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

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

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

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

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

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

DESIGN: Cross-sectional secondary analysis.

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

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

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

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

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

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

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

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

INTERVENTION: Random assignment to CET or ET.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

@article {pmid41372127,
year = {2025},
author = {Bents, SJ and Martin, ET and Stevens-Ayers, T and Andrews, C and Adler, A and Perofsky, AC and Krantz, EM and Blazevic, R and Kimball, L and Prentice, R and Hansen, C and Starita, L and Han, P and Englund, JA and Wolter, N and von Gottberg, A and Maake, L and Moyes, J and Cohen, C and Boeckh, M and Hay, JA and Waghmare, A and Viboud, C},
title = {Multiplex serology reveals age-specific immunodynamics of respiratory pathogens in the wake of the COVID-19 pandemic.},
journal = {Nature communications},
volume = {16},
number = {1},
pages = {11015},
pmid = {41372127},
issn = {2041-1723},
mesh = {Humans ; *COVID-19/immunology/epidemiology/virology/transmission ; Child, Preschool ; SARS-CoV-2/immunology ; Child ; *Antibodies, Viral/blood/immunology ; Adult ; Influenza, Human/immunology/epidemiology/virology ; Middle Aged ; Adolescent ; Age Factors ; Infant ; Young Adult ; Male ; Female ; Aged ; Pandemics ; Washington/epidemiology ; South Africa/epidemiology ; },
abstract = {The rebound of endemic respiratory viruses following the COVID-19 pandemic was marked by atypical transmission dynamics, with children experiencing increased disease burden and out-of-season epidemics as restrictions relaxed. Here we used serology from a newly developed quantitative multiplex assay to assess the post-pandemic immunity debt. We assessed age-specific antibody dynamics across a broad range of respiratory viruses, including influenza, respiratory syncytial virus, seasonal coronaviruses, and SARS-CoV-2 using serology collected in King County, Washington, US, from 2020-2022 (n = 1508). We found that respiratory virus immunodynamics differed between individuals <5 years of age and older individuals, with young children experiencing larger boosts and quicker waning of antibodies across pathogens. We confirmed that these patterns are upheld in a non-pandemic setting by analyzing influenza serology collected in South Africa between 2016-2018 (n = 1028). We incorporated our serological insights into an influenza transmission model calibrated to epidemiological data from King County and show that consideration of age-specific immunodynamics may be important to anticipate the effects of pandemic perturbations.},
}

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

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

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

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

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

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

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

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

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

DESIGN: Multi-methods study.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

FUNDING: Incyte.},
}

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

FUNDING: Gates Foundation.},
}

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

@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