@article {pmid41129124,
year = {2025},
author = {Su, CT and Ramsey, SD and Shankaran, V},
title = {Can We Use Credit Data to Assess Cancer Financial Hardship?.},
journal = {JAMA oncology},
volume = {11},
number = {12},
pages = {1420-1422},
doi = {10.1001/jamaoncol.2025.4371},
pmid = {41129124},
issn = {2374-2445},
}

@article {pmid41129142,
year = {2026},
author = {Jani, S and Bencomo, T and Shasha, C and Pulliam, T and Jojic, A and Church, CD and Gooley, TA and Koelle, DM and Newell, EW and Nghiem, P},
title = {Circulating Neoantigen- and Viral Oncoprotein-Specific CD8+ T Cells Share a Transcriptional Signature.},
journal = {Cancer immunology research},
volume = {14},
number = {1},
pages = {22-31},
pmid = {41129142},
issn = {2326-6074},
support = {P30 CA015704/CA/NCI NIH HHS/United States ; P01 CA225517/CA/NCI NIH HHS/United States ; R01 CA264646/CA/NCI NIH HHS/United States ; F30 CA254168/CA/NCI NIH HHS/United States ; T32 CA080416/CA/NCI NIH HHS/United States ; CA225517//National Cancer Institute (NCI)/ ; CA254168//National Cancer Institute (NCI)/ ; CA080416//National Cancer Institute (NCI)/ ; CA264646//National Cancer Institute (NCI)/ ; CA015704//National Cancer Institute (NCI)/ ; A187769//Odyssey Group Foundation/ ; //National Foundation for Cancer Research (NFCR)/ ; },
mesh = {Humans ; *CD8-Positive T-Lymphocytes/immunology/metabolism ; *Carcinoma, Merkel Cell/immunology/genetics/virology/blood ; *Antigens, Viral, Tumor/immunology ; *Antigens, Neoplasm/immunology ; Female ; Male ; *Transcriptome ; Aged ; *Skin Neoplasms/immunology/genetics ; Gene Expression Profiling ; Middle Aged ; },
abstract = {Tumor-specific CD8+ T cells in blood seem to be important for and predictive of response to anti-PD-1 therapies. However, as most tumor antigens are unique to a given patient, the identification of tumor-specific CD8+ T cells is not routinely feasible. In this study, we characterized polyomavirus-specific CD8+ T cells from the blood of 17 patients with virus-driven Merkel cell carcinoma. We identified a 98-gene signature [Signature of Peripheral Tumor-specific CD8+ T cells (SPoTT)] that discriminated circulating tumor-specific CD8+ T cells from other T cells in immunotherapy-naïve patients. We observed profound transcriptomic differences among tumor-specific CD8+ T cells from blood versus those from tumor. In validation cohorts of Merkel cell carcinoma, as well as neoantigen-driven cancers, the signature of peripheral tumor-specific CD8+ T cells was able to identify viral oncoprotein- and neoantigen-specific CD8+ T cells with both sensitivity and specificity above 75%. We also tested a previously described 151-gene signature (NeoTCRPBL) trained on neoantigen-specific CD8+ T cells and found it was able to recognize Merkel cell polyomavirus-specific T cells with a sensitivity of 66% and a specificity of 88%. These findings show that circulating tumor-specific CD8+ T cells share fundamental characteristics across diverse tumor antigen types. More broadly, insights into antitumor T cells gained from virus-driven cancers are also likely to be relevant in mutationally driven cancers.},
}

Humans
*CD8-Positive T-Lymphocytes/immunology/metabolism
*Carcinoma, Merkel Cell/immunology/genetics/virology/blood
*Antigens, Viral, Tumor/immunology
*Antigens, Neoplasm/immunology
Female
Male
*Transcriptome
Aged
*Skin Neoplasms/immunology/genetics
Gene Expression Profiling
Middle Aged

@article {pmid41129365,
year = {2026},
author = {Watling, CZ and Campbell, PT and Graubard, BI and Wang, Y and Gewirtz, AT and Zhang, X and Barnett, MJ and Buring, JE and Chen, Y and Eliassen, AH and Gaziano, JM and Hofmann, JN and Huang, WY and Kang, JH and Koshiol, J and Loftfield, E and Lee, IM and Moore, SC and Mucci, LA and Neuhouser, ML and Newton, CC and Purdue, MP and Sesso, HD and Shrubsole, M and Sinha, R and Tinker, L and Triplette, M and Um, CY and Visvanathan, K and Watts, EL and Wactawski-Wende, J and Willett, W and Wu, F and Zheng, W and Barupal, D and Petrick, JL and McGlynn, KA},
title = {Pre-diagnostic immunological markers of bacterial translocation and liver cancer risk: A nested case-control analysis of 12 prospective cohorts.},
journal = {International journal of cancer},
volume = {158},
number = {7},
pages = {1801-1812},
pmid = {41129365},
issn = {1097-0215},
support = {187861/CAPMC/CIHR/Canada ; 75N92021D00002/HL/NHLBI NIH HHS/United States ; HL26490/NH/NIH HHS/United States ; U01 CA167462/CA/NCI NIH HHS/United States ; U01 CA164974/CA/NCI NIH HHS/United States ; 75N92021D00005/NH/NIH HHS/United States ; U01CA202979/NH/NIH HHS/United States ; 75N92021D00004/NH/NIH HHS/United States ; 75N92021D00001/NH/NIH HHS/United States ; NCI U01 167552/NH/NIH HHS/United States ; U24 ES035386/ES/NIEHS NIH HHS/United States ; UM1 CA182913/CA/NCI NIH HHS/United States ; R01 HL026490/HL/NHLBI NIH HHS/United States ; R01 CA034944/CA/NCI NIH HHS/United States ; U01CA164974/NH/NIH HHS/United States ; 75N92021D00005/WH/WHI NIH HHS/United States ; U01 CA063673/CA/NCI NIH HHS/United States ; CA097193/NH/NIH HHS/United States ; R01 HL043851/HL/NHLBI NIH HHS/United States ; HL080467/NH/NIH HHS/United States ; P30 DK058404/DK/NIDDK NIH HHS/United States ; R01 HL034595/HL/NHLBI NIH HHS/United States ; U01CA63673/NH/NIH HHS/United States ; 75N92021D00001/HL/NHLBI NIH HHS/United States ; HL043851/NH/NIH HHS/United States ; HL09935/NH/NIH HHS/United States ; 75N92021D00003/WH/WHI NIH HHS/United States ; UM1 CA186107/CA/NCI NIH HHS/United States ; HL34595/NH/NIH HHS/United States ; R01 CA047988/CA/NCI NIH HHS/United States ; UM1CA186107/NH/NIH HHS/United States ; CA40360/NH/NIH HHS/United States ; R01 HL080467/HL/NHLBI NIH HHS/United States ; 75N92021D00003/NH/NIH HHS/United States ; U24ES035386/NH/NIH HHS/United States ; //National Institutes of Health Intramural/ ; 75N92021D00002/NH/NIH HHS/United States ; CA047988/NH/NIH HHS/United States ; R01 CA040360/CA/NCI NIH HHS/United States ; U01CA167462/NH/NIH HHS/United States ; U01 CA182913/CA/NCI NIH HHS/United States ; U01 CA202979/CA/NCI NIH HHS/United States ; UM1CA167462/NH/NIH HHS/United States ; CA182913/NH/NIH HHS/United States ; RC1 HL099355/HL/NHLBI NIH HHS/United States ; UM1 CA167462/CA/NCI NIH HHS/United States ; R01 CA097193/CA/NCI NIH HHS/United States ; //American Cancer Society/ ; CA34944/NH/NIH HHS/United States ; 75N92021D00004/WH/WHI NIH HHS/United States ; },
mesh = {Humans ; Male ; Case-Control Studies ; *Liver Neoplasms/immunology/microbiology/blood/epidemiology ; Female ; Middle Aged ; *Bacterial Translocation/immunology ; Prospective Studies ; Lipopolysaccharide Receptors/blood/immunology ; Aged ; Carrier Proteins/blood/immunology ; Membrane Glycoproteins/blood ; Risk Factors ; Flagellin/immunology ; Immunoglobulin G/blood ; Acute-Phase Proteins ; Lipopolysaccharides/immunology ; Adult ; Immunoglobulin A/blood ; Biomarkers, Tumor ; },
abstract = {The gut-liver axis may play an important role in hepatocarcinogenesis. However, limited prospective research has explored associations with liver cancer risk. We conducted a nested case-control study based in 12 prospective cohort studies from across the United States, which included 867 cases of liver cancer and 867 matched controls. We measured bacterial translocation markers, specifically immunoglobulin (Ig) A, IgG, and IgM against lipopolysaccharide and flagellin; soluble CD14 (a co-receptor for lipopolysaccharide); and lipopolysaccharide-binding protein. Multivariable conditional logistic regression was used to estimate adjusted odds ratios (OR) and 95% confidence intervals (CI) between bacterial translocation marker concentrations per doubling in concentrations and liver cancer risk. Lipopolysaccharide-binding protein concentrations were most strongly associated with higher liver cancer risk (OR per doubling in concentrations: 1.48, 95% CI: 1.23-1.79). Concentrations of anti-flagellin IgA (1.13, 1.01-1.28) and IgG (1.13, 1.01-1.28), anti-lipopolysaccharide IgG (1.20, 1.01-1.42), and soluble CD14 (1.12, 1.01-1.24) were also associated with liver cancer risk. When analyses were separated into hepatocellular carcinoma (HCC, N = 436 cases) and intrahepatic cholangiocarcinoma (ICC, N = 110 cases), no evidence of heterogeneity was observed except for lipopolysaccharide-binding protein concentrations, which were positively associated with HCC (1.77, 1.34-2.33) but not ICC (0.67, 0.37-1.22; p-heterogeneity = .003). Associations did not differ by time to liver cancer diagnosis or other subgroups. These findings support the role of gut barrier dysfunction in hepatocarcinogenesis, necessitating further research to understand the complex interplay among the mechanisms and risk factors disrupting the gut barrier, microbiota, and liver cancer.},
}

Humans
Male
Case-Control Studies
*Liver Neoplasms/immunology/microbiology/blood/epidemiology
Female
Middle Aged
*Bacterial Translocation/immunology
Prospective Studies
Lipopolysaccharide Receptors/blood/immunology
Aged
Carrier Proteins/blood/immunology
Membrane Glycoproteins/blood
Risk Factors
Flagellin/immunology
Immunoglobulin G/blood
Acute-Phase Proteins
Lipopolysaccharides/immunology
Adult
Immunoglobulin A/blood
Biomarkers, Tumor

@article {pmid41129758,
year = {2025},
author = {Bagshaw, P and Potter, JD and Griffiths, N and Hornblow, A and Cox, B and Gower, K},
title = {Nurse endoscopists: a rational response to rising rates of young-onset colorectal cancer in Aotearoa New Zealand.},
journal = {The New Zealand medical journal},
volume = {138},
number = {1624},
pages = {76-86},
doi = {10.26635/6965.7100},
pmid = {41129758},
issn = {1175-8716},
mesh = {Humans ; New Zealand/epidemiology ; *Colorectal Neoplasms/epidemiology/diagnosis/nursing ; Middle Aged ; *Colonoscopy/nursing ; *Early Detection of Cancer ; Sigmoidoscopy/nursing ; Age of Onset ; Incidence ; *Mass Screening ; Aged ; Adult ; Female ; Male ; },
abstract = {Young-onset (<50 years) colorectal cancer (YOCRC) has been increasing in Aotearoa New Zealand since the birth cohort born around the mid-1950s. Possible responses include education and public health measures, none of which are likely to make a major impact in the foreseeable future. Many YOCRCs are presenting at late stages with predominantly distal cancers. Our current National Bowel Screening Programme (NBSP), screening people 60-75 years, was introduced with inadequate resources; as a result, some colonoscopy services have been moved from symptomatic cases to screening, resulting in diagnostic delays and poorer outcomes. Extending screening to 40 or 45 years will markedly increase the need for follow-up colonoscopies and stretch services beyond breaking point. Sigmoidoscopy is associated with a substantial and sustained reduction in risk of distal colorectal cancer incidence and mortality. As there are too few endoscopists for the existing workload, increasing the nurse endoscopist workforce is a rational step. Initial training would focus on flexible sigmoidoscopy (FS) and concentrate on symptomatic patients <50 years. Steadily increasing nurse endoscopist numbers will contribute to management of the rising incidence of YOCRC. Without disrupting the NBSP or putting much extra strain on need for follow-up colonoscopies, nurse-led FS clinical services can expand to anyone with relevant symptoms and, as a longer-term goal, eventually become part of an expanded screening programme that could include one-off FS at age 50. If we are agreed that this is essential, training and service must be adequately funded and accompanied by a public advocacy campaign to ensure sufficient resources.},
}

Humans
New Zealand/epidemiology
*Colorectal Neoplasms/epidemiology/diagnosis/nursing
Middle Aged
*Colonoscopy/nursing
*Early Detection of Cancer
Sigmoidoscopy/nursing
Age of Onset
Incidence
*Mass Screening
Aged
Adult
Female
Male

@article {pmid41129763,
year = {2025},
author = {Einstein, DJ and Abel, ML and Aragon-Ching, JB and Arlen, PM and Autio, KA and Bilusic, M and Carducci, MA and Choyke, PL and Citrin, DE and Figg, WD and Graff, JN and Gulley, JL and Halabi, S and Karzai, F and Lindenberg, L and Markowski, MC and Marshall, CH and McNeel, DG and Mena, E and Moon, H and Pachynski, RK and Paller, CJ and Patel, KR and Posadas, EM and Pienta, KJ and Regan, MM and Sena, LA and Walmsley, CS and Wei, XX and Yu, EY and Tran, PT and Madan, RA},
title = {National Cancer Institute's Working Group on Biochemically Recurrent Prostate Cancer: Clinical Trial Design Considerations.},
journal = {Journal of clinical oncology : official journal of the American Society of Clinical Oncology},
volume = {43},
number = {34},
pages = {3672-3683},
doi = {10.1200/JCO-25-01693},
pmid = {41129763},
issn = {1527-7755},
support = {U54 CA273956/CA/NCI NIH HHS/United States ; },
mesh = {Humans ; Male ; *Prostatic Neoplasms/therapy/pathology/diagnostic imaging/blood ; *Neoplasm Recurrence, Local/therapy/diagnostic imaging/blood ; United States ; National Cancer Institute (U.S.) ; *Research Design ; *Clinical Trials as Topic/methods ; Quality of Life ; Prostate-Specific Antigen/blood ; },
abstract = {PURPOSE: Biochemical recurrence (BCR) of prostate cancer (PCa) after definitive surgery and/or radiation (including salvage strategies) is a burgeoning area of clinical research inspired by ultrasensitive next-generation imaging. Most phase III trials in PCa have focused on metastatic disease, defined by conventional imaging. Despite the emergence of new imaging, clinical trial principles from metastatic studies will not optimize future BCR trials.

METHODS: A Working Group convened at the National Cancer Institute on November 13, 2024 (NCI BCR WG). Key areas of discussion included nomenclature, baseline criteria for data capture, imaging considerations, delineation of high-risk populations to be targeted for trial development, requirements of metastasis-directed therapy (MDT) or hormonal therapy, quality-of-life considerations, and potential study end points.

RESULTS: The NCI BCR WG defined the novel term "prostate-specific membrane antigen (PSMA)+BCR" to identify the emerging concept of recurrent PCa identifiable only on PSMA positron emission tomography (PET), overlapping with BCR and distinct from metastatic hormone-sensitive PCa as traditionally defined by conventional imaging. The WG suggested defining high-risk BCR with a prostate-specific antigen doubling time of ≤6 months, regardless of PET findings. The WG provided recommendations for baseline data capture and imaging requirements. Neither systemic therapy nor MDT were considered mandatory for control arms. The WG also discussed novel end points and quality-of-life metrics in this disease space.

CONCLUSION: These discussions should inform future clinical BCR trials in this distinct disease space relative to metastatic disease defined by conventional imaging. The NCI BCR WG strongly advocates that future trials explore deintensification of treatment to minimize toxicity in this relatively indolent disease state.},
}

Humans
Male
*Prostatic Neoplasms/therapy/pathology/diagnostic imaging/blood
*Neoplasm Recurrence, Local/therapy/diagnostic imaging/blood
United States
National Cancer Institute (U.S.)
*Research Design
*Clinical Trials as Topic/methods
Quality of Life
Prostate-Specific Antigen/blood

@article {pmid41130408,
year = {2026},
author = {Le, X and Baik, C and Cho, BC and Riess, JW and Piotrowska, Z and Johannes de Langen, A and Goldberg, SB and Goldman, JW and Reguart, N and Shiraishi, Y and Ambrose, H and Fraenkel, PG and Ruiz, BM and Smith, PE and Tang, KH and Yu, HA},
title = {Osimertinib Plus Savolitinib in Patients With EGFR-Mutated Advanced NSCLC With MET Alterations After First-Line Osimertinib: Clinical Outcomes, Safety, and Biomarker Analysis: A Brief Report.},
journal = {Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer},
volume = {21},
number = {2},
pages = {318-327},
doi = {10.1016/j.jtho.2025.10.009},
pmid = {41130408},
issn = {1556-1380},
mesh = {Humans ; *Carcinoma, Non-Small-Cell Lung/drug therapy/genetics/pathology ; *Lung Neoplasms/drug therapy/pathology/genetics ; Female ; Male ; *Acrylamides/therapeutic use/pharmacology/administration & dosage ; *Aniline Compounds/therapeutic use/pharmacology ; Middle Aged ; Aged ; ErbB Receptors/genetics ; Mutation ; *Antineoplastic Combined Chemotherapy Protocols/therapeutic use/pharmacology ; *Proto-Oncogene Proteins c-met/genetics ; Biomarkers, Tumor/genetics ; Survival Rate ; Adult ; Prognosis ; Aged, 80 and over ; Indoles ; Pyrazines ; Pyrimidines ; Triazines ; },
abstract = {INTRODUCTION: The ORCHARD (NCT03944772) study was conducted to characterize resistance mechanisms and identify optimal treatments after progressive disease (PD) on first-line osimertinib. We report results from the osimertinib plus savolitinib module.

METHODS: Patients with EGFR-mutated NSCLC with PD on first-line osimertinib with MET gene amplification (≥4 copies of MET over tumor ploidy) per next-generation sequencing of a post-progression biopsy received osimertinib plus savolitinib. Primary end point was investigator-assessed objective response rate (ORR). Secondary end points included progression-free survival, duration of response, overall survival, and safety. Correlation of ORR with baseline molecular alterations was an exploratory analysis.

RESULTS: A total of 32 patients were enrolled; all had tumors with MET amplification. At primary analysis cutoff (January 2023), confirmed ORR was 47% (80% confidence interval [CI]: 34-60). Median duration of response was 14.5 months (95% CI: 5.6-18.7). Median progression-free survival was 7.6 months (95% CI: 3.2-15.9). There was a trend toward increased ORR in patients with high MET gene copy number (≥10 versus <10). Furthermore, 14 patients (44%) had grade 3 or higher treatment-emergent adverse events; most often pneumonia (n = 3; 9%). At final database lock (May 2024), 20 patients (63%) had died; median overall survival was 20.7 months (95% CI: 9.9-34.8).

CONCLUSIONS: Osimertinib plus savolitinib demonstrated encouraging clinical benefit in patients with EGFR-mutated advanced NSCLC and MET amplification after PD on first-line osimertinib. Safety was consistent with profiles of the individual drugs.},
}

Humans
*Carcinoma, Non-Small-Cell Lung/drug therapy/genetics/pathology
*Lung Neoplasms/drug therapy/pathology/genetics
Female
Male
*Acrylamides/therapeutic use/pharmacology/administration & dosage
*Aniline Compounds/therapeutic use/pharmacology
Middle Aged
Aged
ErbB Receptors/genetics
Mutation
*Antineoplastic Combined Chemotherapy Protocols/therapeutic use/pharmacology
*Proto-Oncogene Proteins c-met/genetics
Biomarkers, Tumor/genetics
Survival Rate
Adult
Prognosis
Aged, 80 and over
Indoles
Pyrazines
Pyrimidines
Triazines

@article {pmid41134118,
year = {2025},
author = {Chua, KJ and Quilang, RC and Sallinger, K and Aktipis, CA and Arck, P and Bianchi, DW and Chang, HD and Cleaves, HJ and Eikmans, M and Fjeldstad, HES and Haig, D and Harrington, WE and Horsnell, W and Jacobsen, DP and Kamper-Jørgensen, M and Kanaan, SB and Khosrotehrani, K and Lambert, NC and Nelson, JL and Olsen, MB and Pan, TD and Prins, JR and Schildberg, FA and Staff, AC and Ståhlberg, A and Stelzer, IA and Urbschat, C and Way, SS and Wilson, MA and Ye, J and Kroneis, T and Boddy, AM},
title = {Identifying Key Questions and Challenges in Microchimerism Biology.},
journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)},
volume = {12},
number = {48},
pages = {e14969},
pmid = {41134118},
issn = {2198-3844},
support = {62214//John Templeton Foundation/ ; //Intramural Research Program of the National Human Genome Research Institute, National Institutes of Health/ ; },
mesh = {Animals ; Female ; Humans ; *Chimerism ; Male ; },
abstract = {Microchimerism research has recently gained renewed attention despite known existence of these rare cells for decades. Fetal and maternal microchimeric-derived cells may have functional capabilities, and are increasingly associated with both beneficial and adverse health outcomes. Yet, establishing the role of microchimerism in health has been largely constrained methodologically and theoretically. The Microchimerism, Human Health, and Evolution Project address these challenges by calling on 29 leading microchimerism experts to put forth key research questions that can substantially advance the field. Seven major categories are identified: function and mechanism; microchimerism in interventions, treatment, and transplant; mapping "generational microchimerism"; evolution; microchimerism detection; appropriate experimental model systems; and definition of microchimerism. Identifying these questions - and continuing to find answers - will be crucial for advancing the knowledge of microchimerism in health and disease.},
}

Animals
Female
Humans
*Chimerism
Male

@article {pmid41135058,
year = {2026},
author = {Adesina, OO and Voutsinas, J and Wu, QV and Teos, LY and Rokni, M and Nalbant, H and Nardo, L and Wun, T and Zemel, B},
title = {Low bone mineral density and pain impact in adults with sickle cell disease.},
journal = {Blood advances},
volume = {10},
number = {3},
pages = {748-758},
pmid = {41135058},
issn = {2473-9537},
support = {K23 HL148310/HL/NHLBI NIH HHS/United States ; },
mesh = {Humans ; *Anemia, Sickle Cell/complications ; Female ; Male ; Adult ; *Bone Density ; *Pain/etiology ; Middle Aged ; Absorptiometry, Photon ; Quality of Life ; },
abstract = {Low bone mineral density (BMD) is a prevalent skeletal finding in sickle cell disease (SCD), but its clinical consequences are poorly understood. We hypothesized that low BMD, independent of osteonecrosis (ON), would associate with pain in adults with SCD. In the SCD Bone Pain study, 53 ambulatory adults (64% females; mean age, 38 ± 11 years; 66% hemoglobin [Hb] SS/Sβ0 thalassemia) underwent dual-energy X-ray absorptiometry scans of their lumbar spine, hip, forearm, and whole body. They also completed the Adult Sickle Cell Quality of Life Measurement Information System pain impact questionnaire. Twenty-three participants (43%) had low BMD, defined as lumbar spine, total hip, or femoral neck BMD z scores of -2 or less. In multivariate linear regression, lumbar spine BMD z scores significantly changed by +0.31, -0.29, -0.14, and -1.3 for every unit increase in Hb, indirect bilirubin, and white blood cell count, and with crizanlizumab use, respectively. Pain impact T-scores significantly decreased (worsened) by 6.0 and 6.5 with reduced estimated glomerular filtration rate and chronic opioid therapy but increased (improved) by 3.8 for every unit increase in serum phosphate. The median [interquartile range] pain impact T-scores were significantly lower in participants with low BMD and ON (38.3 [37.4, 40.1]) than those with either low BMD (49.5 [43.6, 54.4]; P = 3 × 10-5) or ON (52.7 [45.3, 57]; P = 2 × 10-4) alone. Whether sickle cell-related low BMD results from impaired bone formation and/or accelerated bone loss remains unclear. Understanding how low bone density, with or without ON, mediates SCD pain warrants further investigation. This trial was registered at www.clinicaltrials.gov as #NCT05283148.},
}

Humans
*Anemia, Sickle Cell/complications
Female
Male
Adult
*Bone Density
*Pain/etiology
Middle Aged
Absorptiometry, Photon
Quality of Life

@article {pmid41135920,
year = {2026},
author = {Medlin, AR and Abrams, HR and Kent, EE and Ogunjesa, BA and Park, S and Tan, KR},
title = {Variations in Mental Distress Among Caregivers of Individuals With Chronic Illnesses and Comorbid Cognitive Impairment.},
journal = {American journal of preventive medicine},
volume = {70},
number = {4},
pages = {108165},
doi = {10.1016/j.amepre.2025.108165},
pmid = {41135920},
issn = {1873-2607},
mesh = {Humans ; *Caregivers/psychology/statistics & numerical data ; Male ; Female ; *Cognitive Dysfunction/epidemiology/psychology ; Middle Aged ; Chronic Disease/psychology ; Aged ; Adult ; Behavioral Risk Factor Surveillance System ; *Mental Disorders/epidemiology ; Comorbidity ; Alzheimer Disease ; *Stress, Psychological/epidemiology ; *Psychological Distress ; },
abstract = {INTRODUCTION: This study was aimed to examine the rates of mentally unhealthy days and frequent mentally unhealthy days among caregivers of patients with cancer, heart disease, mental illness, and Alzheimer's disease and related dementias on the basis of caregiving intensity and how cognitive impairment in non-Alzheimer's disease and related dementias caregiving moderates these relationships.

METHODS: Data from 22,550 caregivers in the 2019-2023 Behavioral Risk Factor Surveillance System were used to explore the relationship between caregiving intensity, mentally unhealthy days, and the presence of cognitive impairment. Zero-inflated negative binomial regressions assessed the associations of caregiving intensity on mentally unhealthy days, and logistic regressions examined the patterns in frequent mentally unhealthy days, controlling for demographics and survey weighting.

RESULTS: Caregivers of individuals with mental illness reported the highest frequent mentally unhealthy days (27.53%), followed by caregivers of those with cancer (20.3%), heart disease (18.57%), and Alzheimer's disease and related dementias (17.82%). Increased caregiving intensity correlated with higher mentally unhealthy day rates, particularly among caregivers of patients with cancer, heart disease, and Alzheimer's disease and related dementias. Caregivers of those with cancer showed increased mentally unhealthy days when moderating for cognitive impairment. Higher caregiving intensity was linked to increased frequent mentally unhealthy days in the caregivers of patients with cancer and Alzheimer's disease and related dementias, with cancer caregivers showing more frequent mentally unhealthy days when moderating for cognitive impairment.

CONCLUSIONS: Caregiving intensity affects mental health outcomes differently across illnesses. Tailored support is needed for caregivers, especially those providing care for individuals with comorbid cognitive impairment.},
}

Humans
*Caregivers/psychology/statistics & numerical data
Male
Female
*Cognitive Dysfunction/epidemiology/psychology
Middle Aged
Chronic Disease/psychology
Aged
Adult
Behavioral Risk Factor Surveillance System
*Mental Disorders/epidemiology
Comorbidity
Alzheimer Disease
*Stress, Psychological/epidemiology
*Psychological Distress

@article {pmid41136348,
year = {2025},
author = {Duran, MC and Shah, PD and Bell-Brown, AM and Rojina, J and Glascock, M and Ramirez, M and Ibarra, G and Garza, L and Linde, S and Bishop, S and Garrison, MM and Pascoe, KM and Drain, PK and Zhou, C and Ko, LK},
title = {Back to school: a qualitative study evaluating a community-informed COVID-19 risk communication intervention for rural elementary school children and their families.},
journal = {Translational behavioral medicine},
volume = {15},
number = {1},
pages = {},
pmid = {41136348},
issn = {1613-9860},
support = {UL1 TR002319/TR/NCATS NIH HHS/United States ; OT2 HD107544/GF/NIH HHS/United States ; },
mesh = {Humans ; *COVID-19/prevention & control ; Child ; Qualitative Research ; Female ; Male ; Rural Population ; Focus Groups ; Schools ; Parents/psychology ; SARS-CoV-2 ; *Students/psychology ; *Return to School ; Communication ; School Health Services ; Health Knowledge, Attitudes, Practice ; Adult ; },
abstract = {BACKGROUND: ReOpening Schools Safely and Educating Youth (ROSSEY) was a cluster randomized controlled trial of a risk communication intervention for COVID-19 prevention to promote safe return to school among students in a rural, agricultural community.

PURPOSE: This qualitative study evaluated the implementation of a risk communication intervention and a school district's COVID-19 testing program through parent focus groups and interviews with school staff and students.

METHODS: Parents (n = 37), students (n = 19), and school staff (n = 14) from seven schools that received the intervention shared their experience via focus groups and interviews informed by the RE-AIM framework. Deductive and inductive coding was conducted by four data analysts. Themes were validated with community members.

RESULTS: Parent focus groups, student and staff interviews provided insight into the ROSSEY study implementation. We identified five main themes: (i) social and financial drivers of participation; (ii) personal beliefs and unique challenges to research participation; (iii) intervention reinforced knowledge and shifted behavior; (iv) the appeal of comic books and videos supported adoption; and (v) multimodal communication and partnerships enhanced implementation.

CONCLUSIONS: The risk communication intervention was deemed culturally appropriate, reinforced previous knowledge, and encouraged adoption of preventive behaviors. The partnership with the school district and collaboration with the district's COVID-19 testing program ensured success of recruitment, study implementation, and adoption of preventive behaviors.},
}

Humans
*COVID-19/prevention & control
Child
Qualitative Research
Female
Male
Rural Population
Focus Groups
Schools
Parents/psychology
SARS-CoV-2
*Students/psychology
*Return to School
Communication
School Health Services
Health Knowledge, Attitudes, Practice
Adult

@article {pmid41136629,
year = {2025},
author = {Corey, L and Ratevosian, J and Beyrer, C and Currier, J and Eron, J and Cohen, MS and Deeks, SG},
title = {How HIV research drives health innovation in multiple diseases.},
journal = {Nature medicine},
volume = {31},
number = {12},
pages = {3965-3967},
pmid = {41136629},
issn = {1546-170X},
support = {UM1 AI068614/AI/NIAID NIH HHS/United States ; UM1AI068636//U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (NIAID)/ ; UM1AI068619//U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (NIAID)/ ; UM1 AI068614/AI/NIAID NIH HHS/United States ; },
}

@article {pmid41137757,
year = {2025},
author = {Fong, Y and Huang, Y and Huang, Y and Woo, W and McGarry, A and Áñez, G and Dunkle, LM and Cho, I and Houchens, CR and Martins, K and Jayashankar, L and Castellino, F and Petropoulos, CJ and Leith, A and Haugaard, D and Webb, W and Lu, Y and Yu, C and Carpp, LN and Randhawa, AK and Andrasik, MP and Kublin, JG and Hutter, J and Keshtkar-Jahromi, M and Beresnev, TH and Rodriguez, CA and Tapia, M and Turley, CB and Zorrilla, CD and Cohen, SH and Kline, SE and Barranco, E and Corey, L and Neuzil, KM and Follmann, D and Ake, JA and Gay, CL and Kotloff, KL and Jones, T and Koup, RA and Donis, RO and Gilbert, PB},
title = {Analysis of antibody markers as immune correlates of risk of severe COVID-19 in the PREVENT-19 efficacy trial of the NVX-CoV2373 recombinant protein vaccine.},
journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America},
volume = {},
number = {},
pages = {},
pmid = {41137757},
issn = {1537-6591},
support = {S10 OD028685/OD/NIH HHS/United States ; C0000008/CL/CLC NIH HHS/United States ; UM1 AI068614/AI/NIAID NIH HHS/United States ; UM1 AI068618/AI/NIAID NIH HHS/United States ; R37 AI054165/AI/NIAID NIH HHS/United States ; UM1 AI148684/AI/NIAID NIH HHS/United States ; UM1 AI068635/AI/NIAID NIH HHS/United States ; UM1 AI068619/AI/NIAID NIH HHS/United States ; UM1 AI068636/AI/NIAID NIH HHS/United States ; },
abstract = {BACKGROUND: We previously showed that ancestral-specific anti-Spike binding IgG concentration and 50% inhibitory dilution neutralizing antibody titer (nAb-ID50) measured at 2 weeks post-dose 2 (∼peak) were inverse correlates of risk (CoRs) of COVID-19 over 2 months post ∼peak in the PREVENT-19 trial of the NVX-CoV2373 vaccine; there were not sufficient data to assess CoRs of severe COVID-19.

METHODS: Here we assessed, in the same vaccinated cohort, Delta- and ancestral-specific Spike IgG and nAb-ID50 at ∼peak and over time as CoRs of severe COVID-19 and of Delta COVID-19 over 3.5-10 months post ∼peak (287 breakthrough Delta cases, including 8 severe; 446 non-cases).

RESULTS: ∼Peak antibody levels were much higher for non-cases vs. severe cases (all inferred Delta), with nAb-ID50 Delta geometric mean 209.5 arbitrary units (AU)/mL (95% CI: 176.1, 249.1) vs. 9.6 AU/mL (95% CI: 2.4, 38.6), respectively. Frequency of detectable nAb-ID50 titer was 98.3% (97.2, 99.0) for non-cases vs. 62.5% (22.3, 93.9) for severe cases. All markers were inverse CoRs of severe COVID-19, with a ∼peak hazard ratio (HR) of 0.13 (95% CI: 0.03, 0.57) per 10-fold nAb-ID50 Delta increase. Severe COVID-19 risk through 305 days post-Day 35 was 0.0338 (0.0043, 0.206) at the nAb-ID50 Delta 2.5th percentile (8.4 AU/ml), and 0.002 (0.0000, 0.0108) and 0.0002 (0.0000, 0.0035) at the 50th and 95th percentiles (210, 2522 AU/ml).

CONCLUSIONS: Post-vaccination NVX-CoV2373 antibody levels are stronger predictors of severe COVID-19 than any-severity Delta COVID-19. Low antibody responses indicate vulnerability to severe COVID-19.},
}

@article {pmid41138741,
year = {2025},
author = {Anderson, BO and Duggan, C},
title = {Lessons from CONCORD and VENUSCANCER: closing global gaps in cancer care for women.},
journal = {Lancet (London, England)},
volume = {406},
number = {10517},
pages = {2298-2300},
doi = {10.1016/S0140-6736(25)01580-6},
pmid = {41138741},
issn = {1474-547X},
}

@article {pmid41138816,
year = {2026},
author = {Shadman, M and Ahmed, S and Byrne, MT and Chavez, JC and Kamdar, M and Sorror, ML and Perales, MA and Hill, JA and Moslehi, J and Miklos, DB},
title = {Who Is Eligible for Chimeric Antigen Receptor T Cell Therapy? Expert Perspectives on Overcoming Referral Barriers.},
journal = {Transplantation and cellular therapy},
volume = {32},
number = {3},
pages = {277-287},
doi = {10.1016/j.jtct.2025.10.025},
pmid = {41138816},
issn = {2666-6367},
mesh = {Humans ; *Immunotherapy, Adoptive/methods ; *Referral and Consultation ; *Receptors, Chimeric Antigen/immunology ; *Hematologic Neoplasms/therapy/immunology ; },
abstract = {CD19-directed chimeric antigen receptor T-cell (CAR-T) therapies, including lisocabtagene maraleucel, axicabtagene ciloleucel, and tisagenlecleucel, have revolutionized the treatment landscape for patients with hematologic malignancies. However, identification and referral of patients who could benefit from treatment remains a significant challenge, Here, we report expert recommendations for CAR-T therapy referral gathered from 10 experts in oncology, hematology, cardiology, and infectious diseases from a roundtable meeting and/or subsequent reviews between November 13, 2024, and June 9, 2025. We considered the following potential factors: age, performance status, disease status, cardiovascular function, pulmonary function, renal function, hepatic function, infections, and psychological health. Based on existing evidence, we agreed that none of the factors discussed should preclude patients from receiving referrals/further evaluation for CAR-T therapy, particularly with current advances in supportive care and integration of services from other specialties. Timely referral should be made by the patient's primary oncologist to specialists as early as the disease is deemed relapsed or refractory, preferably before the starting the subsequent line of therapy to allow better access to care and improve treatment outcomes. Before CAR-T therapy, holding therapy (before leukapheresis) and/or bridging therapy (after leukapheresis) may be given to patients with high-volume disease, in consultation with CAR-T therapy specialists. Based on the safety profile of CAR-T therapies, experts recommended flexible monitoring and transfer of care back to primary/community oncology physicians, starting from 2 weeks after infusion to improve access to this potentially curative therapy. Adaptations to clinical practice based on the most recent regulations, policy requirements, and institutional guidelines should be made as needed. In summary, a panel of 10 experts provided recommendations for timely patient referral for CAR-T therapy on the occurrence of relapsed or refractory disease and before the initiation of subsequent lines of therapy to improve care access and treatment outcomes. Experts noted that with close collaboration between CAR-T therapy specialists and other medical disciplines, CAR-T therapy remains a feasible option for most patients despite their comorbidities. © 2025 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc.},
}

Humans
*Immunotherapy, Adoptive/methods
*Referral and Consultation
*Receptors, Chimeric Antigen/immunology
*Hematologic Neoplasms/therapy/immunology

@article {pmid41138914,
year = {2026},
author = {Zhang, Y and Alver, S and Shan, Z and Mossavar-Rahmani, Y and Hu, J and Zhang, J and St-Onge, MP and Kaplan, R and Xue, X and Qi, Q},
title = {The timing of macronutrient and major food group intake and associations with mortality among United States adults, 1999‒March 2020: a serial cross-sectional study.},
journal = {The American journal of clinical nutrition},
volume = {123},
number = {1},
pages = {101097},
pmid = {41138914},
issn = {1938-3207},
support = {R35 HL155670/HL/NHLBI NIH HHS/United States ; R01 DK128154/DK/NIDDK NIH HHS/United States ; R01 DK126698/DK/NIDDK NIH HHS/United States ; R01 DK119268/DK/NIDDK NIH HHS/United States ; R01 HL170904/HL/NHLBI NIH HHS/United States ; R01 HL142648/HL/NHLBI NIH HHS/United States ; T32 CA094880/CA/NCI NIH HHS/United States ; },
mesh = {Humans ; Cross-Sectional Studies ; Male ; Female ; United States/epidemiology ; Adult ; Middle Aged ; Nutrition Surveys ; *Nutrients/administration & dosage ; *Diet ; Energy Intake ; Aged ; Time Factors ; *Feeding Behavior ; *Mortality ; Young Adult ; *Eating ; },
abstract = {BACKGROUND: Eating timing has been increasingly linked to health, yet national trends in macronutrient/food group timing and their health implications remain unclear.

OBJECTIVES: To characterize trends in the timing of energy, macronutrient, and food group intake among United States adults and examine their associations with mortality.

METHODS: In this serial cross-sectional study of adults aged ≥20 y with ≥1 valid 24-h dietary recall (National Health and Nutrition Examination Survey, 1999‒March 2020), we examined secular trends in timing of energy, macronutrients, and major food group intake. Associations with mortality (through December 2019) were examined using Cox models.

RESULTS: Among 50,264 adults, evening (18:00-22:00) accounted for the highest daily energy intake (weighted mean proportions across years, 31.9%‒33.3%), followed by noon (10:00-14:00, 24.7%‒26.8%), afternoon (14:00-18:00, 19.9%‒21.8%), morning (06:00-10:00, 13.5%‒14.9%), and overnight (22:00-06:00, 5.6%‒6.5%); midnight (22:00-02:00) eating occurred in 23.4%‒28.0% of the population. Macronutrient and food groups followed similar patterns, except whole grain (peaked in the morning) and fruit, egg, and dairy intake (more evenly distributed). Over the years, noon and midnight energy intake proportions declined, whereas the afternoon proportion increased; secular trends varied by macronutrients/food groups. Fasting started at 20:34-20:51 and ended at 08:41-08:51; intake midpoint was 14:37-14:48; intake duration was 11.9‒12.2 h. Male, non-Hispanic Black, and socioeconomically disadvantaged groups had greater midnight intake proportions and later intake midpoints. Reallocating 5% of daily energy to midnight was associated with higher cardiovascular mortality (hazard ratio: 1.09; 95% confidence interval: 1.02,1.17), driven by carbohydrates; reallocating 5% to predawn (02:00-06:00) was associated with higher cancer mortality (hazard ratio: 1.22; 95% confidence interval: 1.05, 1.41), driven by proteins. Each 1-h delay in fasting and intake midpoint was associated with an 8%‒9% higher cardiovascular mortality.

CONCLUSIONS: Overnight intake and delayed eating timing are prevalent among United States adults, especially between socioeconomically disadvantaged groups, and were associated with higher mortality, particularly for specific macronutrients/foods, supporting eating timing recommendations integrating food composition.},
}

Humans
Cross-Sectional Studies
Male
Female
United States/epidemiology
Adult
Middle Aged
Nutrition Surveys
*Nutrients/administration & dosage
*Diet
Energy Intake
Aged
Time Factors
*Feeding Behavior
*Mortality
Young Adult
*Eating

@article {pmid41141367,
year = {2025},
author = {Wick, BJ and Kluesner, MG and Slipek, NJ and Skeate, JG and Niemeyer, EM and Webber, BR and Moriarity, BS},
title = {Installation of dominant-negative mutations in FAS and TGFβR2 via base editing in primary T cells.},
journal = {Molecular therapy. Oncology},
volume = {33},
number = {4},
pages = {201063},
pmid = {41141367},
issn = {2950-3299},
support = {R01 AI161017/AI/NIAID NIH HHS/United States ; P30 CA077598/CA/NCI NIH HHS/United States ; F30 CA305905/CA/NCI NIH HHS/United States ; R61 AG090358/AG/NIA NIH HHS/United States ; U54 CA232561/CA/NCI NIH HHS/United States ; R21 AI163731/AI/NIAID NIH HHS/United States ; T32 HL007062/HL/NHLBI NIH HHS/United States ; U24 OD026641/OD/NIH HHS/United States ; R21 CA237789/CA/NCI NIH HHS/United States ; R37 CA276345/CA/NCI NIH HHS/United States ; P01 CA254849/CA/NCI NIH HHS/United States ; R01 AI146009/AI/NIAID NIH HHS/United States ; U54 CA268069/CA/NCI NIH HHS/United States ; P50 CA136393/CA/NCI NIH HHS/United States ; },
abstract = {Adoptive cell transfer (ACT) of engineered T cells is effective against B cell malignancies but has faltered against solid tumors due to the immunosuppressive tumor microenvironment (TME). FAS ligand (FASL) and transforming growth factor β (TGF-β) are key mediators of T cell dysfunction in the TME and overexpressing dominant negative (dn) forms of their receptors in T cells increases anti-tumor efficacy in solid tumor models. However, an approach that directly targets the endogenous genes would be more amenable to multiplex editing and reduce competition with WT alleles. Here, we employ base editing (BE) in primary human T cells to install naturally occurring dominant negative FAS and TGFβR2 mutations. In vitro survival and proliferation assays demonstrate that BE T cells are resistant to pro-apoptotic and anti-proliferative effects of FAS and TGF-β signaling. Chimeric antigen receptor (CAR)-T cells with BE-installed dn TGFβR2 or dn FAS exhibit improvements in cytotoxicity, while dn TGFβR2 CAR T demonstrate increased persistence and reduced expression of phenotypic markers of exhaustion compared to controls. Moreover, BE-engineered dn CAR T outperform lentiviral-engineered cDNA over expression counterparts in several functional assays. Considering the efficiency of BE and its amenability for multiplex editing, our approach lends itself to engineering strategies necessary to overcome T cell dysfunction in solid tumors.},
}

@article {pmid41141393,
year = {2026},
author = {Choudhury, SR and Kaushal, A and Biswas, P and Padilla, C and Sarthy, JF and Chavan, A and Gonzalez, GA and Meshinchi, S and Farrar, JE},
title = {Transcriptional rewiring by enhancer methylation in CBFA2T3-GLIS2-driven pediatric acute megakaryoblastic leukemia.},
journal = {Genes & diseases},
volume = {13},
number = {1},
pages = {101843},
pmid = {41141393},
issn = {2352-3042},
abstract = {Resistance to chemotherapy and subsequent relapse remain the primary challenge in pediatric acute myeloid leukemia (pAML), particularly in CBFA2T3-GLIS2 (C/G) fusion-positive acute megakaryoblastic leukemia. Here we demonstrate that the C/G fusion drives extensive DNA methylation changes and oncogenic enhancer activation at cis-regulatory elements (CREs), reshaping gene expression. This multi-omics analysis reveals a distinct hypermethylation pattern at promoters of up-regulated genes in C/G[+] pAML across patient samples (n = 24) and representative cell lines, notably enriched in adhesion-related, TGFβ, or Wnt signaling pathways. Hypermethylated regions adjacent to transcription start sites (TSS) maintain open chromatin with H3K27ac enrichment, supporting a mechanism of de novo chromatin looping and active transcription in a non-canonical manner. Additionally, C/G fusion binding near the DNA methyltransferase 3B (DNMT3B) promoter correlates with elevated DNMT3B expression, implicating its role in aberrant DNA methylation changes at CREs. This study elucidates the epigenetic mechanisms driving C/G[+] pAML, showing how the fusion reshapes chromatin and DNA methylation landscapes by impacting the expression (and likely activity) of epigenetic modifiers like DNMT3B. Functionally, DNMT3B inhibition enhances apoptotic sensitivity to BCL2 blockade, indicating that targeting DNMT3B may overcome apoptotic resistance in C/G[+] leukemic cells and offer a therapeutic strategy for this high-risk subtype.},
}

@article {pmid41141451,
year = {2025},
author = {Reed, JC and Hall, L and McKhann, A and Kwak, G and Goecker, EA and Coombs, RW and Chen, H and Roa, J and Vecchio, A and Daar, ES and Hunt, PW and Marra, CM and Campbell, TB and Ma, Q and Swaminathan, S and Macatangay, BJC and Morse, GD and Miller, T and Rusin, D and Ha, B and Alston-Smith, B and Paul, R and Letendre, SL and Spudich, SS and Greninger, AL},
title = {Antiretroviral Therapy Intensification With Dolutegravir and/or Maraviroc Did Not Affect HIV-1 Cell-Associated DNA, RNA, and 2--LTR Circles Over 12 Weeks.},
journal = {Open forum infectious diseases},
volume = {12},
number = {10},
pages = {ofaf594},
pmid = {41141451},
issn = {2328-8957},
support = {P30 AI027757/AI/NIAID NIH HHS/United States ; U01 AI068634/AI/NIAID NIH HHS/United States ; },
abstract = {BACKGROUND: Neurocognitive impairment (NCI) among people living with human immunodeficiency virus (HIV; PWH) on antiretroviral therapy (ART) may result from residual viral replication. The A5324 trial found that ART intensification with dolutegravir (DTG) with or without maraviroc (MVC) did not affect NCI in PWH. We evaluated the impact of ART intensification on peripheral virological measures during the first 12 weeks of intensification.

METHODS: The A5324 study was a randomized, double-blind, placebo (PBO)-controlled, 96-week trial of ART intensification with either dual PBO, DTG + PBO, or DTG + MVC in PWH with NCI on ART who were naive to integrase strand transfer inhibitors and MVC. At baseline and weeks 2, 4, and 12, HIV-1 RNA was measured in plasma with a low-copy assay, while HIV-1 cell-associated DNA (caDNA), cell-associated unspliced RNA (caRNA), and cell-associated 2-long terminal repeat circles (ca2LTR) were quantified from peripheral blood mononuclear cells using droplet digital polymerase chain reaction.

RESULTS: Of the 171 participants, 59 were randomized to dual PBO, 57 to DTG + PBO, and 55 to DTG + MVC. Changes in caDNA and caRNA and detection of plasma RNA did not differ between treatment arms over 12 weeks (P > 0.05). Detection of ca2LTR was less frequent at weeks 2-4 in the DTG + MVC arm (40.4%) than in the dual-PBO (70.7%; P =0 .02) and DTG + PBO (68.4%; P = 0.03) arms. However, this difference diminished by week 12, and baseline ca2LTR detection in the DTG + MVC arm was lower than in the other groups.

CONCLUSIONS: DTG intensification had no effect on peripheral markers of HIV-1 persistence. DTG + MVC intensification reduced ca2LTR detection at weeks 2-4, though this effect did not persist through week 12. These findings indicate the minimal impact of intensification on the HIV-1 peripheral reservoir, consistent with prior studies.},
}

@article {pmid41143136,
year = {2025},
author = {Tanaka, K and Chikowore, TJB and Deeks, SG and Estes, JD and Ho, YC and Jiang, S and Lee, MJ and Li, C and Machinda, A and Martins, M and Mdletshe, P and Ndhlovu, ZM and Neogi, U and Ott, MM and Rasmussen, TA and Reddy, K and Rutishauser, RL and Farrell-Sherman, A and Tiemessen, CT and Voss, JE and Kityo, C and Lewin, SR and Ndung'u, T and McCune, JM},
title = {Meeting Summary for Keystone Symposia on HIV Cure: Antiretroviral Therapy (ART)-Free Control of HIV Infection in Durban, South Africa, 2025.},
journal = {Pathogens & immunity},
volume = {10},
number = {2},
pages = {196-229},
pmid = {41143136},
issn = {2469-2964},
abstract = {Antiretroviral therapy (ART) can effectively control human immunodeficiency virus (HIV) replication; however, lifelong treatment is required due to viral reservoirs, which fuel viral rebound. This necessitates curative interventions that can achieve either eradication of the reservoir or durable remission off ART. Advances in technology have fostered development of multi-omic techniques encompassing molecular tools, proteomic analyses, imaging, and artificial intelligence (AI)-driven data analysis to understand HIV reservoir biology and persistence. These have informed the investigation of therapeutic interventions such as broadly neutralizing antibodies, latency reversal, immune cell augmentation, antivirals, and gene therapy. From April 7-10, 2025, experts in the field convened at the Keystone Symposia conference, HIV Cure: Antiretroviral Therapy (ART)-Free Control of HIV Infection in Durban, South Africa, to discuss novel strategies for eradication and/or durable ART-free control of HIV.},
}

@article {pmid41143601,
year = {2026},
author = {Cliff, ERS and Pelaez, GD and Wan, F and Iyengar, V and Zhou, J and Chung, K and Abdel-Razeq, N and Allen, J and Major, A and Sharp, J and Epperla, N and Gould, P and Cherng, HJ and Houshyar, S and Wallace, DS and Lynch, RC and Kallam, A and Mei, MG and Merryman, RW and Fleyshman, M and Rhodes, JM and Kidwell, A and Fenske, TS and Malakhov, N and Mulvey, E and Watkins, MP and Alhaj Moustafa, M and Hilal, T and Nowakowski, GS and Wang, Y and Torka, P and Russler-Germain, DA},
title = {Cell-of-Origin Subtype Predicts Response to Polatuzumab Vedotin in Large B-cell Lymphoma.},
journal = {Clinical cancer research : an official journal of the American Association for Cancer Research},
volume = {32},
number = {1},
pages = {159-168},
pmid = {41143601},
issn = {1557-3265},
support = {T32CA247815//National Cancer Institute (NCI)/ ; K12 CA167540/CA/NCI NIH HHS/United States ; P30 CA008748/CA/NCI NIH HHS/United States ; K12CA167540//National Cancer Institute (NCI)/ ; //Lymphoma Research Foundation (LRF)/ ; T32 CA247815/CA/NCI NIH HHS/United States ; },
mesh = {Humans ; *Lymphoma, Large B-Cell, Diffuse/drug therapy/pathology/mortality ; Male ; Female ; Middle Aged ; Aged ; *Antineoplastic Combined Chemotherapy Protocols/therapeutic use/adverse effects ; Adult ; *Antibodies, Monoclonal, Humanized/therapeutic use/administration & dosage ; *Immunoconjugates/administration & dosage/therapeutic use ; Aged, 80 and over ; Prognosis ; Treatment Outcome ; Antibodies, Monoclonal ; },
abstract = {PURPOSE: Polatuzumab vedotin (polatuzumab) was approved for up-front treatment of diffuse large B-cell lymphoma in combination with chemoimmunotherapy (Pola-R-CHP) based on the POLARIX trial. However, when stratified by cell of origin (COO), polatuzumab seems to have greater efficacy in activated B-cell than germinal center B-cell (GCB) subtype disease. Most studies of polatuzumab used RNA expression to assess COO, whereas in routine clinical practice, the immunohistochemistry-based Hans algorithm is used.

EXPERIMENTAL DESIGN: To assess the impact of COO by immunohistochemistry on polatuzumab efficacy, we conducted a multicenter real-world study of adults with large B-cell lymphoma (LBCL) receiving polatuzumab from 2015 to 2024, split by receipt of polatuzumab in first-line versus relapsed/refractory settings. The primary endpoint was overall response rate (ORR) to polatuzumab-based treatment in GCB versus non-GCB relapsed/refractory LBCL.

RESULTS: Of 740 patients, 305 received polatuzumab in the first-line setting and 435 in the relapsed/refractory setting. In the relapsed/refractory cohort, the ORR in non-GCB versus GCB LBCL was 59.7% versus 36.3% [OR, 2.6; 95% confidence interval (CI), 1.77-3.84; P < 0.0001], with a complete response rate of 35.7% versus 17.7% (OR, 2.6; 95% CI, 1.66-4.02; P < 0.0001). Progression-free survival was longer for patients with non-GCB versus GCB COO (HR, 0.64; 95% CI, 0.5-0.83; P = 0.0006). In the first-line cohort, ORR, complete response rate, and progression-free survival were similar in non-GCB versus GCB LBCL, as hypothesized based on outcomes in the Pola-R-CHP arm of POLARIX, suggesting that the addition of polatuzumab overcomes the adverse risk of non-GCB COO in patients receiving R-CHOP.

CONCLUSIONS: Based on these data, COO classification by the Hans algorithm is a strong predictor of polatuzumab efficacy in LBCL, informing real-world treatment decisions.},
}

Humans
*Lymphoma, Large B-Cell, Diffuse/drug therapy/pathology/mortality
Male
Female
Middle Aged
Aged
*Antineoplastic Combined Chemotherapy Protocols/therapeutic use/adverse effects
Adult
*Antibodies, Monoclonal, Humanized/therapeutic use/administration & dosage
*Immunoconjugates/administration & dosage/therapeutic use
Aged, 80 and over
Prognosis
Treatment Outcome
Antibodies, Monoclonal

@article {pmid41145253,
year = {2025},
author = {Kataria, I and Selmouni, F and Duggan, C and Sullivan, R and Purushotham, A and Sankaranarayanan, R and Taghavi, K and Basu, P},
title = {Application of implementation science methods and theories for cancer control planning in low-income and middle-income countries: a scoping review.},
journal = {BMJ open},
volume = {15},
number = {10},
pages = {e108755},
pmid = {41145253},
issn = {2044-6055},
support = {001/WHO_/World Health Organization/International ; },
mesh = {Humans ; *Neoplasms/prevention & control/therapy ; *Developing Countries ; *Implementation Science ; Health Policy ; Delivery of Health Care/organization & administration ; *Health Planning ; },
abstract = {INTRODUCTION: Implementation science (IS) is increasingly recognised as vital in cancer control planning and integrating evidence-based interventions across the cancer care continuum. Contextual differences often cause variability in delivering optimised healthcare, which IS approaches could mitigate. While IS improves planning effectiveness, many programme and policy planners remain unaware of its benefits. To address this, we examined IS theories applied to national cancer control plans (NCCPs)/strategies across five domains: stakeholder engagement, situational analysis, capacity assessment, economic evaluation and impact assessment.

METHODS: We conducted a scoping review using the Arksey and O'Malley framework to analyse NCCPs and strategies from 16 and 17 countries belonging to low and medium categories of Human Development Index (HDI), focusing on resource-constrained settings. We identified plans through the International Cancer Control Partnership portal, categorised them by WHO region and included only those available in English or French. We extracted data into a Microsoft Excel database and performed thematic analysis across five IS domains. Multiple IS experts, selected purposively based on their familiarity with resource-constrained settings, validated the findings, assessed policy relevance and helped develop a pathway for integrating IS into national cancer control planning. They reviewed structured questions in advance and provided feedback on analyses, practical utility, dissemination and simplifying IS application, which was used to refine the pathway and reach consensus.

RESULTS: While many NCCPs incorporated key IS elements such as stakeholder engagement, situational analysis and impact measurement, these often needed to be more explicit and consistently applied. None of the plans assessed health system capacity to determine readiness for implementing new interventions. Although most plans described stakeholder engagement, it was typically unstructured and incomplete. Four low HDI and nine medium HDI countries included costed plans, generally using an activity-based approach. All plans included impact measures (eg, key performance indicators), but five lacked mechanisms for engaging stakeholders or responsible entities to achieve the targets. These findings informed a proposed pathway to integrate IS principles into cancer control planning.

CONCLUSION: Integrating IS into national cancer control planning offers a structured framework for achieving equitable and feasible cancer control policies, particularly in resource-constrained settings, by enabling realistic goal setting and benchmarking against regional and global standards.},
}

Humans
*Neoplasms/prevention & control/therapy
*Developing Countries
*Implementation Science
Health Policy
Delivery of Health Care/organization & administration
*Health Planning

@article {pmid41146877,
year = {2025},
author = {Kuhlmann, AS and Madkhali, N and Moskovitz, E and Parrott, JE and Raman, SS and Riker, AO and Martinez-Reyes, J and Gupta, M and Jang, RA and Nelson, V and Gray, MD and Taylor, JJ and Peterson, CW and Kiem, HP},
title = {Heavy-chain immunoglobulin locus editing in rhesus macaque B cells to confer antibody production.},
journal = {Molecular therapy. Methods & clinical development},
volume = {33},
number = {4},
pages = {101598},
pmid = {41146877},
issn = {2329-0501},
support = {P51 OD011092/OD/NIH HHS/United States ; R01 AI167004/AI/NIAID NIH HHS/United States ; },
abstract = {Antibody-based immunotherapies are promising; however, their application remains limited to acute diseases due to rapid clearance of antibodies in vivo. Some chronic conditions could benefit from sustained therapeutic antibody expression. One such instance is human immunodeficiency virus type 1 (HIV-1), where the efficiency of broadly neutralizing antibodies by passive immunization has been limited in clinical trials. B cell editing to enable sustained production of an antibody of interest in vivo could address this issue. However, the long-term potential of this approach and feasibility to perform editing in B cells from people living with HIV remain to be determined. We investigated editing of rhesus macaque B cells from healthy or simian/human immunodeficiency virus (SHIV)-infected animals to model this approach. An antibody-encoding cassette was inserted in the immunoglobulin locus by CRIPSR-Cas9-mediated ex vivo B cell editing. Similar indel efficiencies were achieved in B cells from both uninfected and infected animals, and expression of the antibody of interest was detected in up to 10% of uninfected B cells. This study paves the way for future in vivo work to assess the long-term potential of this approach and its impact on B cell development and function in an immunocompetent in vivo nonhuman primate model of HIV persistence and cure.},
}

@article {pmid41147516,
year = {2025},
author = {Thomas, AB and Matthews, AL and Brooks, O and Winquist, A and Nelson, LA and Arias-Fontenot, R and Buchwald, D and Casaletto, KB and Weintraub, S and Heaton, RK and French, BF and Suchy-Dicey, A and Barbosa-Leiker, C},
title = {Psychometric properties of the NIH Toolbox Cognition Battery composites in older adults at risk for Alzheimer's disease and related dementias: A systematic review.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {21},
number = {10},
pages = {e70673},
pmid = {41147516},
issn = {1552-5279},
support = {P30 AG066509/AG/NIA NIH HHS/United States ; R01 AG071677/AG/NIA NIH HHS/United States ; 1RF1AG071677-01//National Institute of Health/National Institute on Aging/ ; },
mesh = {Humans ; *Alzheimer Disease/diagnosis/psychology ; *Psychometrics ; United States ; National Institutes of Health (U.S.) ; *Neuropsychological Tests ; *Dementia/diagnosis/psychology ; Aged ; *Cognition ; },
abstract = {This systematic review evaluated the psychometric performance of the National Institutes of Health's Toolbox Cognition Battery (NIHTB-CB) composite scores in older adults with and without Alzheimer's disease and related dementias (ADRD). A systematic literature search was conducted using MEDLINE, Embase, PsycINFO, and CINHAL databases. The evidence quality of NIHTB-CB measurement properties was assessed using integrated Consensus-based Standards for the Selection of Health Measurement Instrument (COSMIN) methodology and the Interpretation/Use Argument framework. Fourteen studies met inclusion criteria for this review of the NIHTB-CB. Evidence supporting the scoring, generalization, and extrapolation inferences of the Total, Crystallized, and Fluid composite scores in older adults ranged from developing through exemplary ratings. Findings indicate additional research is warranted on the NIHTB-CB in older adult and ADRD populations. The present study highlights the importance of continued use and research of the NIHTB-CB in diverse, older populations who are at risk for ADRD. HIGHLIGHTS: Limited research focuses on the National Institutes of Health's Toolbox Cognition Battery (NIHTB-CB) composites in older adults. The general psychometric robustness of the NIHTB-CB has been es. The Crystallized composite shows proficient psychometric evidence. The psychometric evidence of Fluid composite is developing due to limited data.},
}

Humans
*Alzheimer Disease/diagnosis/psychology
*Psychometrics
United States
National Institutes of Health (U.S.)
*Neuropsychological Tests
*Dementia/diagnosis/psychology
Aged
*Cognition

@article {pmid41149505,
year = {2025},
author = {Rios-Doria, E and Reichel, JB and Radke, MR and Manhardt, E and Rubin-Saika, M and Lockwood, C and Swisher, EM and Banda, K},
title = {Dynamic Monitoring of Recurrent Ovarian Cancer Using Serial ctDNA: A Real-World Case Series.},
journal = {Current oncology (Toronto, Ont.)},
volume = {32},
number = {10},
pages = {},
pmid = {41149505},
issn = {1718-7729},
support = {T32 CA009515/CA/NCI NIH HHS/United States ; 0000//Brotman Baty Institute/ ; },
mesh = {Humans ; Female ; *Ovarian Neoplasms/genetics/blood/pathology ; *Circulating Tumor DNA/blood/genetics ; *Neoplasm Recurrence, Local/blood/genetics ; Middle Aged ; Aged ; *Biomarkers, Tumor/blood/genetics ; Adult ; CA-125 Antigen/blood ; },
abstract = {Recurrent ovarian cancer (OC) is challenging to detect early using current methods like CA-125 and imaging. Circulating tumor DNA (ctDNA) may improve disease monitoring. Here, we assess the real-world clinical utility of serial ctDNA analyses in patients with recurrent OC. We analyzed serial plasma samples (N = 23) from six patients with recurrent OC using a tumor-informed next-generation sequencing assay targeting 68 cancer-related genes developed at the University of Washington. ctDNA variant allele frequencies (VAFs) were correlated with CA-125 levels, radiographic findings, and clinical outcomes. ctDNA levels generally reflected clinical status, accurately mirroring disease progression and therapeutic response. In one patient, rising ctDNA preceded clinical recurrence by four months, despite normal CA-125 and imaging, highlighting its potential advantage. Conversely, some patients exhibited clinical progression with undetectable ctDNA, indicating limitations in assay sensitivity, biological factors, or metastatic sites (e.g., brain metastases). ctDNA and CA-125 showed complementary value in most cases, suggesting potential combined use in clinical monitoring. Our findings demonstrate that ctDNA is a promising biomarker to complement existing monitoring approaches for recurrent OC. In some cases, capable of predicting relapse and treatment response ahead of current clinical indicators. However, identified discordances underscore technical and biological challenges that warrant further investigation. Larger prospective studies are necessary to refine ctDNA's clinical utility and integration into personalized OC care.},
}

Humans
Female
*Ovarian Neoplasms/genetics/blood/pathology
*Circulating Tumor DNA/blood/genetics
*Neoplasm Recurrence, Local/blood/genetics
Middle Aged
Aged
*Biomarkers, Tumor/blood/genetics
Adult
CA-125 Antigen/blood

@article {pmid41152111,
year = {2026},
author = {Jindal, T and Jiang, CY and Alhalabi, O and Davidsohn, M and Freeman, D and Epstein, IY and Bakaloudi, DR and Talukder, R and Nizam, A and Nguyen, CB and Oh, E and Tsung, I and Glover, MJ and Khaki, AR and Taylor, AK and Jaime-Casas, S and Jang, A and Lemke, E and Pywell, C and Evans, ST and Shin, D and Bilen, MA and Basu, A and Kilari, D and Tripathi, A and Brown, J and Emamekhoo, H and Davis, NB and Shah, S and Gupta, S and Grivas, P and Bellmunt, J and Alva, A and Campbell, MT and Koshkin, VS},
title = {Efficacy of sacituzumab govitecan after enfortumab vedotin in advanced urothelial carcinoma: Analysis of the UNITE study.},
journal = {Urologic oncology},
volume = {44},
number = {1},
pages = {65.e1-65.e11},
doi = {10.1016/j.urolonc.2025.09.025},
pmid = {41152111},
issn = {1873-2496},
mesh = {Humans ; Male ; Female ; Aged ; *Antibodies, Monoclonal, Humanized/therapeutic use/pharmacology ; Retrospective Studies ; Middle Aged ; *Immunoconjugates/therapeutic use ; *Carcinoma, Transitional Cell/drug therapy/pathology/mortality ; *Camptothecin/analogs & derivatives/therapeutic use ; Treatment Outcome ; *Urologic Neoplasms/drug therapy/pathology ; *Urinary Bladder Neoplasms/drug therapy/pathology/mortality ; Aged, 80 and over ; Antibodies, Monoclonal/therapeutic use ; *Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; },
abstract = {BACKGROUND: Sacituzumab govitecan (SG) is an antibody-drug conjugate used for advanced urothelial carcinoma (aUC) refractory to platinum-based chemotherapy and immune checkpoint inhibitors (ICI). Real-world data are needed to better define SG outcomes, particularly following treatment with enfortumab vedotin (EV). In this analysis, we aim to evaluate efficacy of SG after EV and assess putative biomarkers associated with outcomes.

METHODS: In the UNITE retrospective study, we identified patients who received ≥1 SG cycle after therapy with EV. Observed response rate (ORR) was assessed in evaluable patients and correlated with baseline clinical characteristics and biomarkers. ORRs were compared using logistic regression, while progression free survival (PFS) and overall survival (OS) from SG start were estimated via Kaplan-Meier and Cox proportional hazard (PH) model. Biomarkers of response were evaluated in multivariate Cox PH models after accounting for relevant clinical variables.

RESULTS: Among 107 patients treated with SG after EV, 97 (91%) had NGS data. Median age was 69 years, 73% were male, 33% had ≥4 prior lines of therapy, and 42% received G-CSF. ORR was 18% (95% CI: 10%-26%), median PFS 3.2 months, and median OS 6.0 months. In patients with disease control on EV, ORR was 22% compared to 8% in primary progressors on EV. No significant associations were found between molecular biomarkers and SG outcomes in the multivariate analysis.

CONCLUSION: SG showed modest activity after EV in heavily pretreated patients with aUC. ORR with SG after EV was lower than reported in phase 2 and phase 3 clinical trials for SG in the postplatinum/ICI setting.},
}

Humans
Male
Female
Aged
*Antibodies, Monoclonal, Humanized/therapeutic use/pharmacology
Retrospective Studies
Middle Aged
*Immunoconjugates/therapeutic use
*Carcinoma, Transitional Cell/drug therapy/pathology/mortality
*Camptothecin/analogs & derivatives/therapeutic use
Treatment Outcome
*Urologic Neoplasms/drug therapy/pathology
*Urinary Bladder Neoplasms/drug therapy/pathology/mortality
Aged, 80 and over
Antibodies, Monoclonal/therapeutic use
*Antineoplastic Combined Chemotherapy Protocols/therapeutic use

@article {pmid41152450,
year = {2025},
author = {Ding, F and Liu, S and Sun, W},
title = {Exploration of the roles of HLAs when predicting infection status by T cell receptors.},
journal = {Scientific reports},
volume = {15},
number = {1},
pages = {37638},
pmid = {41152450},
issn = {2045-2322},
support = {R01 GM105785/GM/NIGMS NIH HHS/United States ; R56 AI169192/AI/NIAID NIH HHS/United States ; GM105785/GM/NIGMS NIH HHS/United States ; R56AI169192//National Institute of Allergy and Infectious Diseases/ ; },
mesh = {Humans ; *Receptors, Antigen, T-Cell/genetics/immunology ; *HLA Antigens/genetics/immunology ; Alleles ; T-Lymphocytes/immunology ; *Virus Diseases/immunology/genetics ; },
abstract = {T cells are critical components of the human immune system. When a cell is infected by a virus, it presents viral peptides on its surface using human leukocyte antigen (HLA) proteins. These peptide-HLA complexes are recognized by T cells through interactions with T cell receptors (TCRs). A human blood sample can contain millions of unique TCRs, which is a sample from the individual's TCR repertoire. TCR repertoire-wide association studies (TReWAS) aim to evaluate the associations between individual TCRs and disease or exposure status. Previous studies have shown that TCRs associated with viral infections can be identified using TReWAS, and these TCRs can be used to predict current or past infection with high accuracy. Many TCRs are strongly associated with specific HLA alleles, suggesting that the incorporation of HLA information could improve the precision of TReWAS analyses and predictions based on TCRs. In this study, we evaluated TCR-based predictions while conditioning on individual HLA alleles or their k-nearest neighbors. We observed improved prediction accuracy for some HLA alleles. Furthermore, these HLA-specific predictions provide insight into the role of specific HLAs in coordinating immune response to immunogenic antigens, demonstrating the benefit of HLA-aware analysis of TCR data.},
}

Humans
*Receptors, Antigen, T-Cell/genetics/immunology
*HLA Antigens/genetics/immunology
Alleles
T-Lymphocytes/immunology
*Virus Diseases/immunology/genetics

@article {pmid41155216,
year = {2025},
author = {Qin, R and Hua, M and Wang, Y and Zhang, Q and Cao, Y and Dai, Y and Ma, C and Zheng, X and Ge, K and Zhang, H and Li, S and Liu, Y and Cao, L and Wang, L},
title = {Multiomics Investigation of Exhausted T Cells in Glioblastoma Tumor Microenvironment: CCL5 as a Prognostic and Therapeutic Target.},
journal = {International journal of molecular sciences},
volume = {26},
number = {20},
pages = {},
pmid = {41155216},
issn = {1422-0067},
support = {82304250//National Natural Science Foundation of China/ ; 82273734//National Natural Science Foundation of China/ ; 82173629//National Natural Science Foundation of China/ ; },
mesh = {*Glioblastoma/immunology/genetics/drug therapy/pathology/metabolism ; Humans ; *Tumor Microenvironment/immunology/genetics ; *Chemokine CCL5/genetics/metabolism ; Prognosis ; *T-Lymphocytes/immunology/metabolism ; Biomarkers, Tumor/genetics ; Gene Expression Regulation, Neoplastic ; *Brain Neoplasms/immunology/genetics/drug therapy/pathology ; Multiomics ; },
abstract = {Glioblastoma multiforme (GBM) is a common malignancy with poor prognosis, and exhausted T (TEX) cells, a subset of T cells characterized by progressive loss of effector functions, play a critical role in its progression. This study aimed to investigate the impact of TEX-related genes on immune function, prognosis, and drug sensitivity in GBM through multiomics analysis. Initially, we identified a novel set of TEX-related genes specific to GBM and screened hub genes (CCL5, IL18, CXCR6, FCER1G, TNFSF13B) using conventional statistical methods combined with machine learning. A prognostic risk model was subsequently constructed based on TCGA data and validated in the CGGA cohort. Single-cell and pharmacogenomic analyses revealed significant differences in tumor microenvironment composition and drug sensitivity between risk groups. Notably, Palbociclib emerged as a potential therapeutic agent targeting the novel discovered biomarker CCL5. RT-qPCR results showed that T cells with low CCL5 expression exhibited reduced expression of immune checkpoint-related genes (PD1, TIM3, LAG3) and increased expression of CD28, suggesting enhanced immune function. In conclusion, our findings highlight five hub genes as prognostic markers that could stratify GBM patients with different immune landscapes and levels of drug sensitivity. Furthermore, experimental results suggest that low CCL5 expression could alleviate T cell exhaustion and represent a promising therapeutic target, offering new strategies for improving GBM prognosis.},
}

*Glioblastoma/immunology/genetics/drug therapy/pathology/metabolism
Humans
*Tumor Microenvironment/immunology/genetics
*Chemokine CCL5/genetics/metabolism
Prognosis
*T-Lymphocytes/immunology/metabolism
Biomarkers, Tumor/genetics
Gene Expression Regulation, Neoplastic
*Brain Neoplasms/immunology/genetics/drug therapy/pathology
Multiomics

@article {pmid41158962,
year = {2025},
author = {Cummings, CL and Stephan, SB and Fitzgerald, K and Stephan, MT},
title = {Bedside manufacturing of engineered stem cells using gene therapy foam.},
journal = {Molecular therapy. Methods & clinical development},
volume = {33},
number = {4},
pages = {101612},
pmid = {41158962},
issn = {2329-0501},
abstract = {Hematopoietic stem cell (HSC) gene therapies hold immense potential for treating a growing list of genetic disorders, but the field has reached an inflection point where novel technologies are needed to overcome significant challenges, including high costs, unequal access, and prolonged disruption of daily life. Here, we describe a bedside cell manufacturing strategy in which HSCs are genetically targeted within gene therapy foam that is mixed with freshly isolated bone marrow aspirate concentrate and then directly injected back into the marrow. We demonstrate that highly efficient genetic reprogramming of CD34+ HSCs can be accomplished within methylcellulose-based foam, using low vector doses that are inefficient with conventional liquid-based approaches. In an ex vivo model of perfused bone marrow, we show that foam retains vector at the injection site and locally boosts gene transfer into embedded CD34+ progenitor cells while minimizing off-target events. We also establish that this foam technology is compatible with freshly harvested human bone marrow aspirate. Once implemented in the clinic, this new method, which can be performed in an outpatient setting of any regional hospital, could improve the effectiveness of stem cell-based gene therapies, while concomitantly lowering costs to make these treatments accessible to all who need them.},
}

@article {pmid41159270,
year = {2025},
author = {Farooq, MS and Amini, N and Sun, V and Deutsch, GB and Deneve, JL and Grant, M and Arnold, KB and Secord, AA and Anderson, G and Krouse, RS},
title = {Optimizing Palliative Cancer Surgery Trial Completion: Lessons Learned From Qualitative Content Analysis of S1316 - Comparative Effectiveness Trial for Malignant Bowel Obstruction.},
journal = {The American journal of hospice & palliative care},
volume = {},
number = {},
pages = {10499091251391420},
doi = {10.1177/10499091251391420},
pmid = {41159270},
issn = {1938-2715},
abstract = {BackgroundMalignant bowel obstruction (MBO) is a complex clinical entity and there remains a relative lack of high-quality comparative trials on surgical management, in part due to a heterogeneous patient population and different treatment modalities which contribute to challenges in trial design and completion. SWOG S1316 is the only prospective randomized trial evaluating surgical vs non-surgical management of MBO and involved a trial framework in which patients were recruited for a randomization pathway as well as a patient choice pathway. Importantly, successful completion of S1316 required numerous amendment modifications to the trial during its course. We aimed to highlight aspects of S1316 trial design, execution, and modification that potentially contributed to trial completion.MethodsIterative qualitative content analysis of trial modification amendments through the course of the trial from 2015 to 2020.Results133 unique amendments were made to S1316 from 2015 to 2020. We found four dominant domains for the amendments: Accrual Barriers, Study Design Changes, Data Collection Issues, and Clarifications. Accrual amendments were essential to completing the trial and included increasing participating sites from six to 30 (including international sites) and the inclusion of Spanish-speaking participants (11% of final study population).ConclusionsContent analysis of S1316 trial amendments highlighted that Accrual amendments were important in trial completion. Future investigators may benefit from better anticipating trial modifications as they design their studies. It is likely that rapid initiation of trial amendments can lead to improved accrual and study completion.},
}

@article {pmid41159377,
year = {2026},
author = {Smith, KS and Dhanda, SK and Billups, CA and Sioson, E and Lu, C and Peraza, AZ and Gangwani, K and Li, Y and Li, Q and Lin, T and Michalski, JM and Packer, RJ and Olson, JM and Leary, SES and Fouladi, M and Gajjar, A and Zhou, X and Onar-Thomas, A and Northcott, PA and Robinson, GW},
title = {An integrated analysis of three medulloblastoma clinical trials refines risk-stratification approaches for reducing toxicity and improving survival.},
journal = {Neuro-oncology},
volume = {28},
number = {1},
pages = {268-281},
pmid = {41159377},
issn = {1523-5866},
support = {//St. Baldrick's Foundation/ ; P01CA096832//CCSG 5P30CA021765-43 Developmental Funds/ ; //American Lebanese Syrian Associated Charities/ ; R50 CA275857/CA/NCI NIH HHS/United States ; P30CA021765//the National Cancer Institute/ ; 1R01CA270785-01A1//CCSG 5P30CA021765-43 Developmental Funds/ ; },
mesh = {Humans ; *Medulloblastoma/therapy/mortality/genetics/pathology ; *Cerebellar Neoplasms/mortality/therapy/genetics/pathology ; Female ; Male ; Child ; Child, Preschool ; Adolescent ; Survival Rate ; Prognosis ; Craniospinal Irradiation/mortality ; *Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Risk Assessment ; Follow-Up Studies ; Young Adult ; DNA Methylation ; *Chemoradiotherapy/mortality ; Clinical Trials as Topic ; Adult ; Mutation ; },
abstract = {BACKGROUND: The identification of clinical and molecular heterogeneity in medulloblastoma has produced risk-stratified therapy, but establishing the most effective yet least toxic regimens has remained elusive owing to numerous treatment options. To improve risk-stratification, we performed an integrated analysis from three clinical trials.

METHODS: Medulloblastoma patients from ACNS0331/NCT00085735, ACNS0332/NCT00392327, and SJMB03/NCT00085202 were included if they had methylation profiling. Molecular groups [WNT, SHH, Group 3 (G3), and Group 4 (G4)], subgroups, and copy number variations were procured from methylation profiles and mutations from next-generation sequencing. Data was assembled into an interactive portal to capture patient characteristics. Cross-trial comparisons, univariable, and multivariable analyses were conducted and used to derive a risk-stratification schema.

RESULTS: Eight hundred ninety-eight patients (WNT = 131, SHH = 151, G3 = 220, G4 = 396) were included. Progression-free-survival (PFS) distributions among analogous cross-trial cohorts were not different, demonstrating no survival advantage of any one therapy over another. The addition of carboplatin to high-dose craniospinal irradiation (HDCSI) containing regimen was selectively superior in PFS in G3/G4 subgroup 3 (P = 0.048) and G3/G4 subgroup 2 (P = 0.035) to HDCSI regimens without carboplatin. Nine actionable risk-stratified groups were identified consisting of 2 WNT groups (low, high-risk), 3 SHH groups (low-, average-, very-high-risk), and 4 G3/G4 groups (low-, average-, high-, and very-high-risk).

CONCLUSIONS: Our integrated cross-trial analysis suggests toxicity can be reduced by eliminating disproportionate differences in therapy in favor of a more uniform treatment backbone. Moreover, we propose and model a risk-classification system that identifies the most appropriate cohorts on which to trial significant dose reductions in craniospinal irradiation or select treatment intensifications.},
}

Humans
*Medulloblastoma/therapy/mortality/genetics/pathology
*Cerebellar Neoplasms/mortality/therapy/genetics/pathology
Female
Male
Child
Child, Preschool
Adolescent
Survival Rate
Prognosis
Craniospinal Irradiation/mortality
*Antineoplastic Combined Chemotherapy Protocols/therapeutic use
Risk Assessment
Follow-Up Studies
Young Adult
DNA Methylation
*Chemoradiotherapy/mortality
Clinical Trials as Topic
Adult
Mutation

@article {pmid41159380,
year = {2026},
author = {Arora, S and Nuechterlein, N and Jensen, M and Glatzer, G and Sievers, P and Varadharajan, S and Korshunov, A and Sahm, F and Mack, SC and Taylor, MD and Gujral, TS and Holland, EC},
title = {Integrated transcriptomic landscape of medulloblastoma and ependymoma reveals novel tumor subtype-specific biology.},
journal = {Neuro-oncology},
volume = {28},
number = {2},
pages = {505-519},
pmid = {41159380},
issn = {1523-5866},
support = {1R35 CA253119-01A1/NH/NIH HHS/United States ; U54 CA243125/NH/NIH HHS/United States ; C11orf95/NH/NIH HHS/United States ; //RELA fusion-driven ependymoma/ ; 1R35 CA253119-01A1//Fred Hutch Cancer Center/ ; },
mesh = {Humans ; *Medulloblastoma/genetics/classification/pathology ; *Ependymoma/genetics/classification/pathology ; *Transcriptome ; *Cerebellar Neoplasms/genetics/classification/pathology ; *Biomarkers, Tumor/genetics ; Child ; Gene Expression Profiling ; DNA Copy Number Variations ; Female ; Male ; Child, Preschool ; Prognosis ; Gene Expression Regulation, Neoplastic ; Adolescent ; },
abstract = {BACKGROUND: Medulloblastoma and ependymoma are common pediatric central nervous system tumors with significant molecular and clinical heterogeneity. While molecular subgrouping has enabled classification into molecular subtypes, the extent of heterogeneity within these subgroups remains poorly defined.

METHODS: We collected bulk RNA sequencing data from 888 medulloblastoma and 370 ependymoma tumors to establish a comprehensive reference landscape. After rigorous batch effect correction, normalization, and dimensionality reduction, we generated a unified landscape to explore gene expression, signaling pathways, RNA fusions, and copy number variations.

RESULTS: Our transcriptional analysis revealed distinct clustering patterns, including two primary ependymoma compartments, EPN-E1 and EPN-E2, each with specific RNA fusions and molecular signatures. In medulloblastoma, we observed precise stratification of Group 3/4 tumors by subtype and in Sonic Hedgehog (SHH) tumors by patient age. We also identified subtype-specific pathways and gene fusions, enriched in each group.

CONCLUSIONS: This transcriptomic landscape serves as a resource for biomarker discovery, diagnostic refinement, and prediction of tumor biology and outcome. By enabling projection of new patients' bulk RNA-seq data onto the reference map using nearest neighbor analysis, the framework supports accurate subtype classification. The landscape is publicly available via Oncoscape, an interactive platform for global exploration and application.},
}

Humans
*Medulloblastoma/genetics/classification/pathology
*Ependymoma/genetics/classification/pathology
*Transcriptome
*Cerebellar Neoplasms/genetics/classification/pathology
*Biomarkers, Tumor/genetics
Child
Gene Expression Profiling
DNA Copy Number Variations
Female
Male
Child, Preschool
Prognosis
Gene Expression Regulation, Neoplastic
Adolescent

@article {pmid41160408,
year = {2026},
author = {Nyquist, MD and Nelson, PS},
title = {Targeting the Androgen Receptor Pathway in Prostate Cancer: A PROTrACted Struggle.},
journal = {Clinical cancer research : an official journal of the American Association for Cancer Research},
volume = {32},
number = {1},
pages = {13-15},
pmid = {41160408},
issn = {1557-3265},
support = {P50 CA097186/CA/NCI NIH HHS/United States ; R01 CA266452/CA/NCI NIH HHS/United States ; P50CA097186//National Cancer Institute (NCI)/ ; R01CA266452//National Cancer Institute (NCI)/ ; },
mesh = {Humans ; Male ; *Receptors, Androgen/metabolism/genetics ; *Signal Transduction/drug effects ; *Prostatic Neoplasms/drug therapy/metabolism/pathology ; *Androgen Receptor Antagonists/therapeutic use/pharmacology ; Molecular Targeted Therapy ; Drug Resistance, Neoplasm/drug effects ; Animals ; },
abstract = {The androgen receptor (AR) is the most important therapeutic target for metastatic prostate cancer. Though clinical responses to AR inhibition are nearly universal, so is progression, usually accompanied by reactivation of AR signaling. A new small-molecule dual AR degrader/inhibitor shows promise in overcoming resistance and improving clinical outcomes. See related article by Nayak et al., p. 224.},
}

Humans
Male
*Receptors, Androgen/metabolism/genetics
*Signal Transduction/drug effects
*Prostatic Neoplasms/drug therapy/metabolism/pathology
*Androgen Receptor Antagonists/therapeutic use/pharmacology
Molecular Targeted Therapy
Drug Resistance, Neoplasm/drug effects
Animals

@article {pmid41160804,
year = {2026},
author = {Rashidi, A and Gao, F},
title = {Antibiotic risk score for acute graft-versus-host disease.},
journal = {Blood advances},
volume = {10},
number = {3},
pages = {555-561},
pmid = {41160804},
issn = {2473-9537},
support = {P01 CA018029/CA/NCI NIH HHS/United States ; P01 CA078902/CA/NCI NIH HHS/United States ; P30 CA015704/CA/NCI NIH HHS/United States ; },
mesh = {Humans ; *Graft vs Host Disease/etiology/diagnosis/epidemiology ; Middle Aged ; Male ; Female ; Adult ; *Anti-Bacterial Agents/adverse effects/therapeutic use ; Aged ; *Hematopoietic Stem Cell Transplantation/adverse effects ; Risk Factors ; Young Adult ; Acute Disease ; Risk Assessment ; Transplantation, Homologous/adverse effects ; },
abstract = {Certain antibiotic exposures have been associated with increased rates of acute graft-versus-host disease (aGVHD) after allogeneic hematopoietic cell transplant (alloHCT). Using data from 2023 alloHCTs performed at our center (2010-2021), we recently developed an antibiotic risk score based on antibacterial antibiotic exposure between days -7 and +30 of alloHCT. The objective was to estimate the added risk for aGVHD due to exposures to antibiotics in the early peritransplant period. Here, we validated the score in an independent, more recent cohort. Data from 297 recipients of alloHCT (2022-2023) including 8382 antibiotic use records (9 antibiotic classes) were analyzed. Median (range) age was 61 (19-78) years, and 175 (59%) patients were male. Higher scores predicted a greater added antibiotic-related risk for grade 3 to 4 (severe) aGVHD, with the upper 25% score quantile identifying a distinctly high-risk subset of patients (hazard ratio for the upper 25% risk quantile was 2.37 compared with the lower 75%; 95% confidence interval, 1.21-4.63; P = .01). A similar, though less strong, pattern was observed for grade 2 to 4 aGVHD. A free online antibiotic risk calculator was developed, identifying antibiotic exposures associated with higher added risk for severe aGVHD. In addition to its potential future use to identify patients who were at higher risk for aGVHD due to antibiotic exposures, the antibiotic-based risk score provided here can be included as a single continuous covariate in multivariable analysis of future GVHD prophylaxis trials.},
}

Humans
*Graft vs Host Disease/etiology/diagnosis/epidemiology
Middle Aged
Male
Female
Adult
*Anti-Bacterial Agents/adverse effects/therapeutic use
Aged
*Hematopoietic Stem Cell Transplantation/adverse effects
Risk Factors
Young Adult
Acute Disease
Risk Assessment
Transplantation, Homologous/adverse effects

@article {pmid41161981,
year = {2025},
author = {Vishnu, P and Aboulafia, DM},
title = {Hemostatic Disorders Following Severe Acute Respiratory Syndrome Coronavirus 2 Infection, COVID-19 Vaccination, and Long-COVID Syndrome: Current Evidence and Controversies in Clinical Practice.},
journal = {Clinics in laboratory medicine},
volume = {45},
number = {4},
pages = {643-655},
doi = {10.1016/j.cll.2025.07.008},
pmid = {41161981},
issn = {1557-9832},
mesh = {Humans ; *COVID-19/complications/prevention & control ; *COVID-19 Vaccines/adverse effects ; *Hemostatic Disorders/etiology ; SARS-CoV-2 ; *Vaccination/adverse effects ; },
abstract = {The COVID-19 pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has presented profound global health challenges. Beyond acute illness, a substantial proportion of individuals experience persistent symptoms including fatigue, brain fog, and post-exertional malaise, collectively known as Long-COVID. Among the complications associated with SARS-CoV-2 infection and vaccination, hemostatic disorders ranging from mild platelet dysfunction to severe thromboembolic events, and rare but serious coagulation-related adverse effects, such as vaccine-induced immune thrombotic thrombocytopenia, have emerged as a significant concern. Herein we provide an overview of current information and controversies surrounding hemostatic complications in SARS-CoV-2 infection and COVID-19 vaccination.},
}

Humans
*COVID-19/complications/prevention & control
*COVID-19 Vaccines/adverse effects
*Hemostatic Disorders/etiology
SARS-CoV-2
*Vaccination/adverse effects

@article {pmid41161982,
year = {2025},
author = {Vishnu, P and Aboulafia, DM},
title = {Recent Advances in Extended Half-Life Products, Nonfactor Replacement Therapies, and Gene Therpy for the Treatment of Hemophilia.},
journal = {Clinics in laboratory medicine},
volume = {45},
number = {4},
pages = {657-673},
doi = {10.1016/j.cll.2025.07.010},
pmid = {41161982},
issn = {1557-9832},
mesh = {*Hemophilia A/therapy/genetics ; Humans ; *Genetic Therapy/methods ; Half-Life ; *Blood Coagulation Factors/therapeutic use/pharmacokinetics ; Factor VIII/therapeutic use/pharmacokinetics ; },
abstract = {Hemophilia, a rare X-linked hereditary bleeding disorder, is characterized by deficiency of coagulation factors. Symptoms range from spontaneous joint and muscle bleeds to life-threatening hemorrhage, for which patients require frequent infusion of coagulation factors, profoundly impacting their quality of life. Novel therapeutics and advances in gene therapy now offer patients long-term disease control and improved quality of life. Here, we focus on important developments in the use of extended half-life factor products, non-factor replacement therapies, and gene therapy. We also highlight the mechanism of action, clinical efficacy, and safety of these newer approaches.},
}

*Hemophilia A/therapy/genetics
Humans
*Genetic Therapy/methods
Half-Life
*Blood Coagulation Factors/therapeutic use/pharmacokinetics
Factor VIII/therapeutic use/pharmacokinetics

@article {pmid41161984,
year = {2025},
author = {Zhang, C and Lam, BD and Lucas, F and Foy, BH},
title = {Machine Learning and Artificial Intelligence-Based Clinical Decision Support for Modern Hematology.},
journal = {Clinics in laboratory medicine},
volume = {45},
number = {4},
pages = {691-705},
doi = {10.1016/j.cll.2025.07.011},
pmid = {41161984},
issn = {1557-9832},
mesh = {*Machine Learning ; Humans ; *Hematology/methods ; *Decision Support Systems, Clinical ; *Artificial Intelligence ; *Hematologic Diseases/diagnosis ; },
abstract = {Hematology is one of the most data-rich areas of medicine and has consistently been at the forefront of technological innovation. With the increasing integration of machine learning (ML) into the diagnostic process, it is vital that both patient-facing and laboratory-facing members of the care team understand how these tools may interact with existing workflows and affect their work. We review the current landscape of ML research and clinical applications. We cover a wide variety of subdomains (eg, hematopathology, hemoglobinopathies, and coagulopathy) and explore both the success and limitations of corresponding research and deployments.},
}

*Machine Learning
Humans
*Hematology/methods
*Decision Support Systems, Clinical
*Artificial Intelligence
*Hematologic Diseases/diagnosis

@article {pmid41162424,
year = {2025},
author = {Fergus, KB and Newberg, J and Greenstein, R and Fejerman, L and Carvajal-Carmona, L and Collisson, E and Dixit, N and Frampton, G and Huang, FW and Neuhausen, SL and Ziv, E},
title = {Association between ancestry and tumor somatic mutations in a large national cohort of women with breast cancer.},
journal = {NPJ breast cancer},
volume = {11},
number = {1},
pages = {117},
pmid = {41162424},
issn = {2374-4677},
support = {2023YIA-9977333099//American Society of Clinical Oncology/ ; R01CA223978, U54CA283766 and U54CA280811/CA/NCI NIH HHS/United States ; OPR18111//California Initiative to Advance Precision Medicine/ ; OPR18111//California Initiative to Advance Precision Medicine/ ; },
abstract = {Somatic mutations and copy number alterations in breast tumors are important to determine prognosis, predict treatment response, and identify targets for therapy. We utilized somatic sequencing data of breast tumors from Foundation Medicine Inc. to evaluate the association between genetic ancestry and somatic mutations. We used germline variants to infer genetic ancestry with both principal components analysis and ADMIXTURE. Overall, we identified 91 ancestry-specific somatic differences across 58 unique genes, which included potentially targetable genes such as PIK3CA found in higher frequency in European ancestry, and EGFR found in higher frequency in East Asian ancestry. Pan-cancer analysis of East Asian ancestry and EGFR also found higher frequency in prostate, thyroid, and kidney cancers. African ancestry was associated with increased frequency of copy number alterations overall and decreased frequency of multiple genes on the PI3K-AKT pathway. Future research is warranted to elicit the genetic and environmental conditions that underly these findings.},
}

@article {pmid41162557,
year = {2025},
author = {Damera, S and Lee, JR and Hong, YR and Nyame, YA and Hammarlund, N},
title = {Negative perceptions of the health system and racial inequities in PSA screening.},
journal = {Prostate cancer and prostatic diseases},
volume = {},
number = {},
pages = {},
pmid = {41162557},
issn = {1476-5608},
abstract = {BACKGROUND: Black individuals in the U.S. experience significantly higher prostate cancer mortality and are more likely to be diagnosed at younger ages with aggressive disease. This disparity may be influenced by negative healthcare perceptions and racial discordance between patients and providers, impacting lower rates of prostate-specific antigen (PSA) screening. We hypothesized that these factors would be associated with reduced PSA screening uptake, particularly among Black men.

OBJECTIVES: This study aimed to examine the association between negative healthcare perceptions and PSA screening, assess whether this relationship differs by race, and evaluate the role of racial discordance in influencing screening behavior.

METHODS: We analyzed data from the 2018-2022 Medical Expenditure Panel Survey. The sample included 2373 men aged 45-70 who self-identified as non-Hispanic White or Black and had complete data on PSA screening, healthcare perceptions, and demographics. Negative healthcare perceptions were measured using a Health Perceptions Index (HePI), constructed from MEPS items (higher scores reflect more negative perceptions).

RESULTS: Higher HePI scores were significantly associated with lower PSA screening rates (p < 0.01). Interaction models indicated that Black men with higher HePI scores were disproportionately less likely to undergo screening. Racial discordance with providers was independently associated with reduced screening likelihood (~10.2 percentage points; p < 0.01). Models including interaction terms (age, race, and discordance) showed that older Black men with high HePI scores and discordant providers were least likely to be screened.

CONCLUSIONS: PSA screening disparities are shaped by negative healthcare perceptions and racial discordance, particularly among older Black men. Addressing these barriers through culturally tailored education, improved workforce diversity, and strengthened provider-patient relationships may help close screening gaps. These findings highlight the relevance of healthcare system perceptions in understanding screening disparities and may inform future strategies to identify at-risk individuals.},
}

@article {pmid41165693,
year = {2025},
author = {Shadman, M and Gopal, AK},
title = {Bispecific antibodies in action: the reality of engagement.},
journal = {Blood},
volume = {146},
number = {18},
pages = {2148-2150},
doi = {10.1182/blood.2025030376},
pmid = {41165693},
issn = {1528-0020},
}

@article {pmid41165705,
year = {2025},
author = {MacKay, EJ and Talham, CJ and Szeto, WY and Brown, CR and Augoustides, JG and Desai, ND and Groeneveld, PW and Zhang, B},
title = {Surgical Volume and Outcomes of Intraoperative Transesophageal Echocardiography in Coronary Artery Bypass Graft.},
journal = {JAMA network open},
volume = {8},
number = {10},
pages = {e2540559},
pmid = {41165705},
issn = {2574-3805},
mesh = {Humans ; *Coronary Artery Bypass/mortality/statistics & numerical data/methods ; Male ; Female ; *Echocardiography, Transesophageal/statistics & numerical data/methods ; Retrospective Studies ; Aged ; Middle Aged ; Treatment Outcome ; *Intraoperative Care/methods ; },
abstract = {IMPORTANCE: The routine use of intraoperative transesophageal echocardiography (TEE) during coronary artery bypass graft (CABG) surgery remains controversial. Its benefit across different patient populations is unclear.

OBJECTIVES: To identify patient subgroups with the greatest or least likelihood to benefit from intraoperative TEE during CABG, stratified by hospital surgical volume.

This 2-stage, matched retrospective cohort study applied target trial emulation methodologies to the Society of Thoracic Surgeons (STS) Adult Cardiac Surgery Database (ACSD) to quantify the conditional treatment effect of intraoperative TEE among subpopulations undergoing isolated CABG at low, medium, and high surgical volume hospitals. The study cohort consisted of patients aged 18 years or older who underwent isolated CABG surgery between July 1, 2014, and June 30, 2022. Data analysis was conducted from August 8, 2023, to December 15, 2024.

EXPOSURE: Receipt of an intraoperative TEE during CABG surgery.

MAIN OUTCOMES AND MEASURES: The primary outcome was mortality within 30 days of surgery. Statistical analyses included multivariable logistic regression and multiple TEE vs without TEE matched comparisons stratified by surgical volume and patient subpopulations.

RESULTS: Of 1 266 055 patients who underwent isolated CABG, 963 976 (76.1%) were male, and the mean (SD) age was 65.7 (10.0) years. Among these patients, 61.8% received TEE and 39.0% did not receive TEE. Intraoperative TEE use (vs without TEE) was associated with a significant survival benefit among patients treated at hospitals with low surgical volume (2.47% vs 2.94%; odds ratio [OR], 0.83 [95% CI, 0.78-0.89], P < .001) and medium surgical volume (2.09% vs 2.34%; OR, 0.89 [95% CI, 0.85-0.93], P < .001) but not high surgical volume (1.72% vs 1.77%; OR, 0.97 [95% CI, 0.91-1.03], P = .48). Among patients who underwent isolated CABG at low and medium surgical volume hospitals, TEE provided the greatest survival benefit to subpopulations with greater than 50% (vs ≤50%) left-main coronary stenosis, 3 or more (vs <3) diseased coronaries, and (3) a preoperative inotropic requirement.

CONCLUSIONS AND RELEVANCE: In isolated CABG, intraoperative TEE was associated with survival benefit at low- and medium-volume hospitals, particularly in patients with complex coronary disease or hemodynamic instability, but not at high-volume hospitals. These results highlight persistent equipoise and the need for randomized evaluation.},
}

Humans
*Coronary Artery Bypass/mortality/statistics & numerical data/methods
Male
Female
*Echocardiography, Transesophageal/statistics & numerical data/methods
Retrospective Studies
Aged
Middle Aged
Treatment Outcome
*Intraoperative Care/methods

@article {pmid41168411,
year = {2025},
author = {Jiang, SJ and Thomas, M and Rosenthal, EA and Phipps, AI and Sakoda, LC and van Duijnhoven, FJB and Pellatt, AJ and Avery, CL and Berndt, SI and Bishop, DT and Castellví-Bel, S and Chan, AT and Grant, RC and Gignoux, C and Gsur, A and Gunter, MJ and Haiman, CA and Hoffmeister, M and Jarvik, GP and Jenkins, MA and Keku, TO and Küry, S and Lee, JK and Marchand, LL and Moreno, V and Newcomb, PA and Newton, CC and Ogino, S and Palmer, JR and Pearlman, R and Qu, C and Schoen, RE and Um, CY and Van Guelpen, B and Visvanathan, K and Vymetalkova, V and White, E and Woods, MO and Platz, EA and Brenner, H and Corley, DA and Vogelaar, IL and Hsu, L and Peters, U},
title = {Multiple polygenic score approach in colorectal cancer risk prediction.},
journal = {Scientific reports},
volume = {15},
number = {1},
pages = {38006},
pmid = {41168411},
issn = {2045-2322},
support = {001/WHO_/World Health Organization/International ; U01 CA164973, R01 CA126895, R01 CA060987, R01 CA072520, U24 CA074806/CA/NCI NIH HHS/United States ; U01HG008657/HG/NHGRI NIH HHS/United States ; U01 CA137088/CA/NCI NIH HHS/United States ; },
mesh = {Humans ; *Colorectal Neoplasms/genetics/epidemiology ; *Multifactorial Inheritance/genetics ; *Genetic Predisposition to Disease ; Female ; Male ; Machine Learning ; Aged ; Middle Aged ; Risk Factors ; Risk Assessment ; Genome-Wide Association Study ; ROC Curve ; Polymorphism, Single Nucleotide ; Case-Control Studies ; },
abstract = {Recent studies have demonstrated that for various diseases, incorporating polygenic risk scores (PRSs) for other traits and diseases into the PRS-based risk prediction model may improve predictive performance - known as Multiple Polygenic Score (MPS) approach. We aimed to examine whether the MPS approach improves colorectal cancer (CRC) risk prediction. We included 2,187 non-CRC PRSs from the polygenic Score (PGS) Catalog and used machine learning (ML) models to select the most predictive non-CRC PRSs, utilizing individual-level data from 31,257 CRC cases and 33,408 controls. An independent dataset from the Genetic Epidemiology Research in Adult Health and Aging (GERA) cohort (4,852 cases and 67,939 controls) was randomly split into subsets for model estimation and validation. The model combined MPS with two existing CRC-PRSs based on known loci and genome-wide genotyping. We then assessed model performance by calculating the area under the receiver operating curve (AUC) in the validation set and performed 1,000 bootstrapped iterations to evaluate AUC improvements. The ML model selected 337 non-CRC PRSs predictive of CRC risk. Adding MPS to the CRC-PRSs significantly improved AUC by 0.017 (95% CI: 0.011-0.022, p < 0.0001) when combined with known-loci CRC-PRS, 0.005 (95% CI: 0.002-0.007, p = 0.0005) with genome-wide CRC-PRS, and 0.004 (95% CI: 0.002-0.006, p = 0.0005) with both the known loci and genome-wide CRC-PRSs. These findings demonstrate MPS's potential to refine CRC risk prediction models and highlight opportunities for further advancements in risk prediction.},
}

Humans
*Colorectal Neoplasms/genetics/epidemiology
*Multifactorial Inheritance/genetics
*Genetic Predisposition to Disease
Female
Male
Machine Learning
Aged
Middle Aged
Risk Factors
Risk Assessment
Genome-Wide Association Study
ROC Curve
Polymorphism, Single Nucleotide
Case-Control Studies

@article {pmid41168431,
year = {2025},
author = {Jabbar, KS and Priya, S and Xu, J and Das Adhikari, U and Pishchany, G and Mohamed, ATM and Johansen, J and Thurimella, K and McCabe, C and Vlamakis, H and Okello, S and Delorey, TM and Lankowski, A and Mosepele, M and Siedner, MJ and Plichta, DR and Kwon, DS and Xavier, RJ},
title = {Human immunodeficiency virus and antiretroviral therapies exert distinct influences across diverse gut microbiomes.},
journal = {Nature microbiology},
volume = {10},
number = {11},
pages = {2720-2735},
pmid = {41168431},
issn = {2058-5276},
support = {R01 DK101354/DK/NIDDK NIH HHS/United States ; DK120485//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; R01 HL141053/HL/NHLBI NIH HHS/United States ; R01 HL138646/HL/NHLBI NIH HHS/United States ; R01 DK120485/DK/NIDDK NIH HHS/United States ; K24 HL166024/HL/NHLBI NIH HHS/United States ; R21 HL124712/HL/NHLBI NIH HHS/United States ; P30 DK043351/DK/NIDDK NIH HHS/United States ; },
mesh = {Humans ; *Gastrointestinal Microbiome/drug effects ; *HIV Infections/drug therapy/microbiology ; Uganda ; Alkynes ; Metagenomics ; Benzoxazines/therapeutic use/adverse effects ; Male ; Female ; Feces/microbiology ; Cyclopropanes ; Adult ; Botswana ; *Anti-Retroviral Agents/therapeutic use ; Middle Aged ; United States ; Reverse Transcriptase Inhibitors/therapeutic use ; *Anti-HIV Agents/therapeutic use ; Bacteria/classification/genetics/drug effects/isolation & purification ; },
abstract = {Human immunodeficiency virus (HIV) infection alters gut microbiota composition and function, but the impact of geography and antiretroviral therapy remains unclear. Here we determined gut microbiome alterations linked to HIV infection and antiretroviral treatment in 327 individuals with HIV and 260 control participants in cohorts from Uganda, Botswana and the USA via faecal metagenomics. We found that while HIV-associated taxonomic differences were mostly site specific, changes in microbial functional pathways were broadly consistent across the cohorts and exacerbated in individuals with acquired immunodeficiency syndrome. Microbiome perturbations associated with antiretroviral medications were also geography dependent. In Botswana and Uganda, use of the non-nucleoside reverse transcriptase inhibitor efavirenz was linked to depletion of Prevotella, disruption of interspecies metabolic networks, exacerbation of systemic inflammation and atherosclerosis. Efavirenz-associated Prevotella depletion may occur through cross-inhibition of prokaryotic reverse transcriptases involved in antiphage defences, as shown by computational and in vitro experiments. These observations could inform future geography-specific and microbiome-guided therapy.},
}

Humans
*Gastrointestinal Microbiome/drug effects
*HIV Infections/drug therapy/microbiology
Uganda
Alkynes
Metagenomics
Benzoxazines/therapeutic use/adverse effects
Male
Female
Feces/microbiology
Cyclopropanes
Adult
Botswana
*Anti-Retroviral Agents/therapeutic use
Middle Aged
United States
Reverse Transcriptase Inhibitors/therapeutic use
*Anti-HIV Agents/therapeutic use
Bacteria/classification/genetics/drug effects/isolation & purification

@article {pmid41169120,
year = {2025},
author = {Marzinke, MA and Hanscom, B and Haines, D and Scarsi, KK and Agyei, Y and Piwowar-Manning, E and Hendrix, CW and Gollings, R and Rose, S and Mathew, C and Panchia, R and Spooner, E and Singh, N and Bock, P and Rinehart, AR and Ford, SL and Rooney, JF and Soto-Torres, L and Cohen, MS and Hosseinipour, MC and Delany-Moretlwe, S and , },
title = {Evaluation of pharmacokinetic interactions between long-acting cabotegravir or emtricitabine/tenofovir disoproxil fumarate and hormonal contraceptive agents: a tertiary analysis of South African participants in HPTN 084.},
journal = {Journal of the International AIDS Society},
volume = {28},
number = {11},
pages = {e70056},
pmid = {41169120},
issn = {1758-2652},
support = {P30 AI094189/AI/NIAID NIH HHS/United States ; UM1AI068617/NH/NIH HHS/United States ; OPP1154174//Bill and Melinda Gates Foundation/ ; UM1AI068619/NH/NIH HHS/United States ; UM1AI068613/NH/NIH HHS/United States ; },
mesh = {Adolescent ; Adult ; Female ; Humans ; Young Adult ; *Anti-HIV Agents/pharmacokinetics ; *Contraceptive Agents, Hormonal/pharmacokinetics/administration & dosage ; Desogestrel/pharmacokinetics/blood ; Drug Interactions ; *Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination/pharmacokinetics/administration & dosage ; *HIV Infections/prevention & control ; Medroxyprogesterone Acetate/pharmacokinetics/blood ; Norethindrone/analogs & derivatives/pharmacokinetics/blood ; Pre-Exposure Prophylaxis ; *Pyridones/pharmacokinetics/administration & dosage ; South Africa ; Diketopiperazines ; },
abstract = {INTRODUCTION: HPTN 084 found that long-acting cabotegravir (CAB-LA) was well-tolerated and significantly reduced the risk of HIV acquisition in women compared to tenofovir disoproxil fumarate/emtricitabine (F/TDF). During the blinded phase of the trial, participants were required to use an effective method of contraception, including an injectable or implantable hormonal contraceptive (HC) agent. A contraceptive sub-study assessed the pharmacokinetic interactions between pre-exposure prophylaxis agents (CAB-LA or F/TDF) and etonogestrel (ENG), medroxyprogesterone acetate (MPA) or norethindrone enanthate (NET-EN).

METHODS: Participants were enrolled in a nested sub-study between 24 February 2020 and 26 October 2020. Via a convenience sampling strategy, plasma concentrations of ENG, MPA and NET-EN were evaluated at enrolment and weeks 25, 49 and 73; plasma tenofovir (TFV) and CAB concentrations were determined at contemporaneous visits. Participants were allowed to switch contraceptives, and HC assessments were adjusted accordingly. Geometric mean concentrations were calculated and compared using t-tests or Fisher's exact tests.

RESULTS: One hundred and seventy participants were included in this analysis. Hormone concentrations at all study visits were comparable between the CAB-LA and F/TDF study arms. Among participants randomized to the CAB-LA arm, geometric mean concentrations declined from enrolment to the follow-up period for ENG (335 to 202 pg/ml), MPA (1520 to 1138 pg/ml) and NET-EN (3715 to 1888 pg/ml); similar findings were observed among participants randomized to the F/TDF arm. Observed HC declines are likely attributed to the timing of contraceptive administration relative to sampling; the percentage of participants with hormone concentrations above thresholds associated with ovulation suppression was high (73-100%) and did not differ between arms. CAB concentrations were comparable across contraceptive types, with 97.8-98.1% of participants yielding trough CAB concentrations above the protocol-specified target threshold. TFV concentrations were unquantifiable for most participants, irrespective of contraceptive agent, rendering comparisons largely uninformative.

CONCLUSIONS: Given the comparable hormone concentrations between arms and the likely influence of the timing of sample collection on observed measurements, clinically significant interactions between CAB-LA and HC are not expected. Associations between F/TDF and hormone concentrations could not be effectively evaluated due to low adherence to F/TDF.

CLINICAL TRIAL REGISTRATION: NCT0316456.},
}

Adolescent
Adult
Female
Humans
Young Adult
*Anti-HIV Agents/pharmacokinetics
*Contraceptive Agents, Hormonal/pharmacokinetics/administration & dosage
Desogestrel/pharmacokinetics/blood
Drug Interactions
*Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination/pharmacokinetics/administration & dosage
*HIV Infections/prevention & control
Medroxyprogesterone Acetate/pharmacokinetics/blood
Norethindrone/analogs & derivatives/pharmacokinetics/blood
Pre-Exposure Prophylaxis
*Pyridones/pharmacokinetics/administration & dosage
South Africa
Diketopiperazines

@article {pmid41171480,
year = {2025},
author = {Mahdi, J and Gust, JA and Vitanza, NA and Scott, B and Monje, M and Ronsley, R},
title = {Neurotoxicity in central nervous system tumors treated with CAR T cell therapy: a review.},
journal = {Journal of neuro-oncology},
volume = {176},
number = {1},
pages = {60},
pmid = {41171480},
issn = {1573-7373},
}

@article {pmid41172559,
year = {2025},
author = {Ebadi, M and Fan, X and Schoch, G and Gooley, T and Rashidi, A and Smith, SD and Shadman, M and Holmberg, L and Ujjani, C and Poh, C and Raghunathan, V and Ali, N and Vo, PT and Manjappa, S and Menon, M and Di, M and Lynch, R and Ho, C and Till, BG and Ermoian, R and Gopal, AK and Tseng, YD},
title = {Total Body Irradiation Versus Chemotherapy-Only Conditioning in Autologous Haematopoietic Stem Cell Transplantation for Relapsed/Refractory Large B-cell Lymphoma.},
journal = {Clinical oncology (Royal College of Radiologists (Great Britain))},
volume = {48},
number = {},
pages = {103959},
doi = {10.1016/j.clon.2025.103959},
pmid = {41172559},
issn = {1433-2981},
mesh = {Humans ; Male ; Female ; Middle Aged ; *Transplantation Conditioning/methods ; *Lymphoma, Large B-Cell, Diffuse/therapy/pathology/mortality ; *Hematopoietic Stem Cell Transplantation/methods ; Retrospective Studies ; *Whole-Body Irradiation/methods ; Transplantation, Autologous ; Aged ; Adult ; *Neoplasm Recurrence, Local/therapy ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; },
abstract = {AIMS: In the era of chimeric antigen receptor T-cell (CAR-T) therapy, there remains a role for autologous stem cell transplant (ASCT) for patients with large B-cell lymphoma (LBCL) without access to CAR T-cell therapy or who have late, chemosensitive relapse (>12 months). Typically, the ASCT conditioning regimen is chemotherapy only. Given the radioresponsiveness of LBCL, we retrospectively evaluated whether ASCT outcomes are improved with total body irradiation (TBI)-based conditioning compared to chemo-only conditioning.

MATERIALS AND METHODS: We included patients with relapsed/refractory (r/r) LBCL who underwent ASCT at our centre (2012-2021). As TBI is generally offered only to younger patients, we excluded patients in the chemo-only group who were older than the oldest patient in the TBI group, leaving 56 patients in the final dataset (TBI: 19; chemo: 37).

RESULTS: The TBI cohort had more adverse features including male sex (89.5% vs 62.2%), relapse ≤12 months (52.6% vs 32.4%), and shorter time between diagnosis and ASCT (median: 11.7 vs 21.8 months). Two-year progression-free survival (PFS) was 58% (95% confidence interval [CI]: 39%-85%) and 67% (53%-84%) in TBI and chemotherapy cohorts, respectively. Two-year overall survival (OS) was 79% (63%-100%) and 80% (68%-95%) in TBI and chemotherapy cohorts, respectively. Multivariable hazard ratio (HR) of PFS failure (TBI vs chemo) was 1.35 (95% CI: 0.59-3.12). The HR of death was 1.33 (95% CI: 0.49-3.58). While conditioning regimen was not associated with PFS, positron emission tomography (PET) positivity at time of ASCT (HR: 6.97, 95% CI: 2.98-16.27, P < 0.001) was associated with PFS failure.

CONCLUSION: Despite the presence of more adverse features among patients treated with TBI, there was no difference in PFS or OS among patients that underwent chemo-only vs TBI-based conditioning. Though hypothesis generating, this suggests that TBI may be able to partially compensate for adverse fatures.},
}

Humans
Male
Female
Middle Aged
*Transplantation Conditioning/methods
*Lymphoma, Large B-Cell, Diffuse/therapy/pathology/mortality
*Hematopoietic Stem Cell Transplantation/methods
Retrospective Studies
*Whole-Body Irradiation/methods
Transplantation, Autologous
Aged
Adult
*Neoplasm Recurrence, Local/therapy
Antineoplastic Combined Chemotherapy Protocols/therapeutic use

@article {pmid41173578,
year = {2025},
author = {Fairlie, L and Szydlo, DW and Mayo, A and Bunge, K and Mhlanga, F and Piper, J and Dadabhai, S and Gatsi, VM and Horne, E and Ssemambo, PK and Mandiwa, V and Mgodi, NM and Owor, M and Anderson, PL and Marzinke, MA and Nakabiito, C and Scheckter, R and Chappell, C and Hillier, SL and , },
title = {Safety outcomes among infants whose mothers used the dapivirine vaginal ring or oral PrEP during pregnancy (MTN-042/DELIVER): a randomised phase 3b study.},
journal = {The lancet. HIV},
volume = {12},
number = {11},
pages = {e763-e773},
doi = {10.1016/S2352-3018(25)00261-9},
pmid = {41173578},
issn = {2352-3018},
support = {UM1 AI069518/AI/NIAID NIH HHS/United States ; },
mesh = {Adolescent ; Adult ; Female ; Humans ; Infant ; Infant, Newborn ; Male ; Pregnancy ; Young Adult ; Administration, Oral ; *Anti-HIV Agents/administration & dosage/adverse effects ; *Contraceptive Devices, Female ; Emtricitabine/administration & dosage ; *HIV Infections/prevention & control ; *Infectious Disease Transmission, Vertical/prevention & control ; *Pre-Exposure Prophylaxis/methods ; *Pregnancy Complications, Infectious/prevention & control/drug therapy ; *Pyrimidines/administration & dosage/adverse effects ; South Africa ; Tenofovir/administration & dosage ; Uganda ; },
abstract = {BACKGROUND: HIV acquisition risk during pregnancy remains high and additional data supporting pre-exposure prophylaxis (PrEP) in pregnancy are needed. The aim of the MTN-042/DELIVER study was to evaluate the dapivirine vaginal ring (DVR) and daily oral tenofovir disoproxil fumarate plus emtricitabine use as PrEP during pregnancy. We report infant outcomes following confirmed in-utero exposure.

METHODS: This randomised, controlled, open-label, phase 3b study was conducted in four clinical research sites in Malawi, South Africa, Uganda, and Zimbabwe. Pregnant, HIV-negative, healthy women aged 18-40 years were enrolled at 36-37 weeks' (cohort 1), 30-35 weeks' (cohort 2), and 12-29 weeks' (cohort 3) gestation and randomly assigned 2:1 (cohorts 1 and 2) and 4:1 (cohort 3) to receive the DVR (dapivirine 25 mg) or oral PrEP (tenofovir disoproxil fumarate 300 mg plus emtricitabine 200 mg). All infants born to maternal participants were enrolled and included in the primary infant analysis to evaluate infant safety with in-utero exposure to study product. Infant visits were conducted at less than 2 weeks, 6 weeks, 6 months, and 12 months of age. The primary infant composite safety outcome included serious adverse events and grade 3 or higher adverse events. Birth outcomes (livebirth or stillbirth, prematurity), adverse events (including frequency between each study visit), and growth up to 12 months were evaluated and collected. This study is registered with ClinicalTrials.gov (NCT03965923). The trial is completed and the database closed.

FINDINGS: The study was conducted between Feb 7, 2020, and May 13, 2024. In total, 545 infants were included: 147 in cohort 1, 154 in cohort 2, and 244 in cohort 3. Mean intrauterine exposure was 23·3, 59·7, and 113·8 days, respectively. Overall, 545 (99%) of 550 pregnancy outcomes were livebirths. Serious adverse events occurred in 66 (17%) of 398 infants in the DVR group and 15 (10%) of 147 in the oral PrEP group. Grade 3 or higher adverse events occurred in 95 (24%) of 398 and 29 (20%) of 147 infants, respectively, none related to product exposure. 41 (51%) of 81 new-onset serious adverse events occurred by age 6 weeks, and ten (91%) of 11 congenital anomalies were diagnosed by age 6 months. There were no maternal or infant HIV acquisitions.

INTERPRETATION: Over 12 months of follow-up of infants, the DVR and oral PrEP were generally safe, with no composite adverse events related to study product. Together with available maternal safety data, this supports use of the DVR and oral PrEP by pregnant women to prevent HIV.

FUNDING: US National Institutes of Health.},
}

Adolescent
Adult
Female
Humans
Infant
Infant, Newborn
Male
Pregnancy
Young Adult
Administration, Oral
*Anti-HIV Agents/administration & dosage/adverse effects
*Contraceptive Devices, Female
Emtricitabine/administration & dosage
*HIV Infections/prevention & control
*Infectious Disease Transmission, Vertical/prevention & control
*Pre-Exposure Prophylaxis/methods
*Pregnancy Complications, Infectious/prevention & control/drug therapy
*Pyrimidines/administration & dosage/adverse effects
South Africa
Tenofovir/administration & dosage
Uganda

@article {pmid41175446,
year = {2025},
author = {Levine, KM and Uy, NF and Gooley, TA and Voutsinas, J and Tratt, M and Eaton, KD and Santana-Davila, R and Berger, AH and Baik, CS},
title = {Osimertinib retreatment for patients with advanced EGFR-mutated non-small cell lung cancer.},
journal = {Cancer treatment and research communications},
volume = {45},
number = {},
pages = {101026},
pmid = {41175446},
issn = {2468-2942},
support = {P30 CA015704/CA/NCI NIH HHS/United States ; T32 CA009515/CA/NCI NIH HHS/United States ; },
mesh = {Humans ; *Aniline Compounds/therapeutic use/pharmacology ; *Acrylamides/therapeutic use/pharmacology ; *Carcinoma, Non-Small-Cell Lung/drug therapy/genetics/pathology/mortality ; Male ; *Lung Neoplasms/drug therapy/genetics/pathology/mortality ; Female ; Middle Aged ; Aged ; ErbB Receptors/genetics ; Retrospective Studies ; Mutation ; Retreatment ; *Protein Kinase Inhibitors/therapeutic use ; Adult ; Aged, 80 and over ; Indoles ; Pyrimidines ; },
abstract = {Resistance to osimertinib, a third-generation EGFR tyrosine kinase inhibitor, remains a key challenge in the treatment of EGFR-mutated non-small cell lung cancer (NSCLC). Although retreatment with earlier-generation EGFR tyrosine kinase inhibitors has been studied, data on osimertinib rechallenge are limited. We conducted a single institution retrospective analysis of patients with EGFR-mutated NSCLC who were rechallenged with osimertinib following progression on prior osimertinib and interim systemic therapy, including chemotherapy. Seventeen patients met inclusion criteria, all with adenocarcinoma histology and either EGFR exon 19 deletions or L858R mutations. Median interval between osimertinib treatments was 10.5 months. Osimertinib retreatment resulted in a partial response in 18 % (3/17) and stable disease in 35 % of patients (6/17), for a disease control rate of 53 % (9/17). Median retreatment duration was 4.3 months, and median overall survival following retreatment initiation was 8.9 months. Among patients with central nervous system involvement, several experienced intracranial stability without additional radiation. Duration of initial osimertinib therapy did not strongly predict retreatment benefit. These findings suggest that osimertinib rechallenge may provide clinically meaningful disease control in a subset of patients, especially given its tolerability and oral formulation. Further research is needed to identify biomarkers of sensitivity and to optimize patient selection for osimertinib retreatment following interval chemotherapy.},
}

Humans
*Aniline Compounds/therapeutic use/pharmacology
*Acrylamides/therapeutic use/pharmacology
*Carcinoma, Non-Small-Cell Lung/drug therapy/genetics/pathology/mortality
Male
*Lung Neoplasms/drug therapy/genetics/pathology/mortality
Female
Middle Aged
Aged
ErbB Receptors/genetics
Retrospective Studies
Mutation
Retreatment
*Protein Kinase Inhibitors/therapeutic use
Adult
Aged, 80 and over
Indoles
Pyrimidines

@article {pmid41176371,
year = {2025},
author = {Carpenter, PA and Warkentin, PI},
title = {Improving Outcomes in Hematopoietic Cell Transplantation and Cellular Therapy: Evolution of ASTCT Practice Guidelines and FACT Inspections.},
journal = {Transplantation and cellular therapy},
volume = {31},
number = {11},
pages = {843-848},
doi = {10.1016/j.jtct.2025.10.008},
pmid = {41176371},
issn = {2666-6367},
}

@article {pmid41176373,
year = {2025},
author = {Biernacki, MA},
title = {Capturing the Big Picture of HY Antigens and Transplantation Outcomes.},
journal = {Transplantation and cellular therapy},
volume = {31},
number = {11},
pages = {851-853},
doi = {10.1016/j.jtct.2025.10.009},
pmid = {41176373},
issn = {2666-6367},
}

@article {pmid41176520,
year = {2025},
author = {Yu, EY and Suzuki, H and Pieczonka, CM and Gotto, G and Briganti, A and Luz, M and Murphy, D and Malone, R and Hamilton, J and Chan, JE and Sieber, P and Given, RW and Hellmis, E and Kretz, T and Spiegelhalder, P and Gómez-Caamaño, A and Amela, YM and Artignan, X and Uemura, H and Fujita, N and Adorjan, P and Ghadessi, M and Verholen, F and Armstrong, AJ},
title = {DARolutamide ObservationaL (DAROL) study in patients with nonmetastatic castration-resistant prostate cancer: prespecified third interim analysis.},
journal = {Prostate cancer and prostatic diseases},
volume = {},
number = {},
pages = {},
pmid = {41176520},
issn = {1476-5608},
abstract = {BACKGROUND: DAROL is an ongoing study of real-world safety and effectiveness of darolutamide in patients with nonmetastatic castration-resistant prostate cancer (nmCRPC).

SUBJECTS/METHODS: This prespecified interim analysis included 550 patients with nmCRPC who completed ≥6 months of treatment with darolutamide 600 mg twice daily.

RESULTS: Darolutamide showed consistent safety and effectiveness in DAROL vs ARAMIS. Most treatment-emergent adverse events were grade 1/2. Two-year overall survival and metastasis-free survival rates and prostate-specific antigen responses were similar to ARAMIS.

CONCLUSIONS: These findings indicate that darolutamide offers effectiveness and a favorable safety profile in the broad range of patients seen in clinical practice.},
}

@article {pmid41177463,
year = {2025},
author = {Jons, CK and Kasse, CM and Mayer, BT and Hyrien, O and Sen, S and Meany, EL and d'Aquino, AI and Ganesh, P and Eckman, N and Dong, C and Yan, J and Nguyen, LT and Doulames, VM and Song, YE and Saouaf, OM and Williams, CM and Williams, SC and Paredes, J and Raghavan, R and Palomares, M and Alpert, M and Yates, NL and Tomaras, GD and Seaman, MS and Farzan, M and Appel, EA},
title = {Hydrogel formulations for sustained-release of broadly neutralizing antibodies.},
journal = {Journal of controlled release : official journal of the Controlled Release Society},
volume = {388},
number = {Pt 2},
pages = {114349},
pmid = {41177463},
issn = {1873-4995},
support = {INV-036842/GATES/Gates Foundation/United States ; R01 AI154989/AI/NIAID NIH HHS/United States ; INV-010680/GATES/Gates Foundation/United States ; INV-032929/GATES/Gates Foundation/United States ; T32 GM008412/GM/NIGMS NIH HHS/United States ; K01 EB033870/EB/NIBIB NIH HHS/United States ; INV-027411/GATES/Gates Foundation/United States ; S10 OD026831/OD/NIH HHS/United States ; },
mesh = {Animals ; Delayed-Action Preparations/pharmacokinetics/administration & dosage/chemistry ; *Hydrogels/chemistry/administration & dosage ; *Antibodies, Neutralizing/administration & dosage ; Mice ; Humans ; *Broadly Neutralizing Antibodies/administration & dosage ; Female ; Rats ; Nanoparticles/chemistry/administration & dosage ; Male ; Drug Liberation ; Rats, Sprague-Dawley ; },
abstract = {Sustained serum levels of broadly neutralizing antibodies (bnAbs) are crucial for effective passive immunization against infectious diseases as protection persists only while these bnAbs remain at adequate concentrations within the body. Current obstacles, such as poor pharmacokinetics (PK) and burdensome administration, must be overcome to make bnAbs a viable option for pre- and post-exposure prophylaxis. In this work, we explore how a polymer-nanoparticle (PNP) hydrogel depot technology can be engineered to prolong protein delivery and enable drug exposure on the order of weeks to months. In-vivo studies in mice and rats demonstrate extended protein release compared to bolus administration, and modeling efforts predict the impact of both the elimination half-life of the active pharmaceutical ingredient and hydrogel depot volume on overall pharmacokinetics. Moreover, flow cytometry characterization reveals that immune cell infiltration into the hydrogel depot can result in faster-than-expected release of antibody cargo on account of active transport via cellular uptake. We then demonstrate that co-formulation of antibodies with an anti-inflammatory agent reduces cellular infiltration and resulting active transport, further extending delivery and pharmacokinetics. Finally, multicompartmental modeling predicts the human PK profiles of clinically relevant HIV bnAbs delivered via subcutaneous hydrogel injection. These findings aid in the development of next generation hydrogel materials that stabilize and slowly release bnAbs for long-term pre-exposure immunoprophylaxis.},
}

Animals
Delayed-Action Preparations/pharmacokinetics/administration & dosage/chemistry
*Hydrogels/chemistry/administration & dosage
*Antibodies, Neutralizing/administration & dosage
Mice
Humans
*Broadly Neutralizing Antibodies/administration & dosage
Female
Rats
Nanoparticles/chemistry/administration & dosage
Male
Drug Liberation
Rats, Sprague-Dawley

@article {pmid41178332,
year = {2025},
author = {Newell, EW},
title = {Seeing First: Introducing the Resource Report at Cancer Immunology Research.},
journal = {Cancer immunology research},
volume = {13},
number = {11},
pages = {1696-1697},
doi = {10.1158/2326-6066.CIR-25-1175},
pmid = {41178332},
issn = {2326-6074},
support = {R01 CA264646/CA/NCI NIH HHS/United States ; },
}

@article {pmid41178673,
year = {2026},
author = {Gong, IY and Rafinejad-Farahani, B and Majeed, H and Soto, MJ and Oza, A and Ehrlich, T and Fernandez Lynch, H and Guerra, CE and Lofters, A and Unger, JM and Conti, RM and Rosenthal, M and Rodin, D},
title = {Reporting and enrollment disparities in hematologic malignancy trials between 2000-2023.},
journal = {Leukemia & lymphoma},
volume = {67},
number = {1},
pages = {176-189},
doi = {10.1080/10428194.2025.2579735},
pmid = {41178673},
issn = {1029-2403},
mesh = {Humans ; *Hematologic Neoplasms/therapy/epidemiology ; *Healthcare Disparities/statistics & numerical data ; *Patient Selection ; *Clinical Trials as Topic/statistics & numerical data ; United States/epidemiology ; SEER Program ; Ethnicity/statistics & numerical data ; Male ; Female ; },
abstract = {Despite initiatives to enhance diversity in clinical trials (CTs), disparities persist in hematologic malignancy (HM) studies. We reviewed 1,230 US-based phase II-III HM CTs (2000-2023) including 149,434 participants and compared enrollment to SEER benchmarks. Race was reported in 59% of trials and ethnicity in 40%, with significant improvement over time. Trials initiated in 2016 or later were more likely to report race (OR 36.3) and ethnicity (OR 8.0) than those before 2008. Compared with NIH-sponsored studies, institutional (OR 0.34) and industry trials (OR 0.52) had lower odds of reporting demographics. Black and Hispanic individuals were consistently underrepresented, most notably in multiple myeloma (7.0% vs. 20.0% expected) and acute lymphoblastic leukemia (21.5% vs. 36.9% expected). NIH-funded trials enrolled more Black participants than other sponsor types. These findings emphasize the need for enforceable mandates on race and ethnicity reporting, as well as representation targets, to ensure equitable access and generalizability.},
}

Humans
*Hematologic Neoplasms/therapy/epidemiology
*Healthcare Disparities/statistics & numerical data
*Patient Selection
*Clinical Trials as Topic/statistics & numerical data
United States/epidemiology
SEER Program
Ethnicity/statistics & numerical data
Male
Female

@article {pmid41180004,
year = {2025},
author = {Sadowska-Klasa, A and Xie, H and Zamora, D and Waghmare, A and Hill, JA and Duke, ER and Green, ML and Oshima, MU and Sandmaier, BM and Jerome, KR and Leisenring, WM and Boeckh, M},
title = {Cytomegalovirus Viral Load Continues to Predict Poor Outcomes in Adults and Children Despite Improved Hematopoietic Cell Transplantation Success.},
journal = {Open forum infectious diseases},
volume = {12},
number = {11},
pages = {ofaf612},
pmid = {41180004},
issn = {2328-8957},
support = {K23 AI163343/AI/NIAID NIH HHS/United States ; },
abstract = {BACKGROUND: Recent advances of graft-versus-host disease prevention strategies have led to improved overall survival after hematopoietic cell transplantation (HCT). Whether cytomegalovirus (CMV) viral load continues to predict CMV disease, overall mortality, and nonrelapse mortality is poorly defined.

METHODS: CMV-seropositive patients undergoing allogeneic HCT between 2007 and 2017 with weekly CMV DNA polymerase chain reaction surveillance and preemptive therapy were analyzed. Multivariate Cox proportional hazards models were used to estimate the association between CMV viral load by day 100 at different thresholds with CMV disease and overall and nonrelapse mortality up to 1 year post-HCT.

RESULTS: Of 1539 patients who received a transplant in the study period, 1349 survived >100 days after HCT and were included in the analyses. By day 100 post-HCT, CMV reactivation at any level was observed in 76%, with the lowest incidence at all levels in young children. Pediatric patients had significantly less CMV disease compared to the adult population. CMV reactivation was associated with a higher risk of CMV disease (adjusted hazard ratio, 6.8 [95% confidence interval, 3.54-13]); it was also associated with overall and nonrelapse mortality among day 100 survivors, although the association was diminished recently. The strongest correlation was still apparent between viral load and mortality in patients with a viral load >3 log10 and lymphocyte count <300 cells/μL.

CONCLUSIONS: CMV viral load continued to be a strong predictor for CMV disease. With improved transplantation techniques, the association of viral load with overall and nonrelapse mortality is diminished, but the effect was still present in patients with severe immunosuppression.},
}

@article {pmid41180007,
year = {2025},
author = {Moore, HP and Fogel, JM and Marzinke, MA and Halvas, EK and Parikh, UM and Mellors, JW and Penrose, KJ and Seisa, M and Petropoulos, C and Price, AL and Moser, A and Wang, Z and McCauley, M and Valencia-Huamaní, J and Rinehart, AR and Rooney, JF and Soto-Torres, L and Grinsztejn, B and Landovitz, RJ and Eshleman, SH},
title = {Sustained HIV Suppression With Co-formulated Tenofovir Disoproxil Fumarate/Lamivudine/Dolutegravir in a Person With Transmitted Dolutegravir Resistance and Pretreatment Resistance to Lamivudine: a Case Report From HPTN 083.},
journal = {Open forum infectious diseases},
volume = {12},
number = {11},
pages = {ofaf645},
pmid = {41180007},
issn = {2328-8957},
support = {P30 AI094189/AI/NIAID NIH HHS/United States ; },
abstract = {Integrase strand transfer inhibitors (INSTIs) are recommended in most first-line HIV treatment regimens. We describe a participant in a clinical trial with transmitted INSTI resistance. The participant had no history of INSTI use and had no evidence of INSTI exposure prior to HIV acquisition. Treatment with tenofovir disoproxil fumarate, lamivudine (3TC), and dolutegravir (DTG) was started 3 weeks after HIV diagnosis. Viral suppression was achieved within a year and was sustained for >3 years on treatment. Retrospective HIV genotyping of a pretreatment sample detected major resistance mutations in 3 drug classes, with predicted high-level resistance to DTG and 3TC. HIV phenotyping confirmed that the transmitted virus had DTG and 3TC resistance but retained susceptibility to DTG at higher drug concentrations. Pharmacologic testing indicated that the DTG concentrations observed in this case were sufficient to overcome the effects of 2 major baseline INSTI resistance mutations (G140S and Q148H).},
}

@article {pmid41180139,
year = {2025},
author = {Terry, KL and Shafrir, A and Laliberte, A and Vitonis, AF and Garbutt, K and DePari, M and Becker, C and Sasamoto, N and Zondervan, KT and Missmer, SA},
title = {Circulating inflammatory biomarkers and endometriosis lesion characteristics in the WisE consortium.},
journal = {npj women's health},
volume = {3},
number = {1},
pages = {62},
pmid = {41180139},
issn = {2948-1716},
support = {R01 HD111242/HD/NICHD NIH HHS/United States ; },
abstract = {Endometriosis is a chronic inflammatory condition requiring surgical or imaging visualization for definitive diagnosis. How endometriotic lesion characteristics relate to circulating inflammatory markers remains unclear. We evaluated 11 inflammatory biomarkers, including interleukin (IL)-1β, -6, -8, -10, -16, tumor necrosis factor (TNF)-α, thymus and activation regulated chemokine (TARC), monocyte chemotactic protein (MCP)-1, -4, and Interferon gamma-induced protein (IP)-10, in 566 participants with endometriosis from the Women's Health Study: From Adolescence to Adulthood (A2A), Endometriosis Oxford Care & Research (CaRe) study (ENDOX) and Endometriosis: Natural History, Diagnosis, and Outcome (ENDO) study to evaluate associations with endometriosis characteristics, including macrophenotype (superficial lesions only, versus endometrioma and/or deep lesions), lesion appearance (color, vascularity), and anatomic location. We observed nominally statistically significant variation in circulating inflammatory markers by lesion color, vascularity, and location but no significant associations between circulating inflammatory markers and rASRM stage or macrophenotype, which could be due to a small number of participants with non-superficial lesions.},
}

@article {pmid41183215,
year = {2025},
author = {Teets, E and Singhvi, A},
title = {Changing minds epigenetically: Germline genes in neurons disrupt animal behavior.},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
volume = {122},
number = {45},
pages = {e2525456122},
pmid = {41183215},
issn = {1091-6490},
support = {50005899//Washington Research Foundation (WRF)/ ; T32AG066574//HHS | NIH | National Institute on Aging (NIA)/ ; 227823//Esther A. and Joseph Klingenstein Fund (EAJK Fund)/ ; R01 NS114222/NS/NINDS NIH HHS/United States ; BRFSG-2023-10//Brain Research Foundation (BRF)/ ; T32 AG066574/AG/NIA NIH HHS/United States ; NS114222//HHS | NIH | National Institute of Neurological Disorders and Stroke (NINDS)/ ; },
}

@article {pmid41187024,
year = {2026},
author = {Pareek, A and Nguyen, E and Rashidi, A},
title = {Successful Treatment of Steroid-refractory Acute Graft-versus-host Disease With Ruxolitinib in a Liver Transplant Recipient.},
journal = {Transplantation},
volume = {110},
number = {1},
pages = {e277-e278},
doi = {10.1097/TP.0000000000005563},
pmid = {41187024},
issn = {1534-6080},
}

@article {pmid41187375,
year = {2025},
author = {Bashi, A and Chen, L and Rouse, K and Elkin, EB and Ferris, JS and Xu, X and Bickell, NA and Blank, S and Rossi, EC and Hazelton, WD and Wright, JD and Havrilesky, LJ and Myers, ER},
title = {Cost-effectiveness of biomarker-based and universal strategies for the treatment of advanced-stage endometrial cancer.},
journal = {Gynecologic oncology},
volume = {203},
number = {},
pages = {130-138},
doi = {10.1016/j.ygyno.2025.09.019},
pmid = {41187375},
issn = {1095-6859},
support = {U01 CA265739/CA/NCI NIH HHS/United States ; },
mesh = {Humans ; Female ; Cost-Benefit Analysis ; *Endometrial Neoplasms/drug therapy/economics/pathology ; Trastuzumab/economics/administration & dosage ; Neoplasm Staging ; *Antineoplastic Combined Chemotherapy Protocols/economics/therapeutic use ; Quality-Adjusted Life Years ; Biomarkers, Tumor/analysis ; Markov Chains ; Immunotherapy/economics/methods ; Antibodies, Monoclonal, Humanized/economics/administration & dosage ; Erb-b2 Receptor Tyrosine Kinases ; Black or African American ; White ; },
abstract = {OBJECTIVE: To compare cost-effectiveness of targeted therapeutic strategies for non-Hispanic Black (NHB) and non-Hispanic White (NHB) patients with newly diagnosed, advanced-stage endometrial cancer.

METHODS: A Markov-based cost-utility model using a third-party payer perspective compared concurrent and maintenance treatment strategies incorporating dostarlimab and trastuzumab for newly diagnosed stage III-IV endometrial cancer: chemotherapy alone; 3 universal immunotherapy strategies (universal concurrent and maintenance dostarlimab +/- trastuzumab for HER2/neu-positive serous and/or carcinosarcomas); and 3 targeted immunotherapy strategies (dostarlimab for mismatch repair deficient (dMMR) tumors +/- trastuzumab for HER2/neu positive serous and/or carcinosarcomas). Costs (2024 USD), utilities, and clinical estimates were derived from published literature and the National Cancer Database. The base case analysis was a microsimulation with 10,000 runs, accompanied by a Monte Carlo probabilistic sensitivity analysis with 20,000 trials. Cost-effectiveness was assessed using incremental cost-effectiveness ratios (ICERs) with a willingness-to-pay threshold of $150,000/quality-adjusted life year (QALY). We performed one-way and two-way sensitivity analyses on key parameters and analyses stratified by race/ethnicity.

RESULTS: All targeted immunotherapy strategies were cost-effective compared to chemotherapy alone in both NHB and NHW, while universal immunotherapy was never cost-effective. Targeted strategies were more cost-effective in NHB than NHW. Targeted dostarlimab for dMMR plus trastuzumab for HER2 serous and carcinosarcomas was the most cost-effective strategy compared to chemotherapy, with an ICER of $119,945/QALY. In sensitivity analysis, assuming longer durations of treatment benefit resulted in lower ICERs.

CONCLUSIONS: Personalized treatment strategies incorporating HER2 and MMR testing should be considered to optimize both cost-effectiveness and equity in care.},
}

Humans
Female
Cost-Benefit Analysis
*Endometrial Neoplasms/drug therapy/economics/pathology
Trastuzumab/economics/administration & dosage
Neoplasm Staging
*Antineoplastic Combined Chemotherapy Protocols/economics/therapeutic use
Quality-Adjusted Life Years
Biomarkers, Tumor/analysis
Markov Chains
Immunotherapy/economics/methods
Antibodies, Monoclonal, Humanized/economics/administration & dosage
Erb-b2 Receptor Tyrosine Kinases
Black or African American
White

@article {pmid41187759,
year = {2026},
author = {Qi, G and Lila, E and Ji, Z and Shojaie, A and Battle, A and Sun, W},
title = {Transcriptome-wide association studies at cell-state level using single-cell eQTL data.},
journal = {Cell genomics},
volume = {6},
number = {1},
pages = {101060},
pmid = {41187759},
issn = {2666-979X},
mesh = {*Quantitative Trait Loci/genetics ; Humans ; *Single-Cell Analysis/methods ; *Transcriptome/genetics ; *Genome-Wide Association Study/methods ; Autoimmune Diseases/genetics ; Gene Expression Profiling/methods ; },
abstract = {Transcriptome-wide association studies (TWASs) are widely used to prioritize genes for diseases. Current methods test gene-disease associations at the bulk tissue or cell-type-specific pseudobulk level, which do not account for the heterogeneity within cell types. We present TWiST, a statistical method for TWAS at cell-state resolution using single-cell expression quantitative trait locus (eQTL) data. Our method uses pseudotime to represent cell states and models the effect of gene expression on the trait as a continuous pseudotemporal curve. Therefore, it allows flexible hypothesis testing of global, dynamic, and nonlinear associations. Through simulation studies and real data analysis, we demonstrated that TWiST leads to significantly improved power compared to pseudobulk methods. Application to the OneK1K study identified hundreds of genes with dynamic effects on autoimmune diseases along the trajectory of immune cell differentiation. TWiST presents great promise to understand disease genetics using single-cell studies.},
}

*Quantitative Trait Loci/genetics
Humans
*Single-Cell Analysis/methods
*Transcriptome/genetics
*Genome-Wide Association Study/methods
Autoimmune Diseases/genetics
Gene Expression Profiling/methods

@article {pmid41190251,
year = {2025},
author = {Santiago-Torres, M and Mull, KE and Sullivan, BM and Bricker, JB},
title = {Does living near a tobacco retailer impact the efficacy of smoking cessation treatments?: Analysis from a randomized trial.},
journal = {Addictive behaviors reports},
volume = {22},
number = {},
pages = {100635},
pmid = {41190251},
issn = {2352-8532},
abstract = {INTRODUCTION: Whether living near a tobacco retailer impacts the efficacy of smoking cessation treatments remains largely unknown. We used data from a randomized trial comparing two smoking cessation apps among 2415 adults: iCanQuit, based on Acceptance and Commitment Therapy, and QuitGuide, based on standard U.S. Clinical Practice Guidelines. We examined whether tobacco retailer density impacted the efficacy of the treatments on 12-month cessation outcomes.

METHODS: Data on tobacco retailer density per 1,000 people (i.e., "one unit") was linked to each participant's residential ZIP Code. Cessation outcomes included 30-day point prevalence abstinence (PPA) from cigarette smoking, prolonged abstinence, 30-day PPA from nicotine/tobacco products, and relapse. We examined the interaction between density and treatment arm on 12-month 30-day PPA and compared cessation outcomes separately by arm.

RESULTS: The interaction between density and treatment arm on cessation did not reach statistical significance (P = 0.09). For each one-unit increase in density, there was no change in quit rates in the iCanQuit arm (P = 0.62). In the QuitGuide arm, higher density was associated with lower quit rates (OR = 0.54; 95 % CI, 0.27-1.06; P = 0.07), although not-statistically significant. There was a significant interaction between density and treatment arm on prolonged cigarette abstinence (P = 0.03). We found no change in prolonged abstinence in the iCanQuit arm (P = 0.44). In the QuitGuide arm, higher density was associated with lower prolonged abstinence (OR = 0.27; 95 % CI, 0.07-1.02; P = 0.054), although not-statistically significant. Conclusions: Living near tobacco retailers may undermine the effectiveness of standard behavioral treatment but appears to have no impact on the effectiveness of acceptance-based smoking cessation treatments.},
}

@article {pmid41191519,
year = {2026},
author = {Farhadfar, N and El Jurdi, N and Baker, KK and Ghosh, S and Bat-Erdene, M and Chen, H and Sahu, R and Weiss, R and Mi, J and Desatnik, G and Williams, LR and Tkaczyk, ER and Lee, SJ},
title = {Reproducibility and repeatability of the Myoton to quantify sclerotic chronic graft-versus-host disease.},
journal = {Blood advances},
volume = {10},
number = {4},
pages = {1145-1152},
pmid = {41191519},
issn = {2473-9537},
support = {I01 CX002721/CX/CSRD VA/United States ; IK2 CX001785/CX/CSRD VA/United States ; R01 HL169944/HL/NHLBI NIH HHS/United States ; },
mesh = {Humans ; *Graft vs Host Disease/diagnosis/etiology/pathology ; Adult ; Male ; Female ; Reproducibility of Results ; Middle Aged ; Chronic Disease ; Sclerosis ; Observer Variation ; Aged ; Skin/pathology ; Hematopoietic Stem Cell Transplantation/adverse effects ; },
abstract = {There is an urgent need for validated tools to measure sclerotic cutaneous chronic graft-versus-host disease (scGVHD). We examined the interobserver reproducibility within a session and intraobserver repeatability between sessions of the Myoton device for quantifying skin sclerosis in 36 adults with scGVHD. The Myoton was used to measure oscillation frequency and relaxation time of soft tissues at 7 bilateral sites (14 anatomic sites) by 2 study personnel at 2 study sessions. Agreement was measured using mean pairwise absolute difference (MPD), and reliability was measured using intraclass correlation coefficient (ICC). For each of the 2 Myoton parameters, the overall interobserver MPD was <5% of the average overall values and the interobserver ICC was >0.90 between the 2 observers, indicating excellent agreement and reliability within a measurement session. The median time between sessions 1 and 2 was 47.5 days. The overall normalized intraobserver MPD was <7% of the average overall values for each of the 2 Myoton parameters, reflecting good agreement between sessions. The intraobserver ICC for frequency and relaxation time parameters were 0.85 and 0.84, respectively, indicating good reliability between sessions. The reproducibility and repeatability of a bonus site selected at each study visit were similar to the standard 14 anatomic sites. However, no individual site was nearly as reproducible or repeatable as the overall Myoton measurements averaged across the patient. Our findings emphasize the utility of the Myoton for assessing skin properties in scGVHD with patient-level measurements.},
}

Humans
*Graft vs Host Disease/diagnosis/etiology/pathology
Adult
Male
Female
Reproducibility of Results
Middle Aged
Chronic Disease
Sclerosis
Observer Variation
Aged
Skin/pathology
Hematopoietic Stem Cell Transplantation/adverse effects

@article {pmid41192776,
year = {2026},
author = {Abrams, HR and Starks, H and Bandini, L and Harrington, T and Percival, MM and Walter, RB and Russell, K and Mawad, R and Appelbaum, J and Sorror, ML and Halpern, AB},
title = {National Landscape of Logistical and Nonmedical Requirements for Transplantation and Cellular Therapy.},
journal = {Transplantation and cellular therapy},
volume = {32},
number = {2},
pages = {209.e1-209.e13},
doi = {10.1016/j.jtct.2025.10.031},
pmid = {41192776},
issn = {2666-6367},
support = {P30 CA015704/CA/NCI NIH HHS/United States ; },
mesh = {Humans ; *Hematopoietic Stem Cell Transplantation/methods ; Surveys and Questionnaires ; *Cell- and Tissue-Based Therapy/methods ; United States ; Caregivers ; },
abstract = {BACKGROUND: New disease indications and supportive care advances have expanded the populations who may benefit from cellular therapies, including autologous or allogeneic hematopoietic cell transplant (HCT) and/or chimeric antigen receptor T-cell therapy (CAR T). However, nonmedical requirements for these therapies, such as caregiver and housing availability, may limit access. We sought a detailed national assessment of nonmedical requirements for HCT and CAR T-cell therapy to describe and quantify barriers.

OBJECTIVE: Describe the national landscape and implementation of logistical and nonmedical requirements for HCT and CAR T-cell therapy.

STUDY DESIGN: We developed a web-based survey of HCT/CAR T-cell therapy requirements and obtained pilot feedback from 3 centers that regularly perform HCT/CAR T-cell therapy. We distributed the survey via the NCCN Best Practices Committee, which is composed of physician, nursing, and administrative leaders from 34 member institutions. We requested survey completion by an institutional content area expert.

RESULTS: The response rate was 91% (31/34). >80% of centers required a caregiver, local housing, and local transportation, but the number of days required, institutional supports, and acceptable distances varied widely. A subset of centers offered "all-outpatient" procedures and required more stringent logistical criteria, including autologous HCT by 13/19 centers (68%), allogeneic HCT by 4/8 centers (50%), and CAR T-cell therapy by 10/16 centers (63%). Many centers excluded patients with a history of medication nonadherence, substance use, or psychiatric comorbidity, but most did not employ formal adjudication or definition of patient eligibility. Institutions noted "soft" contraindications or case-by-case review for these patients and those experiencing homelessness, lack of insurance, or without citizenship. Overall, caregiving, housing, cost, and insurance coverage emerged as the top nonmedical barriers to HCT and CAR T-cell therapy.

CONCLUSIONS: Significant variability exists in nonmedical requirements for HCT and CAR T-cell therapy, with a lack of standard policies across institutions. We recommend that centers formally track reasons for noneligibility to identify nonmedical barriers to HCT and CAR T-cell therapy and develop targeted interventions to reduce the number of patients who are excluded for nonmedical reasons.},
}

Humans
*Hematopoietic Stem Cell Transplantation/methods
Surveys and Questionnaires
*Cell- and Tissue-Based Therapy/methods
United States
Caregivers

@article {pmid41193051,
year = {2025},
author = {, and Morgan, RL and Bathala, TK and Arora, SS and Chandhok, N and Corey, AS and Dandapani, SV and Kim, L and Law, L and Mansoori, B and Morin, CE and Trout, AT and Wolfman, DJ and Wong, TZ},
title = {ACR Appropriateness Criteria® Staging and Follow-Up of Leukemia.},
journal = {Journal of the American College of Radiology : JACR},
volume = {22},
number = {11S},
pages = {S658-S688},
doi = {10.1016/j.jacr.2025.08.034},
pmid = {41193051},
issn = {1558-349X},
mesh = {Humans ; Neoplasm Staging ; United States ; *Leukemia/diagnostic imaging/pathology ; Societies, Medical ; Evidence-Based Medicine ; Follow-Up Studies ; },
abstract = {Imaging associated with staging and follow-up of leukemia can play an important role in accurately assessing disease; however, the type of imaging and usefulness varies significantly by the subtype of leukemia. This document reviews the current literature regarding the impact of imaging for both staging and surveillance of several of the most common leukemic variants. These include acute lymphoblastic leukemia, acute myeloid leukemia, chronic lymphocytic leukemia, Richter transformation, and chronic myeloid leukemia. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision process support the systematic analysis of the medical literature from peer reviewed journals. Established methodology principles such as Grading of Recommendations Assessment, Development, and Evaluation or GRADE are adapted to evaluate the evidence. The RAND/UCLA Appropriateness Method User Manual provides the methodology to determine the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where peer reviewed literature is lacking or equivocal, experts may be the primary evidentiary source available to formulate a recommendation.},
}

Humans
Neoplasm Staging
United States
*Leukemia/diagnostic imaging/pathology
Societies, Medical
Evidence-Based Medicine
Follow-Up Studies

@article {pmid41193657,
year = {2025},
author = {Li, H and Melnyk, JE and Fu, BXH and Shrestha, R and Zhang, M and Sjöström, M and Feng, S and Anderson, JA and Han, W and Chesner, LN and Shin, HJ and Farsh, T and Suarez, HJ and Nath, S and Chou, J and Das, R and Egusa, EA and Calvert, M and Kishishita, A and Barpanda, A and Zhu, J and Maheshwari, A and Chen, WS and Alshalalfa, M and Winters, A and Hua, JT and Liu, T and Davicioni, E and Wiita, AP and Stohr, BA and Siddiqui, J and Huang, B and Small, EJ and Shokat, KM and Nelson, PS and Quigley, DA and Wasmuth, EV and Gilbert, LA and Feng, FY},
title = {Genome-scale CRISPR screens identify PTGES3 as a direct modulator of androgen receptor function in advanced prostate cancer.},
journal = {Nature genetics},
volume = {57},
number = {12},
pages = {3027-3038},
pmid = {41193657},
issn = {1546-1718},
support = {YI//Prostate Cancer Foundation (PCF)/ ; P50 CA097186/CA/NCI NIH HHS/United States ; R01GM131641//U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS)/ ; 2018-00382//Vetenskapsrådet (Swedish Research Council)/ ; R01 CA221969/CA/NCI NIH HHS/United States ; 1R01CA244550//U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)/ ; PC230420//Prostate Cancer Foundation (PCF)/ ; young investigator//Prostate Cancer Foundation (PCF)/ ; R01 GM131641/GM/NIGMS NIH HHS/United States ; 1R01CA227025//U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)/ ; DP2 CA239597/CA/NCI NIH HHS/United States ; P50 CA186786/CA/NCI NIH HHS/United States ; 1F32CA236347-01//U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)/ ; R01 GM124334/GM/NIGMS NIH HHS/United States ; 1R01CA230516-01//U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)/ ; R01GM124334//U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS)/ ; W81XWH-20-1-0136//U.S. Department of Defense (United States Department of Defense)/ ; P50CA097186 PNW Prostate Cancer SPORE Career Enhancement Program//U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)/ ; P41 GM103481/GM/NIGMS NIH HHS/United States ; P50 CA275741/CA/NCI NIH HHS/United States ; R01 CA227025/CA/NCI NIH HHS/United States ; CA230516-02S1//U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)/ ; R00 CA204602/CA/NCI NIH HHS/United States ; CA204602//U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)/ ; P30 CA015704/CA/NCI NIH HHS/United States ; V2024-016//V Foundation for Cancer Research (V Foundation)/ ; K99 CA204602/CA/NCI NIH HHS/United States ; HT9425-23-1-0462//U.S. Department of Defense (United States Department of Defense)/ ; R01 CA290875/CA/NCI NIH HHS/United States ; 1R01CA221969-01//U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)/ ; R01 CA234715/CA/NCI NIH HHS/United States ; S10 OD016229/OD/NIH HHS/United States ; 17CHAL06//Prostate Cancer Foundation (PCF)/ ; R01 CA230516/CA/NCI NIH HHS/United States ; Young Investigator Award//Prostate Cancer Foundation (PCF)/ ; R01 CA244550/CA/NCI NIH HHS/United States ; R00 GM140264/GM/NIGMS NIH HHS/United States ; 21YOUN12//Prostate Cancer Foundation (PCF)/ ; F32 CA236347/CA/NCI NIH HHS/United States ; Prostate Cancer Program 2021 Pilot Research Awards//UC | UC San Francisco | Department of Medicine, University of California, San Francisco (UCSF Department of Medicine)/ ; P50CA186786//U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)/ ; R01 CA266452/CA/NCI NIH HHS/United States ; },
mesh = {Male ; *Receptors, Androgen/genetics/metabolism ; Humans ; *Prostatic Neoplasms/genetics/pathology/metabolism ; Cell Line, Tumor ; Gene Expression Regulation, Neoplastic ; CRISPR-Cas Systems/genetics ; Homeodomain Proteins/genetics/metabolism ; GATA2 Transcription Factor/genetics/metabolism ; Drug Resistance, Neoplasm/genetics ; },
abstract = {The androgen receptor (AR) is a critical driver of prostate cancer (PCa). Here, to study regulators of AR protein levels and oncogenic activity, we developed a live-cell quantitative endogenous AR fluorescent reporter. Leveraging this AR reporter, we performed genome-scale CRISPRi flow cytometry sorting screens to systematically identify genes that modulate AR protein levels. We identified and validated known AR protein regulators, including HOXB13 and GATA2, and also unexpected top hits including PTGES3-a poorly characterized gene in PCa. PTGES3 repression resulted in loss of AR protein, cell-cycle arrest and cell death in AR-driven PCa models. Clinically, analysis of PCa data demonstrates that PTGES3 expression is associated with AR-directed therapy resistance. Mechanistically, we show PTGES3 binds directly to AR, regulates AR protein stability and is necessary for AR function in the nucleus at AR target genes. PTGES3 represents a potential therapeutic target for overcoming known mechanisms of resistance to existing AR-directed therapies in PCa.},
}

Male
*Receptors, Androgen/genetics/metabolism
Humans
*Prostatic Neoplasms/genetics/pathology/metabolism
Cell Line, Tumor
Gene Expression Regulation, Neoplastic
CRISPR-Cas Systems/genetics
Homeodomain Proteins/genetics/metabolism
GATA2 Transcription Factor/genetics/metabolism
Drug Resistance, Neoplasm/genetics

@article {pmid41195517,
year = {2025},
author = {Patel, J and Gopal, A and Cherniawsky, H and Ram, R and Kamble, R and Hamadani, M},
title = {CD19 directed CAR T therapy for intravascular large B-cell lymphoma.},
journal = {Haematologica},
volume = {},
number = {},
pages = {},
doi = {10.3324/haematol.2025.288838},
pmid = {41195517},
issn = {1592-8721},
abstract = {Not available.},
}

@article {pmid41196629,
year = {2025},
author = {Mehta, RS and Sparapani, RA and Kanakry, CG and McCurdy, SR and Saultz, J and Lazaryan, A and Milano, F and Lee, SJ},
title = {Unrelated Donor Age and Recipient Outcomes After Posttransplant Cyclophosphamide vs Conventional Prophylaxis.},
journal = {JAMA oncology},
volume = {12},
number = {1},
pages = {28-37},
pmid = {41196629},
issn = {2374-2445},
support = {U24 CA076518/CA/NCI NIH HHS/United States ; },
abstract = {IMPORTANCE: Advanced age in unrelated donors (URDs) is a well-established risk factor in allogeneic hematopoietic cell transplant (HCT), leading registries to prioritize younger donors. However, this paradigm relevance is uncertain in the era of posttransplant cyclophosphamide (PTCy) for graft-vs-host disease (GVHD) prophylaxis, a strategy increasingly adopted for its effectiveness. Clarifying this association is crucial for optimizing donor selection and potentially expanding the donor pool.

OBJECTIVE: To determine whether the association of older URD age with overall survival differs between patients receiving PTCy-based vs conventional calcineurin inhibitor (CNI)-based GVHD prophylaxis.

This was a multicenter cohort study using registry data from the Center for International Blood and Marrow Transplant Research for January 2017 through June 2021. Eligible participants were adult patients with acute leukemia or myelodysplastic syndrome who underwent an allogeneic HCT from a URD who was fully matched for 8 of 8 human leukocyte antigen loci (MUD) or mismatched for 7 of 8 human leukocyte antigen loci (MMUD). Data were analyzed from January to June 2025.

EXPOSURES: GVHD prophylaxis regimen (PTCy-based vs CNI-based) and donor age (analyzed continuously and categorically).

MAIN OUTCOMES AND MEASURES: Overall survival was the primary outcome, with associations assessed using a multipronged approach including least absolute shrinkage and selection operator (LASSO)-penalized Cox proportional hazards models, inverse probability of treatment weighting (IPTW), and XGBoost machine learning.

RESULTS: The study analysis included 10 025 patients (mean [SD] age, 56.5 [14.4] years; 4379 female [43.7%] and 5646 male [56.3%] individuals) among whom 7272 (72.5%) had received MUD-CNI; 1681 (16.8%%) MUD-PTCy; 613 (6.1%) MMUD-PTCy; and 459 (4.6%) MMUD-CNI. Increasing donor age was associated with worse OS in CNI-based MUD (hazard ratio [HR], 1.004-1.009 per year increase) and MMUD (HR, 1.022-1.034) cohorts. Conversely, this association was not observed in the combined PTCy cohort (HR, 1.001-1.007). These findings were robust across standard and overlap weighted IPTW, LASSO-penalized models, and XGBoost analyses. The attenuated association in the PTCy cohort was primarily driven by a lack of association between donor age and nonrelapse mortality.

CONCLUSIONS AND RELEVANCE: The findings of this cohort study indicate that the association of donor age with URD HCT outcomes appears to be mitigated in the PTCy setting, suggesting that PTCy may counteract some of the adverse effects associated with increased unrelated donor age. This observation challenges existing paradigms and warrants validation in independent cohorts, and if validated, could substantially expand the donor pool.},
}

@article {pmid41198236,
year = {2026},
author = {Mirshahvalad, SA and Iravani, A and Fendler, WP and Maurer, T and Eiber, M and Sharifian, F and Manoochehry, S and Rendl, G and Schweighofer-Zwink, G and Pirich, C and Sathekge, M and Beheshti, M},
title = {Rechallenge and Extended [[177]Lu]Lu-PSMA Therapy in Metastatic Prostate Cancer.},
journal = {Journal of nuclear medicine : official publication, Society of Nuclear Medicine},
volume = {67},
number = {1},
pages = {4-11},
doi = {10.2967/jnumed.125.270889},
pmid = {41198236},
issn = {1535-5667},
mesh = {Humans ; Male ; *Lutetium/therapeutic use ; Neoplasm Metastasis ; Radioisotopes/therapeutic use ; *Prostatic Neoplasms/pathology/radiotherapy ; Radiopharmaceuticals/therapeutic use ; Prostatic Neoplasms, Castration-Resistant/radiotherapy/pathology ; Prostate-Specific Antigen ; },
abstract = {Continuation of effective and well-tolerated systemic treatment is often performed in care for metastatic castration-resistant prostate cancer. Likewise, continued administration of [[177]Lu]Lu-PSMA radiopharmaceutical therapy beyond the approved number of cycles holds promising potential to enhance therapeutic efficacy. Rechallenge therapy involves readministration of [[177]Lu]Lu-PSMA cycles after a break, whereas extended therapy continues treatment beyond the standard 6 cycles without interruption. Both approaches aim to improve disease control and prolong survival in patients with metastatic castration-resistant prostate cancer. However, practices vary: some clinicians continue treatment in patients with early favorable responses, whereas others recommend pausing therapy after significant prostate-specific antigen declines, even after a few cycles. In this narrative review, we show that safety profiles for continued [[177]Lu]Lu-PSMA radiopharmaceutical therapy are generally favorable, and most adverse events are mild to moderate in severity. Hematotoxicity, particularly anemia and thrombocytopenia, is the most significant concern, with few patients experiencing high-grade adverse events. In addition, cumulative irradiation, particularly during extended therapy, necessitates careful monitoring of hematologic and renal function. Biochemical responses to rechallenge and extended [[177]Lu]Lu-PSMA therapy are promising, with at least 50% reductions in prostate-specific antigen levels observed in a significant proportion of highly selected patients. Moreover, survival outcomes are encouraging, showing the extension of overall and progression-free survival beyond the known data for standard therapy. Despite these advances, challenges remain in optimizing patient selection, managing cumulative toxicities, and harmonizing treatment protocols. In addition, variability in trial designs, influenced by international regulatory differences, limits the current evidence and necessitates consideration of each treatment approach within its regulatory context. Prospective studies are needed to refine therapeutic strategies, implement consistent clinical and imaging response criteria, and identify predictive biomarkers to improve both efficacy and safety.},
}

Humans
Male
*Lutetium/therapeutic use
Neoplasm Metastasis
Radioisotopes/therapeutic use
*Prostatic Neoplasms/pathology/radiotherapy
Radiopharmaceuticals/therapeutic use
Prostatic Neoplasms, Castration-Resistant/radiotherapy/pathology
Prostate-Specific Antigen

@article {pmid41201189,
year = {2025},
author = {Meyer, J and Tran, A and Ma, TM and Chiang, BH and Egan, T and Chen, JJ and Tao, Y and Cao, N and Kim, KH and Liao, JJ and Koufigar, S and Vuong, W and Weg, ES},
title = {A hybrid IGRT workflow using SGRT and CBCT for prostate SBRT: Feasibility, efficiency, and safety.},
journal = {Journal of applied clinical medical physics},
volume = {26},
number = {11},
pages = {e70339},
pmid = {41201189},
issn = {1526-9914},
mesh = {Humans ; Male ; *Prostatic Neoplasms/surgery/diagnostic imaging/radiotherapy ; *Cone-Beam Computed Tomography/methods ; *Radiosurgery/methods ; *Radiotherapy Planning, Computer-Assisted/methods ; *Workflow ; Radiotherapy Dosage ; *Radiotherapy, Intensity-Modulated/methods ; Feasibility Studies ; Prospective Studies ; *Radiotherapy, Image-Guided/methods ; Organs at Risk/radiation effects ; Aged ; Image Processing, Computer-Assisted/methods ; },
abstract = {BACKGROUND AND PURPOSE: Safe delivery of prostate stereotactic body radiotherapy (SBRT) relies on precise target localization. Without access to real-time intrafraction motion management, careful optimization of IGRT protocols is necessary to safeguard treatment accuracy and patient outcomes.

METHODS: An IGRT workflow is proposed that incorporates surface-monitoring (SGRT) to complement cone-beam CT (CBCT) imaging. The study evaluates 23 consecutive SBRT prostate patients who were treated on a prospective registry study. Each patient received pre- and mid-treatment and a subset received post-treatment CBCTs. The frequency and magnitude of SGRT triggered beam interruptions as well as treatment times were recorded.

RESULTS: The median number of CBCTs acquired per fraction was four and the median treatment time was 23 min (IQR 19-27). SGRT detected intra-fraction surface-based motion beyond a combined 4 mm vector isocenter tolerance in 62% of all fractions treated, with a maximum motion of 15 mm. On average < 2 beam interruptions were triggered by SGRT per treatment fraction. There was no statistically significant correlation between overall treatment time and SGRT-triggered beam interruptions (r = 0.048, p = 0.645). There was a weak but statistically relevant correlation of overall treatment time with the maximum detected motion (r = 0.23, p = 0.026). SGRT detected five fractions where the patients had persistently moved outside the SGRT tolerance, and for three of these (60%), a CBCT verified that the target was out of tolerance.

CONCLUSION: SGRT is a valuable tool that complements CBCT-based IGRT. An SGRT motion vector tolerance of 4 mm provides a pragmatic compromise between detecting patient motion and treatment efficiency. Overall, persistent patient motion during treatment was infrequent in this cohort, however, SGRT was able to detect several cases where the internal target was outside of the tolerance highlighting that patient monitoring with SGRT can contribute to improved quality and safety for prostate SBRT.},
}

Humans
Male
*Prostatic Neoplasms/surgery/diagnostic imaging/radiotherapy
*Cone-Beam Computed Tomography/methods
*Radiosurgery/methods
*Radiotherapy Planning, Computer-Assisted/methods
*Workflow
Radiotherapy Dosage
*Radiotherapy, Intensity-Modulated/methods
Feasibility Studies
Prospective Studies
*Radiotherapy, Image-Guided/methods
Organs at Risk/radiation effects
Aged
Image Processing, Computer-Assisted/methods

@article {pmid41201469,
year = {2026},
author = {Damle, SR and Carter, JA and Goodsell, KE and Pineda, JMB and Dickerson, LK and Jiang, X and Mudd, JL and Walsh, T and Kenerson, HL and Cernak, J and Chauhan, SSB and Beirne, E and Jana, S and Koehne, AL and Vij, KR and Ruzinova, MB and Yeung, R and Akilesh, S and Collisson, EA and Fields, RC and Crispe, IN and Pillarisetty, VG},
title = {Intratumoral Three-Cell-Type Clusters Are a Conserved Feature of Endogenous Antitumor Immunity.},
journal = {Cancer immunology research},
volume = {14},
number = {2},
pages = {205-218},
pmid = {41201469},
issn = {2326-6074},
support = {U24 CA258407/CA/NCI NIH HHS/United States ; //Fibrolamellar Cancer Foundation (FCF)/ ; U24CA258407//National Cancer Institute (NCI)/ ; CA230890//U.S. Army Medical Research Acquisition Activity (USAMRAA)/ ; P30 CA015704/CA/NCI NIH HHS/United States ; CA180067//U.S. Army Medical Research Acquisition Activity (USAMRAA)/ ; R38 AI181011/AI/NIAID NIH HHS/United States ; R01 CA181445/CA/NCI NIH HHS/United States ; //Swim Across America (SAA)/ ; CRI Award 4093//Cancer Research Institute (CRI)/ ; R33 CA263703/CA/NCI NIH HHS/United States ; R33CA263703//National Cancer Institute (NCI)/ ; R01CA256969//National Cancer Institute (NCI)/ ; R01 CA256969/CA/NCI NIH HHS/United States ; R01CA181445//National Cancer Institute (NCI)/ ; SR-202221337//M.J. Murdock Charitable Trust (MJMCT)/ ; },
mesh = {Humans ; *Dendritic Cells/immunology ; Tumor Microenvironment/immunology ; *Pancreatic Neoplasms/immunology/pathology ; *T-Lymphocytes, Cytotoxic/immunology ; *Carcinoma, Pancreatic Ductal/immunology/pathology ; *Lymphocytes, Tumor-Infiltrating/immunology ; *T-Lymphocytes, Helper-Inducer/immunology ; },
abstract = {Effective antitumor immunity ultimately depends on the priming and activation of tumor-specific cytotoxic CD8+ T cells; however, the role of intratumoral cell-cell immune interactions remains incompletely understood. Recent work has revealed that the temporospatial co-localization of dendritic cells (DC), T helper (Th) cells, and cytotoxic T lymphocytes (CTL) within the tumor immune microenvironment following immune checkpoint blockade correlates with clinical response. In this study, we report the integration of more than 1 million spatially resolved single-cell profiles across six spatial proteomic and transcriptomic assays, which demonstrated that DC:Th:CTL three-cell-type clusters were common even in immunotherapy-naïve and highly desmoplastic tumors, such as fibrolamellar carcinoma and pancreatic ductal adenocarcinoma. We found that these immune triads were enriched for functionally important type 1 conventional DC, mature DCs enriched in immunoregulatory molecules, CXCL13+ Th, and GZMK+ effector CTL phenotypes. Subsequent multiplex immunofluorescence imaging of more than 450 primary pancreatic ductal adenocarcinoma tumors showed that the density of antigen-presenting cell:Th:CTL three-cell-type clusters was correlated with intratumoral T-cell clonal expansion and improved overall survival. These findings suggest that DC:Th:CTL triads are conserved across solid tumors and highlight the importance of intratumoral spatial niches in mediating endogenous antitumor immunity.},
}

Humans
*Dendritic Cells/immunology
Tumor Microenvironment/immunology
*Pancreatic Neoplasms/immunology/pathology
*T-Lymphocytes, Cytotoxic/immunology
*Carcinoma, Pancreatic Ductal/immunology/pathology
*Lymphocytes, Tumor-Infiltrating/immunology
*T-Lymphocytes, Helper-Inducer/immunology

@article {pmid41202812,
year = {2026},
author = {Hoi, XP and Stangis, MM and Glass, SE and Kim, JH and Kang, SW and Brennen, WN and Li, Z and Grady, WM and Yegnasubramanian, S and Kuhn, P and Lyssiotis, CA and Sagara, A and Shrubsole, MJ and Kadara, H and Yuan, Y and Coffey, RJ and Lau, KS and De Marzo, AM and Maitra, A and Min, J and Yu, M and Chan, KS and , },
title = {Cellular senescence in precancer lesions and early-stage cancers.},
journal = {Cancer cell},
volume = {44},
number = {1},
pages = {6-11},
doi = {10.1016/j.ccell.2025.10.006},
pmid = {41202812},
issn = {1878-3686},
support = {R50 CA233042/CA/NCI NIH HHS/United States ; U54 CA274374/CA/NCI NIH HHS/United States ; },
mesh = {Humans ; *Precancerous Conditions/pathology/metabolism ; *Cellular Senescence/physiology ; Tumor Microenvironment ; *Neoplasms/pathology/metabolism ; Senescence-Associated Secretory Phenotype ; Animals ; },
abstract = {Cellular senescence plays dual roles in precancer lesions: initially serving as a tumor-suppressive barrier within the epithelial compartment and later contributing to a pro-tumoral precancer tissue microenvironment (PreTME) via a sustained, paracrine secretome known as senescent-associated secretory phenotype (SASP). This commentary highlights the role of senescence across various PreTME cell types, explores emerging pharmacologic and lifestyle interception strategies, and outlines current challenges for advancing biomarkers and clinical translation.},
}

Humans
*Precancerous Conditions/pathology/metabolism
*Cellular Senescence/physiology
Tumor Microenvironment
*Neoplasms/pathology/metabolism
Senescence-Associated Secretory Phenotype
Animals

@article {pmid41202991,
year = {2026},
author = {Gillespie, EF and Silverwood, S and Lapen, K and Verdini, NP and Bryl, K and Baser, RE and Khan, AJ and Mao, JJ},
title = {A Virtual Mind-Body Exercise Program During Breast Radiation: Results From a Randomized Controlled Basket Trial.},
journal = {International journal of radiation oncology, biology, physics},
volume = {124},
number = {4},
pages = {961-970},
pmid = {41202991},
issn = {1879-355X},
support = {K08 CA252640/CA/NCI NIH HHS/United States ; P30 CA008748/CA/NCI NIH HHS/United States ; },
abstract = {PURPOSE: National guidelines recommend fitness and mind-body exercise to reduce cancer-related fatigue, but substantial barriers to implementation exist. Virtual programs offer a scalable approach to address this gap. This study aims to evaluate the efficacy of a virtual fitness and mind-body exercise program (Integrative Medicine at Home [IM@Home]) in reducing fatigue in patients undergoing radiation therapy (RT) for breast cancer.

METHODS AND MATERIALS: A prospective randomized controlled patient-reported outcome basket clinical trial was conducted. Patients undergoing breast RT who reported moderate or greater fatigue were randomly assigned 1:1 ratio to either IM@Home, which provided live virtual fitness and mind-body exercise classes, or enhanced usual care (EUC). The primary outcome, fatigue, was measured using the total Brief Fatigue Inventory, a composite score including severity and impact on daily functioning, weekly over 12 weeks. Secondary outcomes included the Insomnia Severity Index, Edmonton Symptom Assessment Scale, and Hospital Anxiety and Depression Scale collected every 4 weeks. Statistical analysis included linear mixed models to compare group differences over time using a statistical significance threshold of P < .05.

RESULTS: Among 73 enrolled patients, 35 were randomly assigned to IM@Home and 38 to EUC. At week 12, patients in the IM@Home group had significantly less fatigue compared to those in the EUC group (2.06 vs 2.79, P = .009). Compared to EUC, patients in the IM@Home group showed greater reductions in insomnia (P = .005), symptom distress (P = .013), and depression (P = .04), but not anxiety (P = .14).

CONCLUSIONS: The IM@Home program significantly reduced fatigue and comorbid symptoms among women with breast cancer undergoing RT. Future research is needed to confirm these findings, explore mechanisms of the observed benefit, and evaluate scalability as well as barriers and facilitators to implementation.},
}

@article {pmid41203676,
year = {2025},
author = {Duggan, C and de Dieu Tapsoba, J and Warner, J and Dash, A and Wang, CY and McTiernan, A},
title = {Effects of acute exercise on inflammatory and metabolic biomarkers in women: a randomized controlled trial.},
journal = {NPJ breast cancer},
volume = {11},
number = {1},
pages = {122},
pmid = {41203676},
issn = {2374-4677},
support = {P30 CA015704/CA/NCI NIH HHS/United States ; BRCF-18-107; BCRF-19-107; BCRF-20-107; BRCF-21-107; BRCF-22;107//Breast Cancer Research Foundation,United States/ ; },
abstract = {Mechanisms linking exercise to reduced breast cancer risk are poorly understood. 103 healthy women, 18-75, were randomized to 45-minutes of acute exercise at 60% VO2max (N = 54, intervention), or 45-minutes of rest (N = 49, control). Blood samples were collected at baseline, 45- and 105-minutes, analytes measured by immunoassay, and mean changes from baseline to 45- and 105-minutes modelled using generalized estimating equations, adjusted for confounders. Mean percent changes levels (Δ%) increased in exercisers vs. controls for monocyte chemoattractant protein (MCP)-1 Δ[45 min] + 17.1% (P < 0.0001), Δ[105 min] + 12.0% (P = 0.005); interleukin(IL)-6, Δ[45 min] + 103.5%, Δ[105 min] + 92.3%; and at 45-minutes for glucose Δ[45 min] + 8.8%; insulin Δ[45 min] + 82.4% (all P < 0.0001). Differences between arms for vascular endothelial growth factor (VEGF) Δ[45 min] + 9.8%; c-reactive protein Δ[45 min]-6.6%; irisin Δ[45 min]-5.1%; or plasminogen activator inhibitor (PAI)-1, Δ[45 min]-3.6% were non-statistically significant, with similar results at 105-minutes. Results suggest that acute exercise has specific effects on circulating metabolic and inflammatory biomarkers, implicated in breast cancer etiology, which differ from weight-loss-induced changes. Trial registration: Clincialtrials.gov identifier NCT03779867.},
}

@article {pmid41205698,
year = {2025},
author = {Dunk, MM and Delac, L and Rapp, SR and Driscoll, I and Latorre-Leal, M and Farland, LV and Haring, B and Harris, HR and Jung, SY and Manson, JE and Ochs-Balcom, HM and Shadyab, AH and Weitlauf, JC and Xu, H and Westman, E and Maioli, S},
title = {Exploring biomarkers of neurodegenerative risk: associations of oxysterols, sex hormones, and reproductive characteristics in older women.},
journal = {Journal of lipid research},
volume = {66},
number = {12},
pages = {100938},
pmid = {41205698},
issn = {1539-7262},
mesh = {Humans ; Female ; Biomarkers/blood ; Aged ; *Oxysterols/blood ; *Gonadal Steroid Hormones/blood ; Middle Aged ; Hydroxycholesterols/blood ; *Neurodegenerative Diseases/blood ; Risk Factors ; *Reproduction ; Apolipoprotein E4/genetics ; Alzheimer Disease/blood ; },
abstract = {Women face a higher lifetime risk of developing neurodegenerative diseases such as Alzheimer's disease and related dementias. The menopausal transition, characterized by a decline in estrogen levels, may affect cholesterol metabolism and neurodegenerative processes. Oxysterols, oxidized cholesterol derivatives, play a role in these pathways, with 24(S)-hydroxycholesterol (24HC) reflecting brain cholesterol turnover and 27-hydroxycholesterol (27HC) linked to systemic cholesterol metabolism. We investigated associations of plasma oxysterols with circulating sex hormones and characteristics of reproductive history in 1,974 postmenopausal women with no history of dementia from the Women's Health Initiative, taking into account APOE4 status and cholesterol-lowering medication. We found that higher levels of bioavailable estradiol were associated with higher 24HC and 27HC levels, and higher estrone was associated with higher 24HC (all P values <0.05). Associations of estradiol with 24HC and 27HC were stronger among APOE4 carriers and those not using cholesterol-lowering medication, with a significant interaction between bioavailable estradiol and APOE4 in relation to 27HC (p for interaction = 0.04). Having an older age at menopause was associated with lower 24HC among those taking cholesterol medication (p for interaction = 0.03). Our findings suggest that 24HC and 27HC may be proxy biomarkers of neuronal health and estrogen status in postmenopausal women. The stronger associations between estradiol and oxysterols among APOE4 carriers and those not using cholesterol medication suggest the need to account for hormonal, genetic, and pharmacological factors when evaluating neurodegenerative risk. Longitudinal studies are warranted to further investigate oxysterols as potential early biomarkers of risk for Alzheimer's disease and related dementias.},
}

Humans
Female
Biomarkers/blood
Aged
*Oxysterols/blood
*Gonadal Steroid Hormones/blood
Middle Aged
Hydroxycholesterols/blood
*Neurodegenerative Diseases/blood
Risk Factors
*Reproduction
Apolipoprotein E4/genetics
Alzheimer Disease/blood

@article {pmid41205872,
year = {2026},
author = {Vaquera-Alfaro, HA and Jeon, Y and Wu, QV and Liang, EC and Portuguese, A and Gómez-De León, A and Valdespino-Valdes, J and Gauthier, J},
title = {A Practical Guide to Competing Risk Analysis for Transplant and Cell Therapy Research.},
journal = {Transplantation and cellular therapy},
volume = {32},
number = {4},
pages = {489-500},
pmid = {41205872},
issn = {2666-6367},
support = {T32 HL007093/HL/NHLBI NIH HHS/United States ; },
mesh = {Humans ; *Hematopoietic Stem Cell Transplantation/methods/adverse effects ; *Cell- and Tissue-Based Therapy/methods ; Risk Assessment/methods ; },
abstract = {Competing risks are common in hematopoietic cell transplantation (HCT) and immune effector cell (IEC) therapy research. Competing risks refer to events that cannot co-occur and complicate time-to-event analyses. The typical example of competing risk in the context of HCT and IEC research is treatment-related mortality, which competes with disease relapse. In this primer, we first aim to introduce - in a clinician-friendly fashion - the core concepts underlying the statistical modelling of competing risks. Next, we propose a practical, step-by-step guide to analyze time-to-event outcomes in the context of competing risks using the open access R environment. Relevant R packages are introduced, enabling the generation of publication-ready tables and figures. We hope our manuscript will encourage more robust analyses in the fields of HCT and IEC therapy when competing risks are at play.},
}

Humans
*Hematopoietic Stem Cell Transplantation/methods/adverse effects
*Cell- and Tissue-Based Therapy/methods
Risk Assessment/methods

@article {pmid41206027,
year = {2026},
author = {Hanscom, B and Marzinke, MA and Li, X and Donnell, D and Bies, R and Hendrix, CW and Wang, Z and Acuipil, C and Rinehart, A and Collins, JW and Rooney, JF and Soto Torres, L and Richardson, P and Chariyalerstsak, S and Valdez Ramalho Madruga, J and Hurt, CB and Magnus, M and Frank, I and McCauley, M and Grinsztejn, B and Landovitz, RJ},
title = {Estimation of Prevention-Effective CAB-LA Concentrations Among Men Who Have Sex With Men (MSM) and Transgender Women (TGW) in HPTN 083.},
journal = {The Journal of infectious diseases},
volume = {233},
number = {2},
pages = {e454-e461},
pmid = {41206027},
issn = {1537-6613},
support = {//National Institute of Allergy and Infectious Diseases/ ; /CD/ODCDC CDC HHS/United States ; /NH/NIH HHS/United States ; /MH/NIMH NIH HHS/United States ; UM1AI068619/DA/NIDA NIH HHS/United States ; UM1AI068617//HIV Prevention Trials Network [HPTN] Leadership and Operations Center/ ; UM1AI068613//HPTN Statistical and Data Management Center/ ; //HPTN Laboratory Center/ ; //ViiV Healthcare/ ; //Gilead Sciences/ ; },
mesh = {Humans ; Male ; *HIV Infections/prevention & control ; *Transgender Persons ; Adult ; *Pre-Exposure Prophylaxis/methods ; Case-Control Studies ; Female ; *Homosexuality, Male ; *Anti-HIV Agents/blood/administration & dosage/therapeutic use ; *Pyridones/blood/administration & dosage/therapeutic use/pharmacokinetics ; Young Adult ; Middle Aged ; Tenofovir/therapeutic use ; Diketopiperazines ; },
abstract = {BACKGROUND: The HIV Prevention Trials Network (HPTN) 083 Trial demonstrated the superiority of long-acting, injectable cabotegravir (CAB) over daily oral tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) for HIV pre-exposure prophylaxis among cisgender men (MSM) and transgender women (TGW) who have sex with men. Plasma CAB concentrations associated with HIV protection in humans are unknown.

METHODS: We conducted a nested case-control study to investigate the association between plasma CAB concentrations and HIV risk. Plasma CAB concentrations were estimated for participants with confirmed HIV and for HIV-negative controls, who were matched on region, gender, and race. The window of HIV acquisition for cases was defined as the time between the last HIV-negative visit and the first HIV-positive visit; this window was used to evaluate CAB exposure for cases and their matched controls. Participants were categorized by the minimum estimated CAB concentration (CABmin) during this window relative to the protein-adjusted 90% CAB inhibitory concentration (1× PA-IC90) and 4× PA-IC90. HIV risk was modeled using conditional logistic regression.

RESULTS: Plasma CABmin was ≥4× PA-IC90 in 26% of HIV-positive cases, compared with 76% of matched controls. Plasma CABmin ≥4× PA-IC90 was associated with a 93% reduction in risk of HIV acquisition compared with CABmin <1× PA-IC90 (95% CI: 76%, 98%, P < .001). CABmin between 1× and 4× PA-IC90 had an estimated risk reduction of 79% compared with CABmin <1× PA-IC90 (95% CI: -19%, 96%, P = .07).

CONCLUSIONS: Consistent plasma CAB concentrations ≥4× PA-IC90 were estimated to provide 93% protection against HIV in MSM and TGW.},
}

Humans
Male
*HIV Infections/prevention & control
*Transgender Persons
Adult
*Pre-Exposure Prophylaxis/methods
Case-Control Studies
Female
*Homosexuality, Male
*Anti-HIV Agents/blood/administration & dosage/therapeutic use
*Pyridones/blood/administration & dosage/therapeutic use/pharmacokinetics
Young Adult
Middle Aged
Tenofovir/therapeutic use
Diketopiperazines

@article {pmid41206886,
year = {2025},
author = {Seth, L and Bhave, A and Kollapaneni, S and Shah, V and Nahle, T and Blaes, A and Dent, S and Hurvitz, SA and Guha, A},
title = {Cardiotoxic Effects of Antibody Drug Conjugates vs Standard Chemotherapy in ERBB2-Positive Advanced Breast Cancer: A Systematic Review and Meta-Analysis.},
journal = {JAMA network open},
volume = {8},
number = {11},
pages = {e2540336},
pmid = {41206886},
issn = {2574-3805},
mesh = {Humans ; *Breast Neoplasms/drug therapy ; Female ; Erb-b2 Receptor Tyrosine Kinases ; *Cardiotoxicity/etiology ; Trastuzumab/adverse effects/therapeutic use ; Ado-Trastuzumab Emtansine/adverse effects/therapeutic use ; *Immunoconjugates/adverse effects/therapeutic use ; *Antineoplastic Agents, Immunological/adverse effects ; Camptothecin/analogs & derivatives ; },
abstract = {IMPORTANCE: Antibody-drug conjugates (ADCs), such as trastuzumab emtansine and trastuzumab deruxtecan, are effective in treating erb-b2 receptor tyrosine kinase 2 (ERBB2)-positive breast cancer (BC) that has progressed on prior ERBB2-targeted therapy, warranting evaluation of their cardiotoxic profiles.

OBJECTIVE: To compare the incidence of cardiotoxic effects of ADCs vs standard-of-care chemotherapy regimens for ERBB2-positive locally advanced or metastatic BC.

DATA SOURCES: PubMed, ScienceDirect, Cochrane Library, and ClinicalTrials.gov databases were searched in December 2024 for studies published between 2000 and 2024.

STUDY SELECTION: The included studies were (1) phase 3 clinical trials that investigated locally advanced or metastatic ERBB2-positive BC; (2) clearly defined left ventricular ejection fraction (LVEF) decrease or heart failure definitions; (3) clearly defined LVEF monitoring frequency by echocardiography or multigated acquisition scan; (4) included studies consisted solely of either trastuzumab emtansine, trastuzumab deruxtecan, or one of the first-line to fourth-line chemotherapy regimens for unresectable stage IV ERBB2-positive breast cancer per the 2025 National Comprehensive Cancer Network guidelines; and (5) clearly defined cardiovascular eligibility criteria.

DATA EXTRACTION AND SYNTHESIS: Data from eligible studies were extracted by 3 reviewers. A random-effects model was used for the pooled analysis. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline was followed.

MAIN OUTCOMES AND MEASURES: The primary outcome was cardiotoxic effects, which were defined as the incidence of LVEF decrease. The pooled analysis was performed using logit-transformed proportions with the inverse variance method and a DerSimonian-Laird random-effects model for between-study variance, with Wilson score 95% CIs.

RESULTS: In this meta-analysis of 9538 patients, a pooled analysis demonstrated a 0.94% (95% CI, 0.56%-1.57%) incidence of LVEF decrease with trastuzumab emtansine, a 4.20% (95% CI, 2.91%-6.01%) incidence with trastuzumab deruxtecan, a 4.85% (95% CI, 3.73%-6.28%) incidence with trastuzumab plus chemotherapy, and a 5.52% (95% CI, 3.41%-8.83%) incidence with trastuzumab plus pertuzumab plus chemotherapy. A trim-and-fill analysis was used if evidence of publication bias was found.

CONCLUSIONS AND RELEVANCE: This meta-analysis found that trastuzumab emtansine was associated with the lowest incidence of LVEF decrease, and trastuzumab deruxtecan, trastuzumab plus chemotherapy, and trastuzumab plus pertuzumab plus chemotherapy had similar incidences. More research is needed into the cardiotoxic effects of these therapies.},
}

Humans
*Breast Neoplasms/drug therapy
Female
Erb-b2 Receptor Tyrosine Kinases
*Cardiotoxicity/etiology
Trastuzumab/adverse effects/therapeutic use
Ado-Trastuzumab Emtansine/adverse effects/therapeutic use
*Immunoconjugates/adverse effects/therapeutic use
*Antineoplastic Agents, Immunological/adverse effects
Camptothecin/analogs & derivatives

@article {pmid41206919,
year = {2026},
author = {El Kassar, N and DeZern, AE and Abkowitz, J and Artz, A and Beerman, I and Bolton, K and Brooks, MM and Borate, U and Ershler, WB and Ganz, T and Kalfa, TA and Kuaban, A and Leng, S and Nakada, D and Nazha, A and Grossmann, C and Pfeilstöcker, M and Qiu, C and Sauver, JS and Sekeres, MA and Simonsick, EM and White, KE and Zhang, D and Ferrucci, L and Kuchel, GA},
title = {A proposed path to explaining the unexplained anemia of aging.},
journal = {The journals of gerontology. Series A, Biological sciences and medical sciences},
volume = {81},
number = {1},
pages = {},
pmid = {41206919},
issn = {1758-535X},
support = {R33 AG058738/AG/NIA NIH HHS/United States ; /NH/NIH HHS/United States ; //US Department of Health and Human Services/ ; },
mesh = {Aged ; Humans ; *Aging/physiology ; *Anemia/epidemiology/etiology/diagnosis ; Erythropoiesis ; United States/epidemiology ; },
abstract = {Approximately 17% of people aged 65 years and older are anemic, and 10% of death certificates report anemia as a secondary cause of death in the United States. Nonetheless, anemia remains unexplained in 30%-50% of older adults. This unexplained anemia of aging (UAA) is a diagnosis of exclusion. The mechanism, impact, and progression of UAA remain unknown. At older ages, anemia adds to pre-existing co-morbidities with significant adverse health consequences, representing a compelling unmet clinical concern. The National Institute on Aging held a workshop in 2024 to discuss current knowledge and research opportunities. Topics included the epidemiology of anemia at older age and its clinical implications; probable mechanism(s) underlying UAA, that is, low-grade inflammation's effects on erythropoiesis; the role of microbiota in iron regulation in bone marrow; the importance of ruling out a diagnosis of leukemic clonal hematopoiesis (CH), which is more prevalent in older age; the role of senescence and aging governing hematopoiesis; and the effects of sex hormones on hematopoietic stem cell aging. Understanding the roles of these factors could reduce the proportion of the older anemic population whose anemia remains unexplained and offer insights into new potential diagnostic and intervention strategies. Speakers reviewed previous clinical trials in patients with UAA and CH. They discussed lessons learned and future research priorities, including efforts to develop new diagnostic algorithms and potential uses of machine learning.},
}

Aged
Humans
*Aging/physiology
*Anemia/epidemiology/etiology/diagnosis
Erythropoiesis
United States/epidemiology

@article {pmid41206949,
year = {2026},
author = {Zhang, T and Hua, X and Mohindroo, C and Wang, X and Dutta, D and Liu, J and Katta, S and Li, SA and Wang, J and Antwi, SO and Arslan, AA and Beane Freeman, LE and Bracci, PM and Canzian, F and Du, M and Gallinger, S and Goodman, PJ and Katzke, V and Kooperberg, C and Le Marchand, L and Neale, RE and Patel, AV and Perdomo, S and Shu, XO and Visvanathan, K and Van Den Eeden, SK and White, E and Zheng, W and Albanes, D and Andreotti, G and Bamlet, WR and Brennan, P and Buring, JE and Chanock, SJ and Chen, Y and Darst, B and Ferrari, P and Giovannucci, EL and Goggins, M and Haiman, C and Hassan, M and Holly, EA and Hung, RJ and Jones, MR and Kraft, P and Kurtz, RC and Malats, N and Moore, SC and Ng, K and Oberg, AL and Orlow, I and Peters, U and Porta, M and Rabe, KG and Rothman, N and Sánchez, MJ and Sesso, HD and Silverman, DT and Southey, MC and Um, CY and Yarmolinsky, J and Yu, H and Yuan, C and Zhong, J and Wolpin, BM and Risch, HA and Amundadottir, LT and Klein, AP and Yu, K and Zhang, H and Stolzenberg-Solomon, RZ},
title = {Different diabetes types and pancreatic ductal adenocarcinoma: a Mendelian randomization and pathway/gene-set analysis.},
journal = {Journal of the National Cancer Institute},
volume = {118},
number = {3},
pages = {437-447},
pmid = {41206949},
issn = {1460-2105},
support = {P30 CA008748/CA/NCI NIH HHS/United States ; Z01 CP010193/ImNIH/Intramural NIH HHS/United States ; Z99 CA999999/ImNIH/Intramural NIH HHS/United States ; 001/WHO_/World Health Organization/International ; 75N910D00024/NH/NIH HHS/United States ; P50 CA257911/CA/NCI NIH HHS/United States ; /NH/NIH HHS/United States ; /HH/HHS/United States ; ZIA CP010193/ImNIH/Intramural NIH HHS/United States ; },
mesh = {Humans ; Mendelian Randomization Analysis ; *Carcinoma, Pancreatic Ductal/genetics/epidemiology/etiology ; *Pancreatic Neoplasms/genetics/epidemiology/etiology ; Genome-Wide Association Study ; *Diabetes Mellitus, Type 2/genetics/complications ; Genetic Predisposition to Disease ; *Diabetes Mellitus, Type 1/genetics ; Polymorphism, Single Nucleotide ; Risk Factors ; Case-Control Studies ; },
abstract = {BACKGROUND: The associations between different types of diabetes, characterized by distinct pathophysiology and genetic architecture, and pancreatic ductal adenocarcinoma (PDAC) risk are not understood.

METHODS: We investigated associations of genetic susceptibility to type 2 diabetes (T2D), 8 T2D mechanistic clusters, type 1 diabetes (T1D), and maturity-onset diabetes of the young (MODY) with PDAC risk. We used genome-wide association study (GWAS) summary-level statistics for T2D (242 283 cases, 1 569 734 controls), T1D (18 942 cases, 501 638 controls), and PDAC (10 244 cases and 360 535 controls) in individuals of European ancestry.

RESULTS: Two-sample Mendelian randomization (MR) using the Robust Adjusted Profile Score (MR-RAPS) method indicated that genetically predicted T2D was associated with PDAC risk (OR = 1.10; 95% CI = 1.05 to 1.15), particularly the T2D obesity (OR = 1.28; 95% CI = 1.15 to 1.42) and lipodystrophy (OR = 1.25; 95% CI = 1.03 to 1.51) clusters. No association was observed for T1D with PDAC risk (OR = 1.01; 95% CI = 0.99 to 1.02). Pathway/gene-set analysis using the summary-based Adaptive Rank Truncated Product (sARTP) method revealed a significant association between the MODY gene-sets and PDAC risk (P = 1.5 × 10-8), which remained after excluding 20 known PDAC GWAS loci (P = 7.6 × 10-4). HNF1A, FOXA3, and HNF4A were the top contributing genes after excluding the previously identified GWAS loci regions.

CONCLUSIONS: Our results from this genetic association study support that T2D, particularly the obesity and lipodystrophy mechanistic clusters, and MODY genomic susceptibility regions play a role in the etiology of PDAC.},
}

Humans
Mendelian Randomization Analysis
*Carcinoma, Pancreatic Ductal/genetics/epidemiology/etiology
*Pancreatic Neoplasms/genetics/epidemiology/etiology
Genome-Wide Association Study
*Diabetes Mellitus, Type 2/genetics/complications
Genetic Predisposition to Disease
*Diabetes Mellitus, Type 1/genetics
Polymorphism, Single Nucleotide
Risk Factors
Case-Control Studies

@article {pmid41207381,
year = {2026},
author = {Wolff, D and Cutler, C and Mercep, I and Jaki, T and Robertson, DS and Schultz, KR and Lee, SJ and Martin, PJ and Pavletic, SZ},
title = {Toward Better and More Effective Clinical Trials for Chronic Graft-Versus-Host Disease.},
journal = {Transplantation and cellular therapy},
volume = {32},
number = {4},
pages = {388-397},
doi = {10.1016/j.jtct.2025.11.008},
pmid = {41207381},
issn = {2666-6367},
mesh = {*Graft vs Host Disease/therapy/drug therapy ; Humans ; Chronic Disease ; *Clinical Trials as Topic ; },
abstract = {While the incidence of chronic Graft-versus-Host Disease (chronic GVHD) is declining due to advances in prophylaxis and survival is improving due to better supportive care, first-line treatment of chronic GVHD continues to be based on corticosteroids. Numerous attempts to establish more effective or less toxic treatment alternatives have largely failed, likely due to the biological heterogeneity of chronic GVHD and uncontrolled use of systemic corticosteroids, indicating the need for new approaches. The 2020 NIH consensus conference proposed the systematic evaluation of steroid-free initial treatment combining clinical and biological assessment to establish personalized approaches. While the first generation of trials evaluating steroid-free single agent first-line therapy approaches are recruiting, they are still not able to consider the biological heterogeneity of chronic GVHD in deciding therapeutic approaches. To advance the field, we propose a two-stage adaptive trial design starting with an intervention under consideration followed by a replication phase after the first phase has identified candidate clinical features and or biomarker predicting success. For second and subsequent lines of treatment, current treatment decisions regarding the use of the four FDA approved agents are based on the product label or a trial-and-error approach, sometimes in combination regimens despite the lack of prospective data. Future trials and prospective observational studies should focus on the development of predictive markers to provide a biological rationale for sequencing treatment options and to identify synergistic combination treatments. The recently released FDA draft guidance document for developing drugs and treatments in GVHD serves as the starting point for clinical trials planning that should yield results during the next several years.},
}

*Graft vs Host Disease/therapy/drug therapy
Humans
Chronic Disease
*Clinical Trials as Topic

@article {pmid41207382,
year = {2025},
author = {Locke, FL and Nikiforow, S and Frigault, MJ and Maloney, DG and Davila, M and Miklos, DB and Lin, Y and Vong, J and Shah, NN and Neelapu, SS and Welch, J and Ng, E and Jacobson, C and Maus, MV},
title = {Recommendations for Defining Chimeric Antigen Receptor T-Cell (CAR T) Dose-Limiting Toxicities (DLTs) for Future Early-Phase CAR T Therapy Studies.},
journal = {Transplantation and cellular therapy},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jtct.2025.11.004},
pmid = {41207382},
issn = {2666-6367},
abstract = {Chimeric antigen receptor T-cell (CAR T) therapies have demonstrated potential to provide long-term remission in incurable hematologic malignancies, and novel approaches for CAR T therapy continue to be developed for treating cancer and other indications. Acute class-effect toxicities, such as cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome, and immune effector cell-associated hemophagocytic lymphohistiocytosis-like syndrome, remain significant concerns despite their potential reversibility. Given the complexities of balancing safety and efficacy of CAR T therapies, the US Food and Drug Administration (FDA) recently published Guidance for Industry, which included suggested definitions for dose-limiting toxicities (DLTs) for clinical trials of emerging CAR T therapies. However, the DLT definitions in the guidance do not reflect what was used in the phase 1 and/or registrational studies for the approved CAR Ts; for example, these studies defined DLTs as treatment-related, included exceptions, and/or allowed for time to resolve the adverse event. Using DLT definitions from the guidance could have prematurely stopped the early-phase studies of the now approved CAR Ts. In 2023, while designing a first-in-human, phase 1 study of a logic-gated cell therapy, an expert panel of academic cell therapists collaborated with industry partners at A2 Biotherapeutics to assess the practical implications of the FDA guidance. This led the panel to draft the revised recommendations contained herein, which integrate the permissibility of reversible events during dose-escalation for trial sponsors, investigators, health authorities, and other parties who may be involved in future CAR T therapy trials. These expert recommendations balance the safety of patients in early-phase trials with the potential long-term therapeutic opportunities for patients with terminal malignancies.},
}

@article {pmid41207385,
year = {2026},
author = {Richardson, AB and Ng, K and Gooley, TA and Cheng, GS and Salit, RB},
title = {Pulmonary Complications Following Hematopoietic Cell Transplantation in Patients with Myelofibrosis: A Single-Center Retrospective Cohort Analysis.},
journal = {Transplantation and cellular therapy},
volume = {32},
number = {3},
pages = {300.e1-300.e11},
doi = {10.1016/j.jtct.2025.10.027},
pmid = {41207385},
issn = {2666-6367},
mesh = {Humans ; *Hematopoietic Stem Cell Transplantation/adverse effects ; Retrospective Studies ; Male ; Female ; *Primary Myelofibrosis/therapy/complications ; Middle Aged ; Adult ; Aged ; Respiratory Function Tests ; *Lung Diseases/etiology ; Graft vs Host Disease/etiology ; },
abstract = {Myelofibrosis (MF) is a clonal hematopoietic stem cell disorder that frequently results in extramedullary hematopoiesis. Hematopoietic cell transplantation (HCT) is the only cure. While a 2-fold increase in pneumonia and respiratory-related mortality was recently reported in MF patients compared to the general population, the incidence and etiology of HCT-related pulmonary complications have not been well studied. We performed a retrospective chart review of consecutive MF patients who underwent HCT between 2002 and 2022. Patients with evidence of pulmonary impairment on pulmonary function tests, defined as a ≥10-point decline in forced expiratory volume in 1 second (FEV1) compared to pre-HCT and/or a decline in the FEV1/forced vital capacity (FVC) ratio to <0.7, received further chart review to determine the etiology of this decline. Of 228 patients evaluated, 126 (55%) met either the FEV1 or FEV1/FVC criteria for pulmonary impairment. After further chart review, 35 patients (15.4%) were diagnosed with broncholitis obliterans (BOS) by a pulmonologist or graft-versus-host disease specialist. Other common causes of impairment included respiratory infections (n =10), cryptogenic organizing pneumonia (n = 8), and deconditioning (n = 8). MF patients have a >50% likelihood of developing pulmonary impairment following HCT and a higher-than-expected incidence of BOS. This study supports increased pulmonary monitoring post-HCT in patients with MF.},
}

Humans
*Hematopoietic Stem Cell Transplantation/adverse effects
Retrospective Studies
Male
Female
*Primary Myelofibrosis/therapy/complications
Middle Aged
Adult
Aged
Respiratory Function Tests
*Lung Diseases/etiology
Graft vs Host Disease/etiology

@article {pmid41210691,
year = {2025},
author = {Meng, L and Psutka, SP and Gheeya, J and Li, M and Noonavath, M and Orcutt, D and Gross, E and Collier, KA and Mortazavi, A and Folefac, E and Monk, P and Yang, Y},
title = {Tyrosine Kinase Inhibitors Outperform Immune Checkpoint Inhibitors in Bone-Predominant Metastatic Renal Cell Carcinoma: A Multicenter Real-World Analysis.},
journal = {Journal of Cancer},
volume = {16},
number = {14},
pages = {4047-4054},
pmid = {41210691},
issn = {1837-9664},
abstract = {Background: Bone-predominant metastatic renal cell carcinoma (mRCC) presents significant clinical challenges due to its associated morbidities and poor prognosis. Optimal first-line treatment remains unclear, largely because these patients are often excluded from clinical trials due to difficulties in measuring bone lesions. Emerging evidence suggests that bone metastases exhibit high angiogenesis gene signatures, potentially predicting favorable responses to tyrosine kinase inhibitors (TKIs). Methods: We conducted a multicenter retrospective analysis of patients with bone-predominant mRCC treated at The Ohio State University Comprehensive Cancer Center and Fred Hutchinson Cancer Center from January 2008 to June 2021. Bone predominance was defined as having a greater number of osseous metastases compared to extra-osseous sites using computed tomography or bone scans. Patients receiving first-line TKIs or immune checkpoint inhibitors (ICIs) were included; those treated with combination TKI-ICI therapies were excluded due to limited numbers. Demographic, clinical, and treatment data were collected. Progression-free survival (PFS) and overall survival (OS) were analyzed using Kaplan-Meier methods and compared using the log-rank test. Univariate Cox regression analysis was conducted to identify factors associated with OS. Results: A total of 69 patients with bone-predominant mRCC were identified, with 40 receiving TKIs and 29 receiving ICIs as first-line therapy. Baseline characteristics were comparable between groups. The median OS was significantly longer for patients treated with TKIs compared to those receiving ICIs (41.3 months vs. 19.3 months; log-rank P = 0.036). A trend toward improved median PFS was observed in the TKI group (7.9 months vs. 4.9 months; P = 0.075). Univariate analysis showed that treatment with ICIs was associated with an increased risk of death compared to TKIs (hazard ratio = 1.96; P = 0.040). Objective response rates were higher in the TKI group (22.9% vs. 12.0%), although this difference was not statistically significant (P = 0.332). Conclusions: In this multicenter real-world analysis, first-line treatment with TKIs was associated with significantly improved OS compared to ICIs in patients with bone-predominant mRCC. These findings suggest that TKI-containing regimens may be the preferred front-line therapy for this patient subgroup. Prospective studies are warranted to validate these results and to optimize treatment strategies for bone-predominant mRCC.},
}

@article {pmid41210956,
year = {2025},
author = {Luedtke, A and Fong, Y and van der Laan, L and Heng, F and Huang, Y and Lu, Y and Yu, C and Carpp, LN and Roels, S and Le Gars, M and Van Roey, GA and Stieh, DJ and Van Dromme, I and Kenny, A and Carone, M and Hyrien, O and Ayala, V and Jayashankar, L and Castellino, F and Amoa-Awua, O and Basappa, M and Flach, B and Lin, BC and Moore, C and Naisan, M and Naqvi, M and Narpala, S and O'Connell, S and Mueller, A and Serebryannyy, L and Castro, M and Wang, J and Dziubla, G and Randhawa, AK and Andrasik, MP and Hendriks, J and Truyers, C and Struyf, F and Schuitemaker, H and Douoguih, M and Kublin, JG and Corey, L and Neuzil, KM and Bekker, LG and Garrett, N and Cardoso, SW and DelaFontaine, P and Magaret, CA and Vingerhoets, J and Casapia, M and Losso, MH and Little, SJ and Gaur, A and Swann, E and Petropoulos, CJ and McDermott, AB and Sadoff, J and Gray, GE and Grinsztejn, B and Goepfert, PA and Follmann, D and Roychoudhury, P and Greninger, AL and Koup, RA and Donis, RO and Gilbert, PB and , and , and , },
title = {Immune correlates analysis of antibody responses against SARS-CoV-2 variants in the ENSEMBLE vaccine efficacy trial.},
journal = {iScience},
volume = {28},
number = {11},
pages = {113660},
pmid = {41210956},
issn = {2589-0042},
support = {R37 AI054165/AI/NIAID NIH HHS/United States ; },
abstract = {In Latin American sites of the ENSEMBLE trial of the Ad26.COV2.S vaccine vs. placebo, binding antibodies and neutralizing antibodies measured 4 weeks post-vaccination (∼peak) against circulating lineages (Ancestral, Gamma, Lambda, Mu, Zeta) were assessed as a correlate of risk of, and correlate of protection against, lineage-specific COVID-19. Comparison of lineage-matched controlled vaccine efficacy (VE) curves showed similar relationships across lineages of lineage-specific antibody with VE against lineage-matched COVID-19, supporting a "variant-invariant correlate of protection model" that undergirds immunobridging inferences of efficacy against new variants based on variant-matched neutralizing antibody titers. Lambda departed from this model at undetectable/just-detectable titers: at ∼ peak Reference-specific titers of 2.7 arbitrary units (AU)/mL (just-detectable) and 30 AU/ml, VE against Ancestral COVID-19 was 53.0% (95% CI: 30.7%, 67.9%) and 84.5% (73.6%, 93.0%), respectively; at the same Lambda-specific titers, VE against Lambda COVID-19 was 12.3% (-54.1%, 50.3%) and 91.1% (68.9%, 98.0%). Additional research is needed for Omicron variants.},
}

@article {pmid41213032,
year = {2025},
author = {El-Khoueiry, AB and Kim, RD and Harris, WP and Sung, MW and Waldschmidt, D and Cabrera, R and Garosi, VL and Ploeger, BA and Zebger-Gong, H and Brennan, BJ and Wang, YA and Mueller, U and Weispfenning, A and Seidel, H and Coppieters, S and Ishida, TC and Galle, PR},
title = {A multicenter dose-defining/expansion phase 1b study of first-line regorafenib plus pembrolizumab in patients with advanced hepatocellular carcinoma.},
journal = {Hepatology (Baltimore, Md.)},
volume = {},
number = {},
pages = {},
doi = {10.1097/HEP.0000000000001585},
pmid = {41213032},
issn = {1527-3350},
abstract = {BACKGROUND AND AIMS: Combinations including an immune checkpoint inhibitor are preferred first-line treatments for advanced HCC. We investigated the safety of regorafenib plus pembrolizumab as first-line systemic therapy for advanced HCC.

APPROACH AND RESULTS: This was a dose-defining/expansion phase 1b study in adults with advanced HCC without prior systemic treatment. Patients received regorafenib 80 or 120 mg/day for 3 weeks plus pembrolizumab 200 mg every 3 weeks in 4-week cycles (rego-80/pembro or rego-120/pembro): rego-80/pembro in the dose-defining phase; rego-80/pembro or rego-120/pembro in 2 dose-expansion cohorts. The primary objective was to assess safety; antitumor activity was a secondary objective. The MTD of regorafenib was 120 mg/day plus pembrolizumab; 4/19 patients receiving rego-120/pembro experienced dose-limiting toxicities [grade 3 increased AST with grade 1/2 increased bilirubin (n=2), and grade 3 rash (n=2)]. The most common treatment-emergent adverse events (TEAEs) in the overall safety cohort (n=57) were diarrhea (53%) and fatigue (51%). The most common grade ≥3 TEAEs were increased AST (18%) and hypertension (16%). Dose modifications due to study drug-related adverse events were less frequent with rego-80/pembro than with rego-120/pembro. The objective response rate (ORR) in 54 response-evaluable patients was 31% and the disease control rate (DCR) was 89%. Exploratory analyses suggested an association between lower angiogenesis and transforming growth factor-β signaling before treatment and response.

CONCLUSIONS: Treatment with rego/pembro is feasible in patients with advanced HCC with a manageable safety profile. ORR and DCR are promising and consistent with other immunotherapy combinations in this setting.},
}

@article {pmid41213454,
year = {2025},
author = {Rioseco, A and Puschel, K and Soto, G and Vescovi, Z and Fuentes, I and Dibiase, F and Ulloa, G and Goic, C and Emery, J and Thompson, B and Martinez-Gutierrez, J},
title = {National cancer plans and primary care a systematic analysis comparing Latin American and non-Latin American countries.},
journal = {Journal of cancer policy},
volume = {46},
number = {},
pages = {100659},
doi = {10.1016/j.jcpo.2025.100659},
pmid = {41213454},
issn = {2213-5383},
mesh = {*Primary Health Care/organization & administration ; Humans ; Latin America/epidemiology ; *Neoplasms/therapy/prevention & control/epidemiology ; United States ; Canada ; *Health Policy ; *National Health Programs ; },
abstract = {BACKGROUND: Cancer is a growing global health issue, particularly in middle- and high-income countries. National Cancer Control Plans (NCCPs) have emerged as a strategic response to reduce this burden. Primary care plays a crucial role across the cancer care continuum, yet its systematic inclusion in NCCPs remains unclear-especially in countries facing significant epidemiological challenges.

METHODS: This study employed a systematic qualitative design based on document analysis. Using the READ (Ready material, Extract data, Analyze, Distil) model, we examined the integration of primary care policies and practices in eight NCCPs: four from non-Latin American high-income countries (NLAHIc-Australia, Canada, the United States, and the United Kingdom) and four from Latin American middle-income countries (LATAMc-Argentina, Colombia, Chile, and Mexico). Covidence software facilitated the systematic text review, and a set of evidence-based key performance indicators (KPIs) was developed to guide the analysis.

RESULTS: Primary care integration varied across countries. LATAMc NCCPs showed greater inclusion of primary care than NLAHIc. Health promotion strategies were more consistently present in NLAHIc, while LATAMc better integrated primary prevention into primary care. However, only 50 % of KPIs for secondary prevention and 15 % for survivorship care were included in LATAMc. Palliative care was more consistently integrated in LATAMc (75 %) than in NLAHIc (33 %). Policy Summary This is the first study to benchmark NCCPs from Latin American and high-income countries using evidence-based KPIs to assess primary care involvement in cancer control. Findings highlight an urgent need to strengthen primary care integration. LATAMc should improve secondary prevention and survivorship care, while NLAHIc need to better incorporate primary prevention and palliative care into their NCCPs.},
}

*Primary Health Care/organization & administration
Humans
Latin America/epidemiology
*Neoplasms/therapy/prevention & control/epidemiology
United States
Canada
*Health Policy
*National Health Programs

@article {pmid41213499,
year = {2026},
author = {Dehn, JG and Logan, B and Lee, SJ and Shaw, BE and Devine, S and Ciurea, SO and Horowitz, M and He, N and Pusic, I and Srour, SA and Arai, S and Juckett, M and Uberti, J and Hill, L and Vasu, S and Hogan, WJ and Hayes-Lattin, B and Westervelt, P and Bashey, A and Farhadfar, N and Grunwald, MR and Leifer, E and Symons, H and Saad, A and Vogel, J and Erickson, C and Buck, K and Pidala, J},
title = {Access to Allogeneic Cell Transplantation Based on Donor Search Prognosis: BMT CTN 1702 Trial.},
journal = {Transplantation and cellular therapy},
volume = {32},
number = {3},
pages = {346-357},
pmid = {41213499},
issn = {2666-6367},
support = {U10 HL069294/HL/NHLBI NIH HHS/United States ; UG1 HL138645/HL/NHLBI NIH HHS/United States ; UG1 HL108945/HL/NHLBI NIH HHS/United States ; UG1 HL108987/HL/NHLBI NIH HHS/United States ; UG1 HL069246/HL/NHLBI NIH HHS/United States ; UG1 HL109137/HL/NHLBI NIH HHS/United States ; U24 CA076518/CA/NCI NIH HHS/United States ; U24 HL138660/HL/NHLBI NIH HHS/United States ; },
mesh = {Humans ; *Hematopoietic Stem Cell Transplantation/methods ; Female ; Male ; Transplantation, Homologous ; Middle Aged ; Prognosis ; Adult ; *Unrelated Donors ; Adolescent ; *Tissue Donors ; *Donor Selection ; Young Adult ; Aged ; },
abstract = {Patients requiring allogeneic hematopoietic cell transplantation (HCT) have variable likelihoods of identifying an 8/8 HLA-matched unrelated donor (MUD). A Search Prognosis calculator can estimate the likelihood. This study (NCT#03904134; https://clinicaltrials.gov/study) evaluates if using a Search Prognosis algorithm results in similar incidence of transplant between patients Very Likely (>90%) versus Very Unlikely (<10%) to have a MUD. An additional objective included understanding barriers resulting in a delay or cancellation of a patient transplant. The national multicenter Blood and Marrow Transplant Clinical Trial Network (BMT CTN) 1702 interventional trial utilized Search Prognosis-based biologic assignment to guide donor selection. HCT eligible patients at participating transplant centers were invited to enroll. Patients assigned to the Very Likely arm were to proceed with MUD, while Very Unlikely were to utilize alternative donors. A third stratum, Less Likely (∼25%), were observed under standard center practices, but were not part of the primary objective. We report here the cumulative incidence of HCT by Search Prognosis group and barriers to HCT. Evaluable patients included 1751 of which 413 (24%) were from racial/ethnic minorities. Seach Prognosis was 958 (55%) Very Likely, 517 (30%) Less Likely, and 276 (16%) Very Unlikely. About 1171 (67%) received HCT, 384 (22%) died without HCT, and 196 (11%) remained alive without HCT. Among the 1234 patients (Very Likely versus Very Unlikely), the adjusted cumulative incidence (95% CI) of HCT at 6 months was 59.8% (56.7 to 62.8) in Very Likely versus 52.3% (46.1 to 58.5) in Very Unlikely (P = .113). Median time to HCT were similar in all Seach Prognosis groups. The predominant barriers resulting in a delay or cancellation of transplant were due to poor patient health (59%). Around 9% of delays and cancellations were attributed to excellent patient disease response, with only 14% of delays and 2% of cancellations due to donor reasons. A prospective Search Prognosis-based algorithm can be effectively implemented in a national multicenter clinical trial, with donor related barriers to transplant representing a small proportion of cases. This approach resulted in rapid alternative donor identification and no statistical difference in rates of HCT in patients Very Likely and Very Unlikely to find a MUD.},
}

Humans
*Hematopoietic Stem Cell Transplantation/methods
Female
Male
Transplantation, Homologous
Middle Aged
Prognosis
Adult
*Unrelated Donors
Adolescent
*Tissue Donors
*Donor Selection
Young Adult
Aged

@article {pmid41216598,
year = {2025},
author = {Wang, R and Stempel, JM and Shallis, RM and Huntington, SF and Zeidan, AM and Neparidze, N and Di, M and Bewersdorf, JP and Mendez, L and Ma, X and Podoltsev, NA},
title = {Second malignancies among older patients with classical myeloproliferative neoplasms treated with ruxolitinib.},
journal = {Blood neoplasia},
volume = {2},
number = {4},
pages = {100159},
pmid = {41216598},
issn = {2950-3280},
support = {N01 PC035136/CA/NCI NIH HHS/United States ; N01 PC035139/CA/NCI NIH HHS/United States ; N02 PC015105/PC/NCI NIH HHS/United States ; T32 CA233414/CA/NCI NIH HHS/United States ; },
abstract = {Polycythemia vera (PV), essential thrombocythemia (ET), and myelofibrosis (MF) are classical Philadelphia chromosome-negative myeloproliferative neoplasms (MPNs) associated with an increased risk of development of second primary malignancies (SMs). The reasons for solid and lymphoid SMs are unclear, but a therapy-related effect has been invoked. Although an increased risk of nonmelanoma skin cancers is associated with the use of ruxolitinib (RUX), its influence on the development of other forms of SMs remains controversial. We conducted a retrospective cohort analysis to assess associations between RUX and SMs among older patients diagnosed with MPN from 2012 to 2019 in the Surveillance, Epidemiology, and End Results-Medicare-linked database. We identified 6043 patients (2396 with PV, 2944 with ET, 703 with MF) with a median age of 76 years (interquartile range [IQR], 71-82). After a median follow-up of 3.66 (IQR, 2.25-5.17) and 3.02 years (IQR, 1.84-4.75) for 513 RUX users and 5530 nonusers, respectively, 469 patients developed an SM: 383 solid and 86 lymphoid. In the multivariable proportional subdistribution hazard regression model with death as a competing risk, the risk of developing any SM did not differ by RUX use status (hazard ratio [HR], 0.96; 95% confidence interval [CI], 0.65-1.42; P = .84) or by proportion of days covered by RUX (every 10% increase; HR, 1.00; 95% CI, 0.96-1.05; P = .95). RUX exposure did not affect the risk of solid SM (HR, 0.77; 95% CI, 0.48-1.23; P = .27) or lymphoid SM (HR, 1.73; 95% CI, 0.79-3.80; P = .17). Our results suggest that RUX use does not increase the risk of SM in older patients with MPN.},
}

@article {pmid41217670,
year = {2025},
author = {Liu, ZY and Chen, GC and LaMonte, MJ and Kamensky, V and Evenson, KR and Shadyab, AH and Luo, J and Allison, M and Wild, RA and Going, SB and Eaton, CB and Stone, KL and Bea, JW and Seguin-Fowler, RA and Johnson, KC and Kaplan, RC and Rohan, TE and Wassertheil-Smoller, S and Qi, Q},
title = {Longitudinal transitions in sedentary behavior and physical activity in relation to all-cause and cause-specific mortality among postmenopausal women.},
journal = {GeroScience},
volume = {},
number = {},
pages = {},
pmid = {41217670},
issn = {2509-2723},
support = {K01HL129892/HL/NHLBI NIH HHS/United States ; R01HL060712/HL/NHLBI NIH HHS/United States ; R01HL140976/HL/NHLBI NIH HHS/United States ; R01-HL146132-01/HL/NHLBI NIH HHS/United States ; R01DK119268/DK/NIDDK NIH HHS/United States ; R01DK120870/DK/NIDDK NIH HHS/United States ; 5R01CA227122//Division of Cancer Epidemiology and Genetics, National Cancer Institute/ ; },
abstract = {To evaluate longitudinal transitions in sedentary behavior and physical activity for the associations with all-cause and cause-specific mortality (i.e., cardiovascular disease [CVD], cancer, respiratory, and Alzheimer's disease/dementia mortality) among postmenopausal women. This prospective cohort study included 58,168 multiethnic US postmenopausal women from the Women's Health Initiative Observational Study, who had self-reported data on various sedentary behaviors and recreational physical activity at baseline (Y0: 1993-1998; age range: 50-79 years) and after 6 years (Y6). According to sedentary time (≥ 8 h/day or not) or physical activity (≥ 8.5 MET-h/week or not) at Y0 and Y6 assessments, participants were grouped by transition in sedentary behavior (consistently non-sedentary, sedentary to non-sedentary, non-sedentary to sedentary, and consistently sedentary) or physical activity levels (consistently low, high to low, low to high, and consistently high). Over a median follow-up of 15.0 years (from Y6 to March 2019), 17,354 all-cause deaths occurred, ranging from 1336 respiratory to 5111 CVD deaths. Compared to the consistently non-sedentary group, the two groups with unfavorable transitions in sedentary behavior (i.e., from non-sedentary to sedentary or being consistently sedentary) both had a higher risk of all-cause mortality and mortality from CVD, cancer, and respiratory disease. Conversely, the two groups with favorable transitions in physical activity (i.e., transitioning to or maintaining high activity), as compared with the consistently-low activity group, both had a lower risk mortality from all causes and several specific causes. Significant interactions were observed between transitions in sedentary behavior and physical activity on the risk of all-cause and CVD mortality (P-interaction < 0.01). Specifically, unfavorable sedentary transitions were associated with an elevated risk only among women with unfavorable transitions in physical activity. Among US postmenopausal women, maintaining or transiting to a sedentary lifestyle over 6 years was associated with a higher risk of mortality, predominantly among those not achieving regular physical activity over the years.},
}

@article {pmid41218661,
year = {2026},
author = {Ford, EC and Evans, S and Salter, B and Bazan, JG and Weintraub, SM and Moran, JM and Olsen, JR and Dalton, AP and Kujundzic, K and Wilson, E and Marks, LB},
title = {Operations and Impact of a Specialty-Specific National Incident Learning System: Ten Years of Radiation Oncology Incident Learning System (RO-ILS).},
journal = {International journal of radiation oncology, biology, physics},
volume = {124},
number = {2},
pages = {265-277},
doi = {10.1016/j.ijrobp.2025.10.027},
pmid = {41218661},
issn = {1879-355X},
mesh = {*Radiation Oncology/education/organization & administration/standards ; Humans ; United States ; *Patient Safety ; *Risk Management/organization & administration ; *Medical Errors/prevention & control/statistics & numerical data ; },
abstract = {Incident learning is recognized by national and international organizations as a key component of maintaining safety and quality in health care. In 2014, RO-ILS: Radiation Oncology Incident Learning System was launched by the American Society for Radiation Oncology and the American Association of Physicists in Medicine with the goal of facilitating safer and higher-quality care in radiation oncology. This review discusses the structure of the RO-ILS program, its foundations and operations, as well as outcomes in terms of engagement and learning opportunities. RO-ILS operates under the auspices and protection of patient safety organization in the United States. As of the end of 2024, 781 facilities have enrolled in the program, representing a mixture of United States practice settings (private practice, community/academic, free-standing/hospital-based, and small/large). A cumulative 41,516 events have been reported to the patient safety organization, the largest volume of events compared to other national and international aggregated incident learning systems in radiation oncology. A minority of events (24%) are incidents, that is, events that actually reached a patient regardless of harm. Approximately 10% of events were rated as potentially severe or critical. A key feature of the RO-ILS program is reports and other releases aimed at education and quality improvement. Over 100 releases have been issued, including case studies, great catches, safety notices, and themed reports, as well as industry webinars and user meetings. While there is evidence of success and engagement in the RO-ILS program, current and future challenges include the quantity and quality of reported data, the ability to effectively extract information, further engagement of key stakeholders, and program sustainability. These must be addressed for RO-ILS to continue to fulfill the mission of supporting safer and higher-quality care in radiation oncology.},
}

*Radiation Oncology/education/organization & administration/standards
Humans
United States
*Patient Safety
*Risk Management/organization & administration
*Medical Errors/prevention & control/statistics & numerical data

@article {pmid41219045,
year = {2025},
author = {Chen, F and Sheng, X and Wang, A and Xu, Y and Hughley, R and Xiong, W and Pooler, L and Wan, P and Gundell, SM and Kigozi, G and Nakigozi, G and Nalugoda, F and Kagaayi, J and Kigozi, GN and Mugamba, S and Kyasanku, E and Nkale, J and Olwa, VO and Lubwama, A and Daama, A and Nakajugo, R and Adusei, B and Jalloh, M and Gueye, SM and Adjei, AA and Mensah, J and Fernandez, PW and Adebiyi, AO and Olufemi Ogunbiyi, J and Aisuodionoe-Shadrach, OI and Petersen, L and Chen, WC and McBride, J and Bensen, JT and Mohler, JL and Taylor, JA and Andrews, C and Kigongo, M and Colline, A and Kiddu, V and Namugambe, J and Owamaani, S and Job, K and Masaba, BJ and Asiimwe, F and Muwanga, P and Namulondo, J and Nagawa, F and Kayiraba, C and Ogwang, M and Okidi, R and Oweka, D and Kitara, E and Obonyo, J and Lajul, D and Matovu, P and Muheki, PA and Natumanya, J and Agaba, E and Aculokin, E and Twongyeirwe, A and Mutema, G and Bitamazire, D and Butler, EN and Ingles, SA and Rybicki, BA and Stanford, JL and Zheng, W and Berndt, SI and Chanock, SJ and Huff, CD and Lachance, J and Multigner, L and Darst, BF and Rebbeck, TR and Brureau, L and Watya, S and Conti, DV and Haiman, CA},
title = {Integrating Pathogenic Variants, Polygenic Risk Score, and Family History for Prostate Cancer Risk Estimation in Men of African Ancestry.},
journal = {European urology},
volume = {},
number = {},
pages = {},
pmid = {41219045},
issn = {1873-7560},
support = {U01 CA164973/CA/NCI NIH HHS/United States ; U19 CA214253/CA/NCI NIH HHS/United States ; },
abstract = {BACKGROUND AND OBJECTIVE: The impact of germline pathogenic variants (PVs) in cancer predisposition genes on risk of prostate cancer (PCa) remains understudied in large populations of African ancestry. This study aims to characterize the range of genetic risk of PCa and aggressive disease phenotypes in men of African ancestry.

METHODS: We analyzed 7176 PCa cases and 4873 controls from seven countries across North America and Africa to assess the association between PVs in 37 cancer predisposition genes and the risk of overall, aggressive, and metastatic PCa. Genes significantly associated with PCa risk were used to estimate lifetime absolute risk based on family history, polygenic risk score (PRS), and PV carrier status.

KEY FINDINGS AND LIMITATIONS: PVs in ATM, BRCA2, CHEK2, HOXB13, and PALB2 were presented in 4% of aggressive/metastatic PCa cases and were significantly associated with an increased risk of aggressive PCa (odds ratio 2.18-5.96, p < 0.05). Lifetime absolute risk varied widely depending on PV carrier status, PRS, and family history, ranging from 3.0% to 74% for overall PCa, 0.6% to 41% for aggressive PCa, and 0.2% to 37% for metastatic PCa. PV carriers with a positive family history and a PRS in the 90th percentile had seven, 18, and 34 times the risks of overall, aggressive, and metastatic PCa, respectively, compared with average-risk individuals. Oversampling of aggressive cases may limit the generalizability of these findings to screening populations.

Integration of PV status, PRS, and family history enables more refined PCa risk estimates. The wide range of PCa risk observed among men of African ancestry in our study supports future prospective studies in the development of risk-stratified cancer screening programs to identify high-risk individuals who may benefit from screening at an earlier age.},
}

@article {pmid41221958,
year = {2026},
author = {Rees, MJ and Khouri, J and Grajales-Cruz, AF and Zanwar, SS and Goel, U and Midha, S and Kelley, J and Puglianini, OC and Corraes, AMS and Raza, S and Davis, JA and Green, K and Hansen, DK and Banerjee, R and Sidana, S and Patel, KK and Bianchi, G and Sborov, DW and Lee, S and Kumar, SK and Baz, R and Anwer, F and Mikkilineni, L and Nadeem, O and Lin, Y and Anderson, LD},
title = {The Real-World Safety and Efficacy of Bispecific T-Cell Engager Therapy in Systemic AL Amyloidosis.},
journal = {American journal of hematology},
volume = {101},
number = {1},
pages = {187-192},
doi = {10.1002/ajh.70140},
pmid = {41221958},
issn = {1096-8652},
}

@article {pmid41222477,
year = {2026},
author = {Takashima, Y and Dias Costa, A and Akimoto, N and Ugai, T and Bell, P and Väyrynen, JP and Hornick, JL and Mino-Kenudson, M and Zhong, Y and Ugai, S and Haruki, K and Yao, Q and Matsuda, K and Higashioka, M and Buchanan, DD and Phipps, AI and Peters, U and Giannakis, M and Song, M and Chan, AT and Fuchs, CS and Nowak, JA and Ogino, S},
title = {T-cell Subset Features and Distributions Evolve across the Colorectal Precancer-Cancer Spectrum.},
journal = {Cancer immunology research},
volume = {14},
number = {1},
pages = {46-59},
pmid = {41222477},
issn = {2326-6074},
support = {R01 CA248857/CA/NCI NIH HHS/United States ; U01 CA167552/CA/NCI NIH HHS/United States ; UM1 CA186107/CA/NCI NIH HHS/United States ; UM1 CA167552/CA/NCI NIH HHS/United States ; C10674/A27140//Cancer Research UK Grand Challenge Award/ ; //American Institute for Cancer Research (AICR)/ ; P01 CA87969//National Institutes of Health (NIH)/ ; R35 CA197735/CA/NCI NIH HHS/United States ; R21 CA230873/CA/NCI NIH HHS/United States ; P01 CA087969/CA/NCI NIH HHS/United States ; P01 CA55075//National Institutes of Health (NIH)/ ; P01 CA055075/CA/NCI NIH HHS/United States ; R01 CA151993/CA/NCI NIH HHS/United States ; R50 CA274122/CA/NCI NIH HHS/United States ; //Prevent Cancer Foundation (PCF)/ ; U01 CA261961/CA/NCI NIH HHS/United States ; },
mesh = {Humans ; *Colorectal Neoplasms/immunology/pathology ; Female ; Male ; *T-Lymphocyte Subsets/immunology/metabolism ; Tumor Microenvironment/immunology ; Aged ; *Precancerous Conditions/immunology/pathology ; Middle Aged ; *Lymphocytes, Tumor-Infiltrating/immunology ; Prospective Studies ; },
abstract = {The immune microenvironment is a crucial component of colorectal carcinoma that has been well characterized, but much less is known about the immune microenvironment of colorectal carcinoma precursors. We hypothesized that T-cell infiltrates might differ across the colorectal neoplastic spectrum. We leveraged the prospective cohort incident-tumor biobank method, which provided formalin-fixed, paraffin-embedded tumor tissue specimens (N = 1,825) from 790 colorectal carcinoma precursors (including hyperplastic polyps, sessile serrated adenomas, traditional serrated adenomas, tubular adenomas, tubulovillous adenomas, and villous adenomas) and 1,035 colorectal carcinomas. We performed an in situ multispectral immunofluorescence assay for CD3, CD4, CD8, FOXP3 (negative, low, or high expression), PTPRC (CD45RO and CD45RA), MKI67 (Ki-67), and KRT (keratin) combined with supervised machine learning. CD3+CD4+ cells were more abundant than CD3+CD8+ cells in most precursors. In conventional adenomas, greater villous component correlated with fewer intraepithelial CD3+CD8+ cells. Serrated lesions, including hyperplastic polyps and sessile serrated lesions, exhibited higher densities of intraepithelial CD3+CD8+ cells compared with other precursors and carcinomas. Age strata of patients with precursors (including early-onset precursors) were not associated with differential T-cell infiltration patterns. Compared with invasive colorectal carcinoma, precursors generally showed higher densities of CD3+CD4+ cells and CD3+CD8+ cells with phenotypes of naive (CD45RA+CD45RO-), memory (CD45RA-CD45RO+), and regulatory (FOXP3+Low and FOXP3+High) in intraepithelial and lamina propria/stromal regions. In conclusion, T-cell infiltration patterns vary across different histopathologic types of the colorectal neoplastic spectrum from precursors to invasive carcinomas. Our findings shed light on how the tumor-immune microenvironment evolves during precursor development and progression to colorectal carcinoma.},
}

Humans
*Colorectal Neoplasms/immunology/pathology
Female
Male
*T-Lymphocyte Subsets/immunology/metabolism
Tumor Microenvironment/immunology
Aged
*Precancerous Conditions/immunology/pathology
Middle Aged
*Lymphocytes, Tumor-Infiltrating/immunology
Prospective Studies

@article {pmid41224138,
year = {2026},
author = {Minus, E and Coley, RY and Shortreed, SM and Williamson, BD},
title = {Behavior of prediction performance metrics with rare events.},
journal = {Journal of clinical epidemiology},
volume = {189},
number = {},
pages = {112046},
pmid = {41224138},
issn = {1878-5921},
support = {R01 MH125821/MH/NIMH NIH HHS/United States ; U19 MH092201/MH/NIMH NIH HHS/United States ; U19 MH121738/MH/NIMH NIH HHS/United States ; },
mesh = {Humans ; *Area Under Curve ; ROC Curve ; Computer Simulation ; *Suicide, Attempted/statistics & numerical data ; Predictive Value of Tests ; Models, Statistical ; },
abstract = {OBJECTIVE: Area under the receiver operating characteristic curve (AUC) is commonly reported alongside prediction models for binary outcomes. Recent articles have raised concerns that AUC might be a misleading measure of prediction performance in the rare event setting. This setting is common since many events of clinical importance are rare. We aimed to determine whether the bias and variance of AUC are driven by the number of events or the event rate. We also investigated the behavior of other commonly used measures of prediction performance, including positive predictive value, accuracy, sensitivity, and specificity.

STUDY DESIGN AND SETTING: We conducted a simulation study to determine when or whether AUC is unstable in the rare event setting by varying the size of datasets used to train and evaluate prediction models. This plasmode simulation study was based on data from the Mental Health Research Network; the data contained 149 predictors and the outcome of interest, suicide attempt, which had event rate 0.92% in the original dataset.

RESULTS: Our results indicate that poor AUC behavior-as measured by empirical bias, variability of cross-validated AUC estimates, and empirical coverage of confidence intervals-is driven by the number of events in a rare-event setting, not event rate. Performance of sensitivity is driven by the number of events, while that of specificity is driven by the number of nonevents. Other measures, including positive predictive value and accuracy, depend on the event rate even in large samples.

CONCLUSION: AUC is reliable in the rare event setting provided that the total number of events is moderately large; in our simulations, we observed near zero bias with 1000 events.

PLAIN LANGUAGE SUMMARY: Predicting self-harm or suicidal behavior is medically important for guiding clinicians in providing care to patients. Several research teams have developed and evaluated suicide risk prediction models based on health records data. Part of evaluating these models is calculating area under the receiver operating characteristic curve (AUC) and other prediction performance metrics. Self-harm and suicide are rare events. Recent research has raised concerns with using AUC in rare-event settings. We aimed to determine whether having a sufficiently large dataset could remove these concerns. In our experiments, we found that AUC can be used without concern in settings with 1000 events or more. Thus, AUC is a valid measure of suicide risk prediction model performance in many large healthcare databases.},
}

Humans
*Area Under Curve
ROC Curve
Computer Simulation
*Suicide, Attempted/statistics & numerical data
Predictive Value of Tests
Models, Statistical

@article {pmid41228468,
year = {2025},
author = {Teruel Camargo, J and Recinos, G and Hinerman, AS and Duong, C and Rodriquez, EJ and Juarez, JJ and McClain, AC and Alver, SK and Daviglus, ML and Van Horn, L and Pérez-Stable, EJ},
title = {Pulse Consumption and Metabolic Syndrome: Findings from the Hispanic Community Health Study/Study of Latinos.},
journal = {Nutrients},
volume = {17},
number = {21},
pages = {},
pmid = {41228468},
issn = {2072-6643},
support = {N01HC65233, N01HC65234, N01HC65235, N01HC65236, N01HC65237/HL/NHLBI NIH HHS/United States ; },
mesh = {Aged ; Female ; Humans ; Male ; Middle Aged ; *Diet ; *Hispanic or Latino/statistics & numerical data ; *Metabolic Syndrome/epidemiology/ethnology/physiopathology/prevention & control ; Risk Factors ; },
abstract = {Background/Objectives: Metabolic syndrome affects half of middle-aged (ages 45-64) Hispanic or Latino (Latino) adults. Pulses, fiber-rich plant proteins common in Latino diets (e.g., dry beans and lentils), may mitigate metabolic syndrome. We evaluated the association between pulse intake and metabolic syndrome. Methods: We analyzed data from 6,958 adults aged ≥ 50 in the Hispanic Community Health Study/Study of Latinos (2008-2011) Visit 1. Pulse intake was assessed using two 24 h dietary recalls and categorized into no, low (<1/2 cup), moderate (≥1/2 to 3/4 cup), and high pulse (>3/4 cup) daily intake groups. Metabolic syndrome was defined by criteria including blood pressure ≥130/85 mmHg or medication use, triglycerides ≥150 mg/dL or medication use, high-density lipoprotein cholesterol (men <40 mg/dL and women <50 mg/dL), and waist circumference (men ≥102 cm and women ≥88 cm). We used multivariate logistic regression models with predicted probability proportions to assess the association adjusted for sociodemographic factors, acculturation, diet quality, energy intake, and physical activity. Results: Of the 6,958 participants, 53.1% had metabolic syndrome and 53.4% had a moderate or high pulse intake. Pulse intake varied, where 19.4% had a high intake, 33.9% had a moderate intake, 12.5% had a low intake, and 34.2% had no intake. Moderate (predicted marginal = 0.52, 95% confidence interval [CI] = 0.49, 0.55) and high (predicted marginal = 0.49, 95%CI = 0.45, 0.53) intakes were associated with a lower prevalence of metabolic syndrome. Conclusions: Among Latino adults ≥50 years old, a moderate or high pulse intake was associated with a lower prevalence of metabolic syndrome. Increasing the pulse intake in the population may be linked to reduced metabolic syndrome.},
}

Aged
Female
Humans
Male
Middle Aged
*Diet
*Hispanic or Latino/statistics & numerical data
*Metabolic Syndrome/epidemiology/ethnology/physiopathology/prevention & control
Risk Factors

@article {pmid41233693,
year = {2025},
author = {Dussault, N and Henderson, K and Daniel, K and Mitchell, NM and Nickolopoulos, E and Hemming, P and Casarett, D and Cho, A and Ma, JE},
title = {Reply to the Letter to the Editor re: Evaluating a Clinical Chaplain Pilot Intervention to Facilitate Advance Care Planning in a Primary Care Clinic.},
journal = {Journal of general internal medicine},
volume = {},
number = {},
pages = {},
doi = {10.1007/s11606-025-10044-4},
pmid = {41233693},
issn = {1525-1497},
}

@article {pmid41235976,
year = {2026},
author = {Hunter, BD and Lunning, M and Shadman, M and Ahmed, S and Abramson, JS and Perales, MA and Ahmed, N and Mirza, AS and Isufi, I and Frigault, MJ and Crombie, JL and Miklos, DB and Vasconcelos, A and Crotta, A and Bernasconi, D and Roy, D and Bleickardt, E and Pasquini, MC and Kamdar, M},
title = {CRS or ICANS Are Rare Beyond 2 Weeks After Lisocabtagene Maraleucel Infusion: Data From Clinical Trials and the Real-World Setting.},
journal = {Transplantation and cellular therapy},
volume = {32},
number = {2},
pages = {171.e1-171.e12},
pmid = {41235976},
issn = {2666-6367},
support = {U01 AI184132/AI/NIAID NIH HHS/United States ; R01 CA231838/CA/NCI NIH HHS/United States ; R21 AG077024/AG/NIA NIH HHS/United States ; U24 HL157560/HL/NHLBI NIH HHS/United States ; U01 AI069197/AI/NIAID NIH HHS/United States ; P30 CA008748/CA/NCI NIH HHS/United States ; OT3 HL147741/HL/NHLBI NIH HHS/United States ; R01 CA100019/CA/NCI NIH HHS/United States ; R01 AI150999/AI/NIAID NIH HHS/United States ; R01 CA218285/CA/NCI NIH HHS/United States ; R01 HL171117/HL/NHLBI NIH HHS/United States ; R01 AI128775/AI/NIAID NIH HHS/United States ; U24 CA076518/CA/NCI NIH HHS/United States ; U24 HL138660/HL/NHLBI NIH HHS/United States ; UG1 HL174426/HL/NHLBI NIH HHS/United States ; P01 CA111412/CA/NCI NIH HHS/United States ; },
mesh = {Humans ; Male ; Female ; Middle Aged ; *Immunotherapy, Adoptive/adverse effects/methods ; *Cytokine Release Syndrome/etiology ; Adult ; Aged ; *Neurotoxicity Syndromes/etiology ; Clinical Trials as Topic ; Receptors, Chimeric Antigen ; },
abstract = {Improved understanding of the timing of cytokine release syndrome (CRS) and immune effector cell-mediated neurotoxicity syndrome (ICANS)/neurological events (NE) after chimeric antigen receptor (CAR) T-cell therapy infusion can inform patient safety monitoring. To report CRS and ICANS/NE outcomes, including incidence, onset, and resolution, in patients treated with lisocabtagene maraleucel (liso-cel) in clinical trials and the real-world setting. This analysis included patients treated with liso-cel in 5 clinical trials across different B-cell non-Hodgkin lymphoma indications (n = 702) and in the real-world setting for large B-cell lymphoma, as captured in the Center for International Blood and Marrow Transplant Research (CIBMTR) Registry (n = 877). All outcomes are reported descriptively. Among 702 patients in clinical trials, 54% had any-grade CRS (grade ≥3 at onset, 1%), with 98% of events occurring ≤day 15 after infusion; median time to resolution was 5 days. Any-grade NEs occurred in 31% of patients (grade ≥3 at onset, 5%), with 88% of events occurring ≤day 15 after infusion; median time to resolution was 7 days. Among 877 patients in the real-world setting, 49% had any-grade CRS (maximum grade ≥3, 3%), with 97% of events occurring ≤day 15 after infusion; median time to resolution was 4 days. Any-grade ICANS occurred in 27% of patients (maximum grade ≥3, 10%). Of 150 patients with reported onset date, 95% had onset ≤day 15 after infusion; median time to resolution was 5.5 days. The vast majority of CRS or ICANS/NEs occurred ≤day 15 after liso-cel infusion. These results support the recently updated United States Food and Drug Administration monitoring requirements aimed to improve treatment access while maintaining patient safety.},
}

Humans
Male
Female
Middle Aged
*Immunotherapy, Adoptive/adverse effects/methods
*Cytokine Release Syndrome/etiology
Adult
Aged
*Neurotoxicity Syndromes/etiology
Clinical Trials as Topic
Receptors, Chimeric Antigen

@article {pmid41236449,
year = {2026},
author = {Kim, NJ and Li, M and Vutien, P and Mecham, B and Borgerding, J and Swarts, K and Atuluru, P and Michel, MC and Barnard Giustini, A and Mezzacappa, C and Berry, K and VoPham, T and Marsh, TL and Feng, Z and Johnson, KM and Beste, LA and Kaplan, DE and Taddei, TH and Ioannou, GN},
title = {Changes in Liver Disease Etiology Support a Lower Alpha-Fetoprotein Threshold for Hepatocellular Carcinoma Screening.},
journal = {Gastroenterology},
volume = {170},
number = {3},
pages = {606-618},
doi = {10.1053/j.gastro.2025.08.021},
pmid = {41236449},
issn = {1528-0012},
mesh = {Humans ; *Carcinoma, Hepatocellular/diagnosis/blood/etiology/epidemiology ; *Liver Neoplasms/diagnosis/blood/etiology/epidemiology ; *alpha-Fetoproteins/analysis ; Male ; *Early Detection of Cancer/methods ; Middle Aged ; Female ; United States/epidemiology ; Aged ; Liver Cirrhosis/blood/diagnosis ; *Biomarkers, Tumor/blood ; Predictive Value of Tests ; Hepatitis C/complications ; Liver Diseases, Alcoholic/blood/complications/diagnosis ; Retrospective Studies ; Sensitivity and Specificity ; },
abstract = {BACKGROUND & AIMS: Serum alpha-fetoprotein (AFP) is a key component of hepatocellular carcinoma (HCC) screening, but its test characteristics are uncertain as alcohol-associated liver disease (ALD) and metabolic dysfunction-associated steatotic liver disease (MASLD) rates increase.

METHODS: We evaluated AFP trends at HCC diagnosis and estimated its test performance for HCC screening in cirrhosis using Veterans Health Administration (VHA) and United Network for Organ Sharing data.

RESULTS: Among the 40,399 VHA patients diagnosed with HCC between 2001 and 2021, median AFP at HCC diagnosis declined over time and was highest in active-hepatitis C (HCV) (32.7 vs cured-HCV 8.3, ALD 9.0, MASLD 7.7 ng/mL). Among the 28,170 VHA patients with cirrhosis receiving care in 2019 (9.6% active-HCV, 43% cured-HCV, 24% ALD, 14% MASLD), 1,029 developed HCC in 2019. At AFP thresholds ≥20 and ≥10 ng/mL, the overall sensitivity/specificity for HCC screening was 31.7%/98.5% and 41.9%/94.1%, respectively. Lowering the AFP threshold to ≥10 ng/mL increased sensitivity with minimal reductions in specificity across all liver disease etiologies: active-HCV (sensitivity/specificity: 43.7% to 60.7%/92.6% to 83.0%), cured-HCV (32.5% to 41.5%/99.0% to 94.7%), ALD (22.8% to 32.3%/99.2% to 95.1%), and MASLD (21.7% to 29.9%/99.4% to 96.7%). Analysis of United Network for Organ Sharing (26,213 patients with HCC) resulted in similar increases in test sensitivity as the AFP threshold declined from ≥20 to ≥10 ng/mL (overall: 31.8% to 48.7%; active-HCV: 36.7% to 58.6%, cured-HCV: 21.4% to 36.4%, MASLD: 19.1% to 33.4%, and ALD: 15.9% to 27.1%).

CONCLUSIONS: For HCC screening in MASLD, ALD, and cured-HCV cirrhosis, reducing the AFP threshold to ≥10 ng/mL would substantially increase sensitivity while maintaining very high specificity.},
}

Humans
*Carcinoma, Hepatocellular/diagnosis/blood/etiology/epidemiology
*Liver Neoplasms/diagnosis/blood/etiology/epidemiology
*alpha-Fetoproteins/analysis
Male
*Early Detection of Cancer/methods
Middle Aged
Female
United States/epidemiology
Aged
Liver Cirrhosis/blood/diagnosis
*Biomarkers, Tumor/blood
Predictive Value of Tests
Hepatitis C/complications
Liver Diseases, Alcoholic/blood/complications/diagnosis
Retrospective Studies
Sensitivity and Specificity

@article {pmid41237309,
year = {2025},
author = {Kanellopoulou, A and Bouras, E and Chan, AT and Marchand, LL and Wolk, A and Wu, AH and Gunter, MJ and Nimptsch, K and Haycock, P and Lewis, SJ and Martin, RM and Zuber, V and Phipps, AI and Peters, U and Van Duijnhoven, FJB and Tsilidis, KK},
title = {Investigating the association between anthropometry and colorectal cancer survival: a two-sample Mendelian randomization analysis.},
journal = {International journal of epidemiology},
volume = {54},
number = {6},
pages = {},
pmid = {41237309},
issn = {1464-3685},
support = {C18281/A29019//Cancer Research UK programme grant, the Integrative Cancer Epidemiology Programme/ ; NIHR202411//Cancer Research UK programme grant, the Integrative Cancer Epidemiology Programme/ ; //NIHR Bristol Biomedical Research Centre/ ; },
mesh = {Humans ; Mendelian Randomization Analysis ; *Colorectal Neoplasms/mortality/genetics ; Male ; Female ; Body Mass Index ; Middle Aged ; Waist Circumference/genetics ; Waist-Hip Ratio ; Aged ; *Anthropometry ; Birth Weight/genetics ; Body Height/genetics ; Proportional Hazards Models ; },
abstract = {BACKGROUND: Observational epidemiologic studies on the association of anthropometric traits and colorectal cancer (CRC) survival provide inconsistent results, and potential limitations prohibit the investigation of causality. We examined the associations between seven genetically predicted anthropometric traits [height, body mass index (BMI), waist circumference (WC), hip circumference (HC), waist-hip circumference ratio, birth weight and body fat percentage] and CRC-specific mortality among CRC cases using two-sample Mendelian randomization (MR).

METHODS: Analyses were performed using 16 964 CRC cases, out of which 4010 died due to their disease, from the Genetics and Epidemiology of Colorectal Cancer Consortium and Colon Cancer Family Registry. We further conducted stratified analyses by anatomical site and stage. We applied the inverse variance weighted approach, and sensitivity analyses were conducted to assess the impact of potential violations of MR assumptions and adjust for collider bias.

RESULTS: One standard deviation (SD 13.4 cm) higher genetically predicted levels of WC were associated with worse CRC survival [hazard ratio (HR); 1.22, 95% confidence interval (CI); 1.02-1.47]. Positive associations were further observed for a SD higher genetically predicted BMI (SD; 4.8 kg/m2, HR; 1.5, 95% CI; 1.15-1.95) and HC (SD; 9.2 cm, HR; 1.32, 95% CI; 1.02-1.73) and CRC-specific mortality in cases of stages II/III. The latter associations were generally robust to sensitivity analyses. Positive but imprecisely estimated associations were found for most other anthropometric traits.

CONCLUSIONS: Despite the limitations of cancer survival research, our findings support that CRC cases should avoid obesity. Further research should inform the development of recommendations targeting overweight/obesity management during cancer surveillance.},
}

Humans
Mendelian Randomization Analysis
*Colorectal Neoplasms/mortality/genetics
Male
Female
Body Mass Index
Middle Aged
Waist Circumference/genetics
Waist-Hip Ratio
Aged
*Anthropometry
Birth Weight/genetics
Body Height/genetics
Proportional Hazards Models

@article {pmid41237667,
year = {2025},
author = {Voillet, V and van Duijn, J and Vanshylla, K and Dintwe, OB and Pattacini, L and Omar, FL and Khuzwayo, S and Euler, Z and Schwedhelm, K and MacMillan, HR and Gilbert, PB and Fiore-Gartland, A and Newell, EW and Hendriks, J and McElrath, MJ and Stieh, DJ and De Rosa, SC and Andersen-Nissen, E},
title = {Unbiased cell clustering analysis of vaccine-induced T cell responses in the Imbokodo HIV-1 vaccine trial.},
journal = {EBioMedicine},
volume = {122},
number = {},
pages = {106017},
pmid = {41237667},
issn = {2352-3964},
mesh = {Humans ; *AIDS Vaccines/immunology/administration & dosage ; *HIV-1/immunology ; *HIV Infections/immunology/prevention & control/virology ; Cluster Analysis ; Female ; Male ; Adult ; *T-Lymphocytes/immunology/metabolism ; CD8-Positive T-Lymphocytes/immunology/metabolism ; CD4-Positive T-Lymphocytes/immunology/metabolism ; Vaccination ; T-Lymphocyte Subsets/immunology/metabolism ; Middle Aged ; Immunophenotyping ; },
abstract = {BACKGROUND: HIV-1 T cell responses are associated with viral control and may be protective in a prophylactic vaccination setting. Traditional methods for analysing these responses might be biased towards specific functionalities or epitopes. This study presents an unsupervised and unbiased clustering analysis workflow, using the Leiden algorithm followed by selection of antigen-specific clusters using MIMOSA positivity calls, for high-dimensional flow cytometry data to identify distinct T cell populations associated with protection in the HVTN 705/HPX2008/Imbokodo HIV-1 vaccine efficacy trial.

METHODS: Participants were vaccinated with Ad26.Mos4.HIV (M0, M3) and Ad26.Mos4.HIV + Clade C gp140 (M6, M12), and a validated 28-colour intracellular cytokine staining assay was performed on PBMC isolated at M7, M13 and M24 in a pilot immunogenicity (n = 60) and case-control cohort (n = 283). 28-colour phenotyping assays were also performed on PBMC from the case-control cohort (n = 334).

FINDINGS: Our clustering analysis workflow allowed identification of vaccine-induced subpopulations of both CD4+ and CD8+ T cells expressing combinations of the 28 markers. Durable HIV-1 antigen-specific CD4+ and CD8+ T cell responses were observed for up to 2 years, comprising mainly clusters of polyfunctional T cells expressing anti-viral cytokines and activation markers. Eight CD4+ and six CD8+ HIV-1 antigen-specific T cell clusters were induced by vaccination; only one CD4+ T cell cluster specific for Gag was mildly elevated in cases (acquiring HIV) compared to controls.

INTERPRETATION: Our study introduces an innovative analysis approach to identify vaccine-induced T cell subpopulations in vaccine trials. Comparison of T cell clusters between cases and controls holds promise for improving the efficacy of future HIV-1 vaccination strategies.

FUNDING: This work was funded by the National Institute of Allergy and Infectious Diseases (NIAID) and the Division of AIDS (DAIDS), both of the US National Institutes of Health (NIH) [NIAID grants to the HIV Vaccine Trials Network (HVTN) (Fred Hutchinson Cancer Center): UM1AI068618 (HVTN LC to M.J.M.) and UM1AI068635 (HVTN SDMC to P.B.G.)] and by Janssen Vaccines & Prevention B.V. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health or Janssen.},
}

Humans
*AIDS Vaccines/immunology/administration & dosage
*HIV-1/immunology
*HIV Infections/immunology/prevention & control/virology
Cluster Analysis
Female
Male
Adult
*T-Lymphocytes/immunology/metabolism
CD8-Positive T-Lymphocytes/immunology/metabolism
CD4-Positive T-Lymphocytes/immunology/metabolism
Vaccination
T-Lymphocyte Subsets/immunology/metabolism
Middle Aged
Immunophenotyping