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

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

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

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

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

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

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

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

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

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

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

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

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

@article {pmid41338709,
year = {2025},
author = {Pandey, S and Anderson, N and Snidarich, M and Tsosie, U and Omernik, B and Brown, MC and Crothers, K and Walsh, C and Budak, JZ and Brooks, E and Echo-Hawk, A and Triplette, M},
title = {Common Determinants of Lung Cancer Screening Uptake in Three High-Risk and Underserved Communities.},
journal = {Journal of the American College of Radiology : JACR},
volume = {22},
number = {12},
pages = {1552-1566},
doi = {10.1016/j.jacr.2025.08.018},
pmid = {41338709},
issn = {1558-349X},
mesh = {Humans ; *Lung Neoplasms/diagnostic imaging/diagnosis ; Male ; Female ; *Early Detection of Cancer/statistics & numerical data ; Focus Groups ; Middle Aged ; Qualitative Research ; United States ; Aged ; *Vulnerable Populations ; Medically Underserved Area ; Adult ; Healthcare Disparities ; },
abstract = {OBJECTIVE: Though lung cancer screening (LCS) has significant mortality benefits and has been recommended by the US Preventive Services Task Force since 2013, uptake has been low, especially in most underserved populations. The objective of this study was to harmonize qualitative data from three parallel studies focused on communities with historically high rates of tobacco use and who face lung cancer disparities-people with human immunodeficiency virus; individuals that identify as lesbian, gay, bisexual, transgender, queer or questioning, and others; and urban-dwelling American Indian or Alaska Native individuals-to understand common barriers and facilitators to LCS to inform clinical programming.

METHODS: This qualitative study re-analyzed deidentified focus group transcripts from three recently conducted qualitative studies performed in partnership with these communities. Participants were all eligible, or near eligible, for LCS by US Preventive Services Task Force 2021 criteria. Transcripts were analyzed using inductive thematic analysis, with final themes mapped to the Health Equity Implementation Framework.

RESULTS: A total of 26 focus groups or interviews were analyzed, including a total of 109 participants (people with human immunodeficiency virus, n = 43; individuals that identify as lesbian, gay, bisexual, transgender, queer or questioning, and others, n = 21; American Indian or Alaska Native, n = 45). Fifteen themes emerged that represented common determinants of LCS behavior across the domains of the Health Equity Implementation Framework. Themes demonstrated broad interest in LCS and preventive health care but multilevel barriers to LCS engagement and completion. Participants endorsed facilitators such as community engagement, patient-provider information sharing, and patient navigation to enhance LCS uptake.

DISCUSSION: Despite several barriers to screening that contribute to low uptake, there are facilitators that could be used through multilevel interventions to support LCS in underserved high-risk populations.},
}

Humans
*Lung Neoplasms/diagnostic imaging/diagnosis
Male
Female
*Early Detection of Cancer/statistics & numerical data
Focus Groups
Middle Aged
Qualitative Research
United States
Aged
*Vulnerable Populations
Medically Underserved Area
Adult
Healthcare Disparities

@article {pmid41338220,
year = {2025},
author = {Shao, Y and Tran, Q and Feng, Y and Kolekar, P and Liu, Y and Liang, Z and Fan, L and McBride, A and Jones, T and Cameron, A and Mulder, H and Ji, L and Huang, BJ and Klco, JM and Meshinchi, S and Zhang, J and Carroll, WL and Loh, ML and Easton, J and Brown, PA and Ma, X},
title = {Analysis of error profiles of indels and structural variants in deep-sequencing data.},
journal = {Cell genomics},
volume = {},
number = {},
pages = {101082},
doi = {10.1016/j.xgen.2025.101082},
pmid = {41338220},
issn = {2666-979X},
abstract = {Despite extensive studies of the error profiles of SNVs, those of insertions/deletions (indels)/structural variants (SVs) remain elusive. Using ultra-deep sequencing, we show that the error rates of indel/SVs are >100-fold lower than those of SNVs, although repeat indels have high error rates of 1%. We validated this pattern in a cohort of 103 patients with relapsed B cell acute lymphoblastic leukemia (B-ALL). We analyzed repeat indels in 339 cancer driver genes and demonstrated that the number of repeat units is highly predictive of the error rate. We then analyzed minimal residual disease samples from 72 patients with relapsed B-ALL and demonstrated that our approach had positive detections in 61% of cases, outperforming clinical flow cytometry (51% detection). Overall, we established indel and SV error profiles in deep next-generation sequencing (NGS) data, enabling superior tumor detection at very low burdens, which has a significant impact on the clinical diagnosis and monitoring of human cancers and other diseases.},
}

@article {pmid41338217,
year = {2025},
author = {Li, Q and Song, Q and Chen, Z and Choi, J and Moreno, V and Ping, J and Wen, W and Li, C and Shu, X and Yan, J and Shu, XO and Cai, Q and Long, J and Huyghe, JR and Pai, R and Gruber, SB and Yang, Y and Casey, G and Wang, X and Toriola, AT and Li, L and Singh, B and Lau, KS and Zhou, L and Zhang, Z and Wu, C and Peters, U and Zheng, W and Long, Q and Yin, Z and Guo, X},
title = {Large-scale integration of omics and electronic health records to identify potential risk protein biomarkers and therapeutic drugs for cancer prevention.},
journal = {American journal of human genetics},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.ajhg.2025.11.008},
pmid = {41338217},
issn = {1537-6605},
abstract = {Identifying risk protein targets and their therapeutic drugs is crucial for effective cancer prevention. Here, we conduct integrative and fine-mapping analyses of large genome-wide association studies data for breast, colorectal, lung, ovarian, pancreatic, and prostate cancers and characterize 710 lead variants independently associated with cancer risk. Through mapping protein quantitative trait loci (pQTLs) for these variants using plasma proteomics data from over 75,000 participants, we identify 365 proteins associated with cancer risk. Subsequent colocalization analysis identifies 101 proteins, including 74 not reported in previous studies. We further characterize 36 potential druggable proteins for cancers or other disease indications. Analyzing >3.5 million electronic health records, we conducted analyses of emulated trials for 11 drugs across 290 comparisons and identified three drugs significantly associated with reduced colorectal cancer risk: caffeine vs. paroxetine (hazard ratio [HR], 0.51; 95% confidence interval [CI], 0.41-0.64), haloperidol vs. prochlorperazine (HR, 0.47; 95% CI, 0.33-0.68), and trazodone hydrochloride vs. paroxetine (HR, 0.49; 95% CI, 0.38-0.63). Conversely, caffeine was associated with increased cancer risk in comparison with finasteride (colorectal cancer) and fluoxetine (breast cancer). Meta-analysis identified six drugs significantly associated with cancer risk, including acetazolamide, which was associated with reduced colorectal cancer risk (HR, 0.79; 95% CI, 0.72-0.87). This study identifies previously unreported protein biomarkers and candidate drug targets across six major cancer types and highlights several approved drugs with potential chemopreventive effects.},
}

@article {pmid41337691,
year = {2025},
author = {Necchi, A and Guerrero-Ramos, F and Crispen, PL and Herrera-Imbroda, B and Garje, R and Szabados, B and Peyton, CC and Pradere, B and Ku, JH and Shore, N and Bögemann, M and Preston, MA and Xylinas, E and Sanchez de Llano, C and Gong, C and Hasan, M and Urtishak, K and Battaglia, S and Stitou, H and Bhanvadia, S and Sweiti, H and Psutka, SP},
title = {Gemcitabine intravesical system plus cetrelimab or cetrelimab alone as neoadjuvant therapy in patients with MIBC: primary analysis and biomarker results of SunRISe-4.},
journal = {Journal of clinical oncology : official journal of the American Society of Clinical Oncology},
volume = {},
number = {},
pages = {101200JCO2502382},
doi = {10.1200/JCO-25-02382},
pmid = {41337691},
issn = {1527-7755},
abstract = {PURPOSE: Standard of care for muscle-invasive bladder cancer (MIBC) is radical cystectomy (RC) with neoadjuvant cisplatin-based chemotherapy (NAC). However, many patients are ineligible for or refuse cisplatin. SunRISe-4 (NCT04919512) is an open-label, multicenter, parallel-cohort phase II study assessing neoadjuvant gemcitabine intravesical system (TAR-200) plus cetrelimab or cetrelimab monotherapy in patients with MIBC.

PATIENTS AND METHODS: Adults with ECOG performance status 0-1, cT2-T4a N0M0, ineligible/refusing NAC, and planned for RC were randomized 5:3, stratified by TURBT completeness (residual tumor ≤3 cm permitted) and T stage, to receive TAR-200 plus cetrelimab (Cohort 1 [C1]) or cetrelimab monotherapy (C2). The primary endpoint was pathologic complete response (pCR) at RC. Secondary endpoints included recurrence-free survival (RFS) and safety. Exploratory endpoints included pathological overall response (pOR; ≤ypT1N0) and circulating and urinary tumor DNA (ct/utDNA) molecular residual disease. Side-by-side descriptive efficacy summary was planned.

RESULTS: At May 9, 2025, data cutoff, 159 patients were treated; 88 in C1 and 46 in C2 underwent RC. pCR, pOR, and 1-year RFS rates were 38%, 53%, and 77%, respectively, in C1 and28%, 44%, and 64% in C2. pCR rates were consistent across subgroups. No new safety signals were observed. Across cohorts, utDNA- status before RC (week 12) and utDNA clearance correlated with pCR (P<10[-5] and <10[-3], respectively). ctDNA- status at baseline and week 12 was associated with longer RFS compared with ctDNA+ status at the same timepoint (P=.04 and .01, respectively).

CONCLUSIONS: TAR-200 plus cetrelimab provided higher pCR, pOR, and 1-year RFS rates compared with cetrelimab monotherapy, supporting further investigation of the neoadjuvant combination in MIBC. utDNA and ctDNA MRD results support further investigation as biomarkers for residual local and non-local disease, respectively.},
}

@article {pmid41337582,
year = {2025},
author = {Dighe, K and Colak, O and Moitra, P and Alafeef, M and Skrodzki, D and Aditya, T and Saha, P and Gunaseelan, N and Hural, J and Pinto, C and Pan, D},
title = {Distinguishing active HIV-1 infection from vaccine-induced seropositivity in HIV vaccine trial participants.},
journal = {Science advances},
volume = {11},
number = {49},
pages = {eadz5639},
pmid = {41337582},
issn = {2375-2548},
mesh = {Humans ; *AIDS Vaccines/immunology/adverse effects ; *HIV-1/immunology ; *HIV Infections/diagnosis/immunology/blood/virology/prevention & control ; HIV Antibodies/immunology/blood ; ROC Curve ; HIV Core Protein p24/immunology ; RNA, Viral/blood ; *HIV Seropositivity/diagnosis/immunology ; Male ; Sensitivity and Specificity ; Female ; },
abstract = {Vaccine-induced seropositivity (VISP) causes antibodies produced by HIV-1 vaccines to react with standard serological tests, complicating diagnosis and leading to false positives. To distinguish VISP from true HIV infections, we developed a rapid, multiplexed companion electrochemical assay that integrates a three-dimensional-printed device with screen-printed electrodes coated with antigen, antibody, and methylene blue-labeled antisense oligonucleotide probes. The test delivers quantitative results within 5 minutes with calculated analytical limits of detection of 5.88 picograms per milliliter for p24 antigen, 10.96 picograms per milliliter for anti-p24 antibody, and 1259 copies per milliliter for HIV-1 RNA, with minimal cross-reactivity. Clinical testing with 104 plasma samples obtained from vaccinated/unvaccinated, HIV-positive/negative individuals demonstrated 95% sensitivity and 98% specificity in distinguishing active HIV-1 infection from VISP cases. Receiver operating characteristic analysis produced area under the curve values of 0.9888 for HIV-1 RNA, 0.9705 for anti-p24 antibody, and 0.9356 for p24 antigen. These findings highlight the potential to reduce false-positive results caused by VISP by integrating this diagnostic test in clinical trials and large-scale vaccination programs.},
}

Humans
*AIDS Vaccines/immunology/adverse effects
*HIV-1/immunology
*HIV Infections/diagnosis/immunology/blood/virology/prevention & control
HIV Antibodies/immunology/blood
ROC Curve
HIV Core Protein p24/immunology
RNA, Viral/blood
*HIV Seropositivity/diagnosis/immunology
Male
Sensitivity and Specificity
Female

@article {pmid41335420,
year = {2025},
author = {Zhao, LP and Papadopoulos, GK 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 = {Profiling Associations Between IGHG-FCGR Ligand-Receptor Interactions and Disease Progression From Stage 1 and 2 to Stage 3 Type 1 Diabetes.},
journal = {Diabetes},
volume = {},
number = {},
pages = {},
doi = {10.2337/db25-0610},
pmid = {41335420},
issn = {1939-327X},
support = {R01 DK132406/DK/NIDDK NIH HHS/United States ; },
abstract = {UNLABELLED: The primary objective of this study was to investigate whether ligand-receptor interactions (LRIs) between IGHG and FCGR gene products are associated with progression to type 1 diabetes (T1D). Using two completed clinical trials (DPT-1 and TN07), we applied next-generation targeted sequencing to genotype IGHG and FCGR genes in a cohort of 1,214 individuals and assessed LRI associations with disease progression. A Cox regression model was used to quantify LRI associations. IGHG or FCGR alone was found to have weak and sporadic associations with progression. Multiple LRIs between IGHG and FCGR gene products were found to be associated with progression, especially LRIs of IGHG2 with multiple FCGR receptors that accelerate progression and those of IGHG4 with multiple FCGR receptors (some overlapping) that delay progression. Furthermore, as several crystal structures of FcγRs complexed with distinct IgG molecules are known, application of this knowledge here was hampered by the absence of any information on the subclass distribution of each of the several T1D-related autoantibodies. It cannot be excluded that their respective state of glycosylation may influence binding affinity to various FcγRs and the function of thus-formed complexes. Our findings suggest that LRIs of the IGHG and FCGR gene products probably influence progression, shedding new insights into some of the immunological mechanisms involved in progression to T1D. Our findings potentially facilitate the search for new immunotherapeutic treatment through intervening at key steps in the progression.

ARTICLE HIGHLIGHTS: This study investigated ligand-receptor interactions (LRIs) between IGHG and FCGR gene products in type 1 diabetes progression. Genes of 1,214 participants from the DPT-1 and TN07 trials were sequenced using next-generation targeted sequencing technology, and LRI associations with the progression time to type 1 diabetes were analyzed using Cox regression modeling. Weak associations were found for IGHG or FCGR variants individually, but multiple LRIs significantly impacted progression. Several IGHG2-FCGR interactions accelerated progression, while a few other IGHG4-FCGR interactions delayed it. The results may provide insights into certain immunogenetic mechanisms of T1D and suggest therapeutic potential of targeting specific LRIs.},
}

@article {pmid41335170,
year = {2025},
author = {Le, H and Baek, G and Huang, I and Siu, C and Shadman, M},
title = {The Evolving Therapeutic Landscape of Richter Transformation.},
journal = {Current hematologic malignancy reports},
volume = {20},
number = {1},
pages = {21},
pmid = {41335170},
issn = {1558-822X},
mesh = {Humans ; *Leukemia, Lymphocytic, Chronic, B-Cell/therapy/pathology ; Immunotherapy/methods ; Molecular Targeted Therapy ; Protein Kinase Inhibitors/therapeutic use ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; *Lymphoma, Large B-Cell, Diffuse/therapy/pathology ; },
abstract = {PURPOSE OF REVIEW: Richter transformation (RT), the progression of chronic lymphocytic leukemia (CLL) to aggressive lymphomas, poses a significant therapeutic challenge with historically poor outcomes. Chemoimmunotherapy (CIT) regimens have demonstrated limited efficacy with short durations of response. This review aims to evaluate the evolving treatment landscape for RT, with a focus on recent advances in targeted therapies, immunotherapies, and cellular therapies that are redefining the current and future standards of care.

RECENT FINDINGS: The treatment paradigm for RT is rapidly shifting away from cytotoxic chemotherapy. The combination of the B-cell lymphoma 2 inhibitor venetoclax with CIT has emerged as a new first-line benchmark with promising response rates and overall survival. Covalent Bruton tyrosine kinase (BTK) inhibitors had modest activity as monotherapy but showed improved responses when given with an immune checkpoint inhibitor. Pirtobrutinib has demonstrated responses even in heavily pretreated patients. Furthermore, advancement in immunotherapy has expanded treatment options for this patient population with bispecific T-cell engagers achieving high response rates and chimeric antigen receptor T-cell therapy providing deep, durable responses and favorable median overall survival in the relapsed/refractory (R/R) setting. The therapeutic landscape for RT has broadened with the introduction of targeted agents and immunotherapy. Venetoclax-based regimens represent a new standard for chemotherapy-eligible patients, allowing for a more effective bridge to potentially curative consolidation with transplantation. For R/R disease, novel BTK inhibitors, bispecific antibodies, and cellular therapies are demonstrating substantial efficacy. Ongoing trials investigating combinations of these agents are poised to further transform RT management.},
}

Humans
*Leukemia, Lymphocytic, Chronic, B-Cell/therapy/pathology
Immunotherapy/methods
Molecular Targeted Therapy
Protein Kinase Inhibitors/therapeutic use
Antineoplastic Combined Chemotherapy Protocols/therapeutic use
*Lymphoma, Large B-Cell, Diffuse/therapy/pathology

@article {pmid41335105,
year = {2025},
author = {Irinyi, L and Mintzes, B and Warning, J and Collie, L and Rush, A and Turtle, CJ and Byrne, JA},
title = {Long-Term Follow-Up of Patients Receiving Cell and Gene Therapy Products.},
journal = {Human gene therapy},
volume = {},
number = {},
pages = {},
doi = {10.1177/10430342251403439},
pmid = {41335105},
issn = {1557-7422},
abstract = {Cell and gene therapies present unique challenges for long-term follow-up as they may lead to adverse events that could emerge years after treatment. Long-term follow-up helps identify potential delayed adverse events, such as oncogenesis or immunogenicity, which might not manifest immediately after treatment. Current regulatory guidelines emphasize a risk-based approach, recommending follow-up durations based on the therapy's mechanism of action between 5 and 15 years. To facilitate long-term monitoring, regulatory authorities recommend the establishment of long-term follow-up protocols, often involving patient registries and supported by real-world data sources to systematically capture and track data from treated patients. These long-term follow-ups are instrumental in both post-approval safety studies and reimbursement decisions, where payers may link payments to treatment outcomes. As the field of cell and gene therapy evolves, regulatory frameworks continue to adapt, balancing the need for comprehensive long-term follow-up with the feasibility of implementation to ensure that therapies are adequately monitored, ensuring patient safety and therapeutic effectiveness over time. However, maintaining patient engagement over extended periods, ensuring high-quality data collection, and addressing privacy concerns present significant challenges. Innovative solutions such as decentralized data collection, digital health technologies, and data linkage with electronic health records aim to alleviate patient burden and improve data reliability.},
}

@article {pmid41282799,
year = {2025},
author = {Ellis, AL and Stauss, M and Tiburcio, PB and Emmen, IE and Edlefsen, PT and Kosmider, E and Barlow, S and Goss, M and Temte, JL and Stachler, E and McMahon, K and Sabeti, P and O'Connor, DH and O'Connor, SL},
title = {Adaptation of the multiplexed CRISPR-Cas13 CARMEN RVP assay for longitudinal detection of respiratory pathogens from air samples.},
journal = {medRxiv : the preprint server for health sciences},
volume = {},
number = {},
pages = {},
pmid = {41282799},
abstract = {Air sampling is a non-invasive alternative to individual testing for respiratory pathogens. Alternative methods to the "gold standard" quantitative RT-PCR (qRT-PCR) are required to enable higher throughput, lower cost, and more multiplexed detection of pathogens. The multiplexed CRISPR-Cas13 CARMEN Respiratory Viral Panel (RVP) was described previously for high-throughput detection of nine respiratory pathogens from nasal swab samples. Here, we modified and optimized the CARMEN RVP assay to overcome the unique challenges of air samples, including low biomass and environmental inhibitors. We monitored for SARS-CoV-2 and influenza A (Flu A) via qRT-PCR in air samples from 15 schools within Dane County, Wisconsin (USA) during the 2023-2024 school year. SARS-CoV-2 was detectable throughout the entire sampling period, while Flu A detection was seasonal from November 2023 to March 2024. We then analyzed a subset of samples from seven schools using an optimized CARMEN RVP assay for air surveillance (RVP_air) and compared results to qRT-PCR. The RVP_air assay detected several additional pathogens beyond our primary targets. The frequencies and patterns of SARS-CoV-2 positivity, but not Flu A, were similar between qRT-PCR and RVP_air across the 2023-2024 sampling period. We developed a secondary panel (RVP_air_flu) to better detect both H1N1 and H3N2 subtypes. Finally, we compared air sample results to clinical nasal swabs collected from the same school district. For several pathogens (SARS-CoV-2, HCoV-OC43, Flu A), positive air detections coincided with positive nasal swabs. These findings demonstrate that the RVP_air assay can effectively detect airborne pathogens from infected individuals within indoor spaces.},
}

@article {pmid41282795,
year = {2025},
author = {Wu, X and Kim, A and Breeze, CE and O'Mara, TA and Ramachandran, D and Dörk, T and Koutros, S and Rothman, N and Prokunina-Olsson, L and Mancuso, N and Lindström, S and Kraft, P},
title = {Prioritizing context-specific genetic risk mechanisms in 11 solid cancers.},
journal = {medRxiv : the preprint server for health sciences},
volume = {},
number = {},
pages = {},
pmid = {41282795},
abstract = {BACKGROUND: While genome-wide association studies (GWAS) have identified hundreds of cancer-associated genetic variants, the specific biological contexts where these variants exert their effects remain largely unknown. We aimed to prioritize context-specific genetic risk mechanisms for 11 solid cancers at both genome-wide and single-variant resolutions.

METHODS: We integrated cancer GWAS summary statistics from European ancestry samples (avg. n cases=47,856) with ~1,500 context-specific annotations representing candidate cis-regulatory elements. For genome-wide analysis, we applied CT-FM, a method that leverages heritability enrichment estimates and an annotation correlation matrix to select likely disease-relevant biological contexts. After identifying putative causal SNPs (PIP≥0.5) via functionally informed fine-mapping, we used CT-FM-SNP to identify relevant contexts for individual variants. A combined SNP-to-gene framework was applied to construct putative {regulatory SNP-context-gene-cancer}
quadruplets.

RESULTS: Stratified LD score regression analysis identified 52 annotations with significant heritability enrichment (Bonferroni-corrected P≤0.05). CT-FM prioritized four high-confidence (PIP≥0.5) biological contexts: mammary luminal epithelial cells for breast cancer, a prostate cancer epithelial cell line (VCaP) for prostate cancer, and bulk tumor tissue contexts for colorectal and renal cancers. Variant-level analysis of hundreds of putatively causal SNPs corroborated these findings and identified additional high-confidence contexts for other malignancies, including estrogen receptor-negative breast cancer and bladder cancer. A total of 489 putative regulatory quadruplets were constructed, proposing specific molecular mechanisms underlying the observed GWAS signals.

CONCLUSION: These findings advance our understanding of genetic susceptibility to different cancers. Future work in larger, more diverse GWAS, coupled with more comprehensive annotation atlases, is essential to expand upon and validate our results.},
}

@article {pmid41279922,
year = {2025},
author = {Mihalas, AB and Mitchell, K and Arora, S and O'Connor, SA and Patel, AP and Plaisier, CL and Paddison, PJ},
title = {Characterization of quiescent subpopulations and proliferative compartments in glioblastoma.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {41279922},
issn = {2692-8205},
abstract = {Glioblastoma (GBM) quiescent (Q) cell populations are hypothesized to contain cancer stem-like cells (CSC) that drive tumor growth, cellular heterogeneity, and recurrence. However, GBM tumors do not neatly resolve into developmental hierarchies and Q stem-like activities are difficult to assess. Here, we evaluated tumor Q subpopulations in patient-derived GBM xenograft tumors using live cell reporters, DNA label retention assays, and single cell genomics. Compared to adult neural stems cells (NSCs), GBM Q populations contain hybrid transcriptional states composed of networks found in both dormant and activated adult NSCs, resulting in constitutive expression of key Q egress transcription factors and their targets (e.g., AP-1 and CCND1/2). As a result, even the longest Q-residing cells (~12 days) in xenograft tumors continuously cycle and fail to enter dormant Q states. We provide evidence and hypothesize that transient Q states in primary tumors arise as part of distinct proliferative compartments rather than deterministic developmental hierarchies driven by CSC activity. We further speculate that increases in basal translation rates drive Q instability in GBM tumors.},
}

@article {pmid41334909,
year = {2025},
author = {Walter, M and Haick, AK and Massa, PA and Klouser, LM and Stensland, L and Santo, TK and Xie, H and Jerome, KR},
title = {Herpes simplex virus 1 strain 17+ with R2 mutation in UL37 has residual retrograde transport.},
journal = {Microbiology spectrum},
volume = {},
number = {},
pages = {e0195925},
doi = {10.1128/spectrum.01959-25},
pmid = {41334909},
issn = {2165-0497},
abstract = {UNLABELLED: Herpes simplex virus 1 (HSV-1) causes lifelong recurrent infections. Following primary infection of the oral or genital mucosa, HSV-1 travels retrogradely through axons and establishes latency in the cell body of ganglionic neurons of the peripheral nervous system. Periodic reactivation in neurons and anterograde transport of virions back to peripheral regions cause oral or genital ulcerations. Many host and viral factors implicated in retrograde and anterograde transport of HSV-1 have been identified. In particular, studies reported that introducing five amino acid substitutions in the R2 region of the viral tegument protein UL37 was sufficient to completely eliminate retrograde transport of HSV-1 strain F. Here, we introduced the same R2 mutations in the highly neurovirulent HSV-1 strain 17+. We show that this R2[17] virus is highly attenuated in mice and acts as a potent vaccine that protects mice against acute HSV-1 infection. However, we report that the R2[17] virus has residual retrograde transport. We show that R2[17] can establish latency in mouse models of ocular and vaginal infection and reactivate. These results contradict published evidence and show that the R2 mutation is not sufficient to fully prevent retrograde transport of HSV-1.

IMPORTANCE: Herpes simplex virus 1 (HSV-1) is a ubiquitous pathogen without a cure or vaccine. HSV-1 travels through nerves between the oral and genital mucosa and the peripheral nervous system, where it establishes lifelong latency. Studies reported that introducing five amino acid substitutions in the R2 region of the viral tegument protein UL37 was sufficient to completely eliminate the retrograde transport of HSV-1 strain F from the mucosa to the nervous system. Here, we present contradictory findings. We report that an HSV-1 virus from strain 17+ with the same R2 mutation has residual retrograde transport. This shows that the R2 mutation is not sufficient to fully prevent the retrograde transport of HSV-1 in all settings. This finding may be particularly relevant for assessing the safety of prospective live-attenuated vaccines that include the R2 mutation.},
}

@article {pmid41334748,
year = {2025},
author = {Fitzgerald, L and Ghosh, S and Khan, W and Bokun, A and Lax, A and Mu, F and Cook, EE and Chen, J and Chen, G and Wu, E and Lin, Y and Shi, L and Qureshi, ZP and Graf, SA},
title = {Real-world overall survival comparison between first-line Bruton tyrosine kinase inhibitors in treating chronic lymphocytic leukemia/small lymphocytic lymphoma: An analysis of Veterans Health Administration data.},
journal = {Journal of managed care & specialty pharmacy},
volume = {},
number = {},
pages = {1-15},
doi = {10.18553/jmcp.2025.25169},
pmid = {41334748},
issn = {2376-1032},
abstract = {BACKGROUND: Three covalent Bruton's tyrosine kinase inhibitors (BTKis) are approved first-line (1L) treatments for patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL). However, limited real-world data, especially in veterans, evaluate long-term outcomes associated with the different BTKis.

OBJECTIVE: To describe and compare real-world overall survival (rwOS) among patients with CLL/SLL treated with BTKis in the Veterans Health Administration electronic medical record database.

METHODS: This was a retrospective cohort study of patients with CLL/SLL who initiated 1L monotherapy of ibrutinib, acalabrutinib, or zanubrutinib between November 2019 and September 2023. Patients were grouped into 3 cohorts based on the BTKi initiated: (1) ibrutinib, (2) acalabrutinib, or (3) acalabrutinib or zanubrutinib (given small sample initiating zanubrutinib). Key inclusion criteria were 1L monotherapy treatment with a BTKi, at least 2 diagnoses of CLL/SLL, and continuous enrollment at least 12 months prior to and at least 28 days after the initiation of the BTKi. rwOS comparing the BTKi cohorts was analyzed using Kaplan-Meier methodology and adjusted Cox proportional hazards models. Sensitivity analyses adjusting for different sets of covariates were conducted.

RESULTS: The study included samples of 1,059, 504, and 612 patients treated with ibrutinib, acalabrutinib, and acalabrutinib or zanubrutinib (108 received zanubrutinib), respectively. Median rwOS was not reached in any cohort. In the main analysis comparing the ibrutinib and acalabrutinib cohorts, after adjustment for baseline characteristics, treatment with acalabrutinib was associated with an increased risk of death compared with ibrutinib (hazard ratio [HR], 1.33; 95% CI, 1.01-1.76; P = 0.042). In the main analysis comparing the ibrutinib and acalabrutinib or zanubrutinib cohorts, the adjusted risk of death was numerically higher for acalabrutinib- or zanubrutinib-treated patients compared with ibrutinib (HR, 1.32; 95% CI, 1.00-1.74; P = 0.050). For both comparisons, sensitivity analyses indicated similar trends in rwOS.

CONCLUSIONS: As new therapies emerge, this study highlights the comparative effectiveness of BTKis in the real world, potentially informing current clinical practice.},
}

@article {pmid41334110,
year = {2026},
author = {Kim, Y and Yang, G and Oh, J and Gwak, SY and Kim, KH and Lee, J and Kim, JS and Lee, CG and Cho, J and Ky, B and Yoon, HI and Grassberger, C},
title = {Consolidation ICIs Alter cardiac subregion radiosensitivity in NSCLC patients treated with Chemo-Radiotherapy.},
journal = {Clinical and translational radiation oncology},
volume = {56},
number = {},
pages = {101069},
pmid = {41334110},
issn = {2405-6308},
abstract = {PURPOSE: he addition of immune checkpoint inhibitor (ICI) as consolidation therapy after chemoradiation (CRT) has improved survival rates in non-small cell lung cancer (NSCLC) patients. However, the cardiotoxicity of CRT combined with ICI remains underexplored. This study assesses if ICI exposure alters the critical cardiac subregion linked to radiation-induced heart disease (RIHD) following CRT.

METHODS: We conducted a retrospective analysis of 321 locally advanced NSCLC patients treated with definitive CRT from August 2008 to December 2019, including 67 who received consolidation ICI. Cardiac contours include the entire heart, chambers, major coronary arteries, and conduction nodes. The primary endpoint was RIHD, defined as a major adverse cardiac event and atrial fibrillation. We used Fine-Gray analysis to investigate associations between RIHD and mean doses to cardiac subregions.

RESULTS: In total, 53 patients (18.4 %) developed RIHD, with no significant difference between CRT and CRT + ICI groups. Doses to cardiac subregions were similar between the groups. In the CRT group, multivariable analysis shows that dose to the base of the heart, especially the sinoatrial node (SAN), correlated with increased RIHD risk (HR = 1.02 per 1 Gy, 95 %CI [1.01-1.03], p < 0.001). In the CRT + IO group, the left ventricle (LV) dose was a significant predictor (1.06 [1.06-1.1], p = 0.006).

CONCLUSIONS: Doses to the SAN and the base of the heart correlate with RIHD in CRT patients, while doses to LV in CRT + ICI patients. While the 2-6 % increased risk per Gy seems modest, it is clinically significant as the subregions, being small structures, can potentially be completely spared with a carefully optimized plan.},
}

@article {pmid41333983,
year = {2025},
author = {Hong, G and Walsh, J and Koshy, A and Hsu, JY and O'Dea, AL and Vesely, EM and Memon, W and Dezube, RH and Goss, CH and Goss, LB and Greene, A and Gross, JE and Wilson, A and Nichols, DP and Zhang, SX and Cramer, RA},
title = {Home sputum collection for Aspergillus fumigatus detection in adults with cystic fibrosis.},
journal = {ERJ open research},
volume = {11},
number = {6},
pages = {},
pmid = {41333983},
issn = {2312-0541},
abstract = {BACKGROUND: Elexacaftor/tezacaftor/ivacaftor (ETI) has impacted the ability for people with cystic fibrosis (PwCF) to spontaneously expectorate sputum, leading to lower respiratory sampling rates and infection detection challenges. Home sampling may permit a potential strategy for fungal detection in PwCF.

METHODS: We conducted a prospective decentralised cohort study of PwCF to test the feasibility of home sputum collection and ambient temperature transport for Aspergillus fumigatus (Af) detection. Participants collected and shipped weekly sputum samples from home to the laboratory for fungal culture and completed electronic questionnaires. Descriptive statistics were calculated for patient factors, sputum characteristics and Af-positive cultures. We used a generalised estimating equations model to determine the association between highly effective modulator therapy (HEMT) and sputum volume.

RESULTS: We enrolled 76 adults with cystic fibrosis (CF) with a median (interquartile range) forced expiratory volume in 1 s (FEV1) % predicted of 72.5% (53.8-86.3). 60 (79%) were on ETI and 44 (58%) had a history of Aspergillus. 70 (92%) successfully collected and shipped three or more sputum samples. Of 284 samples received, 83% arrived within one day. Sputum collection was reported as easy in 83 (29%) and somewhat easy in 114 (40%) collection events. Sputum volume from PwCF on HEMT was 36% lower than those not on HEMT (36%, 95% CI 3-58; p=0.03), adjusting for covariates. Af was detected in 205 (73%) of home sputum samples.

CONCLUSION: Home sputum collection is feasible in adults with CF. Af was detected in remotely collected sputum samples. Further work to assess the validity of home sputum samples in PwCF is necessary to determine the value of remote specimens in clinical and research settings.},
}

@article {pmid41330919,
year = {2025},
author = {Lai, M and Kim, K and Zheng, Y and Castellani, CA and Ratliff, SM and Wang, M and Liu, X and Haessler, J and Huan, T and Bonsu, K and Newcomb, C and McKessy, K and Bielak, LF and Zhao, W and Joehanes, R and Ma, J and Guo, X and Manson, JE and Grove, ML and Bressler, J and Taylor, KD and Lappalainen, T and Kasela, S and Blackwell, TW and Lake, NJ and Faul, JD and Ferrier, KR and Ekker, SC and Hou, L and Kooperberg, C and Reiner, AP and Zhang, K and Peyser, PA and Fornage, M and Boerwinkle, E and Raffield, LM and Carson, AP and Rich, SS and Liu, Y and Levy, D and Rotter, JI and Smith, JA and Arking, DE and Liu, C and , },
title = {Epigenome-wide association study of nuclear DNA methylation in relation to mitochondrial heteroplasmy.},
journal = {Nature communications},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41467-025-65845-2},
pmid = {41330919},
issn = {2041-1723},
abstract = {We analyze 10,986 participants (mean age 77; 63% women; 54% non-White) across seven U.S. cohorts to study the relationship between mitochondrial DNA (mtDNA) heteroplasmy and nuclear DNA methylation. We identify 597 CpGs associated with heteroplasmy burden, generally showing lower methylation. These CpGs are enriched in dynamically regulated island shores and depleted in CpG islands, indicating involvement in context-specific rather than constitutive gene regulation. In HEK293T cells, we introduce a truncating mtDNA mutation (MT-COX3, mt.9979) and observe a positive correlation between variant allele fraction and methylation at cg04569152, supporting a direct mtDNA-nDNA epigenetic link. Many heteroplasmy-associated CpGs overlap with known methylation-trait associations for metabolic and behavioral traits. Composite CpG scores predict all-cause mortality and incident CVD, with one-unit increases associated with 1.27-fold and 1.12-fold higher hazards, respectively. These findings suggest an mtDNA-nDNA epigenetic connection in aging and disease, though its direction and mechanisms remain to be studied.},
}

@article {pmid41330717,
year = {2025},
author = {Park, YH and Cortes, J and Modi, S and Hurvitz, SA and Bianchini, G and Iwata, H and Shitara, K and Siena, S and Goto, Y and Ku, GY and Powell, CA and Swain, SM and Arunachalam, M and Janek, M and Cheng, Y and Chu, C and Verma, P and Kuptsova-Clarkson, N and Mathias, E and Goodman, E and Rugo, HS},
title = {Characterization of the Safety Profile of Trastuzumab Deruxtecan by Dose: A Pooled Analysis Across DESTINY Studies.},
journal = {The oncologist},
volume = {},
number = {},
pages = {},
doi = {10.1093/oncolo/oyaf396},
pmid = {41330717},
issn = {1549-490X},
abstract = {BACKGROUND: Trastuzumab deruxtecan (T-DXd), an approved human epidermal growth factor receptor 2 (HER2)-directed antibody-drug conjugate, may cause treatment-emergent adverse events (TEAEs), most commonly gastrointestinal and hematologic TEAEs. This pooled analysis evaluated TEAEs across two doses of T-DXd in patients with different cancers to support safe and effective real-world use.

PATIENTS AND METHODS: Data were pooled from nine phase I-III clinical trials (DS8201-A-J101; DESTINY-Breast01/02/03/04; DESTINY-Lung01/02; DESTINY-Gastric01/02) of T-DXd 5.4 or 6.4 mg/kg every 3 weeks in patients (N = 1678) with metastatic breast, gastric, or lung cancer with varying HER2 expression or HER2 mutation status. Nausea, vomiting, neutropenia, fatigue, and interstitial lung disease (ILD) were evaluated for time to onset and dose-related outcomes. Antiemetic analysis was limited before a 2020 protocol change recommending prophylaxis.

RESULTS: Common TEAEs (in ≥ 20%) were fatigue, nausea, vomiting, neutropenia, anemia, and thrombocytopenia; mostly grade 1 or 2. TEAEs leading to dose reduction, drug interruption, and discontinuation with T-DXd were 22.6%, 42.8%, and 17.7% (5.4 mg/kg), and 29.7%, 47.6%, and 16.6% (6.4 mg/kg), respectively. Neutropenia, nausea, and fatigue occurred in 34.6%, 74.6%, and 56.5% of patients (5.4 mg/kg) and 49.3%, 65.5%, and 52.8% (6.4 mg/kg). Adjudicated drug-related ILD occurred in 12.0% and 10.9%, respectively.

CONCLUSION: Gastrointestinal and hematologic TEAEs were most common, with nausea, neutropenia, and fatigue most commonly reported. ILD/pneumonitis occurred in ∼11%-12% of patients, with severe cases infrequent. Most TEAEs were low grade, though dose modifications highlight the need for proactive TEAE management, particularly in older patients and those with renal impairment.},
}

@article {pmid41329166,
year = {2026},
author = {Arends, T and Bennett, SR and Tapscott, SJ},
title = {DUX4-induced HSATII RNA accumulation drives protein aggregation, impacting RNA processing pathways.},
journal = {The Journal of cell biology},
volume = {225},
number = {2},
pages = {},
doi = {10.1083/jcb.202501129},
pmid = {41329166},
issn = {1540-8140},
support = {R01AR045203/NH/NIH HHS/United States ; P30 CA015704/NH/NIH HHS/United States ; K99AR081926/NH/NIH HHS/United States ; /AR/NIAMS NIH HHS/United States ; T32CA009657/CA/NCI NIH HHS/United States ; //Fred Hutch/ ; //University of Washington/ ; //Seattle Children's Cancer Consortium/ ; },
mesh = {Humans ; *Homeodomain Proteins/metabolism/genetics ; *Muscular Dystrophy, Facioscapulohumeral/genetics/metabolism/pathology ; *RNA Processing, Post-Transcriptional ; *RNA, Satellite/genetics/metabolism ; Ribonucleoproteins/metabolism/genetics ; *Protein Aggregates ; Animals ; RNA Splicing ; Mice ; },
abstract = {RNA-driven protein aggregation leads to cellular dysregulation and contributes to the development of diseases and tumorigenesis. Here, we show that double homeobox 4 (DUX4), an early embryonic transcription factor and causative gene of facioscapulohumeral muscular dystrophy (FSHD), induces the accumulation of stable intranuclear RNAs, including nucleolar RNA and human satellite II (HSATII) RNA that drive protein aggregation in muscle cells. Specifically, HSATII RNA sequesters RNA methylation factors. HSATII-YBX-1 ribonucleoprotein (RNP) complex formation is mediated by HSATII double-stranded RNA and RNA methylase NSUN2 activity. Aberrant HSATII-RNP complexes affect RNA processing pathways, including RNA splicing. Differential splicing of genes mediated by HSATII-RNP complexes is associated with pathways known to be dysregulated by DUX4 expression. These findings highlight the broader influence of DUX4 on nuclear RNA dynamics and suggest that HSATII RNA could be a critical mediator of RNA processing regulation. Understanding the impact of HSATII-RNP formation on RNA processing provides insight into the molecular mechanisms underlying FSHD.},
}

Humans
*Homeodomain Proteins/metabolism/genetics
*Muscular Dystrophy, Facioscapulohumeral/genetics/metabolism/pathology
*RNA Processing, Post-Transcriptional
*RNA, Satellite/genetics/metabolism
Ribonucleoproteins/metabolism/genetics
*Protein Aggregates
Animals
RNA Splicing
Mice

@article {pmid41282907,
year = {2025},
author = {Reed, JC and Downs, C and McAllister, K and Mauer, C and McClurkan, CL and Wilson, D and Holzhauer, K and Dickerson, JA and Cannon, CA and Babu, TM and Golden, MR and Koelle, DM and Greninger, AL},
title = {Differentiating Mpox Infection and Vaccination Using a Validated Multiplex Orthopoxvirus IgG Serology Assay.},
journal = {medRxiv : the preprint server for health sciences},
volume = {},
number = {},
pages = {},
pmid = {41282907},
abstract = {The resurgence of monkeypox virus (MPXV) outbreaks has increased demand for validated serological assays to assess exposure and immunity. Cross-reactivity among orthopoxivuses, stemming from high sequence conservation, complicates distinguishing antibody responses from natural MPXV infection versus vaccination or other orthopoxvirus exposures. We validated the Meso Scale Discovery (MSD) V-PLEX Orthopoxvirus Panel 1 (IgG) Kit, which quantifies antibody levels to five MPXV antigens and their vaccina virus (VACV) orthologs, following Good Clinical Laboratory Practice (GCLP) guidelines. We assessed assay performance using serum from 26 individuals with prior mpox, 52 JYNNEOS vaccine recipients, and 179 unexposed controls. The assay reliably detected antibody responses in all exposed cohorts with peak levels observed 2-months post-vaccination. Antibody levels to specific antigens also correlated with Modified Vaccinia Ankara (MVA) neutralization titer, particularly for MPXV B6R/VACV B5R, MPXV E8L/VACV D8L, and MPXV M1R/VACV L1. Receiver operating characteristic (ROC) analysis showed that some individual antigens achieved high sensitivity and specificity for exposure detection (AUC > 0.96 for VACV D8L, MPXV B6R, VACV B5R); however, individual antigens performed poorly in distinguishing infection from vaccination. In contrast, antibody level ratios between some MPXV and VACV orthologs effectively differentiated MPXV infection from vaccinia vaccination with high sensitivity and specificity (e.g. MPXV A35R/VACV A33R ortholog ratio, AUC = 0.97, sensitivity = 0.97, specificity = 0.96). Our findings validate the MSD assay for clinical research and serosurveillance to assess MPXV immunity and support the utility of ortholog pair ratio analysis as a strategy to discriminate vaccinated and infected individuals.},
}

@article {pmid41328526,
year = {2025},
author = {Zhang, X and Vasan, S and Zheng, C and Prentice, RL and Navarro, SL and Tinker, L and Raftery, D and Gowda, GAN and Van Horn, L and Sun, Y and Tabung, FK and Pan, K and Lampe, JW and Neuhouser, ML},
title = {Calibrated Dietary Patterns and Cancer Risk in the Women's Health Initiative Cohorts.},
journal = {American journal of epidemiology},
volume = {},
number = {},
pages = {},
doi = {10.1093/aje/kwaf259},
pmid = {41328526},
issn = {1476-6256},
abstract = {We developed calibration equations using metabolomics from fasting blood and 24-hour urine for Healthy Eating Index 2010 (HEI-2010) and Alternative Healthy Eating Index 2010 (AHEI-2010) to address measurement error from self-reported diet. We examined associations between metabolomic-calibrated dietary patterns and cancer risk in the Women's Health Initiative (WHI, n=108,522). Metabolomic signatures were created from a WHI Feeding (n=153;2010-2014) and WHI Observational Study (n=450;2006-2009). Dietary patterns were regressed on metabolites using the feeding study food intake records. Metabolomic-based dietary patterns were estimated from 24-hour dietary recalls, FFQ and 4DFR in the Observational Study using a stepwise approach. Cox regression estimated cancer risk of metabolomic-calibrated dietary patterns with a median follow-up of 15.8 years. Adjusted R2 for HEI-2010 and AHEI-2010 calibration equations were 57.5% and 48.8% for FFQ, 61.6% and 62.6% for 4DFR, and 52.5% and 53.2% for dietary recalls. Without calibration, a 20% increment in HEI-2010 was associated with lower risk of colorectal (HR=0.94, 95% CI=0.90-0.99), lung (HR=0.90, 95% CI=0.86-0.94), bladder (HR=0.86, 95% CI=0.75-0.99), and total invasive cancers (HR=0.98, 95% CI=0.96-0.99). With metabolomic calibration, higher HEI-2010 was associated with lower risk of lung (HR=0.79, 95% CI=0.71-0.88) and total invasive cancers (HR=0.96, 95% CI=0.92-1.00). Metabolomic-calibrated dietary patterns might mitigate measurement errors and strengthen diet-cancer associations.},
}

@article {pmid41326929,
year = {2025},
author = {Hinkel, RE and Kalima, M and Msadabwe, SC and Mwaba, CK and Ng'uni, FC and Fisa, R and Tambatamba, BC and Chuba, A and Trejo, MJ and Lishimpi, K and Soliman, AS},
title = {False-Positive Screening, Over-Referral, and Length of time between Cervical Cancer Early Detection and Confirmed Diagnosis Over Nine Years in Lusaka, Zambia.},
journal = {Journal of epidemiology and global health},
volume = {},
number = {},
pages = {},
doi = {10.1007/s44197-025-00478-8},
pmid = {41326929},
issn = {2210-6014},
abstract = {PURPOSE: While Zambia has an efficient program for early detection of cervical cancer, most cases are diagnosed at advanced stages. This study examined the time between suspecting cancers at screening clinics and histopathologic confirmation of cervical cancer in the Lusaka Province of Zambia.

METHODS: This study included the records of 3,483 women with suspected cancerous lesions identified by visual inspection of the cervix (VIA) who were referred from Lusaka Province screening facilities from 2014 to 2022. The study linked screening records with corresponding histopathologic results of the lesions after examination at the University Teaching Hospital. Variables abstracted from the medical records included age, human immunodeficiency virus (HIV) status, district of residence and referral clinic, and dates of referral and confirmed diagnosis.

RESULTS: False-positive VIA results constituted about 90% of all referrals. Women living with HIV (WLWH) had longer wait times between screening referrals and receipt of histopathologic results, most notably women coming from rural settings (median of 146 days) compared to urban settings (median of 69 days) (p < 0.05). Among women diagnosed with low-grade intraepithelial lesions, WLWH had a 63% higher risk of confirmed cancer diagnosis (CI: 1.16, 2.29) than women not living with HIV. For high-grade intraepithelial lesions, the adjusted HR showed WLWH having a 17% (CI: 0.89, 1.53) higher risk of confirmed cancer diagnosis compared to women not living with HIV.

CONCLUSION: The high rate of false-positives and long wait times call for expanded service infrastructure, particularly in rural settings, and continuing provider education/training to optimize screening sensitivity and shorten wait times in the Lusaka Province. Such measures may reduce the overload on the existing histopathology infrastructure and may provide lessons for other limited-resource countries facing similar cancer control and prevention challenges.},
}

@article {pmid41326736,
year = {2025},
author = {Peluso, MJ and Sandel, DA and Deitchman, AN and Kim, SJ and Dalhuisen, T and Tummala, HP and Tibúrcio, R and Zemelko, L and Borgo, GM and Singh, SS and Schwartz, K and Deswal, M and Williams, MC and Hoh, R and Shimoda, M and Narpala, S and Serebryannyy, L and Khalili, M and Vendrame, E and SenGupta, D and Whitmore, LS and Tisoncik-Go, J and Gale, M and Koup, RA and Mullins, JI and Felber, BK and Pavlakis, GN and Reeves, JD and Petropoulos, CJ and Glidden, DV and Spitzer, MH and Gama, L and Caskey, M and Nussenzweig, MC and Chew, KW and Henrich, TJ and Yukl, SA and Cohn, LB and Deeks, SG and Rutishauser, RL},
title = {Correlates of HIV-1 control after combination immunotherapy.},
journal = {Nature},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41586-025-09929-5},
pmid = {41326736},
issn = {1476-4687},
abstract = {The identification of therapeutic strategies to induce sustained antiretroviral therapy (ART)-free control of HIV infection is a major priority.[1] Combination immunotherapy including HIV vaccination, immune stimulation/latency reversal, and passive transfer of broadly neutralizing antibodies (bNAbs) has shown promise in non-human primate models,[2-6] but few studies have translated such approaches into people. We performed a single-arm, proof-of-concept study in ten people with HIV on ART combining the following three approaches: (1) therapeutic vaccination with an HIV/Gag conserved element (CE)-targeted DNA+IL-12 prime/MVA boost regimen followed by (2) administration of two bNAbs (10-1074, VRC07-523LS) and a toll-like receptor 9 agonist (lefitolimod) during ART suppression, followed by (3) repeat bNAb administration at the time of ART interruption (NCT04357821). Seven of the ten participants exhibited post-intervention control after stopping ART, independent of residual bNAb plasma levels. Robust expansion of activated CD8+ T cells early in response to rebounding virus correlated with lower median viral load following peak viremia off ART. These data suggest that combination immunotherapy approaches might prove effective to induce sustained control of HIV by slowing rebound and improving CD8+ T cell responses, and that these approaches should continue to be optimized.},
}

@article {pmid41326734,
year = {2025},
author = {Gaebler, C and Kor, S and Allers, K and Perotti, M and Mwangi, D and Meixenberger, K and Hanke, K and Trenkner, T and Kraus, T and Sha, Y and Arentowicz, C and Odidika, S and Grahn, N and Scheck, R and Perkins, N and Pardons, M and Igbokwe, V and Corman, V and Burmeister, T and Blau, O and Sürücü, G and Pruß, A and Schneider, CG and Klausen, G and Sauter, J and Klein, F and Sander, LE and Hofmann, J and Vuong, L and Bullinger, L and Penter, L and Gruell, H and Reeves, DB and Schommers, P and Hoelzemer, A and Obermeier, M and Blau, IW and Schneider, T and Penack, O},
title = {Sustained HIV-1 remission after heterozygous CCR5Δ32 stem cell transplantation.},
journal = {Nature},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41586-025-09893-0},
pmid = {41326734},
issn = {1476-4687},
abstract = {HIV cure is exceptionally rare, documented in only six cases among the estimated 88 million individuals who have acquired HIV since the epidemic's onset[1-6]. Successful cures, including the pioneering Berlin patient, are limited to individuals receiving allogeneic stem cell transplants (allo-SCT) for hematological cancers. HIV resistance from stem cell donors with the rare homozygous CCR5 Δ32 mutation was long considered the main mechanism for HIV remission without antiretroviral therapy (ART), but recent reports highlight CCR5-independent mechanisms as important contributors to HIV cure[6-8]. Here, we provide new evidence for this conceptual shift, reporting exceptionally long, treatment-free HIV remission following allo-SCT with functionally active CCR5. A heterozygous CCR5 wild-type/Δ32 male living with HIV received allo-SCT from an HLA-matched unrelated heterozygous CCR5 wild-type/Δ32 donor as treatment for acute myeloid leukemia. Three years after allo-SCT, the patient discontinued ART. To date, HIV remission has been sustained for over six years with undetectable plasma HIV RNA. Reservoir analysis revealed intact proviral HIV before transplantation, but no replication-competent virus in blood or intestinal tissues after allo-SCT. Declining or absent HIV-specific antibody and T cell responses support the absence of viral activity. High antibody-dependent cellular cytotoxicity (ADCC) activity at the time of transplantation may have contributed to HIV reservoir clearance. These results demonstrate that CCR5Δ32-mediated HIV resistance is not essential for durable remission, underscoring the importance of effective viral reservoir reductions in HIV cure strategies.},
}

@article {pmid41326606,
year = {2025},
author = {Yu, TC and Kikawa, C and Dadonaite, B and Loes, AN and Englund, JA and Bloom, JD},
title = {Pleiotropic mutational effects on function and stability constrain the antigenic evolution of influenza haemagglutinin.},
journal = {Nature ecology & evolution},
volume = {},
number = {},
pages = {},
pmid = {41326606},
issn = {2397-334X},
support = {R01AI165821//U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (NIAID)/ ; 75N93021C00015/AI/NIAID NIH HHS/United States ; T32GM007270//U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS)/ ; DGE-2140004//National Science Foundation (NSF)/ ; },
abstract = {The evolution of human influenza virus haemagglutinin (HA) involves simultaneous selection to acquire antigenic mutations that escape population immunity while preserving protein function and stability. Epistasis shapes this evolution, as an antigenic mutation that is deleterious in one genetic background may become tolerated in another. However, the extent to which epistasis can alleviate pleiotropic conflicts between immune escape and protein function/stability is unclear. Here we measure how all amino acid mutations in the HA of a recent human H3N2 influenza strain affect its cell entry function, acid stability and neutralization by human serum antibodies. We find that epistasis has entrenched certain mutations so that reverting to the ancestral amino acid identity in earlier strains is no longer tolerated. Epistasis has also enabled the emergence of antigenic mutations that were detrimental to the cell entry function of HA in earlier strains. However, epistasis appears insufficient to overcome the pleiotropic costs of antigenic mutations that impair the stability of HA, explaining why some mutations that strongly escape human antibodies never fix in nature. Our results refine our understanding of the mutational constraints that shape recent H3N2 influenza evolution: epistasis can enable antigenic change, but pleiotropic effects can restrict its trajectory.},
}

@article {pmid41325870,
year = {2025},
author = {Khouderchah, C and Lynch, RC and Holmberg, LA},
title = {Impact of Post-Autologous Peripheral Blood Stem Cell Transplant (ASCT)- Granulocyte Colony Stimulating Factor (G-CSF) on Toxicity Profiles in Hodgkin Lymphoma (HL) Patients Receiving Pre-ASCT Immune Checkpoint Inhibitors (ICI).},
journal = {Transplantation and cellular therapy},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jtct.2025.11.035},
pmid = {41325870},
issn = {2666-6367},
}

@article {pmid41325737,
year = {2025},
author = {Rillamas-Sun, E and Huang, Y and Langley, BO and Donzella, SM and Cobos, S and Guthrie, KA and Davidson, NE and Di, C and Greenlee, H},
title = {Comparisons of Physical Activity and Sedentary Behavior Measurements From the ActiGraph, International Physical Activity Questionnaire, and Fitbit in Women With History of Breast Cancer.},
journal = {Journal of physical activity & health},
volume = {},
number = {},
pages = {1-9},
doi = {10.1123/jpah.2025-0009},
pmid = {41325737},
issn = {1543-5474},
abstract = {BACKGROUND: Self-reported and wearable device derived data on physical activity (PA) differ in burden, transparency, and validity, underscoring the need for comparison in cancer survivorship research. Physical activity and sedentary behavior measured from the ActiGraph, International Physical Activity Questionnaire (IPAQ), and Fitbit Inspire device in women with early-stage breast cancer were compared.

METHODS: Breast cancer survivors participating in a lifestyle intervention trial concurrently provided ActiGraph and IPAQ data at baseline and 6 months. Fitbit devices were used for PA self-monitoring after randomization and data were available at follow-up only. Comparisons of PA measurements were estimated via Pearson correlation coefficients and visualized using Bland-Altman plots. Prevalence of meeting moderate to vigorous PA guidelines of ≥150 minutes per week were also calculated.

RESULTS: At baseline (n = 73), mean vigorous PA was 2 and 5 minutes per day for ActiGraph and IPAQ, respectively (r = .22, P = .06), while mean sedentary hours per day were 11.4 and 6.2 for ActiGraph and IPAQ, respectively (r = .29, P = .01). Correlations between ActiGraph and IPAQ at 6-month follow-up (n = 50) were not statistically significant. Six-month comparisons of PA measures between ActiGraph and Fitbit (n = 30) were higher than those between IPAQ and Fitbit (n = 30). Prevalence of meeting moderate to vigorous PA guidelines at baseline was 40% for ActiGraph and 59% for IPAQ (P = .01). At 6 months, proportions meeting moderate to vigorous PA guidelines were 50%, 73%, and 67% for ActiGraph, IPAQ, and Fitbit, respectively.

CONCLUSION: Correlations of PA comparing self-report from IPAQ and activity devices from ActiGraph and Fitbit were weak. Strengths and limitations of PA measurement methods should be weighed accordingly in studies of lifestyle interventions for breast cancer survivors.},
}

@article {pmid41325571,
year = {2025},
author = {Tomasini, P and Wang, Y and Li, Y and Felip, E and Wu, L and Cui, J and Besse, B and Spira, AI and Neal, JW and Goto, K and Baik, CS and Marmarelis, ME and Ichihara, E and Zhang, Y and Lee, JS and Lee, SH and Yang, JC and Michels, S and Anastasiou, Z and Curtin, JC and Lyu, X and Mahoney, J and Demirdjian, L and Meyer, CS and Zhang, Y and Leconte, I and Lorenzini, P and Knoblauch, RE and Trani, L and Baig, M and Bauml, JM and Cho, BC and , },
title = {Amivantamab Plus Lazertinib in Atypical EGFR-Mutated Advanced Non-Small Cell Lung Cancer: Results From CHRYSALIS-2.},
journal = {Journal of clinical oncology : official journal of the American Society of Clinical Oncology},
volume = {},
number = {},
pages = {JCO2402835},
doi = {10.1200/JCO-24-02835},
pmid = {41325571},
issn = {1527-7755},
abstract = {PURPOSE: For patients with advanced non-small cell lung cancer (NSCLC) harboring atypical epidermal growth factor receptor (EGFR) mutations (eg, S768I, L861Q, G719X), efficacy of current treatment options is limited.

PATIENTS AND METHODS: CHRYSALIS-2 Cohort C enrolled participants with NSCLC harboring atypical EGFR mutations (G719X, S768I, L861Q, etc) and ≤2 previous lines of therapy. Participants were treatment-naïve or previously received first- or second-generation EGFR tyrosine kinase inhibitors. Coexisting exon 20 insertions, exon 19 deletions, or exon 21 L858R mutations were exclusionary. Participants received 1,050 mg (1,400 mg if ≥80 kg) intravenous amivantamab once weekly for the first 4 weeks and then once every 2 weeks plus 240 mg oral lazertinib once daily. The primary end point was investigator-assessed objective response rate (ORR).

RESULTS: As of January 12, 2024, 105 participants received amivantamab-lazertinib. Most common atypical mutations were G719X (56%), L861X (26%), and S768I (23%), including single and compound mutations. In the overall population (median follow-up: 16.1 months), the ORR was 52% (95% CI, 42 to 62). The median duration of response (mDoR) was 14.1 months (95% CI, 9.5 to 26.2). The median progression-free survival (mPFS) was 11.1 months (95% CI, 7.8 to 17.8); median overall survival (mOS) was not estimable (NE; 95% CI, 22.8 to NE). Adverse events were consistent with previous studies and primarily grade 1 and 2. Among treatment-naïve participants, the ORR was 57% (95% CI, 42 to 71). The mPFS was 19.5 months (95% CI, 11.2 to NE), the mDoR was 20.7 months (95% CI, 9.9 to NE), and mOS was NE (95% CI, 26.3 to NE). Solitary or compound EGFR mutations had no major impact on ORR. The ORR in participants with P-loop and αC-helix compressing, classical-like, and T790M-like mutations was 45% (n = 38), 64% (n = 14), and 67% (n = 3), respectively.

CONCLUSION: In participants with atypical EGFR-mutated advanced NSCLC, amivantamab-lazertinib demonstrated clinically meaningful antitumor activity with no new safety signals.},
}

@article {pmid41325480,
year = {2025},
author = {Johnson, MM and Sung, K and Haddox, HK and Vora, AA and Araki, T and Victora, GD and Song, YS and Fukuyama, J and Matsen Iv, FA},
title = {Nucleotide context models outperform protein language models for predicting antibody affinity maturation.},
journal = {PLoS computational biology},
volume = {21},
number = {12},
pages = {e1013758},
doi = {10.1371/journal.pcbi.1013758},
pmid = {41325480},
issn = {1553-7358},
abstract = {Antibodies play a crucial role in adaptive immunity. They develop as B cell receptors (BCRs): membrane-bound forms of antibodies that are expressed on the surfaces of B cells. BCRs are refined through affinity maturation, a process of somatic hypermutation (SHM) and natural selection, to improve binding to an antigen. Computational models of affinity maturation have developed from two main perspectives: molecular evolution and language modeling. The molecular evolution perspective focuses on nucleotide sequence context to describe mutation and selection; the language modeling perspective involves learning patterns from large data sets of protein sequences. In this paper, we compared models from both perspectives on their ability to predict the course of antibody affinity maturation along phylogenetic trees of BCR sequences. This included models of SHM, models of SHM combined with an estimate of selection, and protein language models. We evaluated these models for large human BCR repertoire data sets, as well as an antigen-specific mouse experiment with a pre-rearranged cognate naive antibody. We demonstrated that precise modeling of SHM, which requires the nucleotide context, provides a substantial amount of predictive power for predicting the course of affinity maturation. Notably, a simple nucleotide-based convolutional neural network modeling SHM outperformed state-of-the-art protein language models, including one trained exclusively on antibody sequences. Furthermore, incorporating estimates of selection based on a custom deep mutational scanning experiment brought only modest improvement in predictive power. To support further research, we introduce EPAM (Evaluating Predictions of Affinity Maturation), a benchmarking framework to integrate evolutionary principles with advances in language modeling, offering a road map for understanding antibody evolution and improving predictive models.},
}

@article {pmid41325432,
year = {2025},
author = {Müller, NF and Wick, RR and Judd, LM and Williamson, DA and Bedford, T and Howden, BP and Duchêne, S and Ingle, DJ},
title = {Quantifying plasmid movement in drug-resistant Shigella species using phylodynamic inference.},
journal = {PLoS pathogens},
volume = {21},
number = {12},
pages = {e1013621},
doi = {10.1371/journal.ppat.1013621},
pmid = {41325432},
issn = {1553-7374},
abstract = {The 'silent pandemic' of antimicrobial resistance (AMR) represents a significant global public health threat. AMR genes in bacteria are often carried on mobile elements, such as plasmids. The horizontal movement of plasmids allows AMR genes and resistance to key therapeutics to disseminate in a population. However, the quantification of the movement of plasmids remains challenging with existing computational approaches. Here, we introduce a novel method that allows us to reconstruct and quantify the movement of plasmids in bacterial populations over time. To do so, we model chromosomal and plasmid DNA co-evolution using a joint coalescent and plasmid transfer process in a Bayesian phylogenetic network approach. This approach reconstructs differences in the evolutionary history of plasmids and chromosomes to reconstruct instances where plasmids likely move between bacterial lineages while accounting for parameter uncertainty. We apply this new approach to a five-year dataset of Shigella, exploring the plasmid transfer rates of five different plasmids with different AMR and virulence profiles. In doing so, we reconstruct the co-evolution of the large Shigella virulence plasmid with the chromosome DNA. We quantify higher plasmid transfer rates of three small plasmids that move between lineages of Shigella sonnei. Finally, we determine the recent dissemination of a multidrug-resistant plasmid between S. sonnei and S. flexneri lineages in multiple independent events and through steady growth in prevalence since 2010. This approach has a strong potential to improve our understanding of the evolutionary dynamics of AMR-carrying plasmids as they are introduced, circulate, and are maintained in bacterial populations.},
}

@article {pmid41325059,
year = {2025},
author = {Zhang, Y and Walker, RW and Kaplan, RC and Qi, Q},
title = {Added sugars, gut microbiota, and host health.},
journal = {Gut microbes},
volume = {17},
number = {1},
pages = {2592431},
doi = {10.1080/19490976.2025.2592431},
pmid = {41325059},
issn = {1949-0984},
mesh = {Humans ; *Gastrointestinal Microbiome/drug effects ; Animals ; Bacteria/classification/metabolism/genetics/isolation & purification ; *Dietary Sugars/adverse effects/metabolism ; Fatty Acids, Volatile/metabolism ; Obesity/microbiology ; },
abstract = {Excessive intake of added sugars is a global public health concern, given its established links with cardiometabolic disease and other chronic conditions. Emerging evidence suggests that the gut microbiota might mediate the harms of high sugar intake. In this review, we summarize evidence from animal and human studies regarding the impact of added sugar intake on gut microbiota diversity and composition, and discuss potential mechanisms linking sugar-induced microbial changes to health outcomes. Added sugars, including glucose, fructose, and sucrose, can alter gut microbial diversity, enrich sugar-utilizing taxa, and deplete short-chain fatty acid-producing bacteria. These microbial changes may impair gut barrier integrity, increase luminal oxygen and alternative electron acceptors under inflammatory conditions, reduce short-chain fatty acid production, alter bile acid and amino acid metabolism, and promote translocation of endotoxin across the gut barrier into the bloodstream. Collectively, these pathways may link added sugar intake to irritable bowel syndrome, obesity, liver steatosis, diabetes, and cardiovascular diseases. However, inconsistent results on alterations in the gut microbiota related to added sugar intake were observed across studies, which may be due to differences in sugar dose and form (liquid vs. solid), as well as population variation in background diet, host genetics, and gut microbial ecology. Future research should focus on mechanistic investigations, characterization of inter-individual variability in response to added sugar intake, and clinical studies to assess whether dietary or therapeutic interventions can reverse sugar-induced gut microbial changes and improve host health outcomes.},
}

Humans
*Gastrointestinal Microbiome/drug effects
Animals
Bacteria/classification/metabolism/genetics/isolation & purification
*Dietary Sugars/adverse effects/metabolism
Fatty Acids, Volatile/metabolism
Obesity/microbiology

@article {pmid41324589,
year = {2025},
author = {Murray, JD and Einhaus, TK and Radtke, S and Bar, KJ and Peterson, CW and Kiem, HP},
title = {Engraftment of gene-edited hematopoietic stem cells after antibody-drug conjugate conditioning in nonhuman primates.},
journal = {Blood advances},
volume = {},
number = {},
pages = {},
doi = {10.1182/bloodadvances.2025017838},
pmid = {41324589},
issn = {2473-9537},
abstract = {Hematopoietic stem cell (HSC) gene therapies provide lifelong benefit in numerous hematological diseases and disorders, but safety and toxicity remain a critical barrier for routine application. In the setting of immunodeficiency syndromes and infectious diseases such as human immunodeficiency virus (HIV) infection, conditioning regimens may exacerbate immune dysfunction, blunting or impairing overall efficacy. Here, we conduct a head-to-head comparison of two novel antibody drug conjugates (ADC) with a pyrrolobenzodiazepine (PDB) payload for autologous transplantation in rhesus macaques: ADCs targeting either CD117 or CD45 and benchmarked against the clinical standard busulfan. We quantified extent of myeloablation and immunosuppression, time to hematopoietic recovery, long-term engraftment of CCR5 CRISPR-edited autologous HSC, and resistance to infection when challenged with increasing concentrations of an HIV-like virus. Both ADCs enabled engraftment of CRISPR-edited HSCs, although with lower levels of long-term editing compared to busulfan. We observed myeloablation with similar times to hematopoietic recovery and preserved lymphocyte counts with all three conditioning regimens, but neither ADC conditioning nor busulfan enabled sufficient CCR5 editing for viral immunity. While these results only apply to the specific ADC conditioning protocols tested here, they are a step towards developing targeted strategies to engraft cells with therapeutic edits and highlight the need for further refinement of antibody-based selection.},
}

@article {pmid41324575,
year = {2025},
author = {Coronado, GD and Hoffman, RM and Llavona-Ortiz, J and Rutter, CM},
title = {The Centers for Medicare and Medicaid Services and others misunderstand stool testing for colorectal cancer.},
journal = {Journal of the National Cancer Institute},
volume = {},
number = {},
pages = {},
doi = {10.1093/jnci/djaf341},
pmid = {41324575},
issn = {1460-2105},
abstract = {The May 2021 Centers for Medicare and Medicaid Services (CMS) coverage determination allowed reimbursement for blood-based biomarker tests and other tests for colorectal cancer (CRC) screening that meet minimum 74% sensitivity and 90% specificity thresholds. However, these performance benchmarks fail to account for the importance of detecting precancerous lesions and the impact of the recommended testing interval on the effectiveness of screening. We review the limitations of the CMS criteria, summarize supporting evidence for stool-based testing and colonoscopy as effective and cost-efficient screening modalities, and offer recommendations to strengthen CMS coverage decisions to better align with public health goals in CRC prevention.},
}

@article {pmid41324241,
year = {2025},
author = {Sadowska-Klasa, A and Lim, FY and Xie, H and Zamora, D and Stevens-Ayers, T and Leisenring, WM and Edmison, BC and De Rosa, SC and Mielcarek, M and Boeckh, M},
title = {New Insights Into Factors Shaping CMV-Specific T-Cell Polyfunctionality After Hematopoietic Cell Transplantation.},
journal = {American journal of hematology},
volume = {},
number = {},
pages = {},
doi = {10.1002/ajh.70152},
pmid = {41324241},
issn = {1096-8652},
support = {//Fred Hutchinson Cancer Research Center/ ; //Gdański Uniwersytet Medyczny/ ; CA15704/NH/NIH HHS/United States ; K23AI163343/NH/NIH HHS/United States ; },
abstract = {Polyfunctional cytomegalovirus (CMV)-specific T cells are critical for antiviral immunity in allogeneic hematopoietic cell transplantation (HCT) recipients. However, gaps remain in managing refractory CMV and optimizing virus-specific cellular therapy (VST). We conducted a comparative analysis of how timing and dosing of immunosuppressive agents, including post-transplant cyclophosphamide (PT-Cy), corticosteroids, mycophenolate mofetil (MMF), and calcineurin inhibitors (CNIs), shape CMV-specific T-cell polyfunctionality. CD4[+] and CD8[+] T-cell responses (IFN-γ plus ≥ 1 functional marker) were assessed following pp65 stimulation within 100 days post-HCT in the pre- and post-letermovir era. Among 243 patients, 31% exhibited polyfunctional CD4[+] and CD8[+] responses. PT-Cy did not significantly impair T-cell functionality. Cyclosporine was associated with higher frequencies of polyfunctional T cells compared to tacrolimus, even at concentrations above the therapeutic range. Intermediate (≥ 0.5 mg/kg) and high-dose (≥ 1 mg/kg) corticosteroids, especially within 2-4 weeks before testing, significantly suppressed T-cell responses, though rapid tapering preserved function. Prolonged administration of MMF (≥ 2000 mg) diminished T-cell polyfunctionality. These findings provide novel insights into the importance of timing and dosing of the immunosuppressive effects of PT-Cy, corticosteroids, MMF and CNIs on CMV-specific immunity. Adjusting immunosuppression in specific time windows may improve the management of refractory CMV infections and optimize VST in HCT recipients.},
}

@article {pmid41279560,
year = {2025},
author = {Sohn, MH and Dubocanin, D and Vollger, MR and Kwon, Y and Minkina, A and Munson, KM and Hart, SF and Ranchalis, JE and Parmalee, NL and Sedeño-Cortés, AE and Ou, J and Au, NY and Bohaczuk, S and Carroll, B and Frazar, CD and Harvey, WT and Hoekzema, K and Huang, MF and Jacques, CN and Jensen, DM and Kolar, JT and Lee, R and Lin, J and Loy, K and Mack, T and Mao, Y and Pham, MM and Ryke, E and Smith, JD and Sutherlin, L and Swanson, EG and Weiss, JM and Wg, SA and Carvalho, C and Coorens, TH and Harris, K and Wei, CL and Eichler, EE and Altemose, N and Bennett, JT and Stergachis, AB},
title = {A telomere-to-telomere map of somatic mutation burden and functional impact in cancer.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {41279560},
issn = {2692-8205},
abstract = {Oncogenesis involves widespread genetic and epigenetic alterations, yet the full spectrum of somatic variation genome-wide remains unresolved. We generated a near-telomere-to-telomere (T2T) diploid assembly of a donor paired with deep short- and long-read sequencing of their melanoma. This revealed that 16% of somatic variants occur in sequences absent from GRCh38, with satellite repeats acting as hotspots for UV-induced damage due to sequence-intrinsic mutability and inefficient repair. Centromere kinetochore domains emerged as focal sites of structural, genetic, and epigenetic variation, leading to remodeling of centromere kinetochore binding domains during tumor evolution. Single-molecule telomere reconstructions uncovered cycles of attrition, deletion, and telomerase-mediated extension that shape cancer telomeres. Finally, diploid chromatin maps exposed that copy number alterations and epimutations, rather than point mutations, predominate in rewiring cancer regulatory programs. These findings define the full landscape of a cancer's somatic variation and their functional impact, establishing a blueprint for T2T studies of mosaicism.},
}

@article {pmid41323215,
year = {2025},
author = {Bobić, M and Bushe, DH and Lee, H and Winey, BA and Efstathiou, JA and Paganetti, H and Pursley, J and Peters, N and Nenoff, L},
title = {Comparison of cone beam computed tomography post-processing methods for online adaptive proton therapy of prostate cancer.},
journal = {Physics and imaging in radiation oncology},
volume = {36},
number = {},
pages = {100858},
pmid = {41323215},
issn = {2405-6316},
abstract = {BACKGROUND AND PURPOSE: Although cone beam computed tomography (CBCT) enables online adaptive radiotherapy, its CT number accuracy may be insufficient for online adaptive proton therapy (OAPT). We compared proton dose distributions calculated directly on CBCT with calculations using additional CBCT image-processing methods in prostate cancer.

MATERIALS AND METHODS: Retrospective proton plans were created for 10 prostate patients originally treated with 5-fraction online adaptive photon radiotherapy using CBCT. These plans were forward-calculated on each CBCT with four different approaches: (1) the clinical CBCT with a dedicated CT number calibration, (2) CBCT with histogram correction, (3) CT deformed to the CBCT, and (4) deformed CT with an air-cavity correction. Additionally, adaptive treatment using an OAPT workflow was simulated for each fraction and compared among the four CBCT-based methods. Dose-volume histograms (DVH) and related parameters were compared between the four methods for both non-adaptive and online adaptive treatment simulations.

RESULTS: Proton dose distributions were comparable across all CBCT-based strategies, with median differences of up to 1% for all DVH metrics compared to a reference method. Larger differences were observed for doses calculated directly on the CBCT for patient geometries deviating from the CBCT-specific calibration. Despite these differences, all four methods indicated the dosimetric benefits of OAPT over non-adaptive treatment.

CONCLUSION: An advanced CBCT system enables proton dose calculations performed directly on the CBCT, demonstrating sufficient accuracy for integration into an OAPT workflow. Additional CBCT-based post-processing techniques are recommended to maximize the dosimetric benefit of plan adaptation in all patient populations.},
}

@article {pmid41323153,
year = {2025},
author = {Ojee, E and Odiyo, J and Adhiambo, J and Mabele, E and Omondi, V and Begnel, ER and Chohan, BH and Kinuthia, J and Gantt, S and Lehman, DA and Aluvaala, J and Were, F and Were, V and Wamalwa, D and Slyker, J},
title = {A cost analysis of postpartum home visit programming in Kenya: estimates to aid policymakers.},
journal = {Frontiers in health services},
volume = {5},
number = {},
pages = {1644078},
pmid = {41323153},
issn = {2813-0146},
abstract = {INTRODUCTION: The World Health Organization (WHO) and UNICEF recommend at least two postnatal home visits by a health provider within the first two weeks of life to improve newborn survival. Kenya's Universal Health Coverage (UHC) initiative includes a home-visit strategy to advance Sustainable Development Goal (SDG) 3.2, which targets reducing neonatal mortality to below 12 per 1,000 live births. We estimated the costs of starting a postnatal home-visit program in a level three health facility in Kenya, based on recommendations from Kenya's Ministry of Health policymakers.

METHODS: An ingredients-based costing method was used to determine the actual costs of home visits incurred during a research project conducted in 2019, and to estimate program costs from the government's perspective as the payer. Per-visit costs were calculated for three staffing approaches: Community Health Promoter (CHP), Registered Nurse (RN), and a Combined model where two providers (RN + CHP) visited each home together.

RESULTS: Staff salaries and transportation costs were the main drivers of recurrent program expenses. The CHP approach had the lowest total cost at $27,302 ($24.46 per visit), followed by the RN-only approach at $36.45 per visit, while the Combined model (RN+CHP) was the most expensive at $52.10 per visit. Discussions with policymakers noted that the RN+CHP approach was least feasible and scalable. They proposed an alternative "Hybrid" model in line with current programs being scaled up: weekly RN visits during the first month of life (neonatal period), and quarterly CHP visits thereafter.

DISCUSSION: This study presents a costing tool and generalizable formula that policymakers can use to estimate program costs based on different facility characteristics and staffing needs. The findings can support Kenya's efforts to scale up postnatal home-visit programs to improve maternal and newborn health outcomes within the UHC framework.},
}

@article {pmid41321622,
year = {2025},
author = {Nukaya, M and Carney, PR and Cafferty, C and Zahed, K and Yun, I and Al-Adra, DP and Kazim, NA and Farghli, AR and Chan, M and Stram, A and Kratz, JD and Berres, ME and Yen, A and Gujral, TS and Sethupathy, P and Bradfield, CA and Ronnekleiv-Kelly, SM},
title = {CDK7 is a novel therapeutic target in fibrolamellar carcinoma.},
journal = {iScience},
volume = {28},
number = {12},
pages = {113925},
pmid = {41321622},
issn = {2589-0042},
abstract = {Fibrolamellar Carcinoma (FLC) is a rare and deadly cancer that arises in young, otherwise healthy patients. For patients that cannot be treated with surgery, only 30%-45% survive to 5 years with current treatment options. These poor survival odds highlight the need for new therapeutic targets. Using patient samples, we identified that abnormal function of cyclin-dependent kinase 7 (CDK7) is a key component of pathways that are essential for FLC cancer cell identity and survival. Consequently, drug inhibitors of CDK7 suppressed these abnormal pathways and also caused cancer cell death in a dose-dependent manner. This held true in several patient-derived models of FLC. We then found that inhibition of CDK7 can combine with other drug candidates to increase the therapeutic response in FLC cells. Taken together, this suggests CDK7 is a promising target for future treatment in human FLC.},
}

@article {pmid41321225,
year = {2025},
author = {Sekeres, MA and Mattison, RJ and Artz, AS and Baer, MR and Chua, CC and Demichelis-Gomez, R and Egan, PC and Fletcher, L and Foucar, CE and Garcia, JS and Gilberto, L and Gómez-De León, A and Lancet, JE and Loh, KP and Malcovati, L and Marini, BL and Platzbecker, U and Sorror, ML and Tinsley-Vance, S and Treitz, J and Oliveros, MJ and Ibrahim, S and Roldan, Y and Guyatt, GH and Brignardello-Petersen, R},
title = {American Society of Hematology 2025 guidelines for treating newly diagnosed acute myeloid leukemia in older adults.},
journal = {Blood advances},
volume = {},
number = {},
pages = {},
doi = {10.1182/bloodadvances.2025017934},
pmid = {41321225},
issn = {2473-9537},
abstract = {Older adults with acute myeloid leukemia (AML) represent a cancer population in whom disease-based risk factors, comorbidities, patient goals, and treatment risks and benefits influence treatment recommendations. These evidence-based guidelines from the American Society of Hematology (ASH) are intended to support patients, clinicians and other health professionals in their decisions about management of AML in older adults. ASH formed a multidisciplinary guideline panel, including patient representatives, that minimized bias from conflicts of interest. Clarity Research Group at McMaster University supported the guideline development process, including updating or performing systematic evidence reviews. The panel prioritized questions and outcomes according to their importance for clinicians and patients. The panel used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach, including Evidence-to-Decision frameworks, to assess evidence and make recommendations. The panel agreed on 9 critical clinical recommendations for managing AML in older adults, mirroring real-time practitioner-patient conversations: the decision to pursue antileukemic treatment vs. best supportive management; traditional induction and post-remission therapy vs. hypomethylating agent or low-dose cytarabine, or combinations with venetoclax; the role and duration of post-remission therapy; combinations with venetoclax vs. monotherapy; the use of targeted therapy, including IDH and FLT3 inhibitors, in appropriate patients; the role of hematopoietic stem cell transplantation in non-favorable prognosis AML; and the role of transfusion support for patients no longer receiving antileukemic therapy. Key recommendations of these guidelines include treatment over best supportive care; venetoclax-based regimens over monotherapies; and incorporation of FLT3 inhibitors into traditional induction and post-remission therapy.},
}

@article {pmid41279611,
year = {2025},
author = {Mullins, JI and Deng, W and Giorgi, EE and Magaret, CA and Rolland, M and Bhattacharya, T and Westfall, DH and Yssel, AEJ and Bumgarner, RE and Murrell, B and Ndung'u, T and Robb, ML and Rossenkhan, R and Edlefsen, PT and Dong, KL and Chen, L and Gwashu-Nyangiri, A and Zhao, H and Thebus, R and Sawe, F and Nitayaphan, S and York, T and Matten, D and Murrell, H and Pankow, AP and Juraska, M and Ludwig, J and Hural, J and Cohen, MS and Corey, L and McElrath, MJ and Gilbert, PB and Williamson, C},
title = {Long-Read Deep Sequencing Reveals High Rates of Multilineage Transmission and Rapid Viral Population Changes in Acute HIV Infection.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {41279611},
issn = {2692-8205},
abstract = {Understanding the selective forces acting upon HIV early in infection is crucial to design prevention strategies. By leveraging deep sequencing and the short diagnostic intervals of the FRESH and RV217 cohorts (median 4 days) between the last-negative and first-positive RNA tests, we captured a precise and early snapshot of acute HIV infection. The frequency of multiple transmitted viruses of 38% in these as well as placebo recipients from the AMP trials was higher than previously published, with the true frequency likely to be higher. The relative abundance of lineages fluctuated substantially over time in two-thirds of the multilineage infections, generating uncertainty in identifying the specific viruses that were transmitted and founding the infection. Viral populations exhibited diversity and selection on the Gag and Env proteins at the earliest times examined, with sites inferred to be undergoing negative selection most evident. These data may help explain vaccination failures and provide new targets for prevention.},
}

@article {pmid41279479,
year = {2025},
author = {Larsen, BB and Harari, S and Gen, R and Stewart, C and Veesler, D and Bloom, JD},
title = {Functional and antigenic constraints on the Nipah virus fusion protein.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {41279479},
issn = {2692-8205},
abstract = {Nipah virus is a highly pathogenic virus in the family Paramyxoviridae that utilizes two distinct surface glycoproteins to infect cells. The receptor-binding protein (RBP) binds host receptors whereas the fusion protein (F) merges viral and host membranes. Here, we use non-replicative pseudoviruses to safely measure the effects of all F single amino-acid residue mutations on its cell entry function and neutralization by monoclonal antibodies. We compare mutational tolerance in F with previous experimental measurements for RBP and show that F is much more functionally constrained than the RBP. We also identify mutationally intolerant sites on the F trimer surface and core that are critical for proper function, and describe mutations that are candidates for stabilizing F in the prefusion conformation for vaccine design. We quantify how F mutations affect neutralization by six monoclonal antibodies, and show that the magnitude of mutational effects on neutralization varies among antibodies. Our measurements of mutational effects on Nipah virus F predict the ability of the antibodies to neutralize the related Hendra virus. Overall, our work defines the functional and antigenic constraints on the F protein from an important zoonotic virus.},
}

@article {pmid41320687,
year = {2025},
author = {Mileto, A and Inoue, A and Mohammadinejad, P and Coveler, AL and Lee, YS and Leng, S and Johnson, MP and Sun, Y and Thomas, JV and Yeh, BM and Bruining, DH and Fletcher, JG},
title = {Prospective pilot evaluation of dark borosilicate oral contrast media for the evaluation of the stomach and small bowel using CT.},
journal = {Abdominal radiology (New York)},
volume = {},
number = {},
pages = {},
pmid = {41320687},
issn = {2366-0058},
support = {R44 DK103495/DK/NIDDK NIH HHS/United States ; },
abstract = {PURPOSE: To evaluate the feasibility of use of dark borosilicate oral contrast media (DBOCM) in abdominopelvic CT in comparison with conventional oral contrast media (COCM) in a multi-institutional setting.

METHODS: Patients with known or suspected inflammatory bowel disease (IBD) (Site A) or suspected peritoneal carcinomatosis (Site B), who had undergone initial standard-of-care CT using COCM (positive, n = 10; neutral n = 22), underwent research CT with DBOCM. Attenuation differences between bowel wall and lumen using COCM and DBOCM were measured. Three radiologists independently examined all examinations with COCM and DBOCM. Patient tolerance and safety were recorded. Bowel wall visualization, distention, distended bowel length, and radiologist preference for bowel visualization were rated. Imaging findings using both oral contrast media were recorded, and a final consensus evaluation was performed to evaluate whether additional findings detected with DBOCM were visible with COCM.

RESULTS: Thirty-two patients (IBD, n = 15; suspected peritoneal carcinomatosis, n = 17) were included. No severe adverse effects were seen with DBOCM. Compared to COCM, DBOCM yielded significantly higher attenuation differences between bowel wall and lumen (P < .001). Bowel wall visualization, distention, and distended bowel length was significantly higher from the stomach to the ileum using DBOCM (P < .001). DBOCM was preferred by each reader over COCM for all intestinal segments, but significance was not achieved in pooled results. Additional imaging findings were found in seven patients (22% [7/32]; 95% CI 9-40%) using DBOCM.

CONCLUSION: Compared to COCM, DBOCM yielded improved bowel wall visualization and distention, also revealing additional imaging findings.},
}

@article {pmid41320342,
year = {2025},
author = {Crown, J and Stroyakovskii, D and Yardley, DA and Huang, CS and Fasching, PA and Bardia, A and Chia, S and Im, SA and Martin, M and Xu, B and Barrios, CH and Untch, M and Moroose, R and Hurvitz, SA and Hortobagyi, GN and Slamon, DJ and Visco, F and Spera, G and Zarate, JP and Halligan, D and Li, Z and Loi, S},
title = {Adjuvant ribociclib plus nonsteroidal aromatase inhibitor therapy in patients with HR-positive/HER2-negative early breast cancer: 5-year follow-up of NATALEE efficacy outcomes and updated overall survival.},
journal = {ESMO open},
volume = {10},
number = {11},
pages = {105858},
doi = {10.1016/j.esmoop.2025.105858},
pmid = {41320342},
issn = {2059-7029},
mesh = {Humans ; *Aminopyridines/therapeutic use/administration & dosage ; *Purines/therapeutic use/administration & dosage ; Female ; *Aromatase Inhibitors/therapeutic use/administration & dosage ; *Breast Neoplasms/drug therapy/mortality/pathology ; Middle Aged ; Male ; Follow-Up Studies ; Receptor, ErbB-2/metabolism ; Aged ; Adult ; *Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Treatment Outcome ; Chemotherapy, Adjuvant/methods ; Receptors, Progesterone/metabolism ; Receptors, Estrogen/metabolism ; Letrozole/administration & dosage/therapeutic use ; },
abstract = {BACKGROUND: At the primary efficacy analysis of the NATALEE phase III trial, ribociclib plus a nonsteroidal aromatase inhibitor (NSAI) demonstrated a statistically significant improvement in invasive disease-free survival (iDFS) versus NSAI alone in patients with hormone receptor (HR)-positive/human epidermal growth factor receptor 2 (HER2)-negative early breast cancer (EBC). Continued follow-up of efficacy outcomes is important in assessing the durability of treatment benefit. We report 5-year estimates of efficacy outcomes, including an udpated analysis of overall survival (OS).

PATIENTS AND METHODS: Eligible patients included pre/postmenopausal women and men with HR-positive/HER2-negative EBC and anatomic stage IIA (N1 or N0 with high-risk factors), IIB, or III disease. Patients were randomized 1 : 1 to ribociclib 400 mg/day (3 weeks on/1 week off for 3 years) + NSAI (letrozole 2.5 mg/day or anastrozole 1 mg/day for 5 years) or NSAI alone. Premenopausal women and men received goserelin. The primary endpoint was iDFS, and secondary/exploratory endpoints included distant disease-free survival, recurrence-free survival, distant recurrence-free survival, and OS.

RESULTS: With a median iDFS follow-up of 55.4 months, ribociclib + NSAI demonstrated persistent iDFS benefit versus NSAI alone [hazard ratio 0.716, 95% confidence interval (CI) 0.618-0.829, nominal one-sided log-rank P < 0.0001]. Absolute iDFS improvement between treatment arms increased from the 3- (Δ2.7%) to the 5-year (Δ4.5%) time points. Persistent benefit over time was also observed across subgroups [including N0 patients (hazard ratio 0.606, 95% CI 0.372-0.986)] and secondary/exploratory endpoints. As OS continues to mature, numerical improvement in favor of ribociclib was observed (hazard ratio 0.800, 95% CI 0.637-1.003, nominal one-sided log-rank P = 0.026).

CONCLUSIONS: This prespecified 5-year follow-up of efficacy outcomes from NATALEE demonstrated that ribociclib + NSAI continued to reduce the risk of recurrence beyond the 3-year treatment window, supporting its use as adjuvant therapy in patients with HR-positive/HER2-negative EBC. An ongoing positive trend for improved OS in favor of ribociclib + NSAI was observed.},
}

Humans
*Aminopyridines/therapeutic use/administration & dosage
*Purines/therapeutic use/administration & dosage
Female
*Aromatase Inhibitors/therapeutic use/administration & dosage
*Breast Neoplasms/drug therapy/mortality/pathology
Middle Aged
Male
Follow-Up Studies
Receptor, ErbB-2/metabolism
Aged
Adult
*Antineoplastic Combined Chemotherapy Protocols/therapeutic use
Treatment Outcome
Chemotherapy, Adjuvant/methods
Receptors, Progesterone/metabolism
Receptors, Estrogen/metabolism
Letrozole/administration & dosage/therapeutic use

@article {pmid41319224,
year = {2024},
author = {Chen, Z and Heng, S and Tapley, A and De Rosa, S and Zhang, B},
title = {Determining vaccine responders in the presence of baseline immunity using single-cell assays and paired control samples.},
journal = {Biostatistics (Oxford, England)},
volume = {26},
number = {1},
pages = {},
doi = {10.1093/biostatistics/kxaf045},
pmid = {41319224},
issn = {1468-4357},
mesh = {Humans ; *Single-Cell Analysis/methods ; *Immunogenicity, Vaccine/immunology ; *COVID-19 Vaccines/immunology ; B-Lymphocytes/immunology ; COVID-19/prevention & control/immunology ; Cytokines/immunology ; Vaccination ; Immunity, Cellular ; },
abstract = {A key objective in vaccine studies is to evaluate vaccine-induced immunogenicity and determine whether participants have mounted a response to the vaccine. Cellular immune responses are essential for assessing vaccine-induced immunogenicity, and single-cell assays, such as intracellular cytokine staining (ICS) and B-cell phenotyping (BCP), are commonly employed to profile individual immune cell phenotypes and the cytokines they produce after stimulation. In this article, we introduce a novel statistical framework for identifying vaccine responders using ICS data collected before and after vaccination. This framework incorporates paired control data to account for potential unintended variations between assay runs, such as batch effects, that could lead to misclassification of participants as vaccine responders or non-responders. To formally integrate paired control data for accounting for assay variation across different time points (ie before and after vaccination), our proposed framework calculates and reports two $ P $-values, both adjusting for paired control data but in distinct ways: (i) the maximally adjusted $ P $-value, which applies the most conservative adjustment to the unadjusted $ P $-value, ensuring validity over all plausible batch effects consistent with the paired control samples' data, and (ii) the minimally adjusted $ P $-value, which imposes only the minimal adjustment to the unadjusted $ P $-value, such that the adjusted $ P $-value cannot be falsified by the paired control samples' data. Minimally and maximally adjusted $ P $-values offer a balanced approach to managing Type I error rates and statistical power in the presence of batch effects. We apply this framework to analyze ICS data collected at baseline and 4 wks post-vaccination from the COVID-19 Prevention Network (CoVPN) 3008 study. Our analysis helps address two clinical questions: (i) which participants exhibited evidence of an incident Omicron infection between baseline and 4 wks after receiving the final dose of the primary vaccination series, and (ii) which participants showed vaccine-induced T cell responses against the Omicron BA.4/5 Spike protein.},
}

Humans
*Single-Cell Analysis/methods
*Immunogenicity, Vaccine/immunology
*COVID-19 Vaccines/immunology
B-Lymphocytes/immunology
COVID-19/prevention & control/immunology
Cytokines/immunology
Vaccination
Immunity, Cellular

@article {pmid41315206,
year = {2025},
author = {Afrough, A and Dima, D and Razzo, B and Goel, U and Sannareddy, A and Pasvolsky, O and Vazquez-Martinez, MA and Ferreri, CJ and Banerjee, R and Khouri, J and Davis, JA and Gaballa, MR and Lieberman-Cribbin, A and Rana, MS and Julian, K and Anwer, F and Shune, L and DeJarnette, S and Grajales-Cruz, AF and Ouchveridze, E and De Avila, G and Susanibar-Adaniya, SP and Portuguese, AJ and Schrum, D and Eberwein, E and Hosoya, H and Mikkilineni, L and Kaur, G and McGuirk, JP and Rossi, A and Herr, MM and Castaneda, O and Locke, FL and Raza, S and Lin, Y and Atrash, S and Sborov, DW and Voorhees, PM and Richard, S and Garfall, AL and Sidana, S and Patel, KK and Hansen, DK and Cowan, AJ and Anderson, LD and Lee, HC},
title = {The impact of extramedullary and paraskeletal plasmacytomas on treatment outcomes in multiple myeloma treated with teclistamab: U.S. Myeloma Immunotherapy Consortium real-world experience.},
journal = {Blood cancer journal},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41408-025-01414-6},
pmid = {41315206},
issn = {2044-5385},
abstract = {Teclistamab, a bispecific antibody targeting B-cell maturation antigen (BCMA), is effective in relapsed or refractory multiple myeloma (RRMM), but its impact on patients with soft tissue plasmacytomas is unclear. We studied 385 RRMM patients treated with teclistamab at 13 U.S. centers through September 2023, with follow-up to April 2024. Soft tissue plasmacytomas were classified as true extramedullary disease (EMD; not contiguous with bone) or paraskeletal plasmacytomas (PSK; contiguous with bone). Patients with the simultaneous presence of both were classified as true-EMD, reflecting its adverse prognosis. Of those, 109 (28%) had true EMD, 33 (9%) had PSK, and 243 (63%) had no soft tissue plasmacytoma (No-STP). Median follow-up was 9.9 months. Overall response rates were 38% in true-EMD, 54.1% in PSK, and 62.4% in No-STP (p < 0.001). Median progression-free survival (PFS) was 1.4 months in true-EMD, 6.51 months in PSK, and 8.95 months in No-STP (p < 0.0001). Median overall survival (OS) was 9.54 months for true EMD, 13.1 months for PSK, and not reached in No-STP (p = 0.00012). In multivariable analysis, true-EMD was independently associated with inferior PFS and OS, while PSK showed numerically lower outcomes. These findings highlight the need for tailored strategies in patients with soft tissue plasmacytomas, particularly those with true-EMD.},
}

@article {pmid41314741,
year = {2025},
author = {Buchbinder, SP and Spinosa Guzman, S and Sanchez, J and Willems, W and Stieh, DJ and van Duijn, J and van Rosmalen, MGM and Hendriks, J and Nijs, S and Lavreys, L and Paez, CA and Grinzstejn, B and Hutter, J and Mann, P and Sierra Madero, JG and Cahn, P and Castagna, A and Truyers, C and Roels, S and Gilbert, PB and Carone, M and Luedtke, A and Corey, L and Pau, MG and Tomaka, F and , },
title = {Efficacy and safety of a mosaic HIV-1 vaccine regimen in men who have sex with men and transgender individuals (HVTN 706/HPX3002/Mosaico): a global, randomised, double-blind, placebo-controlled, phase 3 trial.},
journal = {The lancet. HIV},
volume = {12},
number = {12},
pages = {e823-e835},
doi = {10.1016/S2352-3018(25)00195-X},
pmid = {41314741},
issn = {2352-3018},
mesh = {Humans ; Male ; *HIV Infections/prevention & control/immunology ; Adult ; *AIDS Vaccines/administration & dosage/immunology/adverse effects ; Double-Blind Method ; *HIV-1/immunology ; *Transgender Persons ; Middle Aged ; *Homosexuality, Male ; Young Adult ; Vaccine Efficacy ; Female ; },
abstract = {BACKGROUND: There is a high unmet need for effective HIV prevention options, including vaccines, for individuals at high risk of HIV acquisition who choose not to use pre-exposure prophylaxis or other prevention strategies. This study evaluated the efficacy and safety of an HIV-1 vaccine regimen consisting of tetravalent mosaic adenovirus serotype 26-based vaccine (Ad26.Mos4.HIV) and bivalent clade C glycoprotein (gp) 140-mosaic gp140 vaccine, in a population with high seroincidence.

METHODS: This randomised, double-blind, phase 3 trial enrolled adult cisgender men and transgender individuals without HIV from 52 academic medical centres, health departments, and community-based clinics in Latin America, Europe, and the USA. Participants were randomly assigned (1:1) by use of a centrally prepared, computer-generated randomisation schedule to receive intramuscular injections of vaccine or saline placebo in stratified permuted blocks. Study participants, study site personnel (except for those with primary responsibility for study vaccine preparation and dispensing), and investigators were masked from vaccine allocation. The vaccine regimen consisted of Ad26.Mos4.HIV administered at months 0 and 3 followed by Ad26.Mos4.HIV administered concurrently with aluminium phosphate-adjuvanted clade C gp140-mosaic gp140 at months 6 and 12. The primary endpoint was vaccine efficacy in preventing HIV-1 acquisition between months 7 and 24 or between months 7 and 30 in the per-protocol population, which included all randomly assigned participants who received at least one study vaccination and who had not been diagnosed with HIV-1 4 weeks after the third vaccination, had received all planned vaccinations at the first three vaccination visits within the respective visit windows, and had no major protocol deviations linked to incorrect product administration. Safety outcomes were assessed in all randomised participants who received at least one study vaccination. The trial is registered with ClinicalTrials.gov (NCT03964415) and is complete.

FINDINGS: Between Nov 4, 2019, and Aug 13, 2021, 3900 participants were enrolled and randomly assigned; 3887 received at least one study vaccination (1942 assigned to vaccine, 1945 to placebo). 3870 (99·6%) of 3887 participants were assigned male at birth, seven (0·2%) were assigned female, and one participant's sex at birth was undifferentiated; 3557 (91·5%) participants identified as male gender, 48 (1·2%) as female gender, and 278 (7·2%) as transgender or non-binary. The per-protocol population included 1525 participants in the vaccine group and 1494 in the placebo group. From month 7 to month 24 in the per-protocol population, HIV-1 incidence per 100 person-years was 3·63 (95% CI 2·77 to 4·67) in the vaccine group and 3·35 (2·53 to 4·36) in the placebo group, with an estimated vaccine efficacy (months 7-24) of -0·7% (95% CI -50·9 to 32·8; p=0·97). Vaccine efficacy (months 7-30) was -149·1% (-737·7 to 26·0; p=0·14). Most solicited local and systemic adverse events were mild or moderate and short-lived. Medically attended adverse events occurred in 999 (51·4%) of 1942 participants given vaccine and 1002 (51·5%) of 1945 participants given placebo; serious adverse events occurred in 82 (4·2%) of 1942 participants given vaccine and 77 (4·0%) of 1945 participants given placebo. No fatal adverse events considered related to the study vaccine occurred. Adverse events of special interest (thrombotic events or thrombocytopenia) occurred in four participants with vaccine and two with placebo; none had thrombosis with thrombocytopenia syndrome.

INTERPRETATION: The lack of efficacy in this and other HIV vaccine trials points to the importance of current efforts to develop vaccines that generate broadly neutralising antibodies.

FUNDING: Johnson & Johnson; HIV Vaccine Trials Network; Division of AIDS, a division of National Institute of Allergy and Infectious Diseases; and US Army Medical Materiel Development Activity, a subordinate command of the US Army Medical Research and Development Command.},
}

Humans
Male
*HIV Infections/prevention & control/immunology
Adult
*AIDS Vaccines/administration & dosage/immunology/adverse effects
Double-Blind Method
*HIV-1/immunology
*Transgender Persons
Middle Aged
*Homosexuality, Male
Young Adult
Vaccine Efficacy
Female

@article {pmid41314597,
year = {2025},
author = {Mosher, CE and Shinn, EH and Addington, EL and Wu, W and Bricker, JB and Helft, PR and Turk, AA and Vater, LB and Masood, A and Jalal, SI and Loehrer, PJ and Champion, VL and Johns, SA},
title = {Protocol of a randomized trial of acceptance and commitment therapy for patient fatigue interference and caregiver burden in advanced gastrointestinal cancer.},
journal = {Contemporary clinical trials},
volume = {},
number = {},
pages = {108168},
doi = {10.1016/j.cct.2025.108168},
pmid = {41314597},
issn = {1559-2030},
abstract = {Fatigue's interference with activities, mood, and cognition is one of the most prevalent and distressing problems of patients with advanced gastrointestinal cancer. As fatigue interferes with patient functioning, family caregivers often report feeling burdened by increasing demands. Evidence-based interventions for patient fatigue interference and caregiver burden are lacking in advanced gastrointestinal cancer. In a pilot trial, telephone-based Acceptance and Commitment Therapy (ACT) showed potential for reducing patient fatigue interference and caregiver burden in this population. The current Phase II trial seeks to determine the efficacy of this intervention for patients with advanced gastrointestinal cancer and moderate-to-severe fatigue interference and their family caregivers with significant caregiving burden. In this trial, 244 dyads are randomly assigned to either the ACT intervention or an education/support control. Participants in both conditions attend six weekly 50-min telephone sessions, four of which involve both dyad members, and a 30-min booster session. The primary aim is to test the effects of telephone-delivered ACT on patient fatigue interference and caregiver burden. Secondary outcomes include patient sleep interference and patient and caregiver engagement in daily activities and quality of life. Outcomes are assessed at baseline, 2 weeks post-intervention, and 3 months post-intervention. This trial also examines whether increased psychological flexibility, defined as mindful acceptance of present experiences, including challenges, while pursuing actions aligned with personal values, mediates ACT's effects on primary outcomes. Our ability to demonstrate ACT's efficacy will support its adoption in cancer care. Findings will also inform future ACT trials for dyads coping with other serious illnesses. Trial Registration ID: NCT06532877.},
}

@article {pmid41313144,
year = {2025},
author = {Anderson, BO and Li, CI},
title = {Lobular carcinoma and endocrine biology: Lessons learned and future directions.},
journal = {Cancer},
volume = {131},
number = {23},
pages = {e70194},
doi = {10.1002/cncr.70194},
pmid = {41313144},
issn = {1097-0142},
}

@article {pmid41310247,
year = {2025},
author = {Alves, IM and Termini, CM},
title = {Blocking ferroptosis to expand human HSCs.},
journal = {Nature cell biology},
volume = {},
number = {},
pages = {},
pmid = {41310247},
issn = {1476-4679},
support = {1K01DK126989-01A1//U.S. Department of Health & Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (National Institute of Diabetes & Digestive & Kidney Diseases)/ ; 23CDA1039196//American Heart Association (American Heart Association, Inc.)/ ; SPK-08-25//Damon Runyon Cancer Research Foundation (Cancer Research Fund of the Damon Runyon-Walter Winchell Foundation)/ ; },
}

@article {pmid41310100,
year = {2025},
author = {Hernandez, LE and Smitherman, AB and Santacroce, SJ and Liu, Y and Roy, MM and Ross, WL and Armstrong, H and Appel, B and Casillas, J and Hurtado-de-Mendoza, A and Demedis, J and Horwitz, LI and Mendoza, JA and Kadan-Lottick, NS},
title = {Childhood cancer survivors and their caregivers are amenable to survivorship surveillance with community-based primary care providers.},
journal = {Journal of cancer survivorship : research and practice},
volume = {},
number = {},
pages = {},
pmid = {41310100},
issn = {1932-2267},
abstract = {PURPOSE: A minority of childhood cancer survivors (CCS) receive post-therapy survivorship surveillance at their oncology center (OC) within 5 years of diagnosis. Primary care providers (PCPs) could be a promising alternative. We determined CCS' preferences for the site of surveillance, associated factors, and rationale.

METHODS: CCS diagnosed with cancer at < 21 years at one of four participating hospitals, 2-4 years post-therapy, and English- or Spanish-speaking (or their caregivers if CCS < 18 years) indicated their preference and reasons for site of survivorship surveillance (OC vs. PCP vs. no preference) at baseline prior to randomization into the BRIDGES trial (NCT05448560). Multivariable logistic regression models estimated prevalence ratios for site preference and examined associations with patient characteristics. Qualitative methods examined reasons for preference.

RESULTS: Of 235 participants, 92% (n = 214; 48% female, 36% Hispanic, 46% public insurance, median age 12 years at enrollment) indicated their preference. The majority (63%) were amenable to PCP-based surveillance (21% preferred PCP, 42% no preference). Preference for OC was associated with identifying as non-Hispanic "other" (Black, Asian, multi-racial) vs. non-Hispanic White (PR 4.7, p = 0.005, 95% CI 1.68, 13.84) and older age (PR 1.1/year, p = 0.02, 95% CI 1.01, 1.15), but not insurance or area-level social determinants of health (SDoH) indices. Reasons for preference comprised two themes: practical (facts, logistics) and psychological (emotions, beliefs). OCs were preferred for psychological reasons (46/60; 77%); PCPs were preferred for practical reasons (25/35; 74%).

CONCLUSIONS: Among diverse CCS, most were amenable to PCP-based survivorship surveillance, independent of SDoH factors.

Survivorship surveillance by PCPs may be a useful alternative for CCS.},
}

@article {pmid41309676,
year = {2025},
author = {Yu, Z and Vromman, A and Nguyen, NQH and Schuermans, A and Li, L and Rentz, T and Nakao, T and Vellarikkal, SK and Uddin, MM and Niroula, A and Griffin, G and Honigberg, MC and Lin, AE and Gibson, CJ and Katz, DH and Tahir, UA and Fang, S and Dron, JS and Pan, M and Haidermota, S and Ganesh, S and Antoine, T and Weinstock, J and Austin, TR and Vasan, RS and Peloso, GM and Hornsby, W and Ganz, P and Manson, JE and Haring, B and Kooperberg, C and Reiner, AP and Bis, JC and Psaty, BM and Min, YI and Correa, A and Lange, LA and Post, WS and Rotter, JI and Rich, SS and Wilson, JG and Ebert, BL and Yu, B and Ballantyne, CM and Coresh, J and Sankaran, VG and Bick, AG and Jaiswal, S and Gerszten, RE and , and Libby, P and Gupta, RM and Natarajan, P},
title = {Human plasma proteomic profile of clonal hematopoiesis.},
journal = {Nature communications},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41467-025-66755-z},
pmid = {41309676},
issn = {2041-1723},
support = {R01HL142711, R01HL127564, R01HL148050, R01HL151283, R01HL148565, R01HL135242, and R01HL151152//U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)/ ; R01HL173028, R01HL148565//U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)/ ; K08HL161445//U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)/ ; 1R01 HL159081, R01 HL153499//U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)/ ; R01HL148565//U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)/ ; 1R01HL134892 and 1R01HL163099-01//U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)/ ; K99HL165024//U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)/ ; R01DK125782//U.S. Department of Health & Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (National Institute of Diabetes & Digestive & Kidney Diseases)/ ; 5U01DK108809//U.S. Department of Health & Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (National Institute of Diabetes & Digestive & Kidney Diseases)/ ; TNE-18CVD04//Fondation Leducq/ ; TNE-18CVD04//Fondation Leducq/ ; Paul and Phyllis Fireman Endowed Chair in Vascular Medicine//Massachusetts General Hospital (MGH)/ ; R00HG012956//U.S. Department of Health & Human Services | NIH | National Human Genome Research Institute (NHGRI)/ ; Harold M. English Fellowship Fund//Harvard Medical School/ ; KAW 2020.0239//Science for Life Laboratory (SciLifeLab)/ ; R01 MH104964 and R01 MH123451//U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (NIMH)/ ; 24RGRSG1275749, 25SFRNCCKMS1443062, 25SFRNPCKMS1463898//American Heart Association (American Heart Association, Inc.)/ ; Burroughs Wellcome Foundation Career Award for Medical Scientists//Burroughs Wellcome Fund (BWF)/ ; },
abstract = {Plasma proteomic profiles associated with subclinical somatic mutations in blood cells may offer insights into downstream clinical consequences. Here we explore these patterns in clonal hematopoiesis of indeterminate potential (CHIP), which is linked to several cancer and non-cancer outcomes, including coronary artery disease (CAD). Among 61,833 participants (3881 with CHIP) from TOPMed and UK Biobank (UKB) with blood-based DNA sequencing and proteomic measurements (1,148 proteins by SomaScan in TOPMed and 2917 proteins by Olink in UKB), we identify 32 and 345 proteins from TOPMed and UKB, respectively, associated with CHIP and most prevalent driver genes (DNMT3A, TET2, and ASXL1). These associations show substantial heterogeneity by driver genes, sex, and race, and were enriched for immune response and inflammation pathways. Mendelian randomization in humans, coupled with ELISA in hematopoietic Tet2-/- vs wild-type mice validation, disentangle causal proteomic perturbations from TET2 CHIP. Lastly, we identify plasma proteins shared between CHIP and CAD.},
}

@article {pmid41308682,
year = {2025},
author = {Necchi, A and Stitou, H and Bhanvadia, S and Psutka, SP},
title = {SunRISe-4 perioperative safety and TURBT stratification - Authors' reply.},
journal = {The Lancet. Oncology},
volume = {26},
number = {12},
pages = {e621},
doi = {10.1016/S1470-2045(25)00671-0},
pmid = {41308682},
issn = {1474-5488},
}

@article {pmid41308477,
year = {2025},
author = {Hoggard, NK and Elshafae, SM and Daniels, NA and Young, JA and Premanandan, C and Echols, JB and Chandrashekar, DS and Hildreth, BE and Haffner, MC and Rosol, TJ},
title = {Comparative histologic survey and transcriptomic investigation into canine prostate carcinoma.},
journal = {Research in veterinary science},
volume = {198},
number = {},
pages = {105981},
doi = {10.1016/j.rvsc.2025.105981},
pmid = {41308477},
issn = {1532-2661},
abstract = {Dogs share features in prostate gland anatomy, physiology, and pathology with men. However, human and canine prostate carcinoma (PC) have histologic and molecular differences. Particularly, the histogenesis of canine PC (cPC) is unclear. This study investigated the origin of cPC using histopathology and transcriptomics with comparison to men. Prostate glands retrospectively and prospectively collected from 445 dogs (approximately 95 % autopsy samples) were surveyed for early carcinomas and preneoplastic lesions, particularly high-grade prostatic intraepithelial neoplasia (HGPIN) due to its role in the pathogenesis of PC in men. Lineage gene signatures defining prostate luminal epithelium and urothelium were identified for inter- and intraspecies RNA-sequencing comparisons, including between cPC and canine urinary bladder urothelial carcinoma (UC). Postmortem prostate lesion frequencies were similar to previously reported canine studies. Intraductal/intra-acinar growth (31/35; 88.6 %) was common in representative samples of cPC. Prostate epithelial changes consistent with HGPIN in men were not observed. Proliferative lesions and early carcinomas were rare (7/445; 1.6 %). Patterns in prostate and urothelium marker gene expression signatures differed between human and canine PC. Compared to non-neoplastic prostate gland, cPC had significantly decreased prostate-specific and increased urothelium gene signatures. The results suggest many cases diagnosed as cPC are UC or have urothelial differentiation and thus differ from PC in men, with important implications for canine tumor classification and translational studies.},
}

@article {pmid41308080,
year = {2025},
author = {Gee-Rodriguez, K and Yun, J and Duong, A and Indorf, A},
title = {Comparing relative dose intensity of weekly nab-paclitaxel regimens in early breast cancer: A retrospective study at a large academic outpatient cancer center.},
journal = {Journal of oncology pharmacy practice : official publication of the International Society of Oncology Pharmacy Practitioners},
volume = {},
number = {},
pages = {10781552251399901},
doi = {10.1177/10781552251399901},
pmid = {41308080},
issn = {1477-092X},
abstract = {IntroductionNational guidelines for breast cancer support substitution with nab-paclitaxel for paclitaxel or docetaxel due to medical necessity.[1] This study aimed to assess for correlation between weekly nab-paclitaxel dose and relative dose intensity (RDI) amongst early breast cancer patients.MethodsThis single-center, retrospective cohort study included adult patients with early breast cancer who switched from weekly paclitaxel to nab-paclitaxel after hypersensitivity reaction. The primary outcome of RDI was assessed in patients receiving nab-paclitaxel 80 mg/m[2] (NB80) or 100 mg/m[2] (NB100) intravenously (IV) weekly. Secondary outcomes included adverse effects, incidence of nab-paclitaxel alterations, and growth factor (GCSF) administration for secondary prophylaxis.ResultsAmongst 26 patients, the median age was 43 years (range 33 to 71), with the majority (54%) having stage II or later disease. Median RDI with NB80 was 91% (range 69 to 100%) versus 86% (55 to 100%) with NB100. Fifty percent of all patients underwent dose reductions. Dose delays occurred in a higher proportion of patients on 50% with NB80 vs 33% with NB100. Early nab-paclitaxel discontinuations occurred more on NB100 (33% vs 10%). Incidence of chemotherapy-induced peripheral neuropathy (CIPN) was 80% vs 83% with NB80 and NB100, respectively, while grade 2 CIPN was more common on NB100 (50% vs 35%). A lower rate of neutropenia resulted from NB80 (60 vs 67% with NB100).ConclusionNab-paclitaxel dosed at 80 mg/m[2] IV weekly, after switching due to paclitaxel hypersensitivity, may promote improved RDI and safety compared to nab-paclitaxel 100 mg/m[2] weekly amongst early breast cancer patients.},
}

@article {pmid41308031,
year = {2025},
author = {Gardner, JA and Nusapan, R and Tan, J and Levy, B and Tang, G and Fang, M and Velagaleti, GV and Cao, Y and Astbury, C and Mixon, JC and J Souers, R and Peterson, JF and Zou, YS},
title = {Current and Future Utilization of Optical Genome Mapping: Insights From the 2024 College of American Pathologists Supplemental Questionnaire.},
journal = {Archives of pathology & laboratory medicine},
volume = {},
number = {},
pages = {},
doi = {10.5858/arpa.2025-0472-CP},
pmid = {41308031},
issn = {1543-2165},
abstract = {CONTEXT.—: Optical genome mapping (OGM) represents a promising cytogenomic technology that detects structural variants, including fusions, rearrangements, copy number variants, and loss of heterozygosity, in a single assay. Unlike karyotyping, fluorescence in situ hybridization, or chromosomal microarray, OGM leverages long-molecule imaging to map the whole genome with high resolution. This positions OGM as a novel tool for constitutional and somatic/cancer genomics. However, its current and planned utilization in clinical and research settings remains unknown, necessitating further investigation.

OBJECTIVE.—: To investigate the current utilization of OGM in clinical and research laboratories, assess its applications, and evaluate future utilization strategies.

DESIGN.—: In 2024, a supplemental questionnaire was incorporated into 6 College of American Pathologists proficiency testing programs to evaluate OGM's utilization.

RESULTS.—: Of 921 returned questionnaires, 712 were analyzed after duplicates were removed. Sixty-seven (9.4%) currently offered OGM testing: 5.2% (37) for research only, 1.8% (13) for only clinical use, and 2.4% (17) for both. Future adoption plans showed 7.6% (53 of 700 laboratories) and 7.9% (55 of 700 laboratories) aiming to implement OGM clinically within 12 and 24 months, respectively. The most common applications included hematologic malignancies and constitutional/germline postnatal disorders, followed by prenatal testing. International laboratories demonstrated statistically higher utilization rates than domestic laboratories (P = .001).

CONCLUSIONS.—: This first survey on OGM clinical utilization reveals its status as a niche technology, with 67 laboratories currently using it. Its primary clinical applications are in constitutional/germline analysis and hematologic malignancies. Although international laboratories led in 2024, 108 laboratories (domestic and international) plan clinical adoption within 24 months, signaling OGM's potential for broader integration.},
}

@article {pmid41307621,
year = {2025},
author = {Lopez, K and Silva, M and Briant, KJ and Fox, B and Dee, C and Ceballos, RM and Thompson, B},
title = {Involving Latinas in Understanding Barriers, Facilitators, and Appropriate Outreach for Mammography in Tacoma, Washington, USA.},
journal = {Journal of community health},
volume = {},
number = {},
pages = {},
pmid = {41307621},
issn = {1573-3610},
support = {P30 CA015704/CA/NCI NIH HHS/United States ; },
abstract = {Breast cancer screening rates are lower for Hispanic females (Latinas) than their non-Hispanic White counterparts. This discrepancy is partly due to health disparities, such as limited access to care, inability to take time off work, lack of health insurance, and cultural and emotional barriers. In response to a health department request, the Carol Milgard Breast Center conducted a qualitative assessment, as part of a community grant pilot award from Fred Hutchinson Cancer Center, to better understand the barriers and facilitators influencing Latinas' participation in mammography screening. The objective was to identify key characteristics of an intervention aimed at encouraging mammogram uptake among Latinas. Forty women were recruited and consented to participate in structured interviews, which included questions on their perceptions of mammography. The interviews explored structural barriers (e.g., lack of insurance), cultural issues (e.g., prioritizing family over individual health), and emotional concerns (e.g., fear of embarrassment). By detailing lessons learned and community identified outreach strategies, this work advances the evidence base on community engagement with Latinas for cancer education and outreach. Findings underscore the need for linguistically and culturally tailored resources, trusted messengers, and outreach approaches that meet Latinas where they are. The identified strategies can inform interventions to improve mammography uptake in similar communities and guide larger-scale implementation efforts.},
}

@article {pmid41307276,
year = {2025},
author = {Robins, LI and Gafken, P and Lin, C and Jones, L and Hooper, SE},
title = {Dissecting HOCl Action in Chronic Wound Biofilms: Proteomic Insights From a Host-Relevant Model of Pseudomonas aeruginosa.},
journal = {MicrobiologyOpen},
volume = {14},
number = {6},
pages = {e70181},
pmid = {41307276},
issn = {2045-8827},
support = {//The authors received no specific funding for this work./ ; },
mesh = {*Pseudomonas aeruginosa/drug effects/physiology ; *Biofilms/drug effects/growth & development ; *Hypochlorous Acid/pharmacology/metabolism ; Proteomics ; *Proteome/analysis ; *Bacterial Proteins/analysis/metabolism ; Microbial Viability/drug effects ; Pseudomonas Infections/microbiology ; Humans ; },
abstract = {Pseudomonas aeruginosa is found in 48%-52% of chronic wound biofilms, where its resistance to antimicrobials and host immunity presents a major clinical challenge. Although hypochlorous acid (HOCl) is known to be an effective antimicrobial, its mechanism of action remains unclear because standard experimental conditions often produce a mixture of HOCl and hypochlorite (OCl[-]), making it difficult to isolate the effects of HOCl. Here, we use proteomic profiling to investigate the effects of a pure, stable HOCl gel on P. aeruginosa biofilms in a physiologically relevant chronic wound model. We applied HOCl gel (5.7 mM, pH 6) to mature P. aeruginosa biofilms established in a wound-mimicking flow model. Proteins were analyzed using tandem mass tag (TMT)-based quantitative proteomics, identifying 1,878 proteins. HOCl treatment significantly reduced biofilm viability and altered the abundance of 330 proteins. We observed substantial depletion of proteins involved in biosynthesis, virulence, antibiotic resistance, and biofilm formation, alongside enrichment of stress response proteins. These findings indicate a shift toward survival phenotypes and weakened pathogenicity. Our data reveal that HOCl disrupts multiple pathways essential for P. aeruginosa survival and virulence. Crucially, our experimental design eliminates confounding factors that can lead to unintentional testing of mixed HOCl and OCl[-] species, allowing us to assess the specific effects of HOCl. These findings call for a re-evaluation of HOCl research methodologies and reiterate the importance of realistic infection models in antimicrobial testing.},
}

*Pseudomonas aeruginosa/drug effects/physiology
*Biofilms/drug effects/growth & development
*Hypochlorous Acid/pharmacology/metabolism
Proteomics
*Proteome/analysis
*Bacterial Proteins/analysis/metabolism
Microbial Viability/drug effects
Pseudomonas Infections/microbiology
Humans

@article {pmid41281241,
year = {2025},
author = {Ukogu, OA and Montague, Z and Altan-Bonnet, G and Nourmohammad, A},
title = {Design principles of the cytotoxic CD8[+] T-cell response.},
journal = {ArXiv},
volume = {},
number = {},
pages = {},
pmid = {41281241},
issn = {2331-8422},
support = {R35 GM142795/GM/NIGMS NIH HHS/United States ; ZIA BC012007/ImNIH/Intramural NIH HHS/United States ; },
abstract = {Cytotoxic T lymphocytes eliminate infected or malignant cells, safeguarding surrounding tissues. Although experimental and systems-immunology studies have cataloged many molecular and cellular actors involved in an immune response, the design principles governing how the speed and magnitude of T-cell responses emerge from cellular decision-making remain elusive. Here, we recast the T-cell response as a feedback-controlled program, wherein the rates of activation, proliferation, differentiation and death are regulated through antigenic, pro- and anti-inflammatory cues. By exploring a broad class of feedback-controller designs as potential immune programs, we demonstrate how the speed and magnitude of T-cell responses emerge from optimizing signal-feedback to protect against diverse infection settings. We recover an inherent trade-off: infection clearance at the cost of immunopathology. We show how this trade-off is encoded into the logic of T-cell responses by hierarchical sensitivity to different immune signals. Notably, we find that designs that balance harm from acute infections and autoimmunity produce immune responses consistent with experimentally observed patterns of T-cell effector expansion in mice. Extending our model to immune-based T-cell therapies for cancer tumors, we identify a trade-off between the affinity for tumor antigens ("quality") and the abundance ("quantity") of infused T-cells necessary for effective treatment. Finally, we show how therapeutic efficacy can be improved by targeted genetic perturbations to T-cells. Our findings offer a unified control-logic for cytotoxic T-cell responses and point to specific regulatory programs that can be engineered for more robust T-cell therapies.},
}

@article {pmid41279420,
year = {2025},
author = {Matsen, FA and Dumm, W and Sung, K and Johnson, MM and Rich, D and Starr, T and Song, YS and Fukuyama, J and Haddox, HK},
title = {Separating selection from mutation in antibody language models.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {41279420},
issn = {2692-8205},
support = {R01 AI146028/AI/NIAID NIH HHS/United States ; DP2 AI177890/AI/NIAID NIH HHS/United States ; R56 HG013117/HG/NHGRI NIH HHS/United States ; R01 HG013117/HG/NHGRI NIH HHS/United States ; S10 OD028685/OD/NIH HHS/United States ; },
abstract = {Antibodies are encoded by nucleotide sequences that are generated by V(D)J recombination and evolve according to mutation and selection processes. Existing antibody language models, however, focus exclusively on antibodies as strings of amino acids and are fitted using standard language modeling objectives such as masked or autoregressive prediction. In this paper, we first show that fitting models using this objective implicitly incorporates nucleotide-level mutation processes as part of the protein language model, which degrades performance when predicting effects of mutations on functional properties of antibodies. To address this limitation, we devise a new framework: a Deep Amino acid Selection Model (DASM) that learns the selection effects of amino-acid mutations while explicitly factoring out the nucleotide-level mutation process. By fitting selection as a separate term from the mutation process, the DASM exclusively quantifies functional effects: effects that change some aspect of the function of the antibody. This factorization leads to substantially improved performance on standard functional benchmarks. Moreover, our model is an order of magnitude smaller and multiple orders of magnitude faster to evaluate than existing approaches, as well as being readily interpretable.},
}

@article {pmid41042379,
year = {2025},
author = {Bharadwaj, MC and Holt, SK and Iyer, HS and Lee, JR and Wolff, EM and Rebbeck, TR and Gore, JL and Nyame, YA},
title = {The Legacy of Chattel Slavery and Its Association with Prostate Cancer Incidences in the Southeastern United States.},
journal = {Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology},
volume = {34},
number = {12},
pages = {2186-2193},
pmid = {41042379},
issn = {1538-7755},
support = {P50 CA097186/CA/NCI NIH HHS/United States ; CDMRP W81XWH211053//U.S. Department of Defense (DOD)/ ; P50 CA097186-17//National Cancer Institute (NCI)/ ; FY23-POP-02//Andy Hill CARE Fund (CARE)/ ; //Zhu Family Center for Global Cancer Prevention/ ; },
mesh = {Humans ; Male ; *Prostatic Neoplasms/epidemiology ; Incidence ; Southeastern United States/epidemiology ; *Enslavement/history/statistics & numerical data ; Black or African American/statistics & numerical data ; Middle Aged ; Health Status Disparities ; Aged ; White People/statistics & numerical data ; Socioeconomic Factors ; History, 19th Century ; White ; },
abstract = {BACKGROUND: Present-day disparities in prostate cancer outcomes are a direct result of major historical events, such as chattel slavery. Few studies have evaluated the association between the legacy of historical racism and prostate cancer, a disease with a wide health disparity globally. In this study, we assess the relationship between county-level historical chattel slavery in 1860 and prostate cancer incidences in 2018 among Black and White individuals.

METHODS: Prostate cancer incidences, socioeconomic variables, and 1860 slave data were all obtained from publicly available datasets. Our primary exposure was county-level density of enslaved people in 1860. Our primary dependent variable was prostate cancer incidence per 100,000. We used Poisson log-linear regression models to estimate the difference in county-level cancer counts per 10% increase in enslaved individuals in a county, adjusting for age and numerous social determinants of health.

RESULTS: County-level density of enslaved people correlated with various present-day social determinants of health. In our multivariable adjusted model, increased county-level enslaved populations in 1860 were independently associated with a significant increase in 2018 county-level prostate cancer incidences for both White and Black individuals.

CONCLUSIONS: Our results indicate that the presence of county-level chattel slavery was significantly associated with poorer present-day social determinants of health and increased prostate cancer incidences, regardless of race.

IMPACT: Addressing health inequities requires the acknowledgment of the role historical chattel slavery plays in health disparities affecting marginalized and low socioeconomic communities in America.},
}

Humans
Male
*Prostatic Neoplasms/epidemiology
Incidence
Southeastern United States/epidemiology
*Enslavement/history/statistics & numerical data
Black or African American/statistics & numerical data
Middle Aged
Health Status Disparities
Aged
White People/statistics & numerical data
Socioeconomic Factors
History, 19th Century
White

@article {pmid40779552,
year = {2025},
author = {Ahmed, S and DiPersio, J and Essell, J and Diefenbach, C and Perales, MA and Castilla-Llorente, C and Dahiya, S and Liu, Y and Xu, H and Fanton, C and Chaudhry, S and Lee, ZH and Marcondes, AMQ and Tagliaferri, MA and Zalevsky, J and Miklos, D and Turtle, CJ and McGuirk, J},
title = {NKTR-255 enhances complete response following CD19 CAR T-cell therapy in patients with relapsed/refractory large B-cell lymphoma.},
journal = {Blood advances},
volume = {9},
number = {23},
pages = {6092-6095},
doi = {10.1182/bloodadvances.2025016423},
pmid = {40779552},
issn = {2473-9537},
}

@article {pmid41305628,
year = {2025},
author = {Garfias-Avila, N and Wang, CY and Lampe, JW and Mendoza, JA and Tapsoba, JD and Alcalá, NJ and Levy, L and Neuhouser, ML},
title = {Implications for Dietary Guideline Policy of a Cultural Adaptation of the US Dietary Guidelines for Women of Mexican Descent: A Pilot Study.},
journal = {Nutrients},
volume = {17},
number = {22},
pages = {},
pmid = {41305628},
issn = {2072-6643},
support = {1P50CA148143-16S1/NH/NIH HHS/United States ; },
mesh = {Humans ; Female ; Pilot Projects ; Adult ; *Nutrition Policy ; Middle Aged ; *Mexican Americans ; *Diet, Healthy/ethnology ; United States ; Diet ; Biomarkers/blood ; White ; },
abstract = {Background/Objectives: This study aims to evaluate whether the Dietary Guidelines for Americans (DGA) are effective for maintaining a healthy diet among Mexican-descent populations in the US or if a more culturally tailored policy approach is warranted. Methods: As a first outcome, 20 healthy women of Mexican descent from the Seattle area participated in a pilot randomized controlled trial. They were randomly assigned (10 participants each) to either a group receiving instruction on the standard 2015 DGA or a group receiving an adaptation of the DGA focused on traditional Mexican cuisine and culture. In this 12-week study (with follow-ups at 3 and 6 months), participants' acceptability of the cultural adaptation of the DGA was compared with that of the standard DGA with end-of-study surveys. Ten blood-based metabolic biomarkers were assessed at baseline and 3 months. Dietary changes at 3 months were assessed with a Food Frequency Questionnaire (FFQ) that was translated into Spanish but not culturally adapted. The secondary outcome was dietary change at 6 months. Results: The primary findings at 3 months showed that serum free fatty acids were reduced for the standard DGA arm. Carbohydrate consumption was reduced in the standard DGA arm only. The end-of-study survey results suggested that both interventions were well received by participants. Conclusions: The preliminary findings from this small sample size suggest that depending on a person's priorities, either intervention could be offered, with each arm showing slightly different dietary and biomarker outcomes.},
}

Humans
Female
Pilot Projects
Adult
*Nutrition Policy
Middle Aged
*Mexican Americans
*Diet, Healthy/ethnology
United States
Diet
Biomarkers/blood
White

@article {pmid41305521,
year = {2025},
author = {Swan, DA and Krantz, EM and Byrne, CM and Okuku, F and Nankoma, J and Mutyaba, I and Phipps, W and Schiffer, JT},
title = {Human Herpes Virus-8 Oral Shedding Heterogeneity Is Due to Varying Rates of Reactivation from Latency and Immune Containment.},
journal = {Viruses},
volume = {17},
number = {11},
pages = {},
pmid = {41305521},
issn = {1999-4915},
support = {5R01CA239593-25/NH/NIH HHS/United States ; },
mesh = {Humans ; *Virus Shedding ; *Herpesvirus 8, Human/physiology/immunology ; *Virus Latency ; *Virus Activation ; Viral Load ; Uganda/epidemiology ; Longitudinal Studies ; *Herpesviridae Infections/virology/immunology ; Male ; HIV Infections/virology/complications/immunology ; Female ; Adult ; *Mouth Mucosa/virology ; Sarcoma, Kaposi/virology/immunology ; Models, Theoretical ; },
abstract = {Human herpesvirus-8 (HHV-8) is a gamma herpesvirus linked to the development of Kaposi sarcoma (KS). KS is more common in persons living with HIV (PLWH), but endemic KS in HIV-negative individuals is also common in sub-Saharan Africa. HHV-8 shedding occurs in the oral mucosa and is likely responsible for transmission. The mechanistic drivers of different HHV-8 shedding patterns in infected individuals are unknown. We applied stochastic mathematical models to a longitudinal study of HHV-8 oral shedding in 295 individuals in Uganda who were monitored daily with oral swabs. Participants were divided into four groups based on whether they were HIV-negative or -positive, as well as KS-negative or -positive. In all groups, we observed a wide variance of shedding patterns, including no shedding, brief episodic low viral load shedding, prolonged episodic medium viral load shedding, and persistent high viral load shedding. Our model closely replicates patterns in individual data and attributes higher shedding rates to increased rates of viral reactivation and lower median viral load values to more rapid and effective engagement of cytolytic immune responses. Our model provides a framework for understanding different shedding patterns observed in individuals with HHV-8 infection.},
}

Humans
*Virus Shedding
*Herpesvirus 8, Human/physiology/immunology
*Virus Latency
*Virus Activation
Viral Load
Uganda/epidemiology
Longitudinal Studies
*Herpesviridae Infections/virology/immunology
Male
HIV Infections/virology/complications/immunology
Female
Adult
*Mouth Mucosa/virology
Sarcoma, Kaposi/virology/immunology
Models, Theoretical

@article {pmid41301877,
year = {2025},
author = {Bastin, N and Mezzanotte-Sharpe, J and Alvarez, R and Partridge, SC and Dintzis, SM and Stanton, SE and Gadi, VK and Kennedy, LC},
title = {Exploratory Analysis of the Impact of a Single Dose of Trastuzumab on the Immune Microenvironment in HER2-Positive Early-Stage Breast Cancer.},
journal = {Biomedicines},
volume = {13},
number = {11},
pages = {},
pmid = {41301877},
issn = {2227-9059},
support = {1P30CA015704-20/NH/NIH HHS/United States ; 1R01CA248192-20/NH/NIH HHS/United States ; N/A//Safeway Foundation/ ; 1T32CA009515-20/NH/NIH HHS/United States ; Hayden Family Foundation Young Investigator Award//ASCO/CCF/ ; 2T32CA217834-07/NH/NIH HHS/United States ; 5K12CA090625-25/NH/NIH HHS/United States ; },
abstract = {Background: How the tumor microenvironment (TME) influences treatment response in HER2+ breast cancer following HER2-directed therapy is crucial for individualizing therapies and is currently understudied. The purpose of this exploratory analysis was to elucidate changes in the TME following treatment with trastuzumab. Methods: Fourteen HER2+ early-stage breast cancer patients underwent tissue biopsies before and after a dose of trastuzumab. Samples were evaluated for stromal tumor-infiltrating lymphocytes (TILs) and RNA-based cell and gene expression signatures. Tumor inflammation signature scores were generated to measure whether an adaptive immune response developed to trastuzumab within the tumor. Patients were also stratified as immune responders or non-responders based on changes in TILs. Results: Of the 14 enrolled patients, 13 had samples available for analysis, and 7 had an immune response as assessed by changes in TILs compared to 6 non-responders. Trastuzumab treatment decreased PD-L1 and TGF-Beta signatures and increased CTLA4 gene signatures, although results were not statistically significant, and increased DUSP1 expression. In the TIL responder group, there was increased expression of dendritic cells as well as MARCO expression. Conclusions: These findings, although exploratory in nature, highlight trastuzumab's ability to induce an immune response and suggest that some patients may be more primed to mount an immune response following treatment than others. Patients without a robust response in TILs may benefit from additional agents to favorably modulate the TME for optimized responses to HER2-directed therapy, an area of research which warrants further study.},
}

@article {pmid41301035,
year = {2025},
author = {Lange, KR and de Blank, P and Xing, M and Mirzaei, S and Srivastava, DK and Oeffinger, K and Neglia, J and Krull, K and Nathan, PC and Howell, R and Ness, KK and Turcotte, LM and Leisenring, W and Armstrong, GT and Brinkman, T and Bowers, DC and Okcu, MF},
title = {Late Morbidity and Mortality in Survivors of Childhood Ependymoma: A Report from the Childhood Cancer Survivor Study (CCSS).},
journal = {Cancers},
volume = {17},
number = {22},
pages = {},
pmid = {41301035},
issn = {2072-6694},
support = {CA55727, GT Armstrong PI/CA/NCI NIH HHS/United States ; CA21765, C. Roberts, Principal Investigator//Cancer Center Support Grant/ ; NA//American Lebanese-Syrian Associated Charities/ ; },
abstract = {BACKGROUND/OBJECTIVES: Treatment of childhood ependymoma evolved from 1970 to 1999 by reducing radiation volumes and incorporating chemotherapy. The impact of these changes on long-term health outcomes remains unknown. In this report, we evaluated temporal changes in all-cause and cause-specific late mortality, chronic health conditions (CHCs), and subsequent neoplasms (SNs) in the Childhood Cancer Survivor Study (CCSS) cohort of adult survivors of pediatric ependymoma, diagnosed between 1970 and 1999.

METHODS: A total of 404 five-year survivors of ependymoma (47.5% female, 80.7% non-Hispanic White, median 6 (range 0-20) years at diagnosis, 22 (5-49) years from diagnosis) diagnosed between 1970 and 1999 and enrolled in the Childhood Cancer Survivor Study were evaluated for late (>5 years from diagnosis) mortality, SNs, and CHCs. Outcomes were analyzed by diagnosis decade, radiotherapy, and chemotherapy exposure. Gray's test compared cumulative incidences. Multivariable piecewise exponential models estimated relative risks (RRs).

RESULTS: Whole-brain radiation exposure decreased over time (42.9% (1970s) to 2.7% (1990s)), while focal radiation (21.4% to 68.9%), and chemotherapy (29.5% to 50.2%) use increased. Fifteen-year all-cause late mortality (incidence, 95% CI) remained similar across decades: 1970s (9.3%, 3.4-18.8%), 1980s (14.7%, 9.4-21.2%), 1990s (10.3%, 6.7-14.9%). All-cause late mortality was higher after treatment with whole-brain radiation (22.5%, 11.2-36.5%) compared to focal radiation (11.4%, 7.5-16.1%) or no brain radiation (3.5%, 0.9-9.1%) (p < 0.001), and with chemotherapy (14.4%, 9.6-20.0%) versus without (6.8%, 3.8-11.0%) (p = 0.004). Compared to no brain radiation, the RR (95% CI) of grade 3-4 CHCs increased among survivors treated with focal (2.6, 1.3-5.4) and whole-brain radiation (3.5, 1.5-8.1), while chemotherapy was not associated with CHCs or SNs.

CONCLUSIONS: Despite reduced radiation volumes and increased use of chemotherapy, late mortality and morbidity among pediatric ependymoma survivors remained largely unchanged across treatment decades.},
}

@article {pmid41299886,
year = {2025},
author = {Tu, DS and Olson, AK and Waggie, KS and Garcia, NM and Hoglund, VJ and Walter, SI and Rosinski, JR and Sadeeshkumar, H and Patel, R and Sayar, E and Haffner, MC and Maves, L and Neefjes, J and Sarthy, JF and Lawlor, ER and Ganapathi, SS},
title = {Determining Preclinical Safety of Aclarubicin in Pediatric Malignancies.},
journal = {Pediatric blood & cancer},
volume = {},
number = {},
pages = {e32169},
doi = {10.1002/pbc.32169},
pmid = {41299886},
issn = {1545-5017},
support = {//Burroughs Wellcome Fund/ ; //Andy Hill CARE Fund/ ; //Sunbeam Foundation/ ; /CA/NCI NIH HHS/United States ; //Sam Day Foundation/ ; //CURE Childhood Cancer/ ; },
abstract = {BACKGROUND: Anthracyclines are among the most effective chemotherapeutic agents used to treat pediatric malignancies. However, their clinical use is limited by dose-dependent toxicities, particularly cardiotoxicity and secondary malignancies. Aclarubicin (Acla) is an anthracycline derivative that induces chromatin damage while sparing DNA damage, offering potential therapeutic benefit with reduced long-term toxicity.

METHODS: We evaluated the anti-tumor efficacy and safety profile of Acla in multiple in vitro pediatric cancer models and in vivo mouse models designed to mimic anthracycline re-treatment following prior doxorubicin (Doxo) exposure. Tumor growth, genotoxic stress, survival, and organ toxicity were assessed.

RESULTS: Acla demonstrated robust anti-tumor activity comparable to Doxo across diverse pediatric in vitro models. Unlike Doxo, Acla treatment did not induce significant genotoxic stress. In vivo, mice receiving Acla after Doxo exposure showed no evidence of cumulative cardiotoxicity or end-organ damage. In contrast, a second course of Doxo led to significant toxic mortality but was surprisingly not attributable to classic cardiac injury.

CONCLUSION: Our study highlights Acla as a promising anthracycline derivative for pediatric cancers, with potent anti-tumor efficacy and a superior safety profile, even following prior anthracycline exposure. These results support continued investigation of chromatin-damaging anthracyclines that can kill pediatric cancer cells without inducing genotoxic stress. In addition, our studies underscore the need to refine preclinical models to better understand both acute and chronic anthracycline toxicities in pediatric and adolescent populations.},
}

@article {pmid41299744,
year = {2025},
author = {Saini, J and Stacey, A and Egan, A and Regmi, R and Bloch, C and Schwarz, M and Rengan, R and Chen, J and Halasz, L},
title = {Implementing ocular treatment with pencil beam scanning: the FHCC experience.},
journal = {Radiation oncology (London, England)},
volume = {20},
number = {1},
pages = {178},
pmid = {41299744},
issn = {1748-717X},
mesh = {Humans ; *Radiotherapy Planning, Computer-Assisted/methods ; *Proton Therapy/methods ; Radiotherapy Dosage ; Middle Aged ; *Eye Neoplasms/radiotherapy ; Male ; Female ; Aged ; Organs at Risk/radiation effects ; Monte Carlo Method ; Aged, 80 and over ; },
abstract = {BACKGROUND: The Fred Hutchinson Cancer Center (FHCC) has developed a novel in-house method for ocular proton therapy by adapting a pencil beam scanning (PBS) beamline and using a commercial treatment planning system. This manuscript outlines the workflow from simulation to treatment delivery and presents our experiences with the initial 40 patients.

METHODS: Key innovations of our treatment approach include in-house developed treatment chair and gaze localization systems, CT imaging for planning, and a Monte Carlo algorithm for dose calculation. We gathered data on patient characteristics, dose volume statistics, and total treatment time. Additionally, we examined the distances patients traveled to access ocular proton therapy. An example illustrating our treatment technique is also presented.

RESULTS: The average patient age at the time of treatment was 63.9 years. Tumor apical height ranged from 0.7 to 11.9 mm, and the largest basal diameter from 2.8 to 15.5 mm. GTV volumes ranged from 0.02 to 0.89 cc, while PTV volumes ranged from 0.17 to 2.27 cc. The D99% dose to GTV ranged from 5041 to 5242 cGy (RBE). The median mean dose to the lacrimal gland was 1570 cGy (RBE), while the median D2% doses to the optic nerve, macula, and optic disc were 4188 cGy (RBE), 5024 cGy (RBE), and 5133 cGy (RBE), respectively. Out of the 40 patients, 16 successfully met all treatment planning goals. The remaining patients did not meet some goals due to the target either abutting or being close (< 2 mm) laterally or distally to the OARs. The total treatment duration per fraction was approximately 25 min. Nearly one-third of the patients traveled around 900 miles to receive ocular treatment.

CONCLUSIONS: The approach at FHCC demonstrates that ocular proton therapy can be effectively delivered using a general-purpose PBS beamline, providing a solution for centers without dedicated ocular beamlines.},
}

Humans
*Radiotherapy Planning, Computer-Assisted/methods
*Proton Therapy/methods
Radiotherapy Dosage
Middle Aged
*Eye Neoplasms/radiotherapy
Male
Female
Aged
Organs at Risk/radiation effects
Monte Carlo Method
Aged, 80 and over

@article {pmid41299640,
year = {2025},
author = {Ekwunife, OI and Kuo, AP and Banerjee, P and Zhang, S and Kiptinness, C and Omollo, V and Chen, Y and Roche, SD and Odoyo, J and Bukusi, E and Ngure, K and Sharma, M and Ortblad, KF},
title = {Understanding the cost of pharmacy-delivered HIV pre- and post-exposure prophylaxis service delivery in Kenya: findings from pilot studies.},
journal = {BMC health services research},
volume = {25},
number = {1},
pages = {1536},
pmid = {41299640},
issn = {1472-6963},
support = {INV-033052/GATES/Gates Foundation/United States ; R34 MH120106/NH/NIH HHS/United States ; },
mesh = {Humans ; Kenya ; Pilot Projects ; *HIV Infections/prevention & control ; *Pre-Exposure Prophylaxis/economics ; Male ; *Post-Exposure Prophylaxis/economics ; Female ; Adult ; *Pharmacies/economics ; Anti-HIV Agents/economics/therapeutic use ; },
abstract = {BACKGROUND: Private pharmacies are a primary access point for health services in many African countries. Leveraging private-sector pharmacies to deliver HIV prevention services, including pre- and post-exposure prophylaxis (PrEP/PEP), may expand the reach of these services. Understanding delivery costs is necessary to inform scale-up.

METHODS: We used data from two pilot studies conducted in Kisumu County, Kenya. In the first pilot, pharmacy providers at 12 pharmacies delivered free PrEP/PEP to eligible clients (≥ 18 years) using a prescribing checklist with remote clinician oversight; PrEP/PEP drugs were donated from government stock. Using microcosting, we estimated the economic and financial costs from the provider's perspective for: (1) subsidized delivery (donated commodities excluded), and (2) non-subsidized delivery (donated commodities included). We also assessed client willingness to pay for PrEP services at pharmacies using PrEP client survey data. In the second pilot, pharmacy providers at 20 pharmacies delivered HIV testing services. We assessed providers' anticipated willingness to deliver PrEP services using provider survey data.

RESULT: From February to July 2022, pharmacies in the first pilot recorded 1,564 PrEP/PEP visits, and initiated 691 clients on PrEP. Among clients eligible to continue PrEP at the pharmacy, 69% (479/691) refilled at least once. We collected 694 surveys from PrEP clients. From March to June 2022, 40 providers in the second pilot completed surveys. The estimated economic (financial) costs per client-month on PrEP were $3.66 ($2.17) USD for subsidized and $13.23 ($11.74) USD for non-subsidized delivery, and for PEP were $3.66 ($2.15) USD for subsidized and $10.75 ($9.24) USD for non-subsidized delivery. Most PrEP clients (83%, 575/691) expressed willingness to pay for pharmacy-delivered PrEP services; the median amount they were willing to pay per visit was $3.30 USD (IQR $1.60-$4.10 USD), which exceeded the median maximum amount providers said they would charge per visit ($2.40 USD, IQR $1.60-$4.10 USD).

CONCLUSIONS: When subsidized with drugs from government stock, pharmacies are a low-cost platform for delivering PrEP and PEP services in Kenya. Client out-of-pocket payments could help sustain pharmacy PrEP/PEP delivery at scale, enabling broader coverage of HIV prevention services.},
}

Humans
Kenya
Pilot Projects
*HIV Infections/prevention & control
*Pre-Exposure Prophylaxis/economics
Male
*Post-Exposure Prophylaxis/economics
Female
Adult
*Pharmacies/economics
Anti-HIV Agents/economics/therapeutic use

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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