armstrong, GT and Henderson, TO and Yasui, Y and Howell, RM},
title = {Colorectal-Specific Radiation Dose and Chemotherapy Risk for Subsequent Colorectal Malignancies in Childhood Cancer Survivors: A Childhood Cancer Survivor Study (CCSS) Report.},
journal = {Journal of clinical oncology : official journal of the American Society of Clinical Oncology},
volume = {},
number = {},
pages = {JCO2500531},
doi = {10.1200/JCO-25-00531},
pmid = {41032739},
issn = {1527-7755},
abstract = {PURPOSE: Among childhood cancer survivors, we evaluated not previously explored relationships between colorectal subsequent malignant neoplasm (SMN) incidence and colorectum-specific radiation dose metrics currently used in radiation therapy (RT) planning and expanded upon previously reported chemotherapy associations.

METHODS: The Childhood Cancer Survivor Study (CCSS) includes 5-year survivors of childhood cancer diagnosed between 1970 and 1999. RT was assessed as mean colorectal dose (MCD) and the percent volume (VX Gy) receiving ≥5, 10, 20, 30, and 40 Gy. Chemotherapy was assessed as cumulative doses for procarbazine and platinum agents, cyclophosphamide-equivalent doses for alkylating agents, and doxorubicin-equivalent doses for anthracyclines. Piecewise-exponential models and excess rate ratio (ERR) models evaluated dose-response relationships for the incidence of colorectal SMNs. Reference groups were those not receiving the assessed treatment(s).

RESULTS: Among 25,723 survivors (median follow-up = 28.5 years; range = 5.0-48.9), 104 colorectal SMNs were identified. A dose-response relationship was observed between MCD and colorectal SMN rates; incidence rate ratios (IRRs) for 10 to <20 Gy and ≥20 Gy were 3.6 (95% CI, 1.9 to 6.9) and 8.3 (95% CI, 3.9 to 17.8), respectively. When ≥20% of the colorectum volume was irradiated, IRRs increased with increasing volume. The V20 Gy IRRs were 3.8 (95% CI, 1.9 to 7.6), 4.9 (95% CI, 2.0 to 12.0), and 8.7 (95% CI, 3.5 to 21.6) for irradiated volumes of 20% to <40%, 40% to <80%, and ≥80%, respectively. The IRR was 1.8 (95% CI, 1.0 to 3.0) for doxorubicin-equivalent dose ≥250 mg/m[2], 3.7 (95% CI, 2.2 to 6.4) for cyclophosphamide-equivalent dose ≥6,000 mg/m[2], and 4.5 (95% CI, 2.0 to 10.1) for platinum dose ≥450 mg/m[2]. For procarbazine dose, the IRR was 6.3 (95% CI, 3.0 to 13.2) for 4,200 to <7,036 mg/m[2] and 9.0 (95% CI, 4.3 to 18.9) for ≥7,036 mg/m[2]. In the absence of RT, colorectal SMN rates increased with exposure to any platinum-based agent (IRR, 3.8 [95% CI, 1.1 to 12.7]), alkylator (IRR, 4.8 [95% CI, 1.6 to 14.4]), or procarbazine (IRR, 16.9 [95% CI, 5.9 to 48.8]). Colorectal SMN rates increased linearly with procarbazine dose (ERR per 1,000 mg/m[2] = 73.0 [95% CI, 26.4% to 119.6%]) and MCD (ERR per 1 Gy = 20.8 [95% CI, 9.0% to 32.5%]). Quadratic ERR models did not improve data fit compared with linear ERR models.

CONCLUSION: These RT and chemotherapy dose-response relationships can better inform contemporary RT planning for pediatric patients and surveillance guidelines for high-risk survivors.},
}

@article {pmid41032722,
year = {2025},
author = {Curtis, DJ and Reynolds, J and Hill, GR},
title = {Cyclophosphamide and Cyclosporin for GVHD Prevention. Reply.},
journal = {The New England journal of medicine},
volume = {393},
number = {13},
pages = {1350-1351},
doi = {10.1056/NEJMc2511563},
pmid = {41032722},
issn = {1533-4406},
}

@article {pmid41032518,
year = {2025},
author = {Corey, L},
title = {Operation Warp Speed offers a roadmap for improving the efficiency of bench to bedside medical advances.},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
volume = {122},
number = {40},
pages = {e2502975122},
doi = {10.1073/pnas.2502975122},
pmid = {41032518},
issn = {1091-6490},
support = {UM1 AI068614-14//HHS | NIH | National Institute of Allergy and Infectious Diseases (NIAID)/ ; },
}

@article {pmid41032288,
year = {2025},
author = {Blechter, B and Wang, X and Dai, J and Karsonaki, C and Shi, J and Shiraishi, K and Choi, J and Matsuo, K and Chen, TY and Hung, RJ and Chen, K and Shu, XO and Kim, YT and Choudhury, PP and Williams, J and Landi, MT and Lin, D and Zheng, W and Yin, Z and Zhou, B and Wang, J and Seow, WJ and Song, L and Chang, IS and Hu, W and Chien, LH and Cai, Q and Hong, YC and Kim, HN and Wu, YL and Wong, MP and Richardson, BD and Li, S and Zhang, T and Breeze, C and Wang, Z and Bassig, BA and Kim, JH and Albanes, D and Wong Sm, JY and Shin, MH and Chung, LP and Yang, Y and Zheng, H and Dai, H and Yatabe, Y and Zhang, XC and Kim, YC and Caporaso, NE and Chang, J and Ho, JCM and Daigo, Y and Momozawa, Y and Kamatani, Y and Kobayashi, M and Okubo, K and Honda, T and Hosgood, HD and Kunitoh, H and Watanabe, SI and Miyagi, Y and Matsumoto, S and Horinouchi, H and Tsuboi, M and Hamamoto, R and Goto, K and Takahashi, A and Goto, A and Minamiya, Y and Hara, M and Nishida, Y and Takeuchi, K and Wakai, K and Matsuda, K and Murakami, Y and Shimizu, K and Suzuki, H and Saito, M and Ohtaki, Y and Tanaka, K and Wu, T and Wei, F and Machiela, MJ and Kim, YH and Oh, IJ and Lee, VHF and Chang, GC and Chen, KY and Su, WC and Chen, YM and Seow, A and Park, JY and Kweon, SS and Gao, YT and Liu, J and Schwartz, AG and Houlston, R and Gorlov, IP and Wu, X and Yang, P and Lam, S and Tardon, A and Chen, C and Bojesen, SE and Johansson, M and Risch, A and Bickeböller, H and Ji, BT and Wichmann, HE and Christiani, DC and Rennert, G and Arnold, SM and Brennan, P and McKay, J and Field, JK and Davies, MPA and Shete, SS and Le Marchand, L and Liu, G and Andrew, AS and Kiemeney, LA and Zienolddiny-Narui, S and Grankvist, K and Cox, A and Taylor, F and Yuan, JM and Lazarus, P and Schabath, MB and Aldrich, MC and Jeon, HS and Jiang, SS and Chen, CH and Hsiao, CF and Hu, Z and Burdett, L and Yeager, M and Hutchinson, A and Hicks, B and Liu, J and Berndt, SI and Wu, W and Wang, J and Li, Y and Choi, JE and Park, KH and Sung, SW and Kang, CH and Wang, WC and Xu, J and Guan, P and Tan, W and Yu, CJ and Yang, G and Sihoe, ADL and Choi, YY and Park, IK and Hung, HH and Vermeulen, RCH and Cheng, I and Wu, J and Tsai, FY and Chan, JKC and Li, J and Lin, HC and Liu, J and Song, B and Sawada, N and Yamaji, T and Wyatt, K and Ma, H and Zhu, M and Wang, Y and Qi, T and Li, X and Ren, Y and Chao, A and Iwasaki, M and Zhu, J and Wu, G and Chen, CY and ScD, CC and Yang, PC and Stevens, VL and Fraumeni, JF and Lin, K and Walters, RG and Chen, Z and Chatterjee, N and Gorlova, OY and Amos, CI and Shen, H and Hsiung, CA and Chanock, SJ and Rothman, N and Kohno, T and Lan, Q and Zhang, H},
title = {Stratifying lung adenocarcinoma risk with multi-ancestry polygenic risk scores in East Asian never-smokers.},
journal = {Journal of the National Cancer Institute},
volume = {},
number = {},
pages = {},
doi = {10.1093/jnci/djaf272},
pmid = {41032288},
issn = {1460-2105},
abstract = {BACKGROUND: Lung adenocarcinoma (LUAD) in never-smokers is a major public health burden, especially among East Asian women. Polygenic risk scores (PRSs) are promising for risk stratification but are primarily developed in European-ancestry populations. We aimed to develop and validate single- and multi-ancestry PRSs for East Asian never-smokers to improve LUAD risk prediction.

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

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

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

@article {pmid41031719,
year = {2025},
author = {Nizam, A and Nguyen, CB and Li, J and Zabor, EC and Msaouel, P and Jiang, CY and Alhalabi, O and Oh, E and Davidsohn, MP and Epstein, IB and Bakaloudi, DR and Talukder, R and Jindal, T and Taylor, AK and Glover, MJ and Khaki, AR and Lemke, E and Mabey, H and Abuqayas, B and Jang, A and Brown, JR and Evans, ST and Pywell, C and Basu, A and Bilen, MA and Barata, PC and Zakharia, Y and Milowsky, MI and Kilari, D and Hoimes, CJ and Shah, SA and Emamekhoo, H and Davis, NB and Gupta, S and Grivas, P and Bellmunt, J and Campbell, MT and Alva, AS and Koshkin, VS},
title = {Treatment-Related Adverse Events and Associated Outcomes in Patients With Advanced Urothelial Carcinoma Treated With Enfortumab Vedotin: Analysis of the UNITE Study.},
journal = {Cancer medicine},
volume = {14},
number = {19},
pages = {e71284},
pmid = {41031719},
issn = {2045-7634},
mesh = {Humans ; Male ; Female ; Aged ; Retrospective Studies ; Middle Aged ; *Antibodies, Monoclonal/adverse effects ; Aged, 80 and over ; *Immunoconjugates/adverse effects/therapeutic use/administration & dosage ; *Urologic Neoplasms/drug therapy/mortality/pathology ; *Carcinoma, Transitional Cell/drug therapy/mortality/pathology ; Treatment Outcome ; *Antineoplastic Agents, Immunological/adverse effects ; *Urinary Bladder Neoplasms/drug therapy/mortality/pathology ; },
abstract = {INTRODUCTION: Enfortumab vedotin-ejfv (EV), an antibody-drug conjugate approved for advanced urothelial carcinoma (aUC), has limited real-world safety data and no validated predictive biomarkers. Retrospective studies suggest higher objective response rates (ORR) among patients developing EV-related dermatologic toxicities, but survival implications remain unclear. This analysis assessed the safety of EV monotherapy and the impact of dermatologic and neurologic toxicities on efficacy outcomes in a multi-institutional cohort.

MATERIALS AND METHODS: UNITE is a multicenter, retrospective study across 16 US sites of patients with aUC treated with targeted agents, including EV. Primary endpoints were the incidence of EV treatment-related adverse events (TRAEs, any grade) and TRAE-related treatment modifications. Secondary endpoints included a comparison of ORR, progression-free survival (PFS), and overall survival (OS) between patients with and without dermatologic toxicities and neuropathy. To reduce immortal time bias, Cox regression models incorporated TRAEs as time-dependent covariates to adjust for EV treatment duration as well as Eastern Cooperative Oncology Group performance status (ECOG PS), hemoglobin, and liver metastases.

RESULTS: Between 2018 and 2023, 485 patients with aUC received > 1 dose of EV monotherapy. Most (67%) received > 2 prior therapy lines. Any grade TRAEs occurred in 77%, most frequently neuropathy (36%) and dermatologic toxicities (27%); 57% required treatment modification and 21% discontinued EV, primarily due to neuropathy (9%) and fatigue (3%). Patients with dermatologic toxicities and neuropathy had higher ORR (56% vs. 42%; p = 0.007 and 64% vs. 35%; p < 0.0001, respectively). Neuropathy was independently associated with improved OS (HR 0.66; 95% CI 0.50-0.87; p = 0.002); dermatologic TRAEs were not associated with PFS or OS benefit.

CONCLUSIONS: EV safety outside clinical trials was consistent with prior reports, with no new signals. Treatment modifications were most often due to neuropathy, dermatologic toxicities, and fatigue. Both dermatologic toxicities and neuropathy correlated with higher ORR, but only neuropathy was independently associated with improved OS.},
}

Humans
Male
Female
Aged
Retrospective Studies
Middle Aged
*Antibodies, Monoclonal/adverse effects
Aged, 80 and over
*Immunoconjugates/adverse effects/therapeutic use/administration & dosage
*Urologic Neoplasms/drug therapy/mortality/pathology
*Carcinoma, Transitional Cell/drug therapy/mortality/pathology
Treatment Outcome
*Antineoplastic Agents, Immunological/adverse effects
*Urinary Bladder Neoplasms/drug therapy/mortality/pathology

@article {pmid41031512,
year = {2025},
author = {Chalitsios, CV and Markozannes, G and Aglago, EK and Berndt, SI and Buchanan, DD and Campbell, PT and Cao, Y and Chan, AT and Dimou, N and Drew, DA and French, AJ and Georgeson, P and Giannakis, M and Gruber, SB and Gunter, MJ and Harrison, TA and Hoffmeister, M and Hsu, L and Huang, WY and Hullar, MA and Huyghe, JR and Lynch, BM and Moreno, V and Murphy, N and Newton, CC and Nowak, JA and Obón-Santacana, M and Ogino, S and Qu, C and Schmit, SL and Steinfelder, RS and Sun, W and Thomas, CE and Toland, AE and Trinh, QM and Ugai, T and Um, CY and Van Guelpen, B and Zaidi, SH and Schoen, RE and Woods, MO and Brenner, H and Andreson, L and Pellatt, AJ and Peters, U and Phipps, AI and Tsilidis, KK},
title = {Physical activity and molecular subtypes of colorectal cancer: a pooled observational analysis and mendelian randomisation study.},
journal = {JNCI cancer spectrum},
volume = {},
number = {},
pages = {},
doi = {10.1093/jncics/pkaf095},
pmid = {41031512},
issn = {2515-5091},
abstract = {BACKGROUND: Physical activity is associated with lower colorectal cancer (CRC) risk, but its association with molecular subtypes defined by genetic and epigenetic alterations of the disease is unclear. Such information may enhance the understanding of the mechanisms related to the benefits of physical activity.

METHODS: Pooled observational (ncases=5,386, ncontrols=6,798; nstudies=5) and genome-wide association data (ncases=8,178, ncontrols=10,472; nstudies=5) were utilised. We used multivariable logistic regression models and Mendelian randomisation (MR) to assess the association between physical activity and the risk of CRC subtypes defined by individual tumour markers (and marker combinations), namely microsatellite instability (MSI) status, CpG island methylator phenotype (CIMP) status, BRAF and KRAS mutations. We used case-only analysis to test for differences between molecular subtypes. We applied Bonferroni correction to account for multiple tests.

RESULTS: In the pooled observational analysis, higher levels of physical activity were associated with lower CRC risk (ORObs-per 1SD=0.94, 95%CI 0.90-0.97), with an association that was stronger in males (ORObs-per 1SD=0.91, 95%CI 0.87-0.96) than in females (ORObs-per 1SD=0.97, 95%CI 0.91-1.03) (Pinteraction=0.04). Higher physical activity was associated with a lower risk of CRC across all molecular subtypes, especially in males. There was no difference in the associations by subtypes by pooled observational or MR analyses. The findings did not differ by study design, anatomical site, and early or late age onset of CRC.

CONCLUSIONS: Our findings suggest that physical activity is not differentially associated with the four major molecular subtypes involved in colorectal carcinogenesis, indicating that its benefits extend broadly across colorectal cancer pathogenesis.},
}

@article {pmid41028200,
year = {2025},
author = {Cheung, KJ and Horne-Badovinac, S},
title = {Publisher Correction: Collective cell migration modes in development, tissue repair and cancer.},
journal = {Nature reviews. Molecular cell biology},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41580-025-00911-7},
pmid = {41028200},
issn = {1471-0080},
}

@article {pmid41028170,
year = {2025},
author = {Bot, A and Scharenberg, A and Friedman, K and Guey, L and Hofmeister, R and Andorko, JI and Klichinsky, M and Neumann, F and Shah, JV and Swayer, AJ and Trudeau, K and Weissman, D and Stephan, MT and Buchholz, CJ and June, CH},
title = {In vivo chimeric antigen receptor (CAR)-T cell therapy.},
journal = {Nature reviews. Drug discovery},
volume = {},
number = {},
pages = {},
pmid = {41028170},
issn = {1474-1784},
abstract = {Chimeric antigen receptor (CAR)-T cell therapy has transformed the outcomes of patients with haematological malignancies, yet its use is limited by labour-intensive manufacturing, constrained production capacity and variable clinical performance. In vivo CAR-T cell engineering, in which CAR-T cells are generated directly inside the patient's body, seeks to overcome these challenges by eliminating the need for ex vivo cell processing and complex logistics, as well as improve clinical performance. Recent advances in virology, RNA medicines and nanotechnology have catalysed a radical overhaul of this approach, which uses targeted delivery systems such as lentiviral vectors and lipid nanoparticles to introduce CAR-encoding genetic material into endogenous T cells. Early clinical studies have shown efficient transduction, sustained CAR expression and initial signs of antitumour activity, establishing proof of concept. This Review explores the underlying technologies - including RNA delivered by lipid nanoparticles and engineered viral vectors - and discusses how they are being adapted to develop more broadly applicable, scalable, safe and effective CAR-T cell therapies. By removing the need for ex vivo manipulation and chemotherapeutic conditioning, this strategy could enable the wider application of CAR-T cell therapies not just to blood cancers but to autoimmune diseases for which ex vivo CAR-T cell therapies have shown strong promise, such as systemic lupus erythematosus.},
}

@article {pmid41027579,
year = {2025},
author = {Cheng, GS and Campbell, AP and Xie, H and Ogimi, C and Waghmare, A and Kuypers, J and Nichols, WG and Carpenter, P and Corey, L and Callais, C and Sandmaier, BM and Stevens-Ayers, T and Jerome, KR and Chien, JW and Leisenring, WM and Englund, JA and Boeckh, M},
title = {Respiratory Virus Infections and Pulmonary Impairment after Allogeneic Hematopoietic Cell Transplantation.},
journal = {The Journal of infectious diseases},
volume = {},
number = {},
pages = {},
doi = {10.1093/infdis/jiaf503},
pmid = {41027579},
issn = {1537-6613},
abstract = {BACKGROUND: Respiratory virus infections (RVI) are common after hematopoietic cell transplantation (HCT), but their effect on pulmonary outcomes, including bronchiolitis obliterans syndrome (BOS), and mortality is poorly defined.

METHODS: Prospective cohort study of 471 allogeneic HCT recipients transplanted in the pre-COVID-19 pandemic era in an academic cancer center. Participants were prospectively followed for one year with serial handheld spirometry, symptom questionnaires, and multiplex 11-virus PCR. Pulmonary function testing occurred at recommended intervals. Cox proportional hazard and generalized estimating equation models were used to estimate associations between RVI and weekly spirometry with late airflow obstruction (AFO), BOS, and overall mortality.

RESULTS: The one-year cumulative incidence of at least one RVI was 62%; lower respiratory tract disease (LRTD) occurred in 7.6% of patients. Late AFO developed in 15.6% of patients and BOS in 3.9% of patients. Any symptomatic viral upper respiratory tract infections (URTI) were associated with AFO (adjusted HR [aHR] 1.87, 95% CI 1.11-3.16) and BOS (aHR 2.65, 95% CI 1.02-6.91). Individually, PIV-3 URTI were associated with AFO (aHR 2.83, 95% CI 1.01-7.97) and RSV URTI were associated with BOS (aHR 6.32, 95% CI 2.04-19.6). Short-term airflow decline was associated with AFO. Any LRTD (aHR 3.49, 95% CI 2.18-5.57), as well as symptomatic influenza URTI (aHR 2.68, 95% CI 1.52-4.72), were associated with mortality.

CONCLUSIONS: RVI after HCT, particularly those caused by RSV, PIV-3 and influenza, increase the risk of pulmonary impairment and mortality. These infections should be targeted for specific anti-viral approaches and intensified monitoring for late onset pulmonary disease.},
}

@article {pmid41027557,
year = {2025},
author = {Spellman, SR and Xu, K and Oloyede, T and Ahn, KW and Akhtar, OS and Bolon, YT and Broglie, L and Bloomquist, J and Bupp, C and Chen, M and Devine, SM and Jurdi, NE and Hamadani, M and Hengen, M and Huppler, AH and Jaglowski, S and Kuxhausen, M and Lee, SJ and Moskop, A and Page, KM and Pasquini, MC and Pérez, WS and Phelan, R and Rizzo, D and Saber, W and Stefanski, HE and Steinert, P and Tuschl, E and Visotcky, A and Vogel, R and Auletta, JJ and Shaw, BE and Allbee-Johnson, M},
title = {Corrigendum to: Current Activity Trends and Outcomes in Hematopoietic Cell Transplantation and Cellular Therapy - A Report from the CIBMTR, Transplantation and Cellular Therapy, 31:8, August 2025, 505-532; Article Number: JTCT-S-25-00377.},
journal = {Transplantation and cellular therapy},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jtct.2025.09.001},
pmid = {41027557},
issn = {2666-6367},
}

@article {pmid40924543,
year = {2025},
author = {Baele, G and Carvalho, LM and Brusselmans, M and Dudas, G and Ji, X and McCrone, JT and Lemey, P and Suchard, MA and Rambaut, A},
title = {HIPSTR: highest independent posterior subtree reconstruction in TreeAnnotator X.},
journal = {Bioinformatics (Oxford, England)},
volume = {41},
number = {10},
pages = {},
doi = {10.1093/bioinformatics/btaf488},
pmid = {40924543},
issn = {1367-4811},
support = {//Research Foundation-Flanders/ ; },
mesh = {*Software ; *Phylogeny ; *SARS-CoV-2/genetics/classification ; Bayes Theorem ; *Ebolavirus/genetics/classification ; Algorithms ; Humans ; *Computational Biology/methods ; COVID-19/virology ; },
abstract = {SUMMARY: In Bayesian phylogenetic and phylodynamic studies, it is common to summarize the posterior distribution of trees with a time-calibrated summary phylogeny. While the maximum clade credibility (MCC) tree is often used for this purpose, we here show that a novel summary tree method-the highest independent posterior subtree reconstruction, or (HIPSTR)-contains consistently higher supported clades over MCC. We also provide faster computational routines for estimating both summary trees in an updated version of TreeAnnotator X, an open-source software program that summarizes the information from a sample of trees and returns many helpful statistics such as individual clade credibilities contained in the summary tree.

RESULTS: HIPSTR and MCC reconstructions on two Ebola virus and two SARS-CoV-2 datasets show that HIPSTR yields summary trees that consistently contain clades with higher support compared to MCC trees. The MCC trees regularly fail to include several clades with very high posterior probability (≥0.95) as well as a large number of clades with moderate to high posterior probability (≥50%), whereas HIPSTR-in particular its majority-rule extension MrHIPSTR-achieves near-perfect performance in this respect. HIPSTR and MrHIPSTR also exhibit favourable computational performance over MCC in TreeAnnotator X. Comparison to the recent CCD0-MAP algorithm yielded mixed results and requires a more in-depth investigation in follow-up studies.

TreeAnnotator X is available as part of the BEAST X (v10.5.0) software package, available at https://github.com/beast-dev/beast-mcmc/releases, and on Zenodo (DOI: https://doi.org/10.5281/zenodo.4895234).},
}

*Software
*Phylogeny
*SARS-CoV-2/genetics/classification
Bayes Theorem
*Ebolavirus/genetics/classification
Algorithms
Humans
*Computational Biology/methods
COVID-19/virology

@article {pmid41027157,
year = {2025},
author = {Dominguez Islas, CP and Magaret, CA and Molitor, C and Serebryannyy, L and Narpala, S and Castro, M and Posavad, CM and Roberts, PC and Lyke, KE and Atmar, RL and Janes, H and Deming, ME},
title = {SARS-CoV-2 spike sequence-based distance as a marker of binding antibody response to COVID-19 vaccines.},
journal = {Vaccine},
volume = {65},
number = {},
pages = {127738},
doi = {10.1016/j.vaccine.2025.127738},
pmid = {41027157},
issn = {1873-2518},
abstract = {COVID-19 vaccines based on ancestral SARS-CoV-2 have proven highly effective at reducing the risk of illness, especially severe disease. Both binding and neutralizing antibodies have been demonstrated to be strong predictors of the level of vaccine efficacy (VE). Both VE and vaccine-induced antibody responses have been shown to be lower against emergent SARS-CoV-2 viruses; therefore, predicting COVID-19 VE against emergent viruses is critical for decision-making regarding the composition of new vaccines. The data needed to enable such prediction are unclear. We report on 728 individuals without prior SARS-CoV-2 infection who received primary vaccination with ancestral-virus-based mRNA and vector-based COVID-19 vaccines and who were boosted in a homologous or heterologous fashion with mRNA, vector, or protein-based COVID-19 vaccines including a bivalent B.1.351 mRNA vaccine. Post-prime and post-boost binding antibody responses were used to evaluate the extent and drivers of variability in these responses to 22 SARS-CoV-2 Spike antigens from viruses that emerged between 2020 and 2021. We evaluated how well proteomic distance between the vaccine and assay Spike antigen predicted the vaccine-induced antibody response. Following primary vaccination, antibody responses varied across Spike antigens and were, on average, 36 % lower per 10-amino acid (AA) difference between the vaccine and assay Spike antigen (95 % CI: 30 % to 43 %). The geometric mean antibody response to a given antigen was nearly perfectly predicted by the sequence-based distance of the antigen to the vaccine. Post-boost responses were less variable across antigens and weakly associated with Spike distance (17 % lower per 10-AA difference; 95 % CI: 14 % to 20 %). The high variability in binding antibodies across individuals was only partially explained by participant characteristics. Given that populations now have experienced multiple rounds of prior vaccination and infection, measurement of vaccine-induced antibody responses from representative populations will likely be needed to predict the efficacy of COVID-19 vaccines against future strains.},
}

@article {pmid41025350,
year = {2025},
author = {Jakubek, YA and Smith, AP and Leng, XI and Hall, ME and Ezzat, D and Pershad, Y and Collins, JM and Uddin, MM and Fardo, DW and Natarajan, P and Bick, AG and Kitzman, JO and Honigberg, MC and Hayden, KM and Manson, JE and Jaiswal, S and Whitsel, EA and Reiner, AP},
title = {Clonal hematopoiesis of indeterminate potential and the risk of cognitive impairment in the Women's Health Initiative Memory Study.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {21},
number = {10},
pages = {e70737},
pmid = {41025350},
issn = {1552-5279},
support = {//WHI/ ; /NH/NIH HHS/United States ; 75N92021D00001/HL/NHLBI NIH HHS/United States ; 75N92021D00002/HL/NHLBI NIH HHS/United States ; 75N92021D00003/WH/WHI NIH HHS/United States ; 75N92021D00004/WH/WHI NIH HHS/United States ; 75N92021D00005/WH/WHI NIH HHS/United States ; },
mesh = {Humans ; Female ; *Cognitive Dysfunction/genetics/epidemiology ; Aged ; *Clonal Hematopoiesis/genetics ; Risk Factors ; Women's Health ; *Dementia/genetics/epidemiology ; Aged, 80 and over ; Middle Aged ; Proportional Hazards Models ; Incidence ; },
abstract = {INTRODUCTION: Clonal hematopoiesis of indeterminate potential (CHIP) confers an increased risk of several chronic aging-related diseases. Paradoxically, CHIP was associated with lower risk of dementia in recent studies.

METHODS: We examined associations between baseline CHIP and incident mild cognitive impairment (MCI) and/or probable dementia in the Women's Health Initiative Memory Study. CHIP was detected using blood-based targeted sequencing. Cox proportional hazards models examined time to onset of cognitive impairment, adjusting for traditional risk factors.

RESULTS: Using a conventional variant allele fraction (VAF) threshold of 2%, CHIP was not associated with incident cognitive impairment. The presence of larger CHIP clone (VAF ≥ 8%) was associated with a lower incidence of adjudicated probable dementia (hazard ratio = 0.62 [95% confidence interval = 0.41 to 0.94], p = 0.025), while the association with the composite outcome MCI/probable dementia was weaker and overlapped 1.0.

DISCUSSION: The association of CHIP with lower risk of cognitive impairment in postmenopausal women may be dependent on VAF and impairment severity.

HIGHLIGHTS: The WHIMS comprises ∼5000 postmenopausal women, followed for up to 25 years. CHIP was associated with reduced risk of adjudicated probable dementia in WHIMS. Large CHIP clones (> 8% VAF), but not small clones (<8% VAF), showed an association. CHIP was not associated with MCI in the WHIMS cohort.},
}

Humans
Female
*Cognitive Dysfunction/genetics/epidemiology
Aged
*Clonal Hematopoiesis/genetics
Risk Factors
Women's Health
*Dementia/genetics/epidemiology
Aged, 80 and over
Middle Aged
Proportional Hazards Models
Incidence

@article {pmid41024277,
year = {2025},
author = {Gafken, PR and Paczesny, S},
title = {Blood proteomics for quantitative biomarkers of cellular therapies.},
journal = {Biomarker research},
volume = {13},
number = {1},
pages = {120},
pmid = {41024277},
issn = {2050-7771},
support = {P30CA015704/CA/NCI NIH HHS/United States ; R01CA168814/CA/NCI NIH HHS/United States ; R21AI178981//National Institute of Allergy and Infectious Diseases/ ; R01HL158096/HL/NHLBI NIH HHS/United States ; },
abstract = {Cellular therapies for several blood cancers particularly of lymphoid origin have made remarkable leaps forward. In parallel, blood proteomics, specifically quantitative proteomics, has been a powerful tool for identifying and quantifying protein biomarkers associated with cellular therapies, providing insights into treatment efficacy and toxicity. Both mass spectrometry (MS)-based proteomics and large-scale affinity-based platforms such as Olink and SomaScan have been increasingly implemented in research and clinical laboratories to identify and quantify candidate biomarkers in the blood. Biomarkers are used for risk stratification, early diagnosis, prognosis, and for treatment response prediction and monitoring in context of treatment efficacy and toxicity. These biomarkers might facilitate timely and selective therapeutic intervention and understand pathogenesis mechanisms of responses and adverse events. They are anticipated to undergo faster transition from bench to bedside soon. This review article summarizes recent technical progresses in clinical proteomics. The review also provides current information on validated biomarkers in the field of cellular therapies.},
}

@article {pmid41022768,
year = {2025},
author = {Liu, P and Li, JJ},
title = {mcRigor: a statistical method to enhance the rigor of metacell partitioning in single-cell data analysis.},
journal = {Nature communications},
volume = {16},
number = {1},
pages = {8602},
pmid = {41022768},
issn = {2041-1723},
support = {R35GM140888//U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS)/ ; 1846216//NSF | BIO | Division of Biological Infrastructure (DBI)/ ; 2113754//NSF | Directorate for Mathematical & Physical Sciences | Division of Mathematical Sciences (DMS)/ ; 2022-249355//Silicon Valley Community Foundation (SVCF)/ ; },
mesh = {*Single-Cell Analysis/methods ; Algorithms ; Humans ; RNA-Seq ; Reproducibility of Results ; Gene Expression Profiling/methods ; *Computational Biology/methods ; Software ; },
abstract = {In single-cell data analysis, addressing sparsity often involves aggregating the profiles of homogeneous single cells into metacells. However, existing metacell partitioning methods lack checks on the homogeneity assumption and may aggregate heterogeneous single cells, potentially biasing downstream analysis and leading to spurious discoveries. To fill this gap, we introduce mcRigor, a statistical method to detect dubious metacells, which are composed of heterogeneous single cells, and optimize the hyperparameter(s) of a metacell partitioning method. The core of mcRigor is a feature-correlation-based statistic that measures the heterogeneity of a metacell, with its null distribution derived from a double permutation scheme. As an optimizer for existing metacell partitioning methods, mcRigor has been shown to improve the reliability of discoveries in single-cell RNA-seq and multiome (RNA + ATAC) data analyses, such as uncovering differential gene co-expression modules, enhancer-gene associations, and gene temporal expression. Moreover, mcRigor enables benchmarking and selection of the most suitable metacell partitioning method with optimized hyperparameter(s) tailored to a specific dataset, ensuring reliable downstream analysis. Our results indicate that among existing metacell partitioning methods, MetaCell and SEACells consistently outperform MetaCell2 and SuperCell, albeit with the trade-off of longer runtimes.},
}

*Single-Cell Analysis/methods
Algorithms
Humans
RNA-Seq
Reproducibility of Results
Gene Expression Profiling/methods
*Computational Biology/methods
Software

@article {pmid41021636,
year = {2025},
author = {Giersch, RM and Sevigny, JK and Weinandt, SA and Mayo, C and Garrett, FES and Tindbaek, K and Yonemitsu, MA and Hart, SFM and Metzger, MJ},
title = {Variation in natural infection outcomes and cancer cell release from soft-shell clams (Mya arenaria) with bivalve transmissible neoplasia.},
journal = {PLoS pathogens},
volume = {21},
number = {9},
pages = {e1013537},
doi = {10.1371/journal.ppat.1013537},
pmid = {41021636},
issn = {1553-7374},
support = {R01 CA255712/CA/NCI NIH HHS/United States ; T32 GM007270/GM/NIGMS NIH HHS/United States ; T32 HG000035/HG/NHGRI NIH HHS/United States ; },
abstract = {Bivalve transmissible neoplasias (BTNs) are leukemia-like cancers found in at least 10 bivalve species, in which the cancer cells themselves transfer from one individual to another, spreading as an unusual form of infectious disease. Before the infectious etiology was known, there were reports of lethality and outbreaks of cancer in the soft-shell clam (Mya arenaria) on the east coast of North America. Using sensitive and specific qPCR assays, we followed the outcomes of BTN in naturally-infected soft-shell clams from Maine, USA. We observed variable outcomes, with about half of clams (9/21) progressing to high levels of cancer and death, about half exhibiting long-term non-progression (11/21), and a single animal showing regression of cancer. We also observe a significant decrease in survival in animals that progress to >10% cancer in their hemolymph, while we see no effect on survival in clams with BTN that are long-term non-progressors. As most bivalves do not physically contact each other, and BTN cells can survive in seawater, it has been proposed that BTN is spread through release of cancer cells into the water. We used qPCR to detect BTN-specific sequences in environmental DNA (eDNA) in the tanks of animals throughout this experiment. We show that BTN-specific eDNA (likely from released cancer cells) can be detected in tank water of most clams with >24% cancer in their hemolymph, but not below this level. This detection of BTN eDNA is variable and occurs in bursts, but in clams with >24% cancer, the detection of BTN eDNA correlates with progression of the cancer in the hemolymph. This study demonstrates the lethality of BTN, but the observation that about half of clams with BTN do not progress to death provides evidence suggesting that there may be a block to the progression of BTN in a large portion of clams in a population with this enzootic disease. This study also further supports the hypothesis that BTN cells transmit through seawater and provides insights into the mechanisms of the transmission dynamics.},
}

@article {pmid41021323,
year = {2025},
author = {Etzioni, R and Owens, L},
title = {Learning from prostate cancer statistics.},
journal = {CA: a cancer journal for clinicians},
volume = {},
number = {},
pages = {},
doi = {10.3322/caac.70037},
pmid = {41021323},
issn = {1542-4863},
}

@article {pmid41019149,
year = {2025},
author = {Mohty, M and Banerjee, R},
title = {Networking for a successful career in clinical hematology: a strategic approach.},
journal = {Clinical hematology international},
volume = {7},
number = {3},
pages = {20-23},
pmid = {41019149},
issn = {2590-0048},
abstract = {Networking is fundamental to career development in clinical hematology, providing avenues for knowledge exchange, collaborations, and professional growth. This manuscript examines specific strategies for networking within this specialized field, detailing effective platforms, strategies, overcoming challenges, and illustrating real-world success stories. References to key studies and expert opinions underscore the importance of building a robust professional network through in-person and online activities. An extensive review of literature highlights how networking contributes to scientific collaboration, mentorship, career opportunities, and the dissemination of cutting-edge hematological research.},
}

@article {pmid41018806,
year = {2025},
author = {Li, S and Gilbert, PB and Duan, R and Luedtke, A},
title = {Data fusion using weakly aligned sources.},
journal = {Journal of the American Statistical Association},
volume = {},
number = {},
pages = {},
pmid = {41018806},
issn = {0162-1459},
support = {DP2 LM013340/LM/NLM NIH HHS/United States ; R37 AI054165/AI/NIAID NIH HHS/United States ; UM1 AI068635/AI/NIAID NIH HHS/United States ; },
abstract = {We introduce a new data fusion method that utilizes multiple data sources to estimate a smooth, finite-dimensional parameter. Most existing methods only make use of fully aligned data sources that share common conditional distributions of one or more variables of interest. However, in many settings, the scarcity of fully aligned sources can make existing methods require unduly large sample sizes to be useful. Our approach enables the incorporation of weakly aligned data sources that are not perfectly aligned, provided their degree of misalignment is known up to finite-dimensional parameters. We quantify the additional efficiency gains achieved through the integration of these weakly aligned sources. We characterize the semiparametric efficiency bound and provide a general means to construct estimators achieving these efficiency gains. We illustrate our results by fusing data from two harmonized HIV monoclonal antibody prevention efficacy trials to study how a neutralizing antibody biomarker associates with HIV genotype.},
}

@article {pmid41018563,
year = {2025},
author = {Williamson, BD and King, D and Huang, Y},
title = {Practical Considerations for Variable Screening in the Super Learner.},
journal = {The New England Journal of Statistics in Data Science},
volume = {},
number = {},
pages = {},
pmid = {41018563},
issn = {2693-7166},
support = {S10 OD028685/OD/NIH HHS/United States ; R01 GM106177/GM/NIGMS NIH HHS/United States ; R01 CA277133/CA/NCI NIH HHS/United States ; R37 AI054165/AI/NIAID NIH HHS/United States ; U24 CA086368/CA/NCI NIH HHS/United States ; },
abstract = {Estimating a prediction function is a fundamental component of many data analyses. The super learner ensemble, a particular implementation of stacking, has desirable theoretical properties and has been used successfully in many applications. Dimension reduction can be accomplished by using variable screening algorithms (screeners), including the lasso, within the ensemble prior to fitting other prediction algorithms. However, the performance of a super learner using the lasso for dimension reduction has not been fully explored in cases where the lasso is known to perform poorly. We provide empirical results that suggest that a diverse set of candidate screeners should be used to protect against poor performance of any one screener, similar to the guidance for choosing a library of prediction algorithms for the super learner. These results are further illustrated through the analysis of HIV-1 antibody data.},
}

@article {pmid41017661,
year = {2025},
author = {Lasowski, P and Tollefson, D and Menacho, L and DePierro, J and Duerr, A},
title = {High prevalence of pain and mental health conditions amongst people well-established in HIV care: results of a cross-sectional survey in Lima, Peru.},
journal = {AIDS care},
volume = {},
number = {},
pages = {1-10},
doi = {10.1080/09540121.2025.2562242},
pmid = {41017661},
issn = {1360-0451},
abstract = {People living with HIV (PLWH) are at risk for mental health (MH) disorders and pain, but this burden is largely unknown in low/middle-income countries. From February-October 2023, we conducted a cross-sectional survey at a large HIV clinic in Lima, Peru to quantify the prevalence of MH disorders and pain amongst PLWH established in care and to explore relationships between MH and well-managed HIV. At clinic visits, PLWH were invited to complete validated measures for depression, post-traumatic stress disorder (PTSD), alcohol use disorder (AUD), and pain (PHQ-8, PCL5, AUDIT-C, and BPISF). We abstracted data on treatment and viral suppression from medical charts. We calculated the prevalence of depression (PHQ8 ≥ 10), PTSD (PCL-5 ≥ 30), AUD (AUDIT-C ≥ 4 for men, ≥ 3 for women), and pain severity/interference (none, mild, moderate, or severe). We conducted logistic regression analyses to determine associations between MH/pain and viral suppression. Among 397 participants, 32% (95% CI: 27-37%) reported AUD, 21% (17-26%) reported depression, and 13% (9.5-16%) reported PTSD; 14% (11-18%) and 12% (9.3-16%) reported moderate/severe pain intensity and interference, respectively. There were no associations between MH/pain and viral suppression. High levels of MH disorders and pain among PLWH established in care suggest screening is needed for all PLWH, even those with well-controlled HIV.},
}

@article {pmid41017648,
year = {2025},
author = {Hyde, ET and Bandoli, GE and Zou, J and Crespo, NC and Parada, H and Evenson, KR and Howard, AG and LaMonte, MJ and Stefanick, ML and Tinker, LF and Haring, B and Manson, JE and Lee, IM and LaCroix, AZ},
title = {Prospective associations between accelerometer-measured physical activity, sedentary behavior, and healthy longevity: the Women's Health Accelerometry Collaboration.},
journal = {The journals of gerontology. Series A, Biological sciences and medical sciences},
volume = {},
number = {},
pages = {},
doi = {10.1093/gerona/glaf206},
pmid = {41017648},
issn = {1758-535X},
abstract = {BACKGROUND: The influence of physical activity (PA) and sedentary behavior (SB) on survival to late age with intact mobility is unclear. This study investigated associations between accelerometer-measured daily PA, SB, and survival to age 90 birthyear with and without intact mobility in the Women's Health Accelerometry Collaboration (WHAC).

METHODS: Postmenopausal U.S. women aged 78-89 years without mobility disability were followed for an average of 6.1 years. At age 90 birthyear, participants were categorized as: (1) surviving with intact mobility, (2) surviving with mobility disability, or (3) deceased. Participants wore an accelerometer on the hip for up to 7 days at baseline from 2011-2015. Covariate-adjusted multinomial logistic regression models estimated odds ratios (ORs) of PA (light, moderate-to-vigorous [MVPA], total, steps) and SB (sitting time, mean sitting bout duration) with survival outcomes relative to dying.

RESULTS: Among 2,656 women (mean baseline age 83.1 years), 62.8% survived with intact mobility, 22.3% with mobility disability, and 15.0% died. Compared to dying before age 90, the OR (95% confidence intervals [CI]) for every 1-SD increment in accelerometer variables and survival with intact mobility were 1.36 (1.20, 1.54) for light PA, 1.69 (1.47, 1.96) for MVPA, 1.51 (1.33, 1.71) for total PA, 1.75 (1.51, 2.03) for steps, 0.70 (0.61, 0.80) for sitting time, and 0.79 (0.70, 0.89) for sitting bouts. Similar, weaker trends were present for mobility disability.

CONCLUSIONS: These findings corroborate the potential role of increasing physical activity in preserving physical functioning as an important element of healthy longevity.},
}

@article {pmid41017259,
year = {2025},
author = {Sharma, P and George, N and Srivastava, D and Chow, EJ and Alderfer, MA and Leisenring, W and Long, KA and Lown, AE and Oeffinger, KC and Zeltzer, LK and Armstrong, GT and Krull, KR and Brinkman, TM and Buchbinder, D},
title = {Psychosocial Health and Chronic Health Conditions Among Bereaved Siblings: A Report From the Childhood Cancer Survivorship Study (CCSS).},
journal = {Pediatric blood & cancer},
volume = {},
number = {},
pages = {e32076},
doi = {10.1002/pbc.32076},
pmid = {41017259},
issn = {1545-5017},
support = {CA55727/CA/NCI NIH HHS/United States ; //to St. Jude Children's Research Hospital/ ; CA21765//Cancer Center Support/ ; //American Lebanese-Syrian Associated Charities/ ; },
abstract = {OBJECTIVE: To compare psychosocial health and chronic health conditions (CHCs) in bereaved and non-bereaved adult siblings impacted by childhood cancer and to identify predictors of emotional distress and health-related quality of life among bereaved siblings.

METHODS: A total of 4558 adult siblings (733 bereaved; 3825 non-bereaved) of 5-year survivors of childhood cancer completed measures of emotional distress (Brief Symptom Inventory [BSI]-18) and health-related quality of life (Medical Outcomes Survey Short Form [SF]-36) and reported their social attainment milestones (i.e., educational attainment, employment, and marital status). CHCs' burden was classified as none/low versus medium/high/very severe. Cancer-associated complications prior to the patient's death, sibling age at bereavement, and social attainment variables were examined as predictors of emotional distress and health-related quality of life among bereaved siblings using multivariable modified Poisson regression.

RESULTS: Bereaved siblings in this sample reported excellent psychosocial health long term (e.g., depressive symptoms 6.5%, somatization 4.4%, anxiety 3.5%). Bereaved siblings had an elevated risk of depression (relative risk [RR] 1.53; 1.10-2.13, p = 0.01), reduced social quality of life (RR 1.35; 1.00-1.82, p = 0.05), diminished educational attainment, and greater CHC burden than non-bereaved siblings. No differences were observed for other subscales or social attainment outcomes. Among bereaved siblings, risk factors for depression included male sex (RR 0.42; 0.19-0.93, p = 0.05), never being married (RR 3.02; 1.45-6.28, p = 0.05), and greater CHC burden (RR 2.42; 1.18-4.99, p = 0.05). Risk factors for poor social functioning included unemployment (RR 2.24; 1.12-4.45, p = 0.05) and never being married (RR 2.16; 1.22-3.82, p = 0.05).

CONCLUSION: Bereaved siblings report excellent psychosocial health long-term and demonstrate only a marginally elevated risk of experiencing symptoms of depression and poor social quality of life compared to non-bereaved siblings.},
}

@article {pmid41016483,
year = {2025},
author = {K, R and Ac, H and K, B and Je, G and A, A and G, O and D, M and S, K and Z, N and M, F and M, S and F, F and Mh, A and P, S and Y, B and F, L and C, P and K, M and I, M and J, G and A, B and M, S and A, D and K, K and A, L and B, N and Ks, B and K, R and S, C},
title = {Late Effects After Haematopoietic Stem Cell Transplantation in patients with HLH: A Histiocyte Society, PDWP, IEWP and TCWP EBMT Study.},
journal = {The Journal of allergy and clinical immunology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jaci.2025.09.014},
pmid = {41016483},
issn = {1097-6825},
abstract = {BACKGROUND: Hematopoietic stem cell transplantation is the only curative treatment in primary hemophagocytic lymphohistiocytosis. However, hematopoietic stem cell transplantation is associated with a wide range of late effects.

OBJECTIVE: Characterization of the long-term outcome and late effects following hematopoietic stem cell transplantation in primary hemophagocytic lymphohistiocytosis.

METHODS: 274 children with pHLH from the EBMT registry who underwent allogeneic hematopoietic stem cell transplantation between 2004 and 2015 were included. Multivariable logistic regression models were performed to evaluate the adjusted impact of baseline variables on CNS and hormonal late effects, respectively.

RESULTS: A broad spectrum of late effects was identified, with neurological (31%) and hormonal (34.8%) complications being the most prevalent. Chemotherapy (HLH-94/HLH04) before hematopoietic stem cell transplantation was identified as a significant risk factor for endocrinological late effects (p=0.03), highlighting a novel aspect not previously reported. The presence of neurological abnormality at diagnosis was an independent risk factor for neurological late effects (p<0.001) as was incomplete remission status at time of HCT (p=0.04).

CONCLUSION: Hematopoietic stem cell transplantation has significantly improved survival in primary hemophagocytic lymphohistiocytosis patients, however survivors still face significant risks of late effects.},
}

@article {pmid41015745,
year = {2025},
author = {Samady, H and Drangsholt, M and Sebastian, G and Dean, D},
title = {Osteonecrosis of the jaw as a possible adverse effect of tocilizumab.},
journal = {Oral surgery, oral medicine, oral pathology and oral radiology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.oooo.2025.08.011},
pmid = {41015745},
issn = {2212-4411},
abstract = {We report the case of a 79-year-old female with a complex medical history, presenting with recurrent gingival swelling, progressive gingival hyperplasia, and osteonecrosis of the jaw potentially associated with tocilizumab. Oral complications developed in close proximity to diagnosis of chronic myelomonocytic leukemia, complicating diagnosis and management.},
}

@article {pmid41015336,
year = {2025},
author = {Shoenbill, KA and Ostroff, JS and Taylor, KL and Jafarinia, A and Minion, M and Chichester, LA and Omernik, B and McCall, M and Yeung, S and Wiseman, K and Chen, LS and Salloum, RG and Warren, G},
title = {Recommendations for Standardization of Tobacco Use Treatment Data.},
journal = {Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jtho.2025.09.1756},
pmid = {41015336},
issn = {1556-1380},
abstract = {INTRODUCTION: Although there is widespread acceptance of the importance of assessing and treating tobacco use in cancer care settings, there is much variation in the documentation and reporting of metrics relevant to tobacco treatment. The Cancer Center Cessation Initiative (C3I), as part of NCI's Cancer Moonshot, convened a Metrics Standardization Workgroup to develop a data dictionary and make recommendations for standardized quality measurement, program evaluation, and tobacco treatment program development.

METHODS: A multidisciplinary workgroup of 12 subject matter experts was convened to deliberate and standardize definitions for tobacco assessment and treatment utilization metrics. Decisions on which data elements to include were informed by clinical guidelines, literature reviews, and workgroup members' expertise. Consensus was reached when all members agreed that the proposed metric was clear, clinically relevant, and could be abstracted and reported.

RESULTS: The group considered metrics in the following categories: (1) patient identification, screening, and referral, (2) tobacco treatment process metrics, and (3) treatment outcomes. We developed a tobacco screening, referral and engagement workflow, and a data library for the following terms: patient population, screening rate, tobacco use prevalence, referral rate, reach, unsuccessful reach attempts, enrollment, treatment engagement, and counseling dose. Outcome metrics (i.e., varied "quit rate" terms) were collated and defined.

DISCUSSION: The proposed standardized data definitions can be used to improve communication and measure effectiveness for tobacco use treatment, research, operational performance, policy, quality improvement, and guideline development.},
}

@article {pmid41014345,
year = {2025},
author = {Zhao, LP and Papadopoulos, GK and McFarland, BJ and Skyler, JS and Parikh, HM and Kwok, WW and Lybrand, TP and Bondinas, GP and Moustakas, AK and Wang, R and Pyo, CW and Nelson, WC and Geraghty, DE and Lernmark, Å},
title = {Correction: Profiling associations of interactive ligand-receptors (HLA class I and KIR gene products) with the progression to type 1 diabetes among seroconverted participants.},
journal = {Diabetologia},
volume = {},
number = {},
pages = {},
doi = {10.1007/s00125-025-06557-6},
pmid = {41014345},
issn = {1432-0428},
}

@article {pmid41014159,
year = {2025},
author = {Fernandez Turizo, MJ and Velez, MA and Glenn, B and Cummings, AL and Segarra-Vazquez, B and Gorbatov, S and Park, SJ and Shen, C and Lind-Lebuffe, JP and Unger, JM and Garon, EB},
title = {Characteristics of clinical trials associated with appeal and return on investment to participants, A Review and Framework.},
journal = {The oncologist},
volume = {},
number = {},
pages = {},
doi = {10.1093/oncolo/oyaf313},
pmid = {41014159},
issn = {1549-490X},
abstract = {Despite decades of investment in clinical research infrastructure, patient participation in clinical trials remains strikingly low. In the United States, fewer than 1 in 10 adults report ever being invited to participate in a clinical trial, and among those, less than half ultimately enroll. In oncology, across all adult cancer patients, only about 8% enroll in a clinical trial, regardless of eligibility or trial availability. Active engagement of patients in cancer clinical trials substantially enhances scientific knowledge, and patient participation is required to obtain approval for novel therapeutics. Analyses focusing on evaluating if clinical trial participation improves survival for participants have yielded conflicting results. Yet, there is limited data or metrics to assess the specific attributes of oncology trials that hold greater appeal or return on investment to participants, limiting researchers' ability to determine if these factors vary across different populations. Our group demonstrated that patients with limited English proficiency were unlikely to participate in studies not sponsored by industry as compared to industry-sponsored studies. If trial participation for specific populations can differ by sponsor type, it could also differ by the trial's appeal or return on investment. While the underrepresentation of racial and ethnic minority groups in trials is attributed to multiple factors, it is possible that patients from these groups are less likely to be offered participation in studies with higher appeal or return on investment, due to systemic biases, disparities in recruitment practices and/or lack of access. In this manuscript, we propose a systematic framework for evaluating attributes of interventional oncology clinical trials, with an emphasis on the study's purpose, experimental design and investigational agent. This framework aims to pinpoint characteristics that may enhance trials' appeal or return on investment to participants and could lay a foundation for future research. This will allow investigators to assess the return on investment of appeal of studies offered across different patient populations.},
}

@article {pmid40711480,
year = {2025},
author = {Wesolowski, R and Rugo, HS and Specht, JM and Han, HS and Kabos, P and Vaishampayan, U and Wander, SA and Gogineni, K and Spira, A and Schott, AF and Abu-Khalaf, M and Mutka, SC and Suzuki, S and Sullivan, B and Gorbatchevsky, I and Layman, RM},
title = {Gedatolisib Combined with Palbociclib and Letrozole in Patients with No Prior Systemic Therapy for Hormone Receptor-Positive, HER2-Negative Advanced Breast Cancer.},
journal = {Clinical cancer research : an official journal of the American Association for Cancer Research},
volume = {31},
number = {19},
pages = {4040-4048},
doi = {10.1158/1078-0432.CCR-25-0992},
pmid = {40711480},
issn = {1557-3265},
mesh = {Humans ; Female ; *Breast Neoplasms/drug therapy/pathology/genetics/metabolism/mortality ; Letrozole/administration & dosage ; Pyridines/administration & dosage/adverse effects ; Piperazines/administration & dosage/adverse effects ; *Antineoplastic Combined Chemotherapy Protocols/therapeutic use/adverse effects/administration & dosage ; Receptor, ErbB-2/metabolism/genetics ; Middle Aged ; Receptors, Estrogen/metabolism ; Aged ; Receptors, Progesterone/metabolism ; Adult ; Aged, 80 and over ; Class I Phosphatidylinositol 3-Kinases/genetics ; },
abstract = {PURPOSE: Nonclinical evidence demonstrating that estrogen receptor, cyclin-dependent kinases 4 and 6 (CDK4/6), and PI3K/AKT/mTOR (PAM) pathways cross-promote tumor proliferation in hormone receptor-positive (HR+)/HER2- breast cancer cell lines led to the development of CDK4/6 inhibitors and agents inhibiting single PAM pathway nodes to treat HR+/HER2- advanced breast cancer. Simultaneous blockade of the estrogen receptor, CDK4/6, and PAM pathways may optimize antitumor control in the treatment-naïve advanced breast cancer setting. Gedatolisib, a pan-PI3K/mTOR inhibitor, was evaluated as first-line therapy, combined with standard-of-care palbociclib and letrozole, for patients with HR+/HER2- advanced breast cancer.

PATIENTS AND METHODS: Treatment-naïve patients from a phase Ib study with HR+/HER2- advanced breast cancer treated with gedatolisib plus palbociclib and letrozole were analyzed. The primary endpoint of the overall study was investigator-assessed objective response. Secondary endpoints included safety, duration of response, progression-free survival (PFS), and overall survival.

RESULTS: Of 41 patients, all had stage IV disease, 93% had measurable disease, 78% had visceral metastases, and 22% had detectable PIK3CA mutations. The objective response rate was 79% in patients with evaluable disease (N = 33). The median duration of response was 48 months for confirmed responders. The median PFS was 48.4 months, and the median overall survival was 77.3 months. The overall response rate and PFS were comparable in patients with and without PIK3CA mutations. Fewer than 10% discontinued treatment due to treatment-related adverse events. The most frequent grade 3/4 adverse events were neutropenia (61%), rash (39%), and oral stomatitis (29%).

CONCLUSIONS: Gedatolisib plus palbociclib and letrozole demonstrated preliminary efficacy in patients with no prior systemic therapy for advanced breast cancer. These results warrant further evaluation of gedatolisib added to standard-of-care, first-line therapy for HR+/HER2- advanced breast cancer.},
}

Humans
Female
*Breast Neoplasms/drug therapy/pathology/genetics/metabolism/mortality
Letrozole/administration & dosage
Pyridines/administration & dosage/adverse effects
Piperazines/administration & dosage/adverse effects
*Antineoplastic Combined Chemotherapy Protocols/therapeutic use/adverse effects/administration & dosage
Receptor, ErbB-2/metabolism/genetics
Middle Aged
Receptors, Estrogen/metabolism
Aged
Receptors, Progesterone/metabolism
Adult
Aged, 80 and over
Class I Phosphatidylinositol 3-Kinases/genetics

@article {pmid41012183,
year = {2025},
author = {Pallerla, S and Kallur Siddaramaiah, L and Mundsperger, P and Katinger, D and Fauland, K and Kreismayr, G and Weik, R and Arslan, O and Shen, M and Ozorowski, G and Lee, WH and Ward, AB and Baboo, S and Diedrich, JK and Yates, JR and Paulson, JC and Blumen, T and Craig, D and Swoyer, R and Yuan, M and Stamatatos, L},
title = {GMP Manufacturing and Characterization of the HIV Booster Immunogen HxB2.WT.Core-C4b for Germline Targeting Vaccine Strategies.},
journal = {Vaccines},
volume = {13},
number = {9},
pages = {},
pmid = {41012183},
issn = {2076-393X},
support = {7E11AI093022-02/NH/NIH HHS/United States ; },
abstract = {BACKGROUND/OBJECTIVES: Despite progress in antiretroviral therapy, HIV remains a major global health challenge with over one million new infections annually. An effective vaccine is urgently needed. Germline-targeting immunogens show promise in initiating broadly neutralizing antibody (bNAb) precursors. This study developed a scalable, cGMP-compliant process to manufacture the HIV vaccine booster immunogen HxB2.WT.Core-C4b, a nanoparticle designed to direct bNAb precursor maturation after priming.

METHODS: A CHO cell platform was established through single-cell cloning from a high-producing stable pool. Upstream and downstream processes were optimized for scalability and yield. Three scales were tested 10 L, 40 L, and 400 L. Key parameters (pH, temperature, feeding, metabolite profiles) were systematically refined. Analytical characterization included glycosylation profiling, electron microscopy, and antigenicity testing. Viral clearance was evaluated per ICH Q5A guidelines.

RESULTS: Optimization ensured consistent yields above 130 mg/L, with titers up to 250 mg/L. The selected clone (4E22) demonstrated strong growth, viability, and reproducibility. Glycan occupancy at 18 N-linked sites, including bNAb epitopes (N276, N332), was stable across scales. Over 70% of self-assembling nanoparticle were fully assembled at the GMP level. Antigenicity and purity met cGMP release criteria. Viral clearance achieved >13-log reduction for enveloped and >7-log for non-enveloped viruses.

CONCLUSIONS: This work establishes a robust, scalable platform for HIV nanoparticle immunogens. Consistent quality and yield across scales support clinical development of HxB2.WT.Core-C4b and provide a model for other glycosylated nanoparticle vaccines. The immunogen is being evaluated in clinical study HVTN 320 (NCT06796686), enabling early testing of next-generation vaccines designed to elicit broadly neutralizing antibodies.},
}

@article {pmid41006096,
year = {2025},
author = {Button, E and Zhang, ARY and Thamm, C and Chan, RJ and Charalambous, A and Ee, C and Merlo, G and McErlean, G and Anderson, BO and Kitson, AL},
title = {The Australian Cancer Plan through a Caring Life Course Lens: Moving from Cancer to Care by Placing the Person at the Center of Care.},
journal = {Seminars in oncology nursing},
volume = {},
number = {},
pages = {152020},
doi = {10.1016/j.soncn.2025.152020},
pmid = {41006096},
issn = {1878-3449},
abstract = {OBJECTIVE: We propose the Caring Life Course Theory (CLCT) as a lens that can inform and enrich national cancer policy and clinical practice. The purpose of this discussion paper is to highlight how a CLCT lens can inform the implementation of a national cancer control plan, using sections of the Australian Cancer Plan as examples-Optimal Care Pathways and the Australian Comprehensive Cancer Network.

METHODS: This discussion paper presents novel suggestions by drawing on CLCT concepts-care biographies, care networks, and self-care. Contrasting "current state" and "future state" vignettes are described to demonstrate how CLCT can help cancer policy move from cancer to care. Based on a robust theoretical lens, recommendations for policy and practice have been made at the micro, meso, and macro levels, with reflection on the nurses' role, and application to other national cancer control plans.

RESULTS: Optimal care pathways should include holistic assessments that incorporate broader histories at key clinical time points. The Australian Comprehensive Care Network should consider the holistic needs of people affected by cancer, and harness innovative approaches for how these needs can be met in a networked approach. In addition to clinical considerations, understanding of an individual's care biography, care network, and self-care can inform the delivery of high-quality cancer care. Implementation of these aspects of care will be led by nurses, supported by a multidisciplinary team.

CONCLUSIONS: A CLCT lens can help support implementation of the aspirational person-centered objectives described in the ACP. The potential exists for application of the CLCT approach to other national cancer control plans, including those in low-resource settings.

Nurses play a vital role in leading the implementation of person-centered dimensions of cancer control plans and core aspects of the CLCT approach.},
}

@article {pmid41005288,
year = {2025},
author = {Symonds, LK and Davidson, NE},
title = {RecOVARY? Using anti-Müllerian hormone to predict ovarian function after anti-HER2 therapy for early breast cancer.},
journal = {Journal of the National Cancer Institute},
volume = {},
number = {},
pages = {},
doi = {10.1093/jnci/djaf247},
pmid = {41005288},
issn = {1460-2105},
support = {//Breast Cancer Research Foundation/ ; },
}

@article {pmid41004543,
year = {2025},
author = {Müller, NF and Bouckaert, RR and Wu, CH and Bedford, T},
title = {MASCOT-Skyline integrates population and migration dynamics to enhance phylogeographic reconstructions.},
journal = {PLoS computational biology},
volume = {21},
number = {9},
pages = {e1013421},
doi = {10.1371/journal.pcbi.1013421},
pmid = {41004543},
issn = {1553-7358},
abstract = {The spread of infectious diseases is shaped by spatial and temporal aspects, such as host population structure or changes in the transmission rate or number of infected individuals over time. These spatiotemporal dynamics are imprinted in the genomes of pathogens and can be recovered from those genomes using phylodynamics methods. However, phylodynamic methods typically quantify either the temporal or spatial transmission dynamics, which leads to unclear biases, as one can potentially not be inferred without the other. Here, we address this challenge by introducing a structured coalescent skyline approach, MASCOT-Skyline, that allows us to jointly infer spatial and temporal transmission dynamics of infectious diseases using Markov chain Monte Carlo inference. To do so, we model the effective population size dynamics in different locations using a non-parametric function, allowing us to approximate a range of population size dynamics. We show, using a range of different viral outbreak datasets, potential issues with phylogeographic methods. We then use these viral datasets to motivate simulations of outbreaks that illuminate the nature of biases present in the different phylogeographic methods. We show that spatial and temporal dynamics should be modeled jointly, even if one seeks to recover just one of the two. Further, we showcase conditions under which we can expect phylogeographic analyses to be biased, particularly different subsampling approaches, as well as provide recommendations on when we can expect them to perform well. We implemented MASCOT-Skyline as part of the open-source software package MASCOT for the Bayesian phylodynamics platform BEAST2.},
}