@article {pmid41585364,
year = {2026},
author = {Wang, Z and Langevin, D and Chen, V and Bai, J},
title = {Reversible Chemogenetic Fluorescence Labeling with pFAST in C. elegans.},
journal = {microPublication biology},
volume = {2026},
number = {},
pages = {},
pmid = {41585364},
issn = {2578-9430},
abstract = {The promiscuous fluorescence-activating and absorption-shifting tag (pFAST) enables reversible chemogenetic labeling with multiple fluorogens. We generated a single-copy tandem pFAST (td-pFAST) transgenic Caenorhabditis elegans strain expressed in pharyngeal muscle. In dissected worms, lime fluorogen produced rapid fluorescence that was efficiently quenched by the competing ligand darth, demonstrating reversibility. Amber and coral fluorogens also produced reversible signals with distinct emission spectra, supporting multicolor labeling. However, fluorogen delivery by soaking intact worms failed, indicating cuticle permeability remains a barrier. These findings establish td-pFAST as a functional probe for reversible, multicolor labeling in dissected C. elegans tissues.},
}

@article {pmid41584860,
year = {2026},
author = {Ko, LK and Rillamas-Sun, E and Kratz, M and Jimenez, E and Jang, SH and Mendoza, JA and Bishop, S and Xiao, L},
title = {A Multi-Level Intervention to Address Childhood Obesity in Rural Hispanic Communities.},
journal = {Obesity science & practice},
volume = {12},
number = {1},
pages = {e70116},
pmid = {41584860},
issn = {2055-2238},
abstract = {OBJECTIVES: Pediatric obesity disproportionately affects children of lower socioeconomic status, racial and ethnic minorities, and rural communities, and is influenced by social and physical environments. Community-engaged interventions can address pediatric obesity and have been implemented in rural settings for other conditions, but few have specifically targeted rural childhood obesity. Together We STRIDE study is a community-based trial designed to test the effectiveness of a multi-level obesity prevention intervention in Hispanic children living in rural communities.

METHODS: The trial enrolled 653 children (8-12 years old). The 13-month (March 2017-April 2018) multi-level intervention included comic books, nutrition and physical activity (PA) classes, media literacy education and PA breaks, and an open-street community program (Ciclovía). The primary outcome was between-group differences in BMI z-score, measured at baseline, 6 months, and 18 months.

RESULTS: There were no significant between-group differences in BMI z-scores and BMI-for-age percentile relative to 95th percentile at 6 months or 18 months follow up. The mean difference in BMI z-score between intervention and comparison communities was -0.02 (95% CI -0.05, 0.02; p = 0.31) at 6 months and 0.03 (95% CI -0.03, 0.09; p = 0.32) at 18 months, respectively. BMI z-scores decreased progressively with increased exposure to intervention components (unadjusted p-trend = 0.008 and adjusted p-trend = 0.009).

CONCLUSIONS: Although this multi-level community-based intervention did not show an overall intervention effect on BMI z-scores, greater engagement with the intervention components was associated with higher reductions in BMI z-scores. The findings underscore both the promise and the challenges of community-based obesity prevention interventions in rural communities.

TRIAL REGISTRATION: NCT02982759 (Together We STRIDE) retrospectively registered during study recruitment.},
}

@article {pmid41584692,
year = {2026},
author = {Santiago-Torres, M and Mull, KE and Sullivan, BM and Fogel, CA and Hwang, SB and Keith, AR and David, SP and Bricker, JB},
title = {Overcoming Challenges to Remote Biochemical Verification of Smoking Status: Insights From Participant Interviews.},
journal = {Substance use : research and treatment},
volume = {20},
number = {},
pages = {29768357251414464},
pmid = {41584692},
issn = {2976-8357},
abstract = {OBJECTIVES: Remote biochemical verification of smoking abstinence is limited by low adherence rates and technical problems with test completion. Qualitative data from study participants about their experiences completing these remote tests is lacking. The objectives were to interview participants who provided biochemical verification in a randomized trial of a smoking cessation intervention to (1) learn about participants' actual experiences with cotinine saliva testing; (2) examine willingness to conduct smartphone app-based carbon monoxide (CO) breathalyzer testing; and (3) gather recommendations to minimize barriers and improve adherence.

METHODS: Participants who completed biochemical verification were invited to participate in semi-structured interviews that included watching an instructional video about the breathalyzer test. Audio recordings were professionally transcribed, and 2 independent coders applied an interactive inductive thematic analysis approach.

RESULTS: Ten participants, ages 38.7 (9.5) years (30% male) completed interviews. Barriers to successful saliva cotinine testing included: technical issues submitting results (56%), issues following written instructions (44%), saliva collection sponge discomfort (33%), confusion about invalid results (33%), and concerns with device safety/data usage (22%). While more participants said they would, in concept, prefer the CO test or had no preference, they reported more problems with completing the CO test, including potential inaccessibility for people with respiratory illness. Key recommendations for improving compliance included: increasing monetary incentives, diversifying reminders, amplifying reciprocity messaging, managing expectations, and embedding clear, concise in-app guidance.

CONCLUSION: Results suggest that compliance with remote biochemical verification can be improved through a comprehensive approach that includes increasing incentives, managing expectations, streamlining visual instructions, and diversifying reminders.},
}

@article {pmid41583981,
year = {2026},
author = {Samorodnitsky, S and Campbell, K and Little, A and Ling, W and Zhao, N and Chen, YC and Wu, MC},
title = {Detecting clinically relevant topological structures in multiplexed spatial proteomics using TopKAT.},
journal = {Patterns (New York, N.Y.)},
volume = {7},
number = {1},
pages = {101456},
pmid = {41583981},
issn = {2666-3899},
abstract = {Multiplexed spatial proteomics profiling platforms expose the intricate geometric structure of cells in the tumor microenvironment (TME). The spatial arrangement of cells has been shown to have important clinical implications, correlating with disease prognosis and treatment response. These datasets require new statistical methods to test whether cell-level images are associated with patient-level outcomes. We propose the topological kernel association test (TopKAT), which combines persistent homology with kernel testing to determine whether geometric structures created by cells predict continuous, binary, or survival outcomes. TopKAT quantifies the topological structure of cells in each image using persistence diagrams and compares the similarities between persistence diagrams on the basis of the number and lifespan of the detected homologies among cells. We show that TopKAT can be more powerful than existing approaches, particularly when cells arise along the boundary of a ring and demonstrate its utility in breast cancer and colorectal cancer applications.},
}

@article {pmid41583700,
year = {2026},
author = {Pernikoff, S and Clurman, A and Rötepohl, M and Galanter, N and Bibby, M and Harris, E and Stevens-Ayers, T and Xie, H and Ueda Oshima, M and Cheng, GS and Englund, JA and Boeckh, MJ and Boonyaratanakornkit, J},
title = {Respiratory Syncytial Virus in Hematopoietic Cell Transplant Recipients: Clinical and Humoral Risk Factors for Infection.},
journal = {Open forum infectious diseases},
volume = {13},
number = {1},
pages = {ofag005},
pmid = {41583700},
issn = {2328-8957},
abstract = {BACKGROUND: Respiratory syncytial virus (RSV) frequently causes upper respiratory tract infections, lung disease, and mortality in hematopoietic cell transplant (HCT) recipients. Currently, little is understood about what clinical and immunologic factors increase a patient's risk of infection or are protective against infection in immunocompromised populations.

METHODS: This study analyzed clinical and serologic data from a cohort of HCT recipients followed longitudinally with weekly blood draws and PCR surveillance for respiratory viruses to gain insight into clinical and antibody-based risk factors for RSV infection post-transplant. Serum was analyzed by a plaque reduction neutralization assay to determine neutralizing antibody titers to RSV.

RESULTS: Sixteen of 471 HCT recipients tested positive for RSV within the first 100 days post-transplant. A multivariate analysis of clinical factors revealed that prophylaxis with sirolimus for graft-versus-host disease (GVHD) was significantly correlated with increased risk of RSV infection. Moreover, higher levels of neutralizing antibody to RSV were associated with reduced risk for RSV infection, in a time-varying analysis.

CONCLUSIONS: GVHD prophylaxis with sirolimus and low serum neutralizing antibody titers were correlated with increased risk of RSV infection in the early post-transplant period. These results support the role of developing and implementing strategies that boost neutralizing antibody levels to prevent RSV infections in HCT recipients.},
}

@article {pmid41583333,
year = {2026},
author = {Riviere, P and Morgan, KM and Nelson, T and Minarim, DS and Deshler, L and Banegas, MP and Stewart, TF and McKay, RR and Javier-DesLoges, J and Parsons, JK and Rose, BS},
title = {Natural History and Risk Stratification of Biochemically Recurrent Prostate Cancer Following Definitive Radiation Therapy.},
journal = {Advances in radiation oncology},
volume = {11},
number = {2},
pages = {101936},
pmid = {41583333},
issn = {2452-1094},
abstract = {PURPOSE: Among patients with biochemical recurrent (BCR) prostate cancer following radiation therapy, there is no validated method for identifying those at the highest risk for metastases or death from prostate cancer. We characterized the natural history of BCR after radiation therapy and validated the proposed European consensus guidelines for stratification.

METHODS AND MATERIALS: This retrospective, multicenter, nationwide cohort study used data from patients having postradiation BCR treated in the United States Veterans Administration Health System. High-risk BCR was defined as either Gleason score ≥8 or BCR occurring within 18 months of radiation therapy, per guidelines.

RESULTS: Among 7126 patients who experienced BCR, 35.5% of patients developed metastatic disease and 17.4% died of prostate cancer at 10 years. 38.5% of patients had a high-risk BCR. High-risk BCR resulted in higher 10-year incidence of metastatic disease (56.2% vs 42.0%, adjusted hazard ratio [aHR] = 1.83, 95% CI: 1.69-1.98) and worse prostate cancer-specific survival (69.5% vs 81.6%, aHR = 1.82, 95% CI: 1.63-2.03, P < .001) and all-cause death (67.8% vs 65.0%, aHR = 1.18, 95% CI: 1.11-1.26, P < .001).

CONCLUSIONS: A simple, 2-element risk stratification tool using existing clinical data is the first validated tool for identifying patients at risk of metastases or prostate cancer-specific mortality following postradiation BCR. Most patients experiencing BCR in this context do not develop metastases or lethal prostate cancer, making such stratification essential for treatment decision-making and refinement of patient populations for clinical trials.},
}

@article {pmid41583128,
year = {2026},
author = {Cabre, HE and Marlatt, KL and Fernández-Verdejo, R and Beyl, R and Redman, LM and Ainslie, PN and Alemán-Mateo, H and Andersen, LF and Anderson, LJ and Arab, L and Bedu-Addo, K and Bonomi, AG and Bouten, CV and Bovet, P and Brage, S and Buchowski, MS and Butte, NF and Camps, SG and Casper, R and Close, GL and Colbert, LH and Cooper, JA and Cooper, R and Das, SK and Deb, S and Forrester, T and Gillingham, M and Goris, AH and Gurven, M and Hambly, C and Hu, S and Joosen, AM and Katzmarzyk, P and Kempen, KP and Kimura, M and Kraus, WE and Kriengsinyos, W and Kushner, RF and Lessan, N and Löf, M and Martin, CK and Matsiko, E and Medin, AC and Morehen, JC and Morton, JP and Neuhouser, ML and Prentice, RL and Racette, SB and Raichlen, DA and Reynolds, RM and Roberts, SB and Sardinha, LB and Schuit, AJ and Silva, AM and Urlacher, SS and Valencia, ME and Van Etten, LM and Verbunt, JA and Wilson, G and Wood, BM and Yoshida, T and Zhang, X and Murphy-Alford, AJ and Loechl, CU and Luke, AH and Pontzer, H and Rood, J and Sagayama, H and Schoeller, DA and Westerterp, KR and Wong, WW and Yamada, Y and Speakman, JR and Ravussin, E},
title = {Sex Differences in Measures of Energy Expenditure and Body Composition in Young, Middle-Aged, and Older Adults.},
journal = {Current developments in nutrition},
volume = {10},
number = {1},
pages = {107614},
pmid = {41583128},
issn = {2475-2991},
abstract = {BACKGROUND: Total daily energy expenditure (TDEE) is vital for energy balance and cardiometabolic health, yet its trajectory across the lifespan, particularly in females, remains poorly understood.

OBJECTIVES: We sought to examine the effects of aging and sex on body composition and TDEE.

METHODS: In a cross-sectional analysis of data from research centers across 9 European Countries and the United States from the International Atomic Energy Agency database, TDEE and body composition measures of 2326 participants (1560W/766M; 50.7 ± 12 .6 y) were stratified across age groups: young (30-39 y; YOUNG), middle-aged (40-54 y; MID), and old (55-70 y; OLD). Doubly labeled water was used to estimate TDEE and fat-free mass (FFM). Fat mass (FM) was calculated as the difference between body mass and FFM, and %fat was ratio between FM and body mass as a percentage. Linear models were used for analysis.

RESULTS: Females demonstrated greater FM and lower FFM with each age group, compared with males (P < 0.001). In females, OLD had lower absolute TDEE than YOUNG (-217 kcal/d, P < 0.001) and MID (-208 kcal/d, P < 0.001). Male absolute TDEE was lowered across all age groups (OLD compared with YOUNG: -334 kcal/d; OLD compared with MID: -210 kcal/d; MID compared with YOUNG: -124 kcal/d; P < 0.001). Adjusted TDEE was similar within age groups between females and males.

CONCLUSIONS: These results suggest that age influences changes in body composition and energy expenditure similarly between males and females. The most significant change in TDEE occurs as individuals transition from middle age to older adulthood. Females generally have a higher percentage of %fat and FM, along with lower FFM, compared with males across all age groups. These findings are important for understanding how aging affects metabolism and body composition, which could inform sex-specific health strategies and interventions.},
}

@article {pmid41582039,
year = {2025},
author = {Tawagi, K and Khaki, AR and Chablani, PV and Hoffman-Censits, J and Koshkin, VS and Plimack, ER and Galsky, MD and Gupta, S and Rosenberg, JE and Grivas, P and O'Donnell, PH},
title = {Preferred Treatment Sequencing for Metastatic Urothelial Carcinoma (mUC) in the Era of Perioperative and First-Line (1L) Checkpoint Inhibitor: Results From a National Survey of Genitourinary Oncologists.},
journal = {Clinical genitourinary cancer},
volume = {},
number = {},
pages = {102487},
doi = {10.1016/j.clgc.2025.102487},
pmid = {41582039},
issn = {1938-0682},
abstract = {BACKGROUND: Immune checkpoint inhibitors (ICI) are commonly used in urothelial carcinoma. We sought to understand provider preferences for subsequent treatment of patients after prior ICI.

MATERIALS AND METHODS: We comprised a group of 11 expert genitourinary medical oncologists in the United States and created a survey regarding treatment sequencing. We present the final responses to this survey, using descriptive statistics.

RESULTS: We received 78 responses (34%) from 227 genitourinary oncologists between May and August 2024; most were practicing for >5 years (62%) and were seeing >25 patients with metastatic urothelial carcinoma (mUC) yearly (72%). For patients with progression while receiving adjuvant ICI, 51% of respondents were somewhat/very likely to use enfortumab vedotin/pembrolizumab (EVP) as next therapy line. For patients with progression after prior ICI, 1/3 of respondents would consider first-line (1L) EVP irrespective of the interval from prior ICI completion. For ICI given in nonmuscle invasive bladder cancer and muscle-invasive bladder cancer, 43% and 45%, respectively would consider EVP > 6 months post-ICI completion. After progression on EVP, 77% were somewhat/very likely to give platinum-based chemotherapy, and most would not include combination or switch maintenance ICI. Similarly, 80% were somewhat/very likely to recommend non-ICI clinical trials in the second-line setting after EVP, and 87% were somewhat/very likely to offer erdafitinib for susceptible FGFR3 alterations.

CONCLUSION: Survey-based opinions can effectively capture treatment selection preferences for mUC and could inform future clinical trial design. Additional data, including the impact of residual toxicity from 1L EVP, are needed to better understand real-world treatment sequencing patterns.},
}

@article {pmid41581332,
year = {2026},
author = {Duong, A and Fritzsche, D and Indorf, AL},
title = {Practical Considerations for the Use of Antiemetics in Pregnant Patients With Breast Cancer.},
journal = {Clinical breast cancer},
volume = {26},
number = {2},
pages = {80-86},
doi = {10.1016/j.clbc.2025.12.012},
pmid = {41581332},
issn = {1938-0666},
abstract = {Early breast cancer treatment commonly includes highly emetogenic chemotherapy and immunotherapy regimens. Both pregnancy and chemotherapy treatment are associated with nausea and vomiting, and many agents used to treat pregnancy-associated nausea have limited data for CINV. Guidelines recommend a 4-drug antiemetic regimen for highly emetogenic chemotherapy regimens. Designing antiemetic regimens for pregnant women undergoing treatment for early breast cancer remains a challenge because of a lack of safety data for commonly used antiemetics as well as physiologic changes that occur throughout pregnancy This review aims to discuss current literature and guideline recommendations and provide practical considerations for agents used in chemotherapy-induced nausea and vomiting prevention in pregnant patients with breast cancer. A literature search on nausea pathophysiology, treatment of pregnant breast cancer patients, antiemetic use in pregnancy and chemotherapy-induced nausea and vomiting was conducted. Primary and tertiary literature sources were reviewed and cited. An overview of nausea pathophysiology and general treatment principles of treatment and supportive care in pregnant breast cancer patients is outlined. Five major antiemetic drug classes are reviewed in this article. When designing antiemetic regimens for pregnant patients undergoing chemotherapy treatment, clinicians must consider the current evidence, including safety, side effects, and pharmacokinetics of various agents, as well as pregnancy trimester and associated physiologic changes. Optimal management and prevention of chemotherapy-induced nausea and vomiting is crucial to avoid treatment delays and hospitalization, and to maximize patient quality of life.},
}

@article {pmid41581152,
year = {2026},
author = {Jagana, HL and Shabar, MM and Jackson, TS and Johnson, DE and Hemenway, JM and Mukkamala, V and Lukasik, A and Hathaway, MR and Pattwell, SS},
title = {Oncogenic influences of neurotrophin receptors: Shedding light on Trk biology.},
journal = {Cell reports},
volume = {45},
number = {2},
pages = {116928},
doi = {10.1016/j.celrep.2026.116928},
pmid = {41581152},
issn = {2211-1247},
abstract = {During critical stages of neurodevelopment, tropomyosin receptor kinase receptors, encoded by NTRK genes, exhibit temporally driven differential peaks of expression to properly guide the establishment of the peripheral and central nervous systems. In addition, these neuronal systems exhibit non-canonical regulation of surrounding tissues, impacting organogenesis, homeostasis, plasticity, and regeneration. The same processes that guide neurodevelopment, such as differentiation, plasticity, and neuronal survival, are also hijacked in cancer, making the NTRK family an ideal candidate to study. The Trk receptor family plays a critical role in both normal development and several cancer hallmark pathways such as anti-apoptotic signaling, abnormal cellular proliferation, metastasis, and stemness. It is paramount to understand the molecular underpinnings that Trk receptors play in driving malignancy and the specificity of current therapeutics. This review explores key implications of the NTRK gene family in the pathophysiological mechanisms driving cancers within and outside the central nervous system.},
}

@article {pmid41580163,
year = {2026},
author = {Dhar, A and Siva, S and Tan, VS and Mahadevan, A and Bruynzeel, A and Tang, C and Cury, F and Corkum, M and Ali, M and Zaorsky, NG and Cheung, P and Hannan, R and Hudes, R and Morgan, S and Lo, S and Murthy, V and Correa, RJM and Swaminath, A},
title = {International Radiosurgery Oncology Consortium of the Kidney (IROCK) Contouring Guidelines for Renal Cell Carcinoma treated with Stereotactic Ablative Radiotherapy.},
journal = {International journal of radiation oncology, biology, physics},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.ijrobp.2026.01.008},
pmid = {41580163},
issn = {1879-355X},
abstract = {INTRODUCTION: Stereotactic ablative body radiotherapy (SABR) is an emerging indication for localized renal cell carcinoma (RCC), yet there is a need for standardizing contouring practices, as accurate target delineation is essential to ensure optimal outcomes. Our objective was to develop consensus guidelines for target volume contouring for RCC SABR.

MATERIALS AND METHODS: An international panel of RCC SABR experts affiliated with XXXXXX was convened. All were asked to contour target volumes for four relevant clinical scenarios: a large tumor (>10cm) with IVC tumor thrombus; a central tumor abutting the renal hilum; a local recurrence following nephrectomy; and an ablation cavity recurrence after radiofrequency ablation. Participants also contoured two investigational renal substructures: renal cortex and renal hilum. Contours by case were analyzed using a STAPLE algorithm (95% confidence level). Consensus contours & guidelines statements were discussed and refined over two consensus meetings. Measures of variance and agreement, including Dice Similarity Coefficients (DSC), Mean Distance to Agreement (MDA), and Hausdorff Distance (HD), were measured for each case.

RESULTS: In total, 16 radiation oncologists participated. The median DSC was 0.85, and the median MDA/HD were 2.17 mm/9.00 mm respectively. The median DSC was greater than 0.70 for each case, suggesting 'good agreement' among participants. Based on the consensus discussion, any tumor thrombus or ablation cavity should be included in the target volume; organ at risk dose constraints should take priority over target coverage in planning; and the ipsilateral renal cortex should be defined as the ipsilateral renal parenchyma, excluding the target volume, the renal pelvis, renal vasculature, and proximal ureter.

CONCLUSION: We present the first international consensus contouring guideline for RCC SABR. There was strong agreement amongst experts, yielding high-fidelity consensus contours and guidance statements for each scenario. These results can be used as a guide for radiation oncologists interested in using SABR to treat patients with localized RCC.},
}

@article {pmid41579732,
year = {2026},
author = {Beydoun, HA and Beydoun, MA and Tsai, J and Tinker, LF and Franceschini, N and Nudy, M and Gradidge, PJ and Haring, B and Jung, SY and Price, CA and Nakhoul, M and Manson, JE},
title = {Triglyceride-glucose index and cardiovascular disease by cardiovascular-kidney-metabolic syndrome and socioeconomic status among postmenopausal women.},
journal = {Atherosclerosis},
volume = {414},
number = {},
pages = {120645},
doi = {10.1016/j.atherosclerosis.2026.120645},
pmid = {41579732},
issn = {1879-1484},
abstract = {BACKGROUND AND AIMS: The triglyceride-glucose (TyG) index (ln [fasting triglyceride (mg/dL) × fasting glucose (mg/dL)/2]) is a novel, simple, and inexpensive biomarker of insulin resistance with growing evidence in support of its diagnostic and prognostic value for cardiovascular disease (CVD). We examined the relationship of baseline TyG index with incident CVD, coronary heart disease (CHD), and cerebrovascular disease during up to 32 years of follow-up among postmenopausal women, before and after stratifying by the cardiovascular-kidney-metabolic (CKM) syndrome and socioeconomic status (SES) at baseline.

METHODS: 11,769 participants from Women's Health Initiative (5074 with CKM vs. 6695 without CKM; 4149 low SES vs. 5958 medium SES vs. 1662 high SES) were analyzed.

RESULTS: On average, the TyG index increased with decreasing SES and was higher in women with vs. without CKM. Cox regression and multistate Markov models adjusting for demographic, lifestyle, and health characteristics at baseline were constructed to estimate hazard ratios (HR) and 95 % confidence intervals (CI). A 1-unit increase in the TyG index was associated with greater CVD risk (CVD: HR = 1.54, 95 % CI: 1.39, 1.71; CHD: HR = 1.74, 95 % CI: 1.52, 1.99; Cerebrovascular disease: HR=1.32, 95% CI: 1.15, 1.53). The TyG index was positively associated with probabilities of transitions from a healthy state to CHD, cerebrovascular disease, and death, as well as transitions between CHD or cerebrovascular disease and death. These relationships did not vary by CKM syndrome or SES.

CONCLUSIONS: Among postmenopausal women, irrespective of CKM syndrome or SES, the TyG index is a valuable diagnostic and prognostic tool for CVD outcomes.},
}

@article {pmid41577999,
year = {2026},
author = {Oehler, VG and Sala-Torra, O and Gilderman, N and Beppu, L and Woolston, DW and Namaganda, P and Rynning, J and González, IG and Towlerton, A and Voutsinas, J and Wu, Q and Yeung, CCS and Radich, JP},
title = {Next-generation sequencing from chronic myeloid leukemia dried blood spots: insights and implications for global oncology.},
journal = {Leukemia},
volume = {},
number = {},
pages = {},
pmid = {41577999},
issn = {1476-5551},
abstract = {The goal of the "Spot On CML" program is to provide diagnostic and monitoring tests to chronic myeloid leukemia (CML) patients in low- and middle-income countries (LMICs). Previously, we demonstrated reproducible BCR::ABL1 transcript quantification using dried blood spots (DBS). We have now optimized methods of DNA and RNA extraction from DBS, allowing the detection of myeloid gene variants, including ABL1 tyrosine kinase domain mutations. Among 177 CML patients from nine countries, ABL1 mutations were identified in 61 (34%) patients, with multiple mutations present in some cases. The most common ABL1 mutation was T315I (45.9% of patients with ABL1 mutations). Among 69 patients, 89 Tier I-II variants (pathogenic or likely pathogenic) were identified in other genes, including 52 ASXL1 variants in 49 patients. The detection of ASXL1 variants correlated strongly with the presence of ABL1 mutations (P = 3.51E-04). These methodologies are directly applicable to all assays used for the diagnosis, prognosis, and monitoring of CML and have important implications in bringing state-of-the-art genetic analysis to CML patients in LMICs.},
}

@article {pmid41575736,
year = {2026},
author = {Gupta, AK and Ablona, A and Consolacion, TB and Bartlett, S and Beck, S and Burchell, AN and Darvishian, M and Alvarez, MJ and Yu, A and Wong, S and Woods, RR and Bhatti, P and Salters, K and Wong, J and Gilbert, M and Krajden, M and Janjua, N and Grennan, T},
title = {Trends in the incidence of HPV-associated anal cancer by risk group, 1990-2019: A population-based cohort study in British Columbia, Canada.},
journal = {Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology},
volume = {},
number = {},
pages = {},
doi = {10.1158/1055-9965.EPI-25-0890},
pmid = {41575736},
issn = {1538-7755},
abstract = {BACKGROUND: Anal squamous cell carcinoma, caused by human papillomavirus disproportionately affects people living with HIV (PLWH), particularly gay, bisexual, and other men who have sex with men (GBM). New guidelines recommend screening and treatment of pre-cancerous lesions. We aimed to estimate anal cancer incidence by HIV status, sex, and GBM status in British Columbia, Canada.

METHODS: Using administrative health databases, we assessed anal cancer stratified by HIV-status, sex, and sexual orientation from 1990 to 2019. A phenotypic algorithm was used to classify GBM status. We evaluated the comparative incidence of anal cancer using Fine and Gray's competing risks sub-distribution hazards model. Hazard ratios were estimated and adjusted for age, healthcare utilization, urbanicity, and Charlson co-morbidity index.

RESULTS: Among 571 anal cancer diagnoses assessed, the incidence was highest among GBM with HIV (78.09 per 100,000 person-years [PY]; 95% confidence interval [CI] = 61.24-99.58) followed by heterosexual males with HIV (44.49 per 100,000 PY; 95% CI = 29.56-66.95), and females with HIV (12.05 per 100,000 PY; 95% CI = 4.52-32.11). GBM with HIV experience a 76-fold increased anal cancer risk compared with heterosexual men without HIV (aHR 76.08; 95% CI 55.14-104.97).

CONCLUSIONS: There is an unmet need in anal cancer prevention among PLWH. Screening strategies that are sensitive, specific, acceptable, and cost-effective are necessary.

IMPACT: This study provides the first population-based estimates of anal cancer incidence by HIV and GBM status in British Columbia, highlighting disparities and rising trends. These findings support prioritizing targeted screening programs and improving access to care.},
}

@article {pmid41575713,
year = {2026},
author = {Pi, S and Rutter, CM and Pineda-Antunez, C and Chen, JH and Goldhaber-Fiebert, JD and Alarid-Escudero, F},
title = {Discrete-Event Simulation Modeling Framework for Cancer Interventions and Population Health in R (DESCIPHR): An Open-Source Pipeline.},
journal = {PharmacoEconomics},
volume = {},
number = {},
pages = {},
pmid = {41575713},
issn = {1179-2027},
support = {T15LM007033//U.S. National Library of Medicine/ ; DGE-2146755//National Science Foundation Graduate Research Fellowship Program/ ; U01-CA253913//Division of Cancer Prevention, National Cancer Institute/ ; U01-CA265750//Division of Cancer Prevention, National Cancer Institute/ ; },
abstract = {Simulation models inform health policy decisions by integrating data from multiple sources and forecasting outcomes when there is a lack of comprehensive evidence from empirical studies. Such models have long supported health policy for cancer, the first or second leading cause of death in over 100 countries. Discrete-event simulation (DES) and Bayesian calibration have gained traction in the field of decision science because they enable flexible modeling of complex health conditions and produce estimates of model parameters that reflect real-world disease epidemiology and data uncertainty given model constraints. This uncertainty is then propagated to model-generated outputs, enabling decision-makers to assess confidence in recommendations and estimate the value of collecting additional information. However, there is limited end-to-end guidance on structuring a DES model for cancer progression, estimating its parameters using Bayesian calibration, and applying the calibration outputs to policy evaluation. To fill this gap, we introduce the DES Modeling Framework for Cancer Interventions and Population Health in R (DESCIPHR), an open-source codebase integrating a flexible DES model for the natural history of cancer, Bayesian calibration for parameter estimation, and an example application of screening strategy evaluation. To illustrate the framework, we apply DESCIPHR to calibrate bladder and colorectal cancer models to real-world cancer registry targets. We also introduce an automated method for generating data-informed parameter prior distributions and increase the functionality of a neural network emulator-based Bayesian calibration algorithm. We anticipate that the adaptable DESCIPHR modeling template will facilitate the construction of future decision models evaluating the risks and benefits of health interventions.},
}

@article {pmid41574991,
year = {2026},
author = {Podgorsak, A and Kang, J and Zheng, D and Milano, M and Lo, S and Hardy, S},
title = {The Role of Artificial Intelligence for the Radiotherapeutic Management of Brain Metastases.},
journal = {Cancer journal (Sudbury, Mass.)},
volume = {32},
number = {1},
pages = {},
pmid = {41574991},
issn = {1540-336X},
mesh = {Humans ; *Brain Neoplasms/secondary/radiotherapy/diagnosis ; *Artificial Intelligence ; *Radiosurgery/methods ; Radiotherapy Planning, Computer-Assisted/methods ; Prognosis ; },
abstract = {As the radiotherapeutic management of brain metastases increasingly utilizes stereotactic radiosurgery (SRS) and repeated treatments, artificial intelligence (AI) applications are being investigated in treatment planning, prognostication, and evaluation of treatment effects versus tumor progression. The burden on radiation oncologists increases as more lesions are targeted with SRS. AI algorithms facilitate improved detection and segmentation of lesions, reduce interobserver variability, and save clinician time. Predictive analytics, based on large datasets, enable better prognostication and treatment strategies tailored to individual patients. There is also data for the differentiation between radiation necrosis and tumor progression, which is a difficult issue that comes up more and more in patient care. However, challenges remain regarding data standardization, model validation, and clinical integration. Continued research and interdisciplinary collaboration are essential to fully harness AI's potential in the radiotherapeutic management of brain metastases and improving patient outcomes in neuro-oncology.},
}

Humans
*Brain Neoplasms/secondary/radiotherapy/diagnosis
*Artificial Intelligence
*Radiosurgery/methods
Radiotherapy Planning, Computer-Assisted/methods
Prognosis

@article {pmid41571919,
year = {2026},
author = {Bot, A and Stephan, MT and Gill, S},
title = {The dawn of in vivo immune cell engineering in oncology.},
journal = {Nature biotechnology},
volume = {},
number = {},
pages = {},
pmid = {41571919},
issn = {1546-1696},
}

@article {pmid41571639,
year = {2026},
author = {Nicholas, JC and Katz, DH and Tahir, UA and Debban, CL and Aguet, F and Blackwell, T and Bowler, RP and Broadaway, KA and Chen, J and Clish, CB and Coresh, J and Cornell, E and Cruz, DE and Deo, R and Doyle, MF and Durda, P and Ekunwe, L and Floyd, JS and Gill, D and Guo, X and Hoogeveen, RC and Johnson, C and Lange, LA and Li, Y and Manning, A and Meigs, JB and Mi, MY and Mychaleckyj, JC and Olson, NC and Pratte, KA and Psaty, BM and Reiner, AP and Ruan, P and Sevilla-Gonzalez, M and Shah, AM and Sun, Q and Tracy, RP and Wen, J and Wood, AC and Wilson, JG and Young, KL and Yu, B and Rooney, MR and Manichaikul, A and Dubin, R and Mohlke, KL and Rich, SS and Rotter, JI and Ganz, P and Gerszten, RE and Taylor, KD and Raffield, LM},
title = {Cross-ancestry comparison of aptamer and antibody protein measures.},
journal = {Nature communications},
volume = {17},
number = {1},
pages = {1054},
pmid = {41571639},
issn = {2041-1723},
support = {1F31HL176194-01A1//U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)/ ; T32GM135128//U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS)/ ; R01HL133870//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; R01DK072193//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; },
mesh = {Humans ; *Proteomics/methods ; *Antibodies/genetics ; Genetic Variation ; *Proteins/genetics ; *Aptamers, Nucleotide ; Polymorphism, Single Nucleotide ; },
abstract = {Measures from affinity-proteomics platforms often correlate poorly, challenging interpretation of protein associations with genetic variants and phenotypes. Here, we examine 2157 proteins measured on both SomaScan 7k and Olink Explore 3072 across 1930 participants with genetic similarity to European, African, East Asian, and Admixed American ancestry references. Inter-platform correlation coefficients for these 2157 proteins follow a bimodal distribution (median r = 0.30). We evaluate protein measure associations with genetic variants, and find approximately 25-30% of the signals on each platform are likely driven by protein-altering variants. We highlight 80 proteins that correlate differently across ancestry groups likely in part due to differing protein-altering variant frequencies by ancestry. Furthermore, adjustment for protein-altering variants with opposite directions of effect by platform improves inter-platform protein measure correlation and results in more concordant genetic and phenotypic associations. Hence, protein-altering variants need to be accounted for across ancestries to facilitate platform-concordant and accurate protein measurement.},
}

Humans
*Proteomics/methods
*Antibodies/genetics
Genetic Variation
*Proteins/genetics
*Aptamers, Nucleotide
Polymorphism, Single Nucleotide

@article {pmid41567835,
year = {2025},
author = {Blinka, S and Wong, RL and Holt, SK and Lo, E and Cheng, HH and Conrad, N and Loesch, H and Toulouse, AE and Lai, M and Hsieh, AC and Grivas, P and Yezefski, T and Wright, JL and Schweizer, MT and Montgomery, RB and Chen, DL and Zeng, J and Lin, DW and Yu, EY},
title = {Results from a prospective registry of [18]F-Fluciclovine PET/CT use in prostate cancer management: a cautionary lesson for implementation of PSMA PET.},
journal = {American journal of nuclear medicine and molecular imaging},
volume = {15},
number = {6},
pages = {262-271},
pmid = {41567835},
issn = {2160-8407},
abstract = {BACKGROUND: [18]F-Fluciclovine positron emission tomography (PET) was FDA-approved in the U.S. in 2016 and was the most sensitive imaging modality for prostate cancer (PC) until the approval of prostate-specific membrane antigen (PSMA) PET in 2020. However, providers' reasons for ordering [18]F-Fluciclovine PET/CT (FluPET) in practice and impact on patient care remain poorly defined. This prospective registry at a tertiary academic center describes patterns of FluPET use and outcomes prior to the FDA approval of PSMA PET in December 2020.

METHODS: Providers ordering FluPET for patients with PC were surveyed before, ≤2 weeks after, and ≥1 year after imaging to assess reasons for obtaining FluPET, projected treatment plan, changes in plan due to FluPET findings, and toxicity attributable to the change in treatment plan. Baseline patient characteristics, FluPET results, and longitudinal outcomes were collected.

RESULTS: Between 12/2018-09/2021, 62 patients with localized PC (8.1%), biochemical recurrence (BCR; 80.6%), non-metastatic castration-resistant PC (CRPC) (3.2%), metastatic castration-sensitive PC (3.2%), or metastatic CRPC (4.8%) were enrolled and underwent FluPET. Most scans (90.3%) were performed prior to the FDA approval of PSMA PET 12/2020. FluPET was most often obtained to guide local salvage or metastasis-directed therapies (90.3%); other reasons (non-exclusive) were initial staging (9.6%) or clarifying equivocal lesions from other imaging (9.6%). FluPET detected ≥1 PC lesion in 74.2% of patients. After FluPET, 48.4% of providers reported changing treatment plans, which was more likely when FluPET was positive (60.9% vs 12.5%, P<0.001), and often involved initiation of systemic therapy (19.4%). Treatment changes were reported in 57% of patients with BCR1 and 48.2% of patients with BCR2. In contrast, only 20% of patients with distant metastatic disease had a change in treatment. Among patients in the BCR1 and BCR2 cohort, treatment plan changes were associated with a median time to next treatment that was not reached after a median follow-up of 67.6 months. There was no statistically significant difference in overall survival between patients with biochemical recurrence (BCR) who did and did not have a treatment plan change. A year after FluPET, reported potential toxicities from treatment plan changes were minimal.

CONCLUSION: FluPET was utilized across the disease spectrum of PC, primarily to guide local salvage or metastasis-directed therapies, given its improved sensitivity for detecting prostate bed recurrence due to the slow physiologic excretion of [18]F-fluciclovine. Notably, a positive FluPET frequently prompted initiation of systemic therapy; however, the clinical benefit of such management remains uncertain. Moreover, providers often selected multiple, sometimes conflicting, treatment plans following FluPET, reflecting uncertainty in translating imaging findings into definitive management decisions. A larger, prospective registry using PSMA PET with a requirement for providers to select a single post-scan treatment strategy is warranted to better assess whether imaging-guided treatment changes improve clinical outcomes.},
}

@article {pmid41565815,
year = {2026},
author = {Sng, XYX and Voigt, V and Schuster, IS and Fleming, P and Deuss, FA and Abuwarwar, MH and van Dommelen, SLH and Neate, GEG and Arnold, RM and Horsnell, HL and Daly, S and Golzarroshan, B and Varelias, A and Lyman, SD and Scalzo, AA and Hill, GR and Mueller, SN and Wikstrom, ME and Berry, R and Rossjohn, J and Fletcher, AL and Andoniou, CE and Degli-Esposti, MA},
title = {Fibroblastic reticular cells direct the initiation of T cell responses via CD44.},
journal = {Nature},
volume = {},
number = {},
pages = {},
pmid = {41565815},
issn = {1476-4687},
abstract = {The movement of dendritic cells and T cells within secondary lymphoid organs is critical for the development of adaptive immune responses[1,2]. Central to this process is the fibroblastic reticular cell (FRC) network, which forms a highly organized conduit system that facilitates the movement of and interactions between dendritic cells and T cells[3-6]. Previous studies have partly characterized how FRCs support these interactions[7,8]. However, the molecular mechanisms that operate under physiological conditions remain unknown. Here we show that the viral protein m11, encoded by the herpesvirus murine cytomegalovirus (CMV), inhibits antiviral immunity by targeting the FRC network and interfering with a critical function of cellular CD44. We found that m11 binds to CD44 and established that m11 perturbs the molecular interactions of CD44 with its natural ligand, hyaluronic acid. The interaction of m11 with CD44 impairs the trafficking of dendritic cells within the spleen, thereby impeding efficient priming of naive T cells and the initiation of antiviral CD8 T cell responses. The targeting of CD44 by CMV reveals CD44 as a molecule that is essential to the functioning of the FRC network and uncovers a previously unrecognized stroma-based mechanism that is critical for the generation of effective T cell responses.},
}

@article {pmid41564387,
year = {2026},
author = {Kelkar, AH and Abel, GA and Cutler, CS and Lee, SJ and Soiffer, RJ},
title = {Is It Time to Move Beyond Graft-Versus-Host Disease-Free, Relapse-Free Survival as a Primary End Point in Clinical Trials for Hematopoietic Cell Transplantation?.},
journal = {Journal of clinical oncology : official journal of the American Society of Clinical Oncology},
volume = {},
number = {},
pages = {JCO2502130},
doi = {10.1200/JCO-25-02130},
pmid = {41564387},
issn = {1527-7755},
}

@article {pmid41563741,
year = {2026},
author = {Babu, V and Shin, DB and Onstad, L and Pidala, JA and Chen, G and Lee, CJ and Kitko, CL and Carpenter, PA and Cutler, C and El Jurdi, N and Loren, AW and Gelfand, JM and Lee, SJ and Baumrin, E},
title = {Discordance in Treatment Response Assessment Between Clinicians and Patients With Skin Chronic Graft-vs-Host Disease.},
journal = {JAMA dermatology},
volume = {},
number = {},
pages = {},
pmid = {41563741},
issn = {2168-6084},
abstract = {IMPORTANCE: Clinician-reported and patient-reported outcomes are critical measures of therapeutic efficacy in cutaneous chronic graft-vs-host disease (cGVHD) but are not always correlated. Discordance in treatment response between clinicians and patients hinders interpretation of outcomes in clinical trials and complicates therapeutic decision-making in clinical practice.

OBJECTIVE: To identify factors associated with discordance in clinician-reported and patient-reported treatment response assessments and to evaluate the association of clinician-reported and patient-reported responses with survival.

This multicenter longitudinal cohort study included adults 18 years and older with cutaneous cGVHD at study enrollment, assembled from 2 observational studies and 1 randomized clinical trial. Data were collected from August 2007 to March 2024, and data were analyzed from July 2024 to May 2025.

MAIN OUTCOMES AND MEASURES: A global 8-point cutaneous cGVHD treatment response assessment (with 1 indicating resolved and 8 indicating very much worse) was reported by clinicians and patients 3 to 6 months after study enrollment. Clinician-reported and patient-reported treatment responses were categorized into improved, stable, and worse from the 8-point scale, and discordance was defined as a difference in response between clinicians and patients. Positive clinician discordance indicates the clinician reported a better response than the patient, and negative clinician discordance indicates the clinician reported a worse response than the patient. The association of clinician-reported and patient-reported responses with survival was measured by nonrelapse mortality.

RESULTS: Of 489 adults with cutaneous cGVHD, 192 (39.3%) were female, 297 (60.7%) were male, and the median (IQR) age was 55 (43-62) years. A total of 321 adults (65.6%) had concordant responses and 168 (34.4%) had discordant responses between clinician-reported and patient-reported treatment responses. Patients with sclerotic cGVHD had greater odds of discordance compared with those without sclerosis, with clinicians reporting both better and worse treatment response than patients (positive clinician discordance: adjusted odds ratio, 3.14; 95% CI, 1.41-6.95; P = .005; negative clinician discordance: adjusted odds ratio, 2.33; 95% CI, 1.19-4.56; P = .01). Worsening compared with improved overall cutaneous cGVHD was associated with nonrelapse mortality when reported by clinicians (adjusted hazard ratio, 2.28; 95% CI, 1.46-3.54; P < .001) and patients (adjusted hazard ratio, 1.86; 95% CI, 1.12-3.08; P = .02), while only patient-reported worsening was significantly associated with nonrelapse mortality in patients with sclerotic disease (adjusted hazard ratio, 2.00; 95% CI, 1.02-3.90; P = .04).

CONCLUSIONS AND RELEVANCE: In this cohort study, discordance in treatment response assessments between clinicians and patients was common in cutaneous cGVHD, yet clinician-reported and patient-reported treatment responses were both associated with survival. In patients with sclerosis who were more likely to experience discordance, patient-reported response was a critical treatment end point, and approaches should be developed to bridge discordance.},
}

@article {pmid41562706,
year = {2026},
author = {Ganesh, N and Grady, WM and Kaz, AM},
title = {Epigenetic Alterations in Colitis-Associated Colorectal Cancer.},
journal = {Epigenomes},
volume = {10},
number = {1},
pages = {},
pmid = {41562706},
issn = {2075-4655},
support = {U54 CA274374/CA/NCI NIH HHS/United States ; U2 CCA271902/CA/NCI NIH HHS/United States ; },
abstract = {Colitis-associated colorectal cancer (CAC) represents a distinct subtype of colorectal malignancy that arises in the setting of chronic inflammatory bowel disease (IBD). Unlike sporadic colorectal cancer, CAC develops through inflammation-driven molecular pathways, in which epigenetic alterations play a pivotal role in tumor initiation and progression. This review highlights the major epigenetic mechanisms implicated in CAC, including DNA methylation, histone modifications, and microRNA (miRNA) dysregulation. Aberrant DNA methylation patterns, such as promoter hypermethylation of tumor suppressor genes and global hypomethylation, contribute to genomic instability and altered gene expression. In parallel, inflammation-induced changes in histone configuration modulate chromatin accessibility and transcriptional activity of key oncogenic and tumor-suppressive pathways. Furthermore, deregulated miRNAs influence multiple aspects of CAC pathogenesis by targeting genes involved in inflammation and tumor progression. Understanding these epigenetic processes provides valuable insights into the development of colorectal malignancy and identifies potential biomarkers for early detection and intervention in colitis-associated colorectal cancer.},
}

@article {pmid41562022,
year = {2026},
author = {Childs-Kean, LM and Azimi, SF and Beieler, AM and Castellino, L and Keller, SC and Pertzborn, M and Yamshchikov, A and Yoke, LH and Young, K and Mahoney, MV},
title = {A bundle of the top 10 OPAT publications in 2024.},
journal = {Antimicrobial stewardship & healthcare epidemiology : ASHE},
volume = {6},
number = {1},
pages = {e20},
pmid = {41562022},
issn = {2732-494X},
abstract = {OBJECTIVE: Outpatient parenteral antimicrobial therapy (OPAT) is a mainstay of clinical infectious diseases practice, and OPAT-related publications continue to be prominent in journals. The objective of this article is to summarize ten clinically important OPAT-related publications from 2024.

DESIGN: Narrative review.

METHODS: Eighty-one articles were found in a literature search, and 56 met inclusion criteria. A survey containing 25 articles was sent to an email listserv of clinicians with OPAT experience.

RESULTS: This article summarizes the top 10 OPAT articles published in 2024, based on those survey results.

CONCLUSIONS: Common themes from the top 10 OPAT articles published in 2024 included OPAT clinician workload, patient perspectives of OPAT, tools for OPAT work, and dalbavancin use.},
}

@article {pmid41559522,
year = {2026},
author = {Sassine, D and Huang, Y and Hur, C and Elkin, EB and Ferris, JS and Melamed, A and Kong, CY and Myers, ER and Bickell, NA and Hazelton, WD and Layne, TM and Heckman-Stoddard, B and Samimi, G and Havrilesky, LJ and Blank, SV and Xu, X and Wright, JD},
title = {Neoadjuvant Chemotherapy Versus Primary Cytoreductive Surgery for Metastatic Endometrial Cancer.},
journal = {Cancer medicine},
volume = {15},
number = {1},
pages = {e71539},
pmid = {41559522},
issn = {2045-7634},
support = {U01 CA265739/CA/NCI NIH HHS/United States ; 1U01 CA265739/CA/NCI NIH HHS/United States ; },
mesh = {Humans ; Female ; *Endometrial Neoplasms/pathology/mortality/therapy/drug therapy/surgery ; *Cytoreduction Surgical Procedures/methods ; *Neoadjuvant Therapy ; Middle Aged ; Aged ; Neoplasm Staging ; Treatment Outcome ; Chemotherapy, Adjuvant ; Adult ; Neoplasm Metastasis ; },
abstract = {OBJECTIVE: To evaluate the pattern of use and clinical outcomes associated with neoadjuvant chemotherapy (NACT) compared with primary debulking surgery (PDS) in patients with stage IV endometrial cancer.

METHODS: We utilized the National Cancer Database to identify individuals diagnosed with stage IV endometrial cancer, and categorized them according to receipt of NACT or PDS. Propensity score weighting using inverse probability of treatment weighting was applied. Survival outcomes were evaluated using both an intention-to-treat (ITT) analysis, which included all eligible patients, and a per-protocol (PP) analysis restricted to those who underwent chemotherapy and surgery.

RESULTS: Among 18,205 patients, NACT utilization rose from 30.3% in 2010 to 73.8% in 2021 (p < 0.0001). In the multivariable analysis, patients diagnosed in more recent years, Black and Hispanic race and ethnicity, Medicaid insurance, serous histology, and greater comorbidities were associated with NACT (p < 0.05). In the ITT analysis, there was no mortality difference within 4 months after diagnosis between NACT patients and PDS patients (aHR = 1.03; 95% CI: 0.96-1.11); however, after 4 months, patients treated with NACT experienced higher mortality than those undergoing PDS (aHR = 1.58; 95% CI: 1.51-1.64). In the PP analysis, NACT patients had lower mortality compared to PDS patients within 24 months after diagnosis (aHR = 0.93; 95% CI, 0.88-0.99) but a 34% higher mortality after 24 months (aHR = 1.34; 95% CI, 1.23-1.47).

CONCLUSION: Utilization of NACT has expanded among patients with metastatic endometrial cancer. Primary debulking surgery with postoperative chemotherapy is linked to higher early mortality but improved long-term outcomes relative to treatment strategies beginning with NACT followed by surgery.},
}

Humans
Female
*Endometrial Neoplasms/pathology/mortality/therapy/drug therapy/surgery
*Cytoreduction Surgical Procedures/methods
*Neoadjuvant Therapy
Middle Aged
Aged
Neoplasm Staging
Treatment Outcome
Chemotherapy, Adjuvant
Adult
Neoplasm Metastasis

@article {pmid41542066,
year = {2026},
author = {Montano-Campos, F and Heagerty, P and Haupt, E and Hahn, E and Radich, J and Bansal, A},
title = {A Framework for Locally Imputing and Predicting Biomarker Trajectories Under Irregular Monitoring: Application to Chronic Myeloid Leukemia.},
journal = {Research square},
volume = {},
number = {},
pages = {},
pmid = {41542066},
issn = {2693-5015},
abstract = {Irregular monitoring and missing data limit the utility of longitudinal biomarkers in real-world practice. We developed a generalizable framework that combines interval-aligned preprocessing, localized multiple imputation, and machine-learning forecasting to generate complete trajectories and predict future biomarker values under routine clinical conditions. Using BCR::ABL1 monitoring in chronic myeloid leukemia as a case study, we aligned measurements to 90-day intervals, applied a windowed, uncertainty-propagating imputation strategy, and trained recurrent neural network (RNN) and XGBoost models to forecast values three and six months ahead. Full Information models achieved RMSEs of 1.22-1.24 for 3-month predictions-well below the biomarker's observed variability-and maintained accuracy even when the most recent visit was intentionally omitted, simulating extended follow-up. This framework preserves local temporal structure, supports individualized monitoring decisions, and is directly adaptable to other continuous biomarkers measured under irregular real-world schedules.},
}

@article {pmid41415362,
year = {2025},
author = {Bhatia, V and Tsao, A and Chong, T and Challita, PP and Liang, K and Sayar, E and Huang, J and Lawlor, ER and Haffner, MC and Nabet, B and Lee, JK},
title = {Armoring STEAP1 CAR T cells with IL-18 potentiates antitumor activity in Ewing sarcoma.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {41415362},
issn = {2692-8205},
abstract = {BACKGROUND: Ewing sarcoma (EwS) is a highly aggressive cancer driven by the EWS::FLI1 fusion oncoprotein affecting children, adolescents, and young adults. Six transmembrane epithelial antigen 1 (STEAP1) is a cell surface antigen transcriptionally controlled by EWS::FLI1 that is broadly expressed in EwS, positioning it as a rational immunotherapy target. However, translating CAR T therapy to solid tumors requires overcoming barriers to potency while maintaining safety.

METHODS: Analyses of transcriptome and proteome data were performed to evaluate the effects of EWS::FLI1 perturbation on STEAP1 expression at the transcript and protein levels in EwS models. STEAP1 expression was validated in EwS patient tissues by immunohistochemistry. Second-generation STEAP1-BBζ CAR T cells were tested in orthotopic and disseminated EwS xenograft models. To enhance antitumor activity, an IL-18-armored STEAP1 CAR was engineered. Dose-dependent therapeutic efficacy and safety were evaluated through measurement of tumor burden, survival, and observation for gross toxicities.

RESULTS: STEAP1 was expressed in ~97% of primary EwS tumors and directly associated with EWS::FLI1 fusion protein expression in EwS cell lines. In orthotopic EwS models, STEAP1 CAR T cells induced complete tumor regression at 5 x 10[6] cells. In disseminated disease models, responses were dose-dependent with no evidence of antigen loss. Notably, IL-18 armored STEAP1 CAR T cells achieved complete responses in ~80% of mice at a reduced dose of 10[6] cells without overt toxicity.

CONCLUSIONS: These data establish STEAP1 as a clinically relevant and highly expressed target in EwS and demonstrate that IL-18 armoring significantly improves CAR T cell efficacy by enhancing potency evident through antitumor activity at reduced cell dose. STEAP1 CAR T cells are currently under evaluation in a first-in-human phase 1/2 dose-escalation clinical trial for metastatic castration-resistant prostate cancer (NCT06236139) and these studies support future clinical translation of STEAP1 CAR T cell therapy for relapsed/refractory EwS.},
}

@article {pmid41558886,
year = {2026},
author = {Pichler, R and Subiela, JD and Scilipoti, P and Rehder, P and Grivas, P},
title = {Regional Node-positive Bladder Cancer: Therapeutic Decisions Based on Trial Results in Perioperative and Advanced Disease Settings.},
journal = {European urology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.eururo.2026.01.013},
pmid = {41558886},
issn = {1873-7560},
abstract = {Optimal therapeutic management for cN1 M0 bladder cancer consists of perioperative systemic therapy and radical cystectomy. For patients with cN2-3 M0 disease, evidence supports upfront systemic therapy, preferably with enfortumab vedotin + pembrolizumab. Consolidative locoregional therapy may be an option in selected responders. Questions remain regarding the optimal duration of systemic therapy and the role of biomarkers. Multidisciplinary expert opinion can be critical for informed shared decision-making.},
}

@article {pmid41557860,
year = {2026},
author = {Desai, D and Sager, RA and Basin, M and Jacob, JM and Morris, GJ and Spiess, PE and Li, R and Cheng, L and Necchi, A and Kamat, AM and Grivas, P and Pavlick, D and Goldberg, H and Mollapour, M and Lin, D and Ross, JS and Bratslavsky, G and Basnet, A and Daneshvar, MA},
title = {Fanconi Anemia Complementation Group C Gene (FANCC) Association with Hereditary and Sporadic Renal Tumors.},
journal = {The oncologist},
volume = {},
number = {},
pages = {},
doi = {10.1093/oncolo/oyag012},
pmid = {41557860},
issn = {1549-490X},
abstract = {BACKGROUND: Inactivating genomic alterations (GA) of FANCC gene are associated with genomic instability, DNA cross-linking, and homologous DNA repair deficiency (HRD). Here, we evaluated the incidence of FANCC GA in RT.

METHODS: 463,546 clinically advanced cancers (CAC) underwent hybrid capture-based comprehensive genomic profiling using the FDA-approved F1CDx assay to detect all classes of GA. MSI status, TMB, gLOH, prediction of germline status, and genomic signature were determined with algorithm-based analysis.

RESULTS: 1,993 (0.43%) CAC featured FANCC GA. 27 of these FANCC-mutated tumors (20 male, mean age 57) were RT (0.35% of 7,668 RT). The primary tumor was sequenced in 9 cases and a metastatic site in 18 (5 lymph node, 4 soft tissues, 3 brain, 2 livers, 1 each lung, adrenal, eye, bone). Only 1 of 25 tested FANCC-mutated RT was MSI-high. 4 cases (15%) featured TMB ≥10 mut/Mb. Genomic signature could be assessed in 5 cases: 4 were MMR deficient. The FANCC mutations included inactivating short variant mutations in 24 cases (10 nonsense, 10 frameshift, 2 non-frame and 2 splice-site mutations) and 3 truncating rearrangements (FANCC: SUSD3, FANCC: FANCC, FANCC: C20orf24). Interestingly, 14 (52%) of the FANCC-mutated RT were predicted to be germline.

CONCLUSIONS: Somatic and germline mutations in FANCC occur in an exceedingly small subset of clinically advanced RT but at similar rate to other cancers, and genomic landscape does not appear to be different from RT with wild-type FANCC. Germline testing is warranted, as we see high frequency of germline FANCC mutations.

PATIENT SUMMARY: Our study highlights the rate of FANCC mutation in kidney cancer, which may be a therapeutic target and awaits further assessment and drug development. Also, it shows that FANCC mutation are more germline, requiring further genetic testing.},
}

@article {pmid41557789,
year = {2026},
author = {Li, T and Ilano, A and Arias-Badia, M and Luong, D and Chang, H and Kwek, SS and Allaire, K and Chumber, A and Sakamoto, M and Clark, M and Lea, A and Bridge, M and Chen, B and Liu, E and Porten, S and Meng, MV and Erlich, LIR and Oh, DY and Fong, L},
title = {Functionally heterogeneous intratumoral CD4[+]CD8[+] double-positive T cells can give rise to single-positive T cells.},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
volume = {123},
number = {4},
pages = {e2506168123},
doi = {10.1073/pnas.2506168123},
pmid = {41557789},
issn = {1091-6490},
support = {1R35CA253175//HHS | NIH | National Cancer Institute (NCI)/ ; P50CA275741//HHS | NIH | National Cancer Institute (NCI)/ ; },
mesh = {Humans ; *Carcinoma, Renal Cell/immunology/pathology ; *CD8-Positive T-Lymphocytes/immunology ; *Kidney Neoplasms/immunology/pathology ; *CD4-Positive T-Lymphocytes/immunology ; Tumor Microenvironment/immunology ; Lymphocytes, Tumor-Infiltrating/immunology ; },
abstract = {Conventional single-positive (SP) CD4[+] and CD8[+] T cells recognize tumor antigens and help mediate clinical responses with cancer immunotherapy. Double-positive CD4[+]CD8[+] (DP) T cells have also been described in human cancers, but their role in the tumor microenvironment remains unclear. By generating a multiomic single cell atlas of DP and SP T cells, we find that DP T cells possess phenotypic heterogeneity similar to SP T cells that includes multiple clonally expanded populations of cytotoxic DP T cells in human renal cell carcinoma (RCC). These intratumoral DP T cells can mediate both MHC class I- and class II-dependent killing of autologous tumor cells. In addition, transcriptional profiling of DP TCR-bearing T cells revealed a gene signature enriched for clinical responders to PD-1 blockade in advanced RCC. We confirm prior observations of SP T cells transitioning into DP T cells and more notably, demonstrate that intratumoral T cells are capable of bidirectional differentiation in which DP T cells serve as precursors to SP T cell sin vivo. In the latter scenario, intratumoral DP T cells are shown to express Rag2, suggesting that the tumor may act as an extrathymic site of T cell development. These findings reveal the multiple roles that DP T cells can possess in antitumor immunity.},
}

Humans
*Carcinoma, Renal Cell/immunology/pathology
*CD8-Positive T-Lymphocytes/immunology
*Kidney Neoplasms/immunology/pathology
*CD4-Positive T-Lymphocytes/immunology
Tumor Microenvironment/immunology
Lymphocytes, Tumor-Infiltrating/immunology

@article {pmid41557352,
year = {2026},
author = {Alagoz, O and Lu, Y and Gil Quessep, E and Kerlikowske, K and Mandelblatt, JS and Sprague, BL and Trentham-Dietz, A and Hampton, J and Groeneweg, R and de Koning, HJ and Miglioretti, DL and Schechter, CB and van Ravesteyn, NT and Tosteson, ANA and Stout, NK and Lowry, KP},
title = {Five-Year Absolute Risk-Based and Age-Based Breast Cancer Screening in the US.},
journal = {JAMA network open},
volume = {9},
number = {1},
pages = {e2552944},
pmid = {41557352},
issn = {2574-3805},
mesh = {Humans ; Female ; *Breast Neoplasms/diagnosis/diagnostic imaging/epidemiology/mortality ; Middle Aged ; *Early Detection of Cancer/methods/statistics & numerical data ; *Mammography/methods/statistics & numerical data ; Aged ; Adult ; United States/epidemiology ; Risk Assessment/methods ; Age Factors ; *Mass Screening/methods ; },
abstract = {IMPORTANCE: General mammography screening guidelines target women at average risk within a specified age range (age based) and do not consider absolute risk of individual women at a given age (risk based).

OBJECTIVE: To compare outcomes of mammography screening strategies that vary by 5-year risk of invasive breast cancer vs age-based strategies.

This decision analytical model used 2 established Cancer Intervention and Surveillance Modeling Network (CISNET) breast cancer models and simulated US women born in 1980 who were aged 40 years or older without a prior history of breast cancer. Modeling analyses were conducted from April 2023 to April 2025.

INTERVENTION: Digital breast tomosynthesis delivered via 50 screening strategies (3 age based and 47 risk based) vs a no-screening scenario. Five-year absolute invasive breast cancer risk was based on the validated Breast Cancer Surveillance Consortium, version 3 calculator. Women's 5-year breast cancer risk was categorized as low, average, intermediate, or high.

MAIN OUTCOMES AND MEASURES: Primary outcomes included lifetime number of breast cancer deaths averted and false-positive screening recalls. Lifetime outcomes were averaged across models and expressed per 1000 women screened.

RESULTS: Nine risk-based screening strategies were associated with a comparable or greater number of deaths averted than biennial age-based screening from ages 40 to 74 years (B40-74) (range across strategies for mean model estimates, 6.8-7.5 per 1000 women vs 6.8 per 1000 women) as well as reduced false-positive recalls by 8% to 23% (1050-1257 per 1000 women for risk-based screening strategies vs 1365 per 1000 women for B40-74). For example, a risk-based approach using a combination of biennial screening (for women at low risk aged 55-74 years, at average risk aged 50-59 years, at intermediate risk aged 45-54 years, and at high risk aged 40-49 years) and annual screening (for women at average risk aged 60-74 years, at intermediate risk aged 55-74 years, and at high risk aged 50-74 years) would be associated with 6% more breast cancer deaths averted than B40-74 (7.2 vs 6.8 per 1000 women) and 13% fewer false-positive recalls (1190 vs 1365 per 1000 women). Results were consistent across the 2 CISNET models, and the relative difference in breast cancer deaths averted between B40-74 and risk-based screening strategies was more pronounced than for life-years gained.

CONCLUSIONS AND RELEVANCE: In this decision analytical modeling study of breast cancer screening, population risk-based screening using 5-year invasive breast cancer risk was associated with similar or greater benefits than age-based screening as well as reduced false-positive recalls. As personalized medicine advances, risk-based screening is poised to become a cornerstone of breast cancer prevention, offering a more nuanced and tailored approach to patient care.},
}

Humans
Female
*Breast Neoplasms/diagnosis/diagnostic imaging/epidemiology/mortality
Middle Aged
*Early Detection of Cancer/methods/statistics & numerical data
*Mammography/methods/statistics & numerical data
Aged
Adult
United States/epidemiology
Risk Assessment/methods
Age Factors
*Mass Screening/methods

@article {pmid41556857,
year = {2026},
author = {Tsai, YY and Thomas, CE and Law, PJ and Chen, Z and Gruber, SB and Schmit, SL and , },
title = {HLA Heterozygosity Influences Colorectal Cancer Risk and Survival Outcome.},
journal = {Gastroenterology},
volume = {},
number = {},
pages = {},
doi = {10.1053/j.gastro.2025.10.020},
pmid = {41556857},
issn = {1528-0012},
}

@article {pmid41556483,
year = {2026},
author = {Rosen, EA and Krantz, EM and Thibodeau, A and Kennedy, K and Yoke, LH and Tverdek, F and Kassamali Escobar, Z and Cooper, JP and Ueda Oshima, M and Hendrie, P and Mielcarek, M and Liu, C},
title = {Diagnostic Yield of Repeat Blood Cultures and Risk Factors for Bloodstream Infection in Persistent Febrile Neutropenia.},
journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America},
volume = {},
number = {},
pages = {},
doi = {10.1093/cid/ciag014},
pmid = {41556483},
issn = {1537-6591},
abstract = {BACKGROUND: The optimal frequency of repeat blood cultures in persistent febrile neutropenia (FN) remains unknown. This study aims to identify opportunities for blood culture diagnostic stewardship in persistent FN.

METHODS: This is a retrospective cohort study of patients with hematology/oncology diagnoses and an FN episode >3 days. Generalized estimating equation logistic regression models were used to evaluate risk factors for new bloodstream infection (BSI) after FN day 3.

RESULTS: Among 620 patients, median FN duration was 5 days and median blood culture bottles collected per patient was 12. On FN day 1, 25% of patients had a positive blood culture; on FN days 2-9, <5% of patients per day had a new organism isolated. Among 31 new organisms isolated after FN day 3, 8 (26%) were contaminants. Of 503 patients with ≥1 blood culture collected after FN day 3, 19 (4%) had a new BSI after FN day 3. FN onset in the peri-hematopoietic cell transplant (HCT) period (day -7 to +30) was associated with lower odds of new BSI after FN day 3 (OR 0.18; 95%CI [0.04-0.71]; p=0.01).Thirty-six patients died within 30 days after FN day 3, including 4 with a new BSI after FN day 3; 1 death was attributable to BSI after FN day 3.

CONCLUSIONS: Detection of new BSI after FN day 3 was uncommon, demonstrating low diagnostic yield of repeat blood cultures after FN day 3. FN episodes in the peri-HCT period may be a potential focus for blood culture diagnostic stewardship initiatives.},
}

@article {pmid41553230,
year = {2026},
author = {Shadman, M and Bouwmeester, W and Mohseninejad, L and Xu, S and Jevdjevic, M and Yang, K and Williams, R and Jansen, JP},
title = {Prolonged progression-free survival with zanubrutinib in relapsed/refractory CLL: an indirect treatment comparison versus other BTK inhibitors using multilevel network meta-regression.},
journal = {Journal of medical economics},
volume = {29},
number = {1},
pages = {180-192},
doi = {10.1080/13696998.2025.2609514},
pmid = {41553230},
issn = {1941-837X},
mesh = {Humans ; Adenine/analogs & derivatives/therapeutic use/analogs & derivatives ; Agammaglobulinaemia Tyrosine Kinase/antagonists & inhibitors ; *Antineoplastic Agents/therapeutic use ; Benzamides/therapeutic use ; Clinical Trials, Phase III as Topic ; *Leukemia, Lymphocytic, Chronic, B-Cell/drug therapy/mortality ; *Piperidines/therapeutic use ; Progression-Free Survival ; *Protein Kinase Inhibitors/therapeutic use/economics ; Pyrazines/therapeutic use ; *Pyrazoles/therapeutic use/economics ; *Pyrimidines/therapeutic use ; Randomized Controlled Trials as Topic ; },
abstract = {BACKGROUND: Bruton tyrosine kinase inhibitors (BTKis) are therapeutic agents for relapsed/refractory chronic lymphocytic leukemia (R/R CLL). Previous indirect treatment comparisons are limited in simultaneously comparing multiple interventions and adjusting for population differences. This study aimed to use a more rigorous approach called multilevel network meta-regression (ML-NMR) to estimate the relative treatment effects of zanubrutinib compared to acalabrutinib and ibrutinib in two target populations: a general R/R CLL population similar to the phase 3 ALPINE trial's intention-to-treat (ITT) population, and a high-risk population with del(17p) and/or del(11q), similar to the ITT population of the phase 3 ELEVATE-RR trial.

METHODS: The ML-NMR was conducted using data from three phase 3 randomized controlled trials: ALPINE (N = 652), ELEVATE-RR (N = 533), and ASCEND (N = 310). Progression-free survival (PFS) and overall survival (OS) were the outcomes of interest. The ML-NMR integrated individual patient data from ALPINE with aggregate data from the other trials, incorporating important effect modifiers to estimate relative treatment effects for the target populations.

RESULTS: In the general R/R CLL population, zanubrutinib showed an improved PFS compared to ibrutinib (HR = 0.67, 95% Credible Interval [CrI] = 0.52-0.87) and acalabrutinib (HR = 0.57, 95% CrI = 0.34-0.95). In the high-risk population, zanubrutinib maintained its PFS advantage over ibrutinib and acalabrutinib. OS was similar across BTKis in both populations, with wide CrIs that included an estimate of no difference between treatments.

CONCLUSION: This ML-NMR suggests that zanubrutinib offers improved PFS compared to ibrutinib and acalabrutinib in both general and high-risk R/R CLL populations. OS results were uncertain due to limited follow-up.},
}

Humans
Adenine/analogs & derivatives/therapeutic use/analogs & derivatives
Agammaglobulinaemia Tyrosine Kinase/antagonists & inhibitors
*Antineoplastic Agents/therapeutic use
Benzamides/therapeutic use
Clinical Trials, Phase III as Topic
*Leukemia, Lymphocytic, Chronic, B-Cell/drug therapy/mortality
*Piperidines/therapeutic use
Progression-Free Survival
*Protein Kinase Inhibitors/therapeutic use/economics
Pyrazines/therapeutic use
*Pyrazoles/therapeutic use/economics
*Pyrimidines/therapeutic use
Randomized Controlled Trials as Topic

@article {pmid41550315,
year = {2025},
author = {Chandrasekhar, S and Finberg, A and Jabbour, A and Dang, L and Hanson, J and Behnia, S and Goff, P and Nghiem, P},
title = {A single dose of neoadjuvant radiation for Merkel cell carcinoma: Complete pathologic response with minimal morbidity in a rapidly growing lesion of the eye.},
journal = {JAAD case reports},
volume = {66},
number = {},
pages = {137-140},
pmid = {41550315},
issn = {2352-5126},
support = {P01 CA225517/CA/NCI NIH HHS/United States ; P30 CA015704/CA/NCI NIH HHS/United States ; },
}

@article {pmid41549755,
year = {2026},
author = {Heitner, JA and Stansfield, SE and Mitchell, KM and Doyle, CM and Milwid, RM and Moore, M and Donnell, DJ and Xia, Y and Maheu-Giroux, M and Barnabas, RV and Boily, MC and Dimitrov, DT},
title = {Cost-effectiveness of leveraging long-acting injectable cabotegravir to expand PrEP coverage among MSM in two contrasting North American cities.},
journal = {Journal of the International AIDS Society},
volume = {29},
number = {1},
pages = {e70061},
pmid = {41549755},
issn = {1758-2652},
mesh = {Male ; Humans ; *Pre-Exposure Prophylaxis/economics/methods ; *Cost-Benefit Analysis ; *HIV Infections/prevention & control/epidemiology/transmission ; Homosexuality, Male ; *Pyridones/economics/administration & dosage ; *Anti-HIV Agents/economics/administration & dosage ; Adult ; Georgia/epidemiology ; Middle Aged ; Injections ; Young Adult ; Canada ; Quebec/epidemiology ; Cities ; *Disease Transmission, Infectious/prevention & control ; Diketopiperazines ; },
abstract = {INTRODUCTION: Long-acting injectable cabotegravir (CAB-LA) is superior to daily oral tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) for HIV pre-exposure prophylaxis (PrEP) and could expand PrEP usage. Given price differentials between CAB-LA and TDF/FTC, evaluating the cost-effectiveness of potential PrEP coverage scenarios is warranted.

METHODS: We simulated PrEP coverage expansion among men who have sex with men (MSM) via introducing CAB-LA using two age- and risk-stratified HIV transmission models separately calibrated to local data from a high-incidence (Atlanta, USA) and a low-incidence (Montréal, Canada) North American setting. PrEP coverage of HIV-negative MSM was simulated to increase from 6% to 15%, 30%, 40% or 50% (Montréal) or from 29% to 40% or 50% (Atlanta), within 5 or 10 years, with 0%, 15%, 30%, 50% or 100% of current TDF/FTC users switching to CAB-LA. Costing took a healthcare payer perspective and included PrEP pharmaceuticals, PrEP programmatic costs and HIV-related care. Atlanta scenarios considered oral PrEP acquired at average recent market prices (primary analysis), and both settings modelled universal acquisition at the lowest available generic price (LAGP). Simulations were compared to baseline projections without CAB-LA-based expansions over 20 years, with costs and disability-adjusted life years (DALYs) discounted 3% annually. Incremental cost-effectiveness ratios (ICERs) of expansions were assessed against a $100,000 per DALY averted threshold.

RESULTS: In Atlanta, scenario median ICERs at recent prices ranged from $141,600 (90% CI $60,100-$256,000) to $203,800 ($99,300-$359,200) per DALY averted. All uncertainty intervals covered $100,000. Under universal LAGP TDF-FTC, median ICERs ranged from $255,800 ($112,900-$452,30) to $370,700 ($172,200-$669,100). The strongest expansion scenarios were expected to remain cost-effective until approximately $2800/dose, or approximately $1350 with universal LAGP TDF/FTC. In Montréal, scenarios had median ICERs from $920,000 to $2,540,000, excluding dominated runs.

CONCLUSIONS: In a high-incidence Atlanta MSM population, CAB-LA-based PrEP expansions are not projected to be cost-effective, though a minority of simulations achieved cost-effectiveness. However, lower prices could achieve cost-effectiveness. In a low-incidence Montréal MSM population, broad expansions are not expected to be cost-effective at modelled prices. Prioritizing CAB-LA to Montréal MSM facing access, adherence or persistence barriers to oral PrEP warrants a cost-effectiveness assessment.},
}

Male
Humans
*Pre-Exposure Prophylaxis/economics/methods
*Cost-Benefit Analysis
*HIV Infections/prevention & control/epidemiology/transmission
Homosexuality, Male
*Pyridones/economics/administration & dosage
*Anti-HIV Agents/economics/administration & dosage
Adult
Georgia/epidemiology
Middle Aged
Injections
Young Adult
Canada
Quebec/epidemiology
Cities
*Disease Transmission, Infectious/prevention & control
Diketopiperazines

@article {pmid41549659,
year = {2026},
author = {Okinaka, K and Schiffer, JT},
title = {Strategies for mitigating severe COVID-19 in patients with haematological malignancy during the omicron era.},
journal = {The Journal of antimicrobial chemotherapy},
volume = {81},
number = {2},
pages = {},
doi = {10.1093/jac/dkaf489},
pmid = {41549659},
issn = {1460-2091},
mesh = {Humans ; *COVID-19/prevention & control/complications ; *Hematologic Neoplasms/complications/virology ; *SARS-CoV-2/drug effects ; *Antiviral Agents/therapeutic use ; Pre-Exposure Prophylaxis/methods ; Antibodies, Monoclonal/therapeutic use ; Immunocompromised Host ; COVID-19 Drug Treatment ; },
abstract = {Despite a decrease in disease severity since the emergence of the severe acute respiratory syndrome coronavirus 2 Omicron variant, coronavirus disease-2019 (COVID-19) continues to pose a significant threat to patients with haematological malignancies (HM). Although repeated booster vaccinations enhance protection against severe illnesses in immunocompromised individuals, they remain at heightened risk of adverse outcomes. This underscores the crucial need for effective pharmacologic strategies to prevent and treat infection. This review examines current strategies for preventing severe COVID-19 in patients with HM, focusing on pre-exposure prophylaxis and early treatment of COVID-19. New monoclonal antibodies have been developed, offering effective pre-exposure prophylaxis. Antiviral agents and monoclonal antibodies demonstrated efficacy in limiting severe COVID-19 outcomes in patients with HM, though some patients, particularly the elderly, remain at risk of critical illness and death. Prolonged infection over months is also common, particularly in patients with lymphoid malignancies. Sustained viral shedding and ongoing mutation may be associated with chronic symptoms and is the likely source of several novel variants of concern that prolonged the pandemic. While HM subtype and advanced age are risk factors for severe or persistent COVID-19, there are no accurate tools for predicting individual risk. Given this uncertainty, prompt medical consultation, timely prescription of antiviral agents, and close monitoring are essential to minimize the risk of adverse outcomes in this vulnerable population.},
}

Humans
*COVID-19/prevention & control/complications
*Hematologic Neoplasms/complications/virology
*SARS-CoV-2/drug effects
*Antiviral Agents/therapeutic use
Pre-Exposure Prophylaxis/methods
Antibodies, Monoclonal/therapeutic use
Immunocompromised Host
COVID-19 Drug Treatment

@article {pmid41547989,
year = {2026},
author = {Xu, J and Halloran, ME and Moore, M and Zhang, L and Hyrien, O and Luedtke, A and El Sahly, HM and Baden, LR and Goepfert, PA and Gray, G and Grinsztejn, B and Sobieszczyk, ME and Falsey, AR and Robinson, ST and Garcia, NMG and Zhou, H and van Dromme, I and Truyers, C and Hirsch, I and Neuzil, KM and Corey, L and Kublin, JG and Follmann, D and Janes, HE and Gilbert, PB and Huang, Y},
title = {Association between COVID-19 vaccine efficacy and epidemic force of infection.},
journal = {NPJ vaccines},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41541-026-01374-3},
pmid = {41547989},
issn = {2059-0105},
abstract = {The association between vaccine efficacy (VE) and force of infection (FoI) remains incompletely understood. Previous analyses have been primarily based on trial-level summary data-not accounting for the effect of time and constrained by the number of trials. Here, we leverage individual-level data from three phase 3 randomized, placebo-controlled COVID-19 vaccine trials-the COVE trial (Moderna, CoVPN3001), the AZD1222 trial (AstraZeneca, CoVPN3002), and the ENSEMBLE trial (Janssen/Johnson & Johnson, CoVPN3003)-and contemporaneous geographic-location-specific SARS-CoV-2 surveillance data from the start of the pandemic through November 14, 2021 (including the blinded follow-up periods of the trials) to conduct five cohort- and vaccine-specific analyses: COVE (U.S.), AZD1222 overall (U.S. + non-U.S.), AZD1222 U.S., ENSEMBLE overall (U.S. + non-U.S.), and ENSEMBLE U.S. In AZD1222 U.S., higher VE was associated with higher FoI (p = 0.01). In ENSEMBLE overall, lower VE was marginally associated with higher FoI (p = 0.21), further supported by a region-specific analysis. In COVE, AZD1222 overall, and ENSEMBLE U.S., no VE-FoI association was found. These findings highlighted a new perspective: the VE-FoI association appears complex, potentially influenced by FoI levels, with patterns suggesting an inverted U-shaped relationship, showing a positive association at low FoI levels and a negative association at high levels.},
}

@article {pmid41547399,
year = {2026},
author = {Pidala, J 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 Dehn, JG},
title = {Donor search and selection strategy to facilitate comparable transplant rates across donor search prognosis groups: A report from the BMT CTN 1702 trial.},
journal = {Transplantation and cellular therapy},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jtct.2026.01.014},
pmid = {41547399},
issn = {2666-6367},
abstract = {BACKGROUND/OBJECTIVE: In a secondary analysis from the BMT CTN 1702 trial, we report on donor search and selection strategies per baseline recipient search prognosis (SP).

STUDY DESIGN: A total of 1751 patients were analyzed (SP groups: very likely 958, less likely 517, very unlikely 276).

RESULTS: Target time to HCT was most often 6-12 weeks (SP p=NS) and was associated with AML remission status (p<0.01). Baseline preferred alternative donor (Alt-D) across all SP was most commonly haploidentical (haplo) donor (62.2% overall), whereas mismatched unrelated (MMUD) increased over time during the study period. Those in less/very unlikely groups prioritized more Alt-D types at baseline and had more priority ranking changes (SP p<0.01). While comparable number of donors were typed (all SP, median 3 donors, median time 1.1 months), less/very unlikely SP had greater use of Alt-D, (SP p<0.01). Reasons for non-selection of typed donors varied by SP: For less/very unlikely, degree of HLA mismatching and donor specific antibodies were more common, while for very likely SP, other preferred donors were more common. Of 1751, 65% reached HCT: 94% of the very likely used 8/8 matched unrelated donor (MUD) and 91% of very unlikely used Alt-D (haplo 61%, MMUD 22%, UCB 8%). HCT occurred within initial desired timeline for 38% of all subjects. HCT delays occurred in 29% mostly for disease or patient health overall, and of these 52% reached HCT after delay.

CONCLUSION: In this prospective, multicenter evaluation of donor search and selection practices, we demonstrate that patients with poor likelihood of 8/8 MUD matching can reach HCT at comparable rates and with similar effort (time spent typing, number of donors typed) using an early Alt-D-centered strategy. Uniformly across SP, target time to HCT is not commonly reached and is disrupted mostly by disease/patient health delays, not commonly donor availability.},
}

@article {pmid41542557,
year = {2026},
author = {Ahn, JJ and Yu, TC and Dadonaite, B and Radford, CE and Bloom, JD},
title = {Influenza hemagglutinin subtypes have different sequence constraints despite sharing extremely similar structures.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {41542557},
issn = {2692-8205},
abstract = {Hemagglutinins (HA) from different influenza A virus subtypes share as little as ~40% amino acid identity, yet their protein structure and cell entry function are highly conserved. Here we examine the extent that sequence constraints on HA differ across three subtypes. To do this, we first use pseudovirus deep mutational scanning to measure how all amino-acid mutations to an H7 HA affect its cell entry function. We then compare these new measurements to previously described measurements of how all mutations to H3 and H5 HAs affect cell entry function. We find that ~50% of HA sites display substantially diverged preferences for different amino acids across the HA subtypes. The sites with the most divergent amino-acid preferences tend to be buried and have biochemically distinct wildtype amino acids in the different HA subtypes. We provide an example of how rewiring the interactions among contacting residues has dramatically shifted which amino acids are tolerated at specific sites. Overall, our results show how proteins with the same structure and function can become subject to very different site-specific evolutionary constraints as their sequences diverge.},
}

@article {pmid41509424,
year = {2025},
author = {Richardson, RB and Kikawa, C and Garg, A and Bednarski, E and Salim, M and Bacsik, D and Veit, EC and Hermacinski, A and Hamilton, R and García-Sastre, A and Bloom, JD and Lim, JK and Evans, MJ},
title = {Coevolutionary constraints of Zika virus nonstructural protein 5 replication and interferon antagonism activities.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {41509424},
issn = {2692-8205},
support = {F31 AI191695/AI/NIAID NIH HHS/United States ; R01 AI166594/AI/NIAID NIH HHS/United States ; R01 AI175303/AI/NIAID NIH HHS/United States ; },
abstract = {The flavivirus nonstructural protein 5 performs multiple functions during infection, including RNA replication and type I interferon signaling antagonism. Although flavivirus NS5 proteins inhibit IFN signaling through distinct mechanisms, which suggests evolutionary flexibility, the evolutionary constraints for these activities to coexist within a single protein remain to be determined. Here, we mapped the Zika virus NS5 STAT2 antagonism determinants and compared them with replication constraints defined by deep mutational scanning. Antagonism and replication determinant extensively overlapped, and no single amino acid substitution eliminated antagonism without impairing replication. Resolving these fitness landscapes in parallel identified specific combinations of partially functional substitutions that retained replication capacity while markedly reducing antagonism. These viruses were profoundly attenuated in human STAT2 knock-in mice. Our results uncover a fundamental evolutionary constraint linking replication and immune evasion activities in NS5, highlight that STAT2 antagonism is essential for ZIKV pathogenesis and provide new avenues for attenuated ZIKV vaccines.},
}

@article {pmid41546844,
year = {2026},
author = {Donzella, SM and VoPham, T and Weaver, MD and Patel, AV and Phipps, AI and Zhong, C},
title = {Sleep midpoint, social jetlag, and cancer risk in the Cancer Prevention Study-3.},
journal = {Cancer causes & control : CCC},
volume = {37},
number = {2},
pages = {29},
pmid = {41546844},
issn = {1573-7225},
mesh = {Humans ; Female ; Middle Aged ; *Neoplasms/epidemiology/prevention & control/etiology ; Male ; Adult ; *Sleep/physiology ; Prospective Studies ; Aged ; Risk Factors ; Incidence ; United States/epidemiology ; *Jet Lag Syndrome/epidemiology/complications ; Follow-Up Studies ; },
abstract = {PURPOSE: Sleep timing and regularity are associated with various health and performance outcomes, but limited research has investigated the relationship of these sleep dimensions with cancer incidence. The objective of this study was to investigate the associations of sleep midpoint and social jetlag with cancer risk among US adults.

METHODS: The Cancer Prevention Study-3 is a large prospective study of US adults aged 30-65 years. At the first triennial follow-up (2015), participants were asked to report the average time they spent sleeping during a 24-h weekday and weekend, respectively. Sleep midpoint was calculated as the wake time minus half of sleep duration on a weekday and weekend to create a 5:2 weekday:weekend weighted average which was categorized as < 2:30AM, 2:30- < 3:30AM (referent), and ≥ 3:30AM. Social jetlag measures were calculated to estimate the difference in sleep midpoint on the weekend and weekday and categorized as < 1 h (referent), 1- < 2 h, and ≥ 2 h. Cancer incidence was determined via linkage to state registries; follow-up time ended at the time of cancer diagnosis or death or end of follow-up (12/31/2020). We used multivariable Cox proportional hazards models to estimate adjusted hazard ratios and 95% confidence intervals adjusted for socio-demographics, socioeconomic status, comorbidities, and lifestyle behaviors.

RESULTS: A total of 5,537 incident cancer cases were reported among 145,386 CPS-3 participants. We found no statistically significant associations of sleep midpoint or measures of social jetlag with overall cancer or breast cancer-specific risk.

CONCLUSION: Our findings suggest no significant associations of sleep midpoint and social jetlag with cancer risk.},
}

Humans
Female
Middle Aged
*Neoplasms/epidemiology/prevention & control/etiology
Male
Adult
*Sleep/physiology
Prospective Studies
Aged
Risk Factors
Incidence
United States/epidemiology
*Jet Lag Syndrome/epidemiology/complications
Follow-Up Studies

@article {pmid41546729,
year = {2026},
author = {Karvonen, KA and McDougall, JA and Hohl, SD and Carosso, EA and Burrows, T and Mecham, SH and Stohr, E and Devine, A and Linden, H and Gopal, AK and Yu, EY and Cowan, AJ and Mendoza, JA},
title = {Perspectives on GUIDE (Guiding participation toward understanding, inclusion, diversity, and equity for cancer trials): a clinical trial access intervention.},
journal = {Cancer causes & control : CCC},
volume = {37},
number = {2},
pages = {19},
pmid = {41546729},
issn = {1573-7225},
support = {FY23-IDCT-01//Andy Hill CARE Fund/ ; },
mesh = {Humans ; *Neoplasms/therapy/psychology ; Female ; Male ; *Clinical Trials as Topic/economics ; Middle Aged ; Adult ; *Health Services Accessibility ; Aged ; *Patient Participation ; Patient Selection ; Qualitative Research ; },
abstract = {BACKGROUND: We sought to examine key patient and provider perspectives to develop GUIDE (Guiding participation toward Understanding, Inclusion, Diversity, and Equity for Cancer Clinical Trials), an intervention aimed to improve access to clinical trials through reimbursement of trial-related out-of-pocket costs and navigation. We sought patient and provider perspectives to optimize future GUIDE implementation.

METHODS: Study team members conducted semi-structured 1:1 qualitative interviews with oncology patients (n = 20) and providers (n = 20) to identify influences on clinical trial participation and GUIDE acceptability, appropriateness, and feasibility. Data were analyzed using a deductive, rapid framework analysis. We applied a Consolidated Framework for Implementation Research and constructs of Proctor's taxonomy of implementation outcomes to organize themes and inform the development of GUIDE.

RESULTS: Patients reported clinical trial-related expenses as significant barriers for trial participation. Providers unanimously found GUIDE acceptable, appropriate, and feasible. Participants indicated program success would depend on establishing clarity around reimbursement and the role of the trial navigator ('Guide') within an existing multidisciplinary team and equipping the Guide with skills and affect to build trust with patients.

CONCLUSION: Health-related social needs (HRSN) are a critical influence on trial participation. Providers perceived the GUIDE program has potential to address HRSN and enhance trial diversity. For successful implementation, clear reimbursement protocols and infrastructure, integration of the Guide as part of the care team, and training for the Guide to screen for HRSN and connect patients to trial/institutional resources are needed.

IMPACT: We report patient and provider-identified elements critical for future trial navigator programs.},
}

Humans
*Neoplasms/therapy/psychology
Female
Male
*Clinical Trials as Topic/economics
Middle Aged
Adult
*Health Services Accessibility
Aged
*Patient Participation
Patient Selection
Qualitative Research

@article {pmid41545303,
year = {2026},
author = {Huang, JJ and YousefiAsl, M and Singh, N and Grivas, P and Bhatia, S},
title = {Steroid-sparing strategies for managing immune-related adverse events.},
journal = {Journal for immunotherapy of cancer},
volume = {14},
number = {1},
pages = {},
pmid = {41545303},
issn = {2051-1426},
mesh = {Humans ; *Neoplasms/drug therapy/immunology ; *Immune Checkpoint Inhibitors/adverse effects ; *Drug-Related Side Effects and Adverse Reactions/drug therapy/etiology ; *Steroids/therapeutic use ; *Immunotherapy/adverse effects/methods ; },
abstract = {Although immune checkpoint inhibitors (ICI) have greatly improved outcomes in several cancer types, their use is also associated with immune-related adverse events (irAEs) that can impact any organ system and lead to significant morbidity and even mortality. Current approaches to treatment of irAEs largely rely on the use of systemic corticosteroids, which can compromise antitumor immune responses and oncologic outcomes. Prolonged use of systemic corticosteroids is also associated with its own set of toxicities. Thus, there is a critical need for steroid-sparing treatment approaches for irAEs.In this article, we review the literature for alternative therapeutic approaches for irAEs, which include targeted delivery (alternate routes of administration) of steroids (eg, budesonide) as well as systemic non-steroidal strategies using other mechanisms of action, such as integrin/cytokine blockade, antibody depletion, disease-modifying antirheumatic drugs and fecal microbiota transplant, among others. Many of these approaches have shown significant promise in their ability to induce a clinical response and improve symptoms, even in the setting of steroid-refractory or steroid-dependent irAEs. These approaches are being increasingly used as primary and secondary prophylaxis in patients at high risk of irAEs. Importantly, these strategies may mitigate steroid-associated toxicities, preserve antitumor immune responses and allow continuation of ICI after development of irAEs, hence enabling the full potential of ICI against cancer.},
}

Humans
*Neoplasms/drug therapy/immunology
*Immune Checkpoint Inhibitors/adverse effects
*Drug-Related Side Effects and Adverse Reactions/drug therapy/etiology
*Steroids/therapeutic use
*Immunotherapy/adverse effects/methods

@article {pmid41545094,
year = {2026},
author = {Nowicka, Z and Grassberger, C and Beekman, C},
title = {The Challenges Discovering the Mechanisms Underlying Radiation-Induced Lymphopenia From Clinical Data.},
journal = {International journal of radiation oncology, biology, physics},
volume = {124},
number = {2},
pages = {484-487},
doi = {10.1016/j.ijrobp.2025.11.002},
pmid = {41545094},
issn = {1879-355X},
}

@article {pmid41544713,
year = {2026},
author = {Prentice, RL and Tinker, LF and Neuhouser, ML and Lampe, JW and Raftery, D and Gowda, GAN and Song, X and Navarro, SL and Huang, Y and Vasan, S and Orchard, TS and Brasky, TM and Manson, JE and Zheng, C},
title = {Biomarkers for dietary fatty acid densities among postmenopausal U.S. females derived using a habitual-diet human feeding study.},
journal = {The American journal of clinical nutrition},
volume = {},
number = {},
pages = {101197},
doi = {10.1016/j.ajcnut.2026.101197},
pmid = {41544713},
issn = {1938-3207},
abstract = {BACKGROUND: Although measures of blood and tissue fatty acid (FA) concentrations are available, objective measures of dietary FA densities (g/kcal) are generally lacking.

OBJECTIVES: We aimed to explore the development of biomarkers for specific and composite dietary FA densities, not including contributions from dietary supplements, using metabolite profiles from serum and 24-hour urine, along with separately measured serum phospholipid fatty acid (PLFA) concentrations in the Women's Health Initiative (WHI).

METHODS: Potential biomarker equations were based on linear regression of feeding study dietary FA densities on metabolite concentrations, each log-transformed, among participants in a habitual-diet human feeding study (n=153) within WHI. Corresponding biomarker equations were also considered for total saturated (SFA), monounsaturated (MUFA), and polyunsaturated (PUFA) fatty acid densities and for total n-3 and n-6 PUFA densities. Dietary FA density estimates derived from these equations were evaluated by correlation with feeding study intake densities, and by other important biomarker criteria.

RESULTS: Regression cross-validated R[2] values >30% for specific SFAs were 64.7 butyric, 60.9 caprioc, 48.7 caprylic, 53.0 capric, 39.9 lauric, 61.0 myristic, 42.2 palmitic, 34.2 stearic, 34.8 arachidic, 49.9 decosanoic; for specific MUFAs were 31.3 oleic; and for specific PUFAs were 51.7 linoleic, 50.1 alpha linolenic, 39.7 arachidonic, 40.2 EPA, 53.5 DPA, and 47.9 DHA. Corresponding values were 46.4, 52.8, 46.1, and 52.4 for total SFA, total PUFA, total n-3, and total n-6 densities. Many FA density equations had contributions from multiple metabolites, mostly serum metabolites, and from total energy expenditure. Sensitivity and specificity criteria are plausibly satisfied for proposed biomarkers, based on the feeding study design and on the sets of selected metabolites.

CONCLUSION: Combinations of log-transformed metabolite concentrations can lead to objective intake density estimates for multiple FAs in the diets of U.S. postmenopausal females, with relevance to the reliable study of dietary FA densities and chronic disease risk.},
}

@article {pmid41544638,
year = {2026},
author = {Duncombe, CJ and Hergott, DEB and Staubus, W and Balke-Buijs, M and Kublin, JG and Duffy, PE and Healy, SA and Talley, A and Jackson, L and Sim, BKL and Hoffman, SL and Sauerwein, RW and Roestenberg, M and Murphy, SC},
title = {Sex-based differences in Plasmodium infection in the control groups of controlled human malaria infection trials in malaria-naive populations in the USA and the Netherlands: a pooled analysis.},
journal = {The Lancet. Microbe},
volume = {},
number = {},
pages = {101265},
doi = {10.1016/j.lanmic.2025.101265},
pmid = {41544638},
issn = {2666-5247},
abstract = {BACKGROUND: Before infecting red blood cells and causing the clinical manifestations of malaria, the hepatotropic parasite Plasmodium falciparum completes a complex liver stage. Sex-based differences in pathogenesis by hepatotropic micro-organisms are well documented but unstudied for P falciparum in humans. We aimed to evaluate the effect of sex on the time to blood-stage positivity and initial blood-stage parasite densities as indicators of liver-stage dynamics and parasite replication.

METHODS: We conducted a pooled analysis of data from malaria-naive participants in control groups from controlled human malaria infection (CHMI) studies conducted between Jan 1, 2010, and Dec 31, 2024, in which samples were tested using Plasmodium 18S ribosomal RNA nucleic acid amplification tests (18S NAATs) at laboratories in Seattle (WA, USA) and Leiden (Netherlands). Participants aged 18-48 years were eligible for inclusion if they were in placebo or infectivity control groups in any CHMI study at the two laboratories and developed parasitaemia following CHMI. Patient demographics and 18S NAAT data were obtained from study leads at each centre and collated, standardised, and reviewed. Information on P falciparum strain, challenge route, and sampling schedule were extracted from study protocols or publications. The main outcome, time to positivity (TTP), was calculated as the study day of the first positive 18S NAAT of any density, measured during a 28-day monitoring period following CHMI. Using an interval-censored generalised gamma accelerated failure time model, we compared time to blood-stage positivity by sex, adjusting for challenge route, P falciparum strain, and study site. Odds of developing detectable infection after 7 days post-challenge was compared between male and female participants using a linear mixed-effects model adjusted for the same terms.

FINDINGS: Evaluable data were available from 102 control participants (48 [47%] female and 54 [53%] male) across 13 CHMI studies. There was moderate heterogeneity between studies (I[2]=31% [95% CI 0-57]). There were no notable demographic differences between male and female participants regarding age, challenge route, or strain. The mean time to first detectable parasitaemia was slightly longer in male participants (7·59 days [SD 1·15]) than in female participants (7·17 days [0·91]). Adjusted accelerated failure time analysis suggested that TTP occurred 8% later in male participants than female participants (time ratio 1·08 [1·03-1·16]). Male participants were significantly more likely than female participants to have a detectable infection after day 7 (19 [35%] of 54 male participants vs six [13%] of 48 female participants), with adjusted odds of delayed infection 5·20 times (95% CI 1·52-17·70) higher in male than female participants.

INTERPRETATION: Our findings suggest that male individuals are more likely to have a delayed detection of blood-stage parasites following CHMI with P falciparum compared with female individuals. Although the inability to directly measure liver-stage burden is a limitation, CHMI offers a controlled system to infer liver-stage dynamics. Thus, P falciparum infection is likely to involve a sex-specific host-pathogen interaction in the liver, emphasising the importance of considering sex as a biological variable in liver-targeting clinical interventions.

FUNDING: The Gates Foundation and the University of Washington.},
}

@article {pmid41544219,
year = {2026},
author = {Patel, K and Vose, JM and Nasta, SD and Brown, JR and Maddocks, KJ and Woyach, JA and Shah, NN and Fakhri, B and Tessoulin, B and Ma, S and Jagadeesh, D and Lech-Maranda, E and Coombs, CC and Patel, MR and Rhodes, JM and Ujjani, CS and Hoffmann, MS and Cheah, CY and Munir, T and Lewis, DJ and Scarfò, L and Eyre, TA and Alencar, AJ and Cohen, JB and Zelenetz, AD and Tsai, DE and Li, M and Bian, Y and Abada, PB and Balbas, M and Zinzani, PLL},
title = {Pirtobrutinib, a Highly Selective, Non-covalent (Reversible) BTKi in R/R Marginal Zone Lymphoma: Phase 1/2 BRUIN Study.},
journal = {Blood advances},
volume = {},
number = {},
pages = {},
doi = {10.1182/bloodadvances.2025017489},
pmid = {41544219},
issn = {2473-9537},
abstract = {Marginal zone lymphoma (MZL) is a group of indolent B-cell malignancies that have a natural history that follows a remitting and relapsing course. For systemic disease, available first-line therapies include anti-CD20 antibody as monotherapy with or in combination with chemotherapy (chemoimmunotherapy), with second-line options such as covalent (c) Bruton tyrosine kinase inhibitors (BTKi). However, management of relapsed and refractory (R/R) MZL remains a challenge. Pirtobrutinib, a highly selective, non-covalent BTKi has shown promising efficacy and tolerability in patients with poor-prognosis B-cell malignancies following prior therapy, including cBTKi. Here we report the safety and efficacy of pirtobrutinib in patients with MZL from the phase 1/2 BRUIN study. Endpoints included investigator assessed ORR by Lugano 2014 criteria, DOR, PFS, OS, and safety. Among 36 R/R MZL patients (EMZL: n=6; NMZL: n=17; SMZL: n=13), median age was 68 years (range, 22-83) and median prior lines of therapy were 3 (range, 2-10) including anti-CD-20 antibody (100%), chemotherapy (86%) and cBTKi therapy (72%). The ORR was 55.6% (95% confidence interval [CI], 38.1- 72.1) including 3 (8.3%) complete responses and 17 (47.2%) partial responses. Median DOR was 17.8 months (95%CI, 7.4-non-estimable [NE]), and median PFS was 16.6 months (95%CI, 9.0-22.1). With median follow-up of 32.4 months (IQR, 28.0, 41.3), median OS was NE (95%CI, 29.5-NE). The ORR for patients with prior cBTKi therapy was 53.8% (95%CI, 33.4-73.4). Pirtobrutinib was well-tolerated with dose reductions in 4 patients (11.1%) and permanent discontinuation due to TEAEs in 4 (11.1%). Pirtobrutinib showed promising efficacy and safety in patients with heavily pre-treated R/R MZL, including prior cBTKi. NCT03740529.},
}

@article {pmid41544105,
year = {2026},
author = {Mayer-Blackwell, K and Minervina, A and Pogorelyy, M and Rawat, P and Shapiro, MR and Peters, LD and Ford, ES and Posgai, AL and Vegesana, K and Minot, S and Koelle, DM and Greiff, V and Bradley, P and Brusko, TM and Thomas, PG and Fiore-Gartland, A},
title = {TCR2HLA: Calibrated inference of HLA genotypes from TCR repertoires enables identification of immunologically relevant metaclonotypes.},
journal = {PLoS computational biology},
volume = {22},
number = {1},
pages = {e1013767},
pmid = {41544105},
issn = {1553-7358},
mesh = {Humans ; Genotype ; *HLA Antigens/genetics/immunology ; Computational Biology/methods ; Alleles ; *Receptors, Antigen, T-Cell/genetics ; COVID-19/immunology/genetics ; *Software ; Receptors, Antigen, T-Cell, alpha-beta/genetics ; SARS-CoV-2/immunology ; },
abstract = {T cell receptors (TCRs) recognize peptides presented by polymorphic human leukocyte antigen (HLA) molecules, but HLA genotype data are often missing from TCR repertoire sequencing studies. To address this, we developed TCR2HLA, an open-source tool that infers HLA genotypes from TCRβ repertoires. Expanding on work linking public TRBV-CDR3 sequences to HLA genotypes, we incorporated "quasi-public" metaclonotypes - composed of rarer TCRβ sequences with shared amino acid features - enriched by HLA genotypes. Using four TCRβseq datasets from 3,150 individuals, we applied TRBV gene partitioning and locality-sensitive hashing to identify ~96,000 TCRβ features strongly associated with specific HLA alleles from 71M input TCRs. Binary HLA classifiers built with these features achieved high balanced accuracy (>0.9) across common HLA-A (9/12), B (9/12), C (6/13), DRB1 (11/11) alleles and prevalent DPA1/DPB1 (6/10), DQA1/DQB1 (8/17) heterodimers. We also introduced a high-sensitivity calibration to support predictions in samples with as few as 5,000 unique clonotypes. Calibrated predictions with confidence filtering improved reliability. Beyond genotype imputation, TCR2HLA enables the discovery of novel HLA- and exposure-associated TCRs, as shown by the identification of SARS-CoV-2 related TCRs in a large COVID-19 dataset lacking HLA data. TCR2HLA provides a scalable framework for bridging the gap between TCRseq data and HLA genotype for biomarker discovery.},
}

Humans
Genotype
*HLA Antigens/genetics/immunology
Computational Biology/methods
Alleles
*Receptors, Antigen, T-Cell/genetics
COVID-19/immunology/genetics
*Software
Receptors, Antigen, T-Cell, alpha-beta/genetics
SARS-CoV-2/immunology

@article {pmid41543884,
year = {2026},
author = {Bryl, KL and Silverwood, S and Desai, K and Schobert, K and Li, X and Chimonas, S and Mao, JJ and Gillespie, EF},
title = {Benefits and Challenges of a Digital Exercise and Mind-Body Program During Active Cancer Treatment: Qualitative Study of Patients' Perceptions.},
journal = {JMIR cancer},
volume = {12},
number = {},
pages = {e80075},
doi = {10.2196/80075},
pmid = {41543884},
issn = {2369-1999},
mesh = {Humans ; Female ; *Neoplasms/therapy/psychology ; Qualitative Research ; Middle Aged ; Male ; *Mind-Body Therapies/methods ; *Quality of Life ; Aged ; *Exercise Therapy/methods ; *Exercise ; Telemedicine ; },
abstract = {BACKGROUND: Individuals undergoing cancer treatment often face a high symptom burden that impairs quality of life. Exercise and mind-body therapies have been shown to reduce symptoms but are underused. We developed a digital exercise and mind-body therapy program that effectively reduces symptoms while overcoming in-person delivery barriers. Understanding patient experiences can inform treatment mechanisms and guide digital health interventions in cancer care.

OBJECTIVE: This study aimed to explore patient experiences with Integrative Medicine at Home (IM@Home), a 12-week live digital program delivering exercise and mind-body therapies tailored to the needs of individuals undergoing cancer treatment.

METHODS: This qualitative study was embedded in a randomized clinical basket trial (NCT05053230) evaluating the effects of IM@Home versus enhanced usual care on symptoms and acute health care utilization in adults with solid tumors undergoing active treatment and experiencing moderate or greater fatigue. Using maximum variation sampling, 20 participants were selected for semistructured interviews. Interviews explored participants' experiences with the program, its impact on outcomes, unmet needs, and suggestions for improvement. Transcripts were analyzed using a combined inductive and deductive thematic analysis.

RESULTS: Twenty participants (mean age 63, SD 9.6 years; 18/20, 90% female) were interviewed. Five major themes emerged: (1) IM@Home alleviated symptom burden and supported symptom self-management; (2) IM@Home facilitated social support and information exchange; (3) IM@Home offered a flexible, tailored program in a group setting; (4) IM@Home facilitated accessible, cost-effective support; and (5) recommendations for program enhancement. IM@Home was perceived as an accessible, flexible, and supportive program that promoted physical and emotional well-being during treatment.

CONCLUSIONS: IM@Home demonstrates a promising model for delivering integrative supportive care during cancer treatment. Findings highlight patient-valued features such as real-time guidance, tailored content, and community support. These insights can inform future implementation, integration into clinical care, and efforts to enhance digital mind-body interventions in oncology.

TRIAL REGISTRATION: ClinicalTrials.gov NCT05053230; https://www.clinicaltrials.gov/study/NCT05053230.

RR2-10.1038/s41746-024-01387-z.},
}

Humans
Female
*Neoplasms/therapy/psychology
Qualitative Research
Middle Aged
Male
*Mind-Body Therapies/methods
*Quality of Life
Aged
*Exercise Therapy/methods
*Exercise
Telemedicine

@article {pmid41543856,
year = {2026},
author = {Barata, PC and Corrigan, JK and La, J and Culnan, JM and Akama-Garren, E and Dulberger, KN and Dumontier, C and Hansen, J and Bihn, JR and Bitting, RL and Brophy, MT and Cheng, HH and Cooperberg, MR and Do, NV and Dorff, T and Fojo, AT and Gaziano, JM and Goryachev, SD and Halabi, S and Hauger, RL and Nanus, DM and Rebbeck, TR and Pan, CX and Schoen, MW and Swinnerton, KN and Myrie, K and Ramoni, RB and Fillmore, NR and Paller, CJ and Rettig, MB},
title = {Docetaxel Rechallenge vs Cabazitaxel in Patients With Metastatic Castration-Resistant Prostate Cancer.},
journal = {JAMA network open},
volume = {9},
number = {1},
pages = {e2551231},
pmid = {41543856},
issn = {2574-3805},
mesh = {Humans ; Male ; *Docetaxel/therapeutic use/administration & dosage ; *Prostatic Neoplasms, Castration-Resistant/drug therapy/mortality/pathology ; Aged ; *Taxoids/therapeutic use ; Retrospective Studies ; *Antineoplastic Agents/therapeutic use ; Middle Aged ; Treatment Outcome ; Neoplasm Metastasis ; },
abstract = {IMPORTANCE: Docetaxel has been a standard treatment for metastatic castration-resistant prostate cancer (mCRPC) since 2004. Cabazitaxel, a related taxane, was approved in 2010 for patients with mCRPC who had been previously treated with docetaxel. The comparative effectiveness of docetaxel rechallenge vs switching to cabazitaxel after prior docetaxel for mCRPC remains unclear.

OBJECTIVE: To compare the clinical outcomes associated with docetaxel rechallenge vs cabazitaxel in patients with mCRPC who did not experience disease progression during prior administration of docetaxel in the mCRPC setting.

This retrospective cohort study was conducted in the nationwide Veterans Affairs health care system, using inverse probability of treatment weighting to control for potential confounders. Patients who were diagnosed with chemonaive mCRPC between January 1, 2010, and December 31, 2023, received initial docetaxel treatment, and did not experience disease progression were eligible to participate.

EXPOSURES: Treatment with docetaxel rechallenge or cabazitaxel.

MAIN OUTCOMES AND MEASURES: The primary outcome was overall survival (OS) from the initiation of the second course of taxane, which was compared in patients treated with docetaxel rechallenge vs cabazitaxel using weighted Kaplan-Meier analysis and Cox proportional hazards regression models. Secondary outcomes included prostate-specific antigen response, time to next systemic treatment or death, and subsequent treatments received.

RESULTS: A total of 669 patients (407 receiving cabazitaxel and 262 receiving docetaxel rechallenge) with a median age of 72 (IQR, 67-77) years were included. Patients treated with docetaxel rechallenge had a significantly longer OS (median, 12.3 [IQR, 10.5-13.8] months) compared with those treated with cabazitaxel (median, 9.6 [IQR, 8.6-11.1] months), with a hazard ratio of 0.81 (95% CI, 0.55-0.99; P = .04). Descriptive analysis of secondary outcomes was consistent with this finding, including prostate-specific antigen response (weighted 9.8% achieving reduction of 90% or more in the docetaxel rechallenge group vs 3.0% in the cabazitaxel group) and time to next treatment or death (median, 10.7 [IQR, 7.8-12.7] months in the docetaxel rechallenge group vs 8.9 [IQR, 7.1-10.5 months] in the cabazitaxel group). Use of platinum, immunotherapy, or poly (ADP-ribose) polymerase inhibitors was similar between patients treated with cabazitaxel and docetaxel rechallenge.

CONCLUSIONS AND RELEVANCE: In this cohort study of patients with mCRPC, docetaxel rechallenge was associated with improved OS compared with cabazitaxel among patients who did not experience disease progression during prior docetaxel for mCRPC. These findings support docetaxel rechallenge as a treatment option for patients in this scenario.},
}

Humans
Male
*Docetaxel/therapeutic use/administration & dosage
*Prostatic Neoplasms, Castration-Resistant/drug therapy/mortality/pathology
Aged
*Taxoids/therapeutic use
Retrospective Studies
*Antineoplastic Agents/therapeutic use
Middle Aged
Treatment Outcome
Neoplasm Metastasis

@article {pmid41543300,
year = {2026},
author = {Ko, YJ and Castor, J and Kuralt, TD and Goecker, EA and Pepper, G and Reed, JC and Greninger, AL},
title = {Analytical Performance Comparison of Three Quantitative Hepatitis B Surface Antigen Assays.},
journal = {Clinical chemistry},
volume = {},
number = {},
pages = {},
doi = {10.1093/clinchem/hvaf191},
pmid = {41543300},
issn = {1530-8561},
support = {//Department of Laboratory Medicine/ ; //University of Washington/ ; F208422001//Chosun University/ ; },
abstract = {BACKGROUND: Quantitative hepatitis B surface antigen (qHBsAg) assays are important tools for monitoring hepatitis B virus (HBV) infection and treatment response and constitute the primary endpoint in most HBV antiviral trials. To date, no qHBsAg assay has been authorized by the FDA for use in the United States, highlighting the need for performance evaluation and harmonization of available methods.

METHODS: We evaluated the analytical performance of three commercial assays for qHBsAg measurement: Architect HBsAg Qualitative (Abbott) adapted for quantitative use, Elecsys HBsAg II quant II (Roche), and LIAISON XL Murex HBsAg Quant (DiaSorin). Performance characteristics including precision, accuracy, analytical sensitivity, linearity, and lot-to-lot variability were assessed using World Health Organization (WHO) International Standards 12/226 and 03/262, following CLSI guidelines. Clinical accuracy was also evaluated using 72 HBsAg-positive clinical specimens.

RESULTS: The lower limit of quantification was 0.02 IU/mL for Architect, 0.07 IU/mL for Elecsys, and 1.02 IU/mL for LIAISON. The LIAISON exhibited limited linearity and significantly greater variability in samples with high HBsAg levels, as well as significant lot-to-lot variability. Ultimately, all three assays demonstrated acceptable precision and accuracy, though the LIAISON had to be recalibrated specifically with WHO International Standard 03/262.

CONCLUSIONS: The Architect and Elecsys qHBsAg assays demonstrated sufficient analytical performance for clinical use, while the LIAISON was limited by its linearity, lower limit of quantification, and lot-to-lot variability. Standardization is essential to ensure consistent and accurate quantification of HBsAg for effective clinical monitoring and the establishment of treatment goals.},
}

@article {pmid41541249,
year = {2026},
author = {Pan, X and Pan, Y and Su, Y and Xu, Y and Du, J and Cheng, H and Li, G},
title = {Chronic TCR signaling-driven suppression of the FOXO1-KLHL6 axis promotes T cell exhaustion.},
journal = {Immunity & inflammation},
volume = {2},
number = {1},
pages = {8},
pmid = {41541249},
issn = {3059-4774},
}

@article {pmid41541220,
year = {2026},
author = {Mishra, DK and Morris, SM and Popovski, D and Girard, EJ and Bondoc, A and Senthil Kumar, S and Andrade, AF and Zhu, X and Yao, F and Brusniak, MY and Umaru, B and Crotty, EE and Brasel, K and Pakiam, F and Russo, C and Zeinieh, M and Biery, MC and Coxon, M and Conti, H and Clarke, M and Lu, M and Rutka, J and Llivichuzhca-Loja, D and Konnikova, L and Fouladi, M and Jabado, N and Huang, A and Olson, JM and Drissi, R},
title = {Preclinical assessment of checkpoint blockade combined with DNA methyltransferase inhibition in high-risk pediatric brain tumors reveals limited therapeutic synergy.},
journal = {Neuro-oncology advances},
volume = {8},
number = {1},
pages = {vdaf241},
pmid = {41541220},
issn = {2632-2498},
abstract = {ABSTRACT: BackgroundDespite intensive therapies, outcomes for high-risk pediatric brain tumors (PBTs) remain dismal, prompting the search for novel treatments. DNA methyltransferase inhibitors (DNMTi) have been shown to prime tumors to improve response to checkpoint inhibition. The aim of this study was to investigate the potential of decitabine (DAC), in combination with a PD-1 inhibitor, to improve survival in pediatric high-risk brain tumor models.

METHODS: Analysis of human PBT datasets was performed to determine gene expression levels of immune cell markers. Tumor response to DAC, with or without a PD-1 inhibitor, was tested in murine models representing H3-wildtype diffuse intrinsic pontine glioma (DIPG), H3K27-mutant diffuse midline glioma (DMG), atypical teratoid rhabdoid tumor (ATRT), and medulloblastoma (MB). CyTOF analysis of allograft tumors was performed to characterize changes within the tumor microenvironment.

RESULTS: Analysis of PBT subtypes revealed heterogeneous expression of immune cell markers, checkpoint receptors, and MHC molecules. DAC treatment decreased DNA methylation and increased neoantigen expression in human and mouse tumor cells. DAC treatment resulted in prolonged survival in syngeneic mouse models of DIPG and ATRT but not DMG and MB models. However, no added survival benefit was observed when combined with a PD-1 inhibitor. CyTOF analysis of mouse tumors revealed changes in local immune cell infiltration.

CONCLUSIONS: DAC alone or in combination with a checkpoint inhibitor can alter the immune microenvironment in mouse tumor models. Changes were observed in H3-wildtype DIPG and ATRT models, suggesting that certain tumor subtypes may respond to immune priming with DNMTi.},
}

@article {pmid41540901,
year = {2026},
author = {Xu, P and Ueha, S and Aoki, H and Kitabatake, M and Mingyu, C and Shichino, S and Hara, A and Ouji-Sageshima, N and Ito, T and Motozono, C and Matsushima, K},
title = {Repeated mRNA vaccination and breakthrough infection reveal durable dominance but diminishing recall of vaccine-induced CD8[+] T-cell clones.},
journal = {International immunology},
volume = {},
number = {},
pages = {},
doi = {10.1093/intimm/dxag004},
pmid = {41540901},
issn = {1460-2377},
abstract = {Successive mRNA vaccinations preserve SARS-CoV-2-specific T-cell immunity, but how individual CD8[+] T-cell clones behave across repeated booster doses and breakthrough infection (BTI) remains poorly defined. We longitudinally tracked bulk CD8[+] TCRβ repertoires and spike-specific tetramer[+] CD8[+] T cells in adult participants across the third and fourth vaccine doses and subsequent BTI. Each booster continued to recruit previously unexpanded "new" responder clonotypes, but both the number and summed frequency of newly engaged clones declined with successive doses. In contrast, clones first recruited by the initial prime-boost doses-particularly those expanded after dose 2-formed a durable, hierarchically dominant memory pool that persisted for more than two years yet displayed progressively attenuated recall with later boosters. BTI revealed a complementary mode of repertoire remodeling: newly engaged clones that had not responded to prior vaccinations showed the strongest, but transient, expansion, broadening the antigenic targets beyond spike. On the other hand, vaccine-induced clones showed limited recall response while sustaining their dominance in the long term. Together, these findings indicate that repeated mRNA vaccination maintains a stable pool of early-established CD8[+] T-cell clones but progressively limits their recall capacity, whereas BTI mobilizes additional, partially distinct clonotypes that expand robustly and broaden antigenic coverage.},
}

@article {pmid41540004,
year = {2026},
author = {Chen, Z and Song, W and Li, Q and Li, C and Wen, W and Huyghe, JR and Law, PJ and Fernandez-Rozadilla, C and Timofeeva, MN and Thomas, M and Schmit, SL and Martin, V and Devall, M and Dampier, C and Moratalla-Navarro, F and Cai, Q and Wang, J and Shi, J and Kweon, SS and Tanikawa, C and Jia, WH and Shu, X and Long, J and Gao, J and Kim, J and Shin, A and Matsuo, K and Jee, SH and Jung, KJ and Wang, N and Kim, DH and Ping, J and Yang, G and Shin, MH and Ren, Z and Oh, JH and Oze, I and Ahn, YO and Gao, YT and Pan, ZZ and Kamatani, Y and Van Kaer, L and Wu, L and Li, B and Matsuda, K and Shu, XO and Hsu, L and Dunlop, MG and Gruber, SB and Houlston, R and Tomlinson, I and Li, L and Lau, KS and Moreno, V and Casey, G and Peters, U and Zheng, W and Guo, X},
title = {Mixed-model and transcriptome-wide association analyses identify transcription factors and genes associated with colorectal cancer susceptibility.},
journal = {Nature communications},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41467-025-68127-z},
pmid = {41540004},
issn = {2041-1723},
abstract = {Susceptibility transcription factors (TF) whose DNA bindings are altered by genetic variants regulating colorectal cancer (CRC) risk genes remain poorly defined. Using generalized linear mixed models, we analyze 218 TF ChIP-Seq datasets alongside GWAS data from 100,204 CRC cases and 154,587 controls of East Asian and European ancestries. We identify 51 TFs and TF-cofactor interactions, including VDR-cofactors, as key regulators of CRC risk. Integrating these TF insights with transcriptome-wide association studies (TWAS), we further evaluate associations between genetically predicted gene expression, alternative splicing, and alternative polyadenylation with CRC risk, using RNA-seq data from 364 Asian-ancestry and 707 European-ancestry individuals. Multi-ancestry TWAS identify 222 risk genes, including 95 novel genes and 48 potentially druggable targets. Single-cell analysis provides additional functional evidence supporting ~45% of these genes, and experimental validation confirms oncogenic roles for RHPN2, IRS2, and TXN. Our findings elucidate key TF-gene regulatory networks and uncover novel CRC risk genes.},
}

@article {pmid41539488,
year = {2026},
author = {Markova, A and Lee, SJ and Modi, B and Baumrin, E and Rosenstein, RK and Tkaczyk, ER and Lehman, JS and Inamoto, Y and Carpenter, PA and Schultz, KR and Pidala, JA and Martin, P and Pusic, I and Goklemez, S and Stockmann, C and Pinal-Fernandez, I and Paczesny, S and Harris, A and Ponce, DM and Holtzman, NG and Jurdi, NE and Pavletic, SZ and Cowen, EW},
title = {Towards Better Response Assessment of Cutaneous Chronic Graft-Versus-Host Disease: A Report from the National Institutes of Health Consensus Project Task Force.},
journal = {Transplantation and cellular therapy},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jtct.2026.01.009},
pmid = {41539488},
issn = {2666-6367},
abstract = {The National Institutes of Health (NIH) chronic graft-versus-host disease (cGVHD) Consensus Project established response criteria that enabled clinical trials and facilitated regulatory approval of multiple therapies. Nonetheless, organ-specific assessments have limitations, particularly for severe sclerotic skin involvement. Cutaneous manifestations occur in approximately half of patients with chronic GVHD but are difficult to evaluate due to heterogeneous clinical features. To address these challenges, the NIH Consensus Skin Task Force convened in 2024-2025 to refine skin response measures for use in clinical trials. This report (a) summarizes current diagnosis and scoring of skin chronic GVHD, (b) reviews existing response assessments, (c) identifies gaps in their performance, (d) proposes refinements to the 2014 NIH skin response criteria, and (e) outlines future directions incorporating patient-reported outcomes, novel technologies, and biomarker research. Current NIH scoring relies on a 4-point body surface area (BSA) scale and a 3-point sclerosis features scale. While standardized, these measures have limited sensitivity to clinically meaningful change. Proposed refinements include: (i) separate BSA assessments for epidermal involvement and sclerotic features; (ii) modification of sclerosis descriptors, with removal of impaired mobility and specification of GVHD-related ulceration, and addition of sclerosis-associated edema with or without erythema; and (iii) replacement of the exploratory severity scale with two new clinician instruments. The Sclerosis Quality and Physical Signs (SQPS) scale (0-10) captures qualitative physical changes, while the Sclerosis Daily Function Impact (SDFI) scale (0-4) evaluates functional compromise. These proposed refinements aim to improve the accuracy, reproducibility, and clinical relevance of skin chronic GVHD assessments, strengthening trial endpoints and patient care.},
}

@article {pmid41539205,
year = {2026},
author = {Lee, J and Rodriguez, CJ and Daviglus, ML and Kaplan, R and Isasi, CR and Sotres-Alvarez, D and Blaha, MJ and Mok, Y and Perreira, KM and Oren, E and Elfassy, T and Telzak, A and Ejiri, K and Vu, TT and Matsushita, K},
title = {Electronic Cigarette Use and Risk of Hypertension: The Hispanic Community Health Study/Study of Latinos (HCHS/SOL).},
journal = {JACC. Advances},
volume = {5},
number = {2},
pages = {102525},
doi = {10.1016/j.jacadv.2025.102525},
pmid = {41539205},
issn = {2772-963X},
abstract = {BACKGROUND: Acute increases in blood pressure (BP) after electronic cigarette (e-cigarette) use have been reported, but its long-term association with hypertension is unclear.

OBJECTIVES: The purpose of this study was to assess whether e-cigarette use is associated with prevalent and incident hypertension.

METHODS: We analyzed visit 2 (2014-2017) and visit 3 (2020-2024) data from the HCHS/SOL (Hispanic Community Health Study/Study of Latinos), a population-based cohort study including 11,623 individuals aged 18 to 74 years across 4 U.S. communities. The primary exposure was ever e-cigarette use at visit 2. We also explored current use and dual use with combustible cigarette use. Hypertension was defined as measured BP ≥ 140/90 mm Hg or self-reported antihypertensive medication use. Multivariable Poisson and Cox regression were used for prevalent and incident hypertension, respectively. Longitudinal BP change from visit 2 to 3 was assessed using mixed-effects models. All analyses accounted for the complex survey design.

RESULTS: Of 11,593 participants with e-cigarette data (mean age 47 years; 52.2% female), 937 reported ever use (136 current users). Ever vs never e-cigarette use was not associated with prevalent hypertension. Over a median follow-up of 6.0 years, 1,409 participants developed hypertension. Ever vs never e-cigarette use was associated with incident hypertension (HR: 1.49; 95% CI: 1.14-1.95), as were current use (HR: 1.89; 95% CI: 1.12-3.18), former use (HR: 1.43; 95% CI: 1.07-1.93), and dual ever use (HR: 1.85; 95% CI: 1.37-2.49), compared to never use. Longitudinal BP change did not differ by e-cigarette use.

CONCLUSIONS: Ever e-cigarette use was associated with increased risk of incident hypertension, suggesting potential long-term cardiovascular harm.},
}

@article {pmid41509475,
year = {2026},
author = {Liu, Z and Niu, Y and Le, T and Chen, DG and Su, Y and Zheng, Y},
title = {Single-cell Tree-based Model for Genomic-Disease Association.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {41509475},
issn = {2692-8205},
support = {K99 CA293142/CA/NCI NIH HHS/United States ; K99 HG012797/HG/NHGRI NIH HHS/United States ; R00 HG012797/HG/NHGRI NIH HHS/United States ; },
abstract = {The rapid maturation of single-cell multi-omics technologies has enabled unprecedented resolution for mapping disease states and identifying disease-associated biomarkers. In practice, biomarkers are often discovered through differential detection that treat genomic features as independent contributors to phenotypes, while the combinatorial interactions that drive clinical outcomes remain a practical challenge. We present scanCT (single-cell analysis of Clinical Tree), a tree-based framework that identifies groups of genomic features associated with distinct disease phenotypes in a highly interpretable manner. scanCT uses an unbiased, model-based variable-selection procedure for data-driven split selection, which is important for handling the diverse distributional properties of single-cell data across modalities. The tree architecture captures feature interaction effects, and the association modeling enables adjustment for confounding factors. We apply scanCT to longitudinal single-cell multi-omics COVID-19 datasets spanning diverse clinical outcomes and multiple time points per patient. scanCT identifies phenotype-specific gene and protein markers while accounting for age and sex, and it reveals interpretable synergistic marker combinations that help explain differences in patient clinical phenotypes.},
}

@article {pmid41538162,
year = {2026},
author = {Qureshi, S},
title = {A Completely Unfair Time of Ultimate Suffering.},
journal = {JAMA oncology},
volume = {},
number = {},
pages = {},
doi = {10.1001/jamaoncol.2025.5921},
pmid = {41538162},
issn = {2374-2445},
}

@article {pmid41538746,
year = {2026},
author = {Sepassi, A and Ramsey, SD and Fendrick, AM and Gabriel, N and Zell, JA and Mukamel, DB and Sullivan, SD},
title = {Potential Impact of the Medicare Prescription Payment Plan for Medicare Part D Beneficiaries With a Cancer Diagnosis.},
journal = {Journal of clinical oncology : official journal of the American Society of Clinical Oncology},
volume = {},
number = {},
pages = {JCO2501788},
doi = {10.1200/JCO-25-01788},
pmid = {41538746},
issn = {1527-7755},
abstract = {PURPOSE: To address high out-of-pocket (OOP) medication costs among Medicare Part D beneficiaries, the 2022 Inflation Reduction Act introduced the Medicare Prescription Payment Plan (M3P), a voluntary program that allows beneficiaries to spread OOP costs over the calendar year. We examined M3P's potential impact among beneficiaries with cancer, who frequently incur substantial early-year Part D medication costs.

MATERIALS AND METHODS: We evaluated a 2022 5% random sample of Medicare beneficiaries with a cancer diagnosis and ≥1 fill for a cancer-indicated Part D medication. We estimated 2025-adjusted annual true OOP spending and median monthly beneficiary OOP payment obligations with and without M3P enrollment. Subgroup analyses were performed by demographics, nonadherence status in 2022, and Part D benefit phase.

RESULTS: Among 168,480 beneficiaries with cancer, most were diagnosed with breast (47.6%), dermatologic (17.6%), or prostate (13.3%) cancers. Overall, 46.7% were projected to reach catastrophic coverage in 2025, with 32.4% doing so in January. Breast (29.7%), prostate (21.20%), and hematologic (20.0%) cancers were most common among those reaching catastrophic coverage. Overall, 43.0% were nonadherent to cancer-indicated Part D medications, with 31.5% reaching catastrophic coverage in January 2025. M3P reduced beneficiary payment obligation variability, especially among those reaching the catastrophic phase in January (IQR, $1,798 US dollars [USD] no M3P v $118 USD M3P). Of those reaching catastrophic coverage with a cancer-indicated drug (58.6% overall), 89.2% did so in January.

CONCLUSION: Early-year entry into catastrophic coverage is common among beneficiaries with certain high-cost cancers. M3P may most effectively reduce financial burden when enrollment occurs before January. Targeted outreach from cancer care teams and Part D plans to nonadherent patients and those considering costly therapies could maximize program impact and improve treatment outcomes.},
}

@article {pmid41537594,
year = {2026},
author = {Snow, JA and Hatzios, SK and Salama, NR},
title = {Managing dangerous liaisons: lessons from Helicobacter pylori for understanding bacterial carcinogenesis.},
journal = {Journal of bacteriology},
volume = {},
number = {},
pages = {e0045725},
doi = {10.1128/jb.00457-25},
pmid = {41537594},
issn = {1098-5530},
abstract = {As the first bacterium to be deemed a class I carcinogen by the World Health Organization in 1994, Helicobacter pylori has paved the way for studying complex host-pathogen interactions. While 1982 marked the discovery of this helical-shaped microorganism found in gastric biopsies by Drs. Robin Warren and Barry Marshall, it took years to link H. pylori infection to gastric inflammation, ulcers, and adenocarcinoma (recognized by a Nobel Prize in 2005). Further investigations into how H. pylori colonizes the stomach, the identification of key virulence factors (such as VacA, CagA, and outer membrane proteins), and global epidemiological studies solidified the impact of H. pylori on gastric disease. This review details the seminal discovery of H. pylori and subsequent work that cemented its status as a microbial carcinogen. Because chronic H. pylori infection and progressive changes to the tissue environment prior to cancer development can span years/decades, studying H. pylori pathogenesis has been challenging. We focus on the importance of using animal models, in particular mouse models, to recapitulate hallmarks of H. pylori-driven human disease. Finally, we highlight recent findings illustrating how H. pylori has adapted to survive and utilize oxidative stress induced during infection, which potentiates cancer development. Due to the long-lasting nature of H. pylori infection and associated remodeling of the host environment that, in turn, promotes carcinogenesis, H. pylori stands as a model organism for understanding other chronic bacterial infections in humans and pathogen-associated malignancies.},
}

@article {pmid41537347,
year = {2026},
author = {Yeung, CCS and Eacker, SM and Sala-Torra, O and Wood, M and Beppu, L and Woolston, DW and Liachko, I and Malig, M and Stirewalt, D and Muratov, A and Fang, M and Radich, J},
title = {Evaluation of acute myeloid leukemia using genomic proximity mapping-based next generation cytogenomics.},
journal = {Haematologica},
volume = {},
number = {},
pages = {},
doi = {10.3324/haematol.2025.288461},
pmid = {41537347},
issn = {1592-8721},
abstract = {Cytogenetic analysis encompasses a suite of standard-of-care diagnostic testing methods that is applied routinely in cases of acute myeloid leukemia (AML) to assess chromosomal changes that are clinically relevant for risk classification and treatment decisions. In this study, we assess the use of Genomic Proximity Mapping® (GPM) for cytogenomic analysis of AML diagnostic specimens for detection of cytogenetic risk variants included in the European Leukemia Network (ELN) risk stratification guidelines. Archival patient samples (n = 48) from the Fred Hutchinson Cancer Center (FH) leukemia bank with historical clinical cytogenetic data were processed for GPM and analyzed with the CytoTerra cloud-based analysis platform. Genomic proximity mapping showed 100% concordance for all specific variants that have associated impacts on risk stratification as defined by ELN 2022 criteria and 78% concordance when considering all variants reported by the FH Cytogenetics Lab. Notably, the percentage of blasts (ranging from 5- 96%) did not have a clear effect on the ability to detect these variants. In two cases, GPM identified a recurrent inv(9)(p13.3p13.1). These findings demonstrate GPM's effectiveness for the evaluation of known AML-associated risk variants and a source for biomarker discovery.},
}

@article {pmid41536779,
year = {2026},
author = {Martinelli, G and Solomon, SR and Mukherjee, S and Santoro, A and Strickland, SA and Vives, S and Ravandi, F and Walter, RB and Cook, RJ and Lech-Maranda, E and Calbacho, M and Wierzbowska, A and Marconi, G and Acuña-Cruz, E and Cano-Ferri, I and Bertolini, F and Rzymski, T and Paoli, A and Merlo, GM and Auriol, FK and Zicari, S and Galleu, A and Gupta, I and Montesinos, P},
title = {Dual FLT3/PIM inhibitor dapolsertib in acute myeloid leukemia: results from the phase 1/2 DIAMOND-01 trial.},
journal = {Blood neoplasia},
volume = {3},
number = {1},
pages = {100178},
pmid = {41536779},
issn = {2950-3280},
abstract = {Acute myeloid leukemia (AML) is an aggressive hematopoietic cancer with poor survival outcomes. Despite improvements with recent FMS-like tyrosine kinase 3 (FLT3) inhibitors, resistance is common, and responses are short. Dapolsertib (MEN1703) is a novel, first-in-class dual inhibitor of PIM (proviral integration site for Moloney murine leukemia virus) and FLT3 kinases, with activity in both FLT3-mutated and wild-type cells. A phase 1/2 open-label, multicenter, dose-escalation study (DIAMOND-01) investigated the maximum tolerated dose (MTD) of single-agent dapolsertib and assessed its safety, efficacy, pharmacokinetic (PK) profile, pharmacodynamic biomarkers, and genomics in patients with AML with no standard therapeutic options available. Seventy-three patients received oral doses of dapolsertib ranging from 25 to 150 mg per day (14 consecutive days over 21-day cycles). In the dose-escalation phase, the MTD was 125 mg and was selected for dose expansion. The most common grade ≥3 adverse events in patients receiving 125 mg were pneumonia (38%), thrombocytopenia (30%), and anemia (27%); most of these events were deemed not treatment related. For patients receiving 125 mg dapolsertib (n = 55), the overall response rate was 9%, with a median 2.07-month duration of response, and 4 of 5 responses were observed in patients with isocitrate dehydrogenase 1 (IDH1)/IDH2 mutations. PK analysis indicated rapid absorption of oral dapolsertib, an elimination half-life suitable for once daily dosing and a PK independent of formulation and IDH mutational status. Pharmacodynamic activity was confirmed in 50% of evaluable patients. Overall, dapolsertib demonstrated modest single-agent activity in patients with AML. This trial was registered at www.clinicaltrials.gov as #NCT03008187.},
}

@article {pmid41535609,
year = {2026},
author = {Gottimukkala, KSV and Lane, DD and Cunningham, R and Malik, HS and Jwa, Y and Cassidy, ME and Castelli, JMP and Enstrom, MR and Poljakov, K and Gastelum, G and Ho, SH and Tassa, C and Adair, JE},
title = {CRISPR-AuNP: physicochemical optimization of a gold nanoparticle platform for cost-effective and modular non-viral gene editing in HSPCs.},
journal = {Gene therapy},
volume = {},
number = {},
pages = {},
pmid = {41535609},
issn = {1476-5462},
abstract = {Efficient delivery of CRISPR ribonucleoproteins into primary hematopoietic stem and progenitor cells (HSPCs) is essential for durable gene editing therapies but remains challenging. Here, we advance a modular, benchtop-assembled gold-polymer hybrid nanoparticle (CRISPR-AuNP) platform that enables non-viral delivery of multiple CRISPR systems into HSPCs. Guided by a mechanistic understanding of Cas9's interaction with gold surfaces, we engineered the formulation by conjugating pre-formed RNP-polymer complexes, assembled using thiolated polyethyleneimine-polyethylene glycol, to gold nanoparticles. This system achieved efficient editing in primary CD34+ HSPCs for Cas9, Cas12a, and Cas12a-M29-1 without compromising cell viability. Notably, the nanoformulation can be assembled in under 2 h in a PCR tube for less than $70/million HSPCs treated. This work establishes a scalable, cost-effective, and accessible gene editing system with the potential to democratize CRISPR applications in HSPC research and therapy.},
}

@article {pmid41535474,
year = {2026},
author = {Cheng, H and Su, Y and Pan, X and Xu, Y and Xie, E and Du, J and Chen, DG and Dai, X and Gottardo, R and Greenberg, PD and Li, G},
title = {The ubiquitin ligase KLHL6 drives resistance to CD8[+] T cell dysfunction.},
journal = {Nature},
volume = {},
number = {},
pages = {},
pmid = {41535474},
issn = {1476-4687},
abstract = {The multifaceted dysfunction of tumour-infiltrating T cells, including exhaustion and mitochondrial dysfunction, remains a major obstacle in cancer immunotherapy[1-6]. Transcriptomic and epigenomic regulation of T cell dysfunction have been extensively studied[7-9], but the role of proteostasis in regulating these obstacles remains less defined. Here we combined computational analyses of atlases of T cell exhaustion and mitochondrial fitness with performed targeted in vivo CRISPR screens, which identified the E3 ubiquitin ligase KLHL6 as a dual-negative regulator of both T cell exhaustion and mitochondrial dysfunction. Mechanistically, KLHL6 expression promoted TOX poly-ubiquitination and subsequent proteasomal degradation, thereby attenuating the transition of progenitor exhausted T cells towards terminal exhaustion. Simultaneously, KLHL6 maintained mitochondrial fitness by constraining the excessive mitochondrial fission that occurs during chronic T cell receptor stimulation by means of post-translational regulation of the PGAM5-Drp1 axis. However, KLHL6 is naturally downregulated by T cell receptor ligation, mitigating its potentially beneficial ubiquitin ligase activities during exposure to chronic stimulation. Enforcing KLHL6 expression in T cells markedly improved efficacy and long-term persistence against tumours and during viral infections in vivo. These findings uncover KLHL6 as a multifunctional, clinically actionable target for cancer immunotherapy, and highlight the potential of modulating proteostasis and ubiquitin modification to improve immunotherapy.},
}

@article {pmid41535386,
year = {2026},
author = {Li, J and Hu, J and Yun, H and Mei, Z and Wang, X and Luo, K and Guasch-Ferré, M and Han, X and Truong, B and Merino, J and Jia, C and Ruiz-Canela, M and Rebholz, CM and Moon, EH and Alkis, T and Liu, G and Yao, J and Zhang, X and Porneala, BC and Salas-Salvadó, J and Wang, TJ and Dupuis, J and Selvin, E and Guo, X and Bhupathiraju, SN and Brody, JA and Liu, Y and Wood, AC and North, KE and Jung, SY and Liu, CT and Sotoodehnia, N and Liu, S and Tinker, LF and Eliassen, AH and Manson, JE and Florez, JC and Gerszten, RE and Clish, CB and Liang, L and Lemaitre, RN and Tucker, KL and Rich, SS and Rotter, JI and Martínez-González, MA and Rexrode, KM and Meigs, JB and Boerwinkle, E and Kaplan, RC and Hu, FB and Yu, B and Qi, Q},
title = {Circulating metabolites, genetics and lifestyle factors in relation to future risk of type 2 diabetes.},
journal = {Nature medicine},
volume = {},
number = {},
pages = {},
pmid = {41535386},
issn = {1546-170X},
support = {R00DK122128//U.S. Department of Health & Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (National Institute of Diabetes & Digestive & Kidney Diseases)/ ; U01DK140761//U.S. Department of Health & Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (National Institute of Diabetes & Digestive & Kidney Diseases)/ ; R01DK081572//U.S. Department of Health & Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (National Institute of Diabetes & Digestive & Kidney Diseases)/ ; R01DK134672//U.S. Department of Health & Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (National Institute of Diabetes & Digestive & Kidney Diseases)/ ; R01DK119268; R01DK126698; U01DK140761; R01DK120870//U.S. Department of Health & Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (National Institute of Diabetes & Digestive & Kidney Diseases)/ ; 23POST1020455//American Heart Association (American Heart Association, Inc.)/ ; NNF24OC0095435//Novo Nordisk Fonden (Novo Nordisk Foundation)/ ; R01HL153178//U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)/ ; K24HL152440//U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)/ ; R01HL136266//U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)/ ; R01HL060712//U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)/ ; R01HL060712; R01HL170904//U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)/ ; R01AG085320//U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging)/ ; },
abstract = {The human metabolome reflects complex metabolic states affected by genetic and environmental factors. However, metabolites associated with type 2 diabetes (T2D) risk and their determinants remain insufficiently characterized. Here we integrated blood metabolomic, genomic and lifestyle data from up to 23,634 initially T2D-free participants from ten cohorts. Of 469 metabolites examined, 235 were associated with incident T2D during up to 26 years of follow-up, including 67 associations not previously reported across bile acid, lipid, carnitine, urea cycle and arginine/proline, glycine and histidine pathways. Further genetic analyses linked these metabolites to signaling pathways and clinical traits central to T2D pathophysiology, including insulin resistance, glucose/insulin response, ectopic fat deposition, energy/lipid regulation and liver function. Lifestyle factors-particularly physical activity, obesity and diet-explained greater variations in T2D-associated versus non-associated metabolites, with specific metabolites revealed as potential mediators. Finally, a 44-metabolite signature improved T2D risk prediction beyond conventional factors. These findings provide a foundation for understanding T2D mechanisms and may inform precision prevention targeting specific metabolic pathways.},
}

@article {pmid41534004,
year = {2026},
author = {Liang, EC and Jeon, Y and Qiao, Y and Wu, X and Huang, JJ and Portuguese, AJ and Basom, R and Torkelson, A and Kirchmeier, D and Braathen, K and Cowan, AJ and Shadman, M and Hirayama, AV and Till, BG and Kimble, EL and Wu, Q and Gauthier, J},
title = {Time-Series Clustering Captures Patterns of Early Immune Effector Cell-Associated Hematotoxicity That Are Predictable Using Tree-Based Models.},
journal = {JCO clinical cancer informatics},
volume = {10},
number = {},
pages = {e2500148},
doi = {10.1200/CCI-25-00148},
pmid = {41534004},
issn = {2473-4276},
mesh = {Humans ; Cluster Analysis ; *Immunotherapy, Adoptive/adverse effects/methods ; Male ; Female ; Middle Aged ; Time Factors ; },
abstract = {PURPOSE: Immune effector cell-associated hematotoxicity (ICAHT) is a major cause of nonrelapse mortality after chimeric antigen receptor (CAR) T-cell therapy. We hypothesized that unsupervised time-series clustering could better identify archetypal patterns of early hematotoxicity compared to the early ICAHT (eICAHT) grading system.

METHODS: We applied unsupervised k-means time-series clustering based on Euclidean distances to longitudinal absolute neutrophil count (ANC) data from days +0 through +30 post-CAR T-cell infusion in 691 patients treated at our center (training set: n = 483, 70%; test set: n = 208, 30%).

RESULTS: Within our training set, we identified an optimal cluster solution based on four ANC recovery clusters, which were labeled as very good, good, poor, and very poor. We trained a random forest (RF) model including the top five most important features (day +3, +4, +5, +26, and +27 ANC values) to predict the cluster assignments. Within our test set, we applied the RF model to predict cluster assignments. Compared with the eICAHT criteria, the RF-predicted clusters were more compact and better separated (Dunn index: 0.078 v 0.034; average silhouette width: 0.12 v 0.010). In addition, the RF model identified patients in the good recovery cluster with intermediate overall survival (hazard ratio [HR], 1.70 [95% CI, 1.05 to 2.74]; P = .029; reference, very good), which was not captured by grade 2 eICAHT (HR, 1.37 [95% CI, 0.80 to 2.35]; P = .25; reference, grade 0-1).

CONCLUSION: Unsupervised time-series clustering identified distinct and clinically relevant patterns of hematotoxicity after CAR T-cell therapy. We trained and tested an RF model that accurately predicted cluster assignments using only five features. Predictions can be generated using our online web application.},
}

Humans
Cluster Analysis
*Immunotherapy, Adoptive/adverse effects/methods
Male
Female
Middle Aged
Time Factors

@article {pmid41533748,
year = {2025},
author = {Boeckh, M and Xie, H and Stevens-Ayers, T and Sircy, L and Zamora, D and Goldman, JD and Woods, CW and Stapleton, RD and Rubenfeld, G and Kalil, A and Jerome, KR and Dasgupta, S and Limaye, AP},
title = {Cytomegalovirus DNAemia in Hospitalized Adults With SARS-CoV-2 Infection Requiring Supplemental Oxygen: Virologic and Clinical Characteristics and Association With Outcomes.},
journal = {The Journal of infectious diseases},
volume = {},
number = {},
pages = {},
doi = {10.1093/infdis/jiaf649},
pmid = {41533748},
issn = {1537-6613},
support = {//Merck Investigator Study/ ; },
abstract = {BACKGROUND: Cytomegalovirus (CMV) reactivation occurs in the context of coronavirus disease 2019 (COVID-19); however, the viral kinetics, risk factors, and clinical outcomes are poorly defined.

METHODS: We examined the association of CMV DNAemia with clinical outcomes among participants of a randomized trial of remdesivir with or without baricitinib (National Institute of Allergy and Infectious Diseases [NIAID], Adaptive COVID-19 Treatment Trial 2 [ACTT-2]). Plasma CMV DNAemia from CMV-seropositive participants with COVID-19 (NIAID ordinal scale [OS] 5, 6, or 7 at entry) were assessed longitudinally by quantitative polymerase chain reaction. Factors associated with CMV DNAemia, and clinical outcomes were analyzed by Cox regression and proportional odds models.

RESULTS: Of 772 trial participants with available samples, 643 (83%) were CMV seropositive. Baseline CMV serostatus was not associated with COVID-19 outcomes. The cumulative incidence of CMV DNAemia among seropositive persons by day 28 was overall 11% (baseline OS 5, 6.3%; OS 6, 16.4%; OS 7, 24.7%), and was associated with older age, baseline OS, male sex, lymphopenia, and systemic corticosteroid use, while remdesivir and baricitinib did not affect risk. CMV DNAemia was associated with a lower probability of improvement by day 29 (adjusted hazard ratio, 0.3 [95% confidence interval, .17-.56]), with a more pronounced delay of recovery with higher CMV viral load. CMV DNAemia was also associated with higher severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral load and death.

CONCLUSIONS: In hospitalized adults with COVID-19 requiring oxygen, CMV viremia occurs within well-defined clinical risks and is independently associated with delayed recovery from illness, higher SARS-CoV-2 viral load, and increased mortality.},
}

@article {pmid41532388,
year = {2026},
author = {Cassaday, RD and DeAngelo, DJ},
title = {Patients First: Navigating Asparaginase-Based Treatment in Young Adults With Acute Lymphoblastic Leukemia.},
journal = {American journal of hematology},
volume = {},
number = {},
pages = {},
doi = {10.1002/ajh.70195},
pmid = {41532388},
issn = {1096-8652},
abstract = {This CME/CE integrates real patient stories, current evidence, evolving guideline recommendations, and expert clinical experience to equip hematology/oncology clinicians with practical strategies for successful asparaginase-based therapy in young adults with acute lymphoblastic leukemia (ALL). The overarching goal is to improve outcomes for young adults with ALL through more consistent application of pediatric-inspired regimens, optimized asparaginase use, and comprehensive, patient-centered care. Leukemia experts synthesize the latest evidence on the efficacy and safety of asparaginase-based ALL treatment for young adults. Using a case-based approach, the curriculum provides structured guidance on mitigation, monitoring, and management of key asparaginase-related toxicities. Practical recommendations include therapeutic drug monitoring of asparaginase activity, detection of clinical and silent hypersensitivity reactions, and timely substitution of Escherichia coli-derived asparaginase with Erwinia-derived asparaginase to preserve therapeutic activity and efficacy after immune-mediated inactivation. Beyond treatment selection and toxicity management, the activity addresses system-level and psychosocial barriers that uniquely affect young adults with ALL, such as distance from specialty centers, employment and family responsibilities, lower rates of clinical trial participation, and survivorship concerns. To view this activity, and obtain CME/CE credit, click here.},
}

@article {pmid41531135,
year = {2026},
author = {Hayek, H and Halasa, NB and Hill, JA},
title = {Establishing Permanence, Not Patchwork: Sustaining Coordinated Research Networks for Immunocompromised Populations.},
journal = {Transplant infectious disease : an official journal of the Transplantation Society},
volume = {},
number = {},
pages = {e70168},
doi = {10.1111/tid.70168},
pmid = {41531135},
issn = {1399-3062},
}

@article {pmid41530145,
year = {2026},
author = {Brzoska, T and Kaminski, TW and Katoch, O and Menchikova, EV and Alagbe, AE and Tashbook, SE and Tofovic, SP and Jonassaint, JC and St Croix, CM and Watkins, SC and Howe, S and Field, JJ and Seyerle, AA and Pradhan-Sundd, T and Laurie, C and Pankratz, ND and Smith, NL and Goode, EL and Pankow, JS and Kooperberg, C and Kato, GJ and Zhang, Y and Novelli, EM and Gladwin, MT and Jackson, EK and Nouraie, SM and Sundd, P},
title = {CD39 polymorphism enables lung thrombosis in sickle cell disease.},
journal = {Nature communications},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41467-026-68396-2},
pmid = {41530145},
issn = {2041-1723},
support = {R01HL128297//U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)/ ; R01HL141080//U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)/ ; R01HL166345//U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)/ ; 18TPA34170588//American Heart Association (American Heart Association, Inc.)/ ; 23TPA1074022//American Heart Association (American Heart Association, Inc.)/ ; },
abstract = {Sickle cell disease (SCD) is the most common monogenic-hemolytic disorder affecting people of African ancestry. Adenosine diphosphate (ADP) released following intravascular hemolysis activates platelets by stimulating purinergic receptors to promote thrombosis. Despite brisk intravascular hemolysis, which releases high levels of ADP into plasma, and evidence of platelet and hemostatic activation, it remains elusive why only a subset of SCD patients develop lung thrombosis. Using real-time in vivo lung microscopy, we report a surprising finding that humanized SCD mice are protected from ADP-induced lung thrombosis, which is secondary to the degradation of ADP by CD39 present in circulating extracellular vesicles released by the lung endothelium. ADP-induced platelet aggregation is also impaired in the blood of SCD patients with elevated levels of CD39[+] extracellular vesicles. CD39 polymorphism rs3176891A→G is associated with the incidence of lung thrombosis in SCD patients but not healthy humans of African ancestry. Remarkably, CD39[+] extracellular vesicles are fewer and ADP-induced platelet aggregation is higher in the blood of SCD patients with rs3176891G allele. This study identifies a novel extracellular vesicle-dependent mechanism preventing lung thrombosis in SCD and reveals how CD39 polymorphisms may impair this protection to increase the risk for lung thrombosis in a subset of SCD patients.},
}

@article {pmid41530119,
year = {2026},
author = {Ykema, MR and Davis, MA and Kasal, DN and Jennewein, MF and Lo, E and Singh, J and Beaver, S and Cross, N and Melief, E and Reed, S and Press, C and Brandt, DS and McClary, WD and Mohamath, R and Fusco, P and Bakken, J and Casper, C and Hartwig, AT and Gerhardt, A and Bowen, RA and Voigt, EA},
title = {Intranasal replicon vaccine establishes mucosal immunity and protects against H5N1 and H7N9 influenza.},
journal = {Nature communications},
volume = {17},
number = {1},
pages = {434},
pmid = {41530119},
issn = {2041-1723},
mesh = {Animals ; *Influenza Vaccines/immunology/administration & dosage/genetics ; Administration, Intranasal ; *Immunity, Mucosal/immunology ; *Influenza A Virus, H5N1 Subtype/immunology/genetics ; Ferrets ; Mice ; *Orthomyxoviridae Infections/prevention & control/immunology/virology ; *Replicon/immunology ; Female ; *Influenza A Virus, H7N9 Subtype/immunology/genetics ; Humans ; Mice, Inbred BALB C ; Antibodies, Viral/immunology ; *Influenza, Human/prevention & control/immunology/virology ; Injections, Intramuscular ; Hemagglutinin Glycoproteins, Influenza Virus/immunology/genetics ; },
abstract = {Seasonal and pandemic influenza viruses are continuous threats to human health, requiring rapid development of vaccines to multiple evolving viral strains. RNA vaccine technologies have the adaptability and manufacturability to facilitate pandemic preparedness but have limited flexibility in their route of administration, reducing the ability to establish local protective immune responses such as respiratory mucosal immunity. Here, we describe monovalent and bivalent replicon vaccines against A/Vietnam/1203/2004 H5N1 and A/Anhui/PA-1/2013 H7N9. These replicon vaccines express either H5 or H7 hemagglutinin and are formulated with a nanostructured lipid carrier (NLC) that permits both intramuscular (IM) and intranasal (IN) dosing. In mice, IM vaccination established systemic humoral and cellular responses but no detectable mucosal response, while IN administration induced robust systemic and mucosal immunity. The replicon-NLC vaccines protected against morbidity and mortality in ferret challenge models, establishing this intranasally-administered replicon-NLC vaccine platform as a potential pandemic response tool.},
}

Animals
*Influenza Vaccines/immunology/administration & dosage/genetics
Administration, Intranasal
*Immunity, Mucosal/immunology
*Influenza A Virus, H5N1 Subtype/immunology/genetics
Ferrets
Mice
*Orthomyxoviridae Infections/prevention & control/immunology/virology
*Replicon/immunology
Female
*Influenza A Virus, H7N9 Subtype/immunology/genetics
Humans
Mice, Inbred BALB C
Antibodies, Viral/immunology
*Influenza, Human/prevention & control/immunology/virology
Injections, Intramuscular
Hemagglutinin Glycoproteins, Influenza Virus/immunology/genetics

@article {pmid41528117,
year = {2026},
author = {Johnson, M and Cai, Y and Vasconcelos, AG and Orchard, P and Auer, PL and Lettre, G and Wen, J and Franceschini, N and Kooperberg, C and Sun, W and Hsu, L and Raffield, LM and Reiner, AP},
title = {Whole Blood Transcriptomic Analysis of Sickle Cell Trait.},
journal = {European journal of haematology},
volume = {},
number = {},
pages = {},
doi = {10.1111/ejh.70114},
pmid = {41528117},
issn = {1600-0609},
support = {phs001237/HL/NHLBI NIH HHS/United States ; R01HL152439/HL/NHLBI NIH HHS/United States ; R01HL146500/HL/NHLBI NIH HHS/United States ; U01HG01172/HG/NHGRI NIH HHS/United States ; /NH/NIH HHS/United States ; 75N92021D00002/HL/NHLBI NIH HHS/United States ; 75N92021D00003/WH/WHI NIH HHS/United States ; 75N92021D00004/WH/WHI NIH HHS/United States ; 75N92021D00005/WH/WHI NIH HHS/United States ; //Fred Hutchinson Cancer Center/ ; 3U54HG003067-13S1//Broad Institute of MIT and Harvard, and the Northwest Genomics Center (NWGC)/ ; HHSN268201500014C/HL/NHLBI NIH HHS/United States ; X01HL153408//Broad Institute of MIT and Harvard, and the Northwest Genomics Center (NWGC)/ ; },
abstract = {Sickle cell trait (SCT) is the heterozygous carrier state for the HBB missense variant which causes sickle cell disease (SCD). SCT has been associated with increased risk of venous thromboembolism and chronic kidney disease as well as alterations in clinical laboratory parameters. To investigate differential gene expression in SCT, we used RNA sequencing of whole blood samples collected from 805 African American female participants (143 SCT; 660 controls) from the Women's Health Initiative Long Life Study (mean age = 76). We identified 226 differentially expressed genes (DEGs) in SCT compared to non-carriers (FDR < 0.05). Enriched pathways included those related to erythropoiesis, hemoglobin synthesis, and proteasomal degradation. Many of the SCT-associated DEGs were previously reported as differentially expressed in blood from individuals with SCD. Among the DEGs associated with SCT, we observed enrichment of upregulated ubiquitin-related genes normally downregulated during the later stages of erythroid differentiation, a pattern previously reported in SCD. Several of the SCT-associated DEGs highlight mechanisms that potentially link hemolysis or erythropoiesis to hypoxic kidney tubular injury. Future investigation of these genes using single cell transcriptomic analysis in relevant tissues may be useful in understanding mechanisms for adverse health outcomes in individuals with SCT.},
}

@article {pmid41526345,
year = {2026},
author = {Strickler, JH and Cercek, A and Siena, S and André, T and Ng, K and Van Cutsem, E and Wu, C and Paulson, AS and Hubbard, JM and Coveler, AL and Fountzilas, C and Kardosh, A and Kasi, PM and Lenz, HJ and Ciombor, K and Elez, E and Bajor, DL and Cremolini, C and Sanchez, F and Nayeri, M and Feng, W and Bieda, M and Bekaii-Saab, TS},
title = {Tucatinib plus trastuzumab for chemotherapy-refractory, HER2 + , RAS wild-type metastatic colorectal cancer (MOUNTAINEER): final analysis.},
journal = {Nature communications},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41467-025-67824-z},
pmid = {41526345},
issn = {2041-1723},
abstract = {MOUNTAINEER was a multicenter, open-label, phase 2 trial (NCT03043313) that evaluated the efficacy and safety of tucatinib plus trastuzumab, a dual HER2-targeted chemotherapy-free regimen. Patients were included if they had chemotherapy-refractory, HER2+, RAS wild-type unresectable or metastatic colorectal cancer. This final analysis reports updated efficacy and safety after a median follow-up of 32.4 months. Of the 84 patients who received tucatinib plus trastuzumab, the confirmed objective response rate was 39.3%; median duration of response was 15.2 months. Median progression-free survival was 8.1 months and overall survival was 23.9 months. Efficacy was relatively similar across central HER2+ testing methods. No clear association of treatment response with co-occurring biomarker alterations was seen. Few patients discontinued treatment due to adverse events; no treatment-emergent deaths occurred. Tucatinib plus trastuzumab showed clinically meaningful efficacy and favorable safety. Efficacy was observed irrespective of central HER2+ testing methods and in patients with heterogeneous tumor biomarker profiles.},
}

@article {pmid41524276,
year = {2026},
author = {Tan, Y and Kim, BJ and Mujal, AM and Chen, ACY and Weis, AM and Bergaggio, E and Micevic, G and Xie, H and Park, JS and Hor, JL and Papanicolaou, M and Shobaki, N and Domizi, P and Delconte, RB and Vendramin, R and Hegde, S and Han, S and Su, Y and Hacohen, N},
title = {Training Tomorrow's Leaders in Cancer Immunology.},
journal = {Cancer immunology research},
volume = {},
number = {},
pages = {OF1-OF8},
doi = {10.1158/2326-6066.CIR-25-1479},
pmid = {41524276},
issn = {2326-6074},
abstract = {The transition from trainee to independent investigator is one of the most challenging and formative phases of a scientific career. It requires not only scientific expertise but also the skills to lead, mentor, manage, and communicate effectively. The Arthur and Sandra Irving Cancer Immunology Symposium serves as a platform for established investigators to mentor trainees and early-career faculty as they navigate this transition to independence. Through sharing personal experiences and lessons from their own careers, senior leaders provide guidance on the scientific, professional, and personal challenges that shape a successful career in cancer immunology-emphasizing how curiosity, persistence, and a translational mindset can make a lasting real-world impact. This commentary highlights key themes, including leadership, communication, recruitment, and fundraising. Altogether, these insightful thoughts provide a framework for the next generation of cancer immunologists as they establish their independent careers as future leaders in the field.},
}

@article {pmid41524253,
year = {2026},
author = {Stolla, M and Bailey, SL and Chauhan, A and Byrne, DA and Ting, L and Klotz, P and Pulido, JN and Lehr, EJ and Youssef, S and Lawrence, J and Limanek, A and Alcorn, K and Ryan, P and Stout, DM},
title = {A pilot trial of long-distance shipped, extended- and cold-stored platelets in 100% plasma for cardiothoracic surgical bleeding.},
journal = {Transfusion},
volume = {},
number = {},
pages = {},
doi = {10.1111/trf.70076},
pmid = {41524253},
issn = {1537-2995},
support = {W81XWH-12-1-0441//U.S. Department of Defense/ ; },
abstract = {BACKGROUND: In this pilot trial, we tested the feasibility of conducting a randomized controlled trial in cardiac surgery patients using extended-, 100% plasma-, cold-stored, and long-distance-shipped platelets (CSPs).

STUDY DESIGN AND METHODS: We conducted a single center, controlled, double-blind pilot study in adult patients undergoing elective redo or complex cardiothoracic surgery. Patients were allocated in a week-based block randomization scheme to receive either room temperature-stored platelets (RTPs) or CSPs shipped from a Texas-based blood center and stored between 10 and 14 days. The primary outcome was defined as the feasibility of recruitment and accrual. Several other secondary endpoints were assessed. All platelet units were screened for aggregates using RTP release criteria.

RESULTS: In a post-hoc "as treated" analysis, 15 patients received RTPs, and 9 received CSPs (including 3 who received both). We found that most CSPs (58%) were not usable for transfusion due to the presence of aggregates. This resulted in an excess of subjects receiving RTPs; consequently, the final nine transfused participants were allocated to receive CSPs without randomization. We accrued 0.7 evaluable subjects/month of active enrollment, which was below our desired primary outcome feasibility target of ≥1.2. One death within 28 days occurred in the RTP transfusion group, while none occurred in the CSPs group. In vitro testing yielded contradictory results.

CONCLUSION: Due to slow recruitment and the abundance of aggregates in CSPs, this pilot trial does not support the feasibility of the study protocol.},
}

@article {pmid41521409,
year = {2025},
author = {Lindsay, J and Yeoh, D and Teh, BW and Reynolds, GK and Henden, A and McQuilten, Z and Wheeler, M and Hamilton, A and Nelson, A and Nakagaki, M and Sandhu, S and Slavin, MA and , },
title = {Consensus guidelines for antibacterial prophylaxis in patients with neutropenia.},
journal = {Internal medicine journal},
volume = {55 Suppl 7},
number = {},
pages = {115-135},
doi = {10.1111/imj.70250},
pmid = {41521409},
issn = {1445-5994},
mesh = {Humans ; *Anti-Bacterial Agents/therapeutic use ; *Antibiotic Prophylaxis/standards/methods ; Australia/epidemiology ; Neoplasms/drug therapy ; *Neutropenia/drug therapy/chemically induced ; },
abstract = {Since the publication of the Australian consensus guidelines in 2011, the routine use of prophylactic antibiotics in patients with neutropenia has remained controversial, because of concern that the risks of promoting antimicrobial resistance outweighed the level of evidence that their use reduced mortality. Populations at risk have changed over this period and now include a multitude of new cancer therapies, such as targeted cancer therapies and immunotherapies. Emerging understanding about the importance and role of the microbiome in defining treatment response and patterns of antibiotic resistance has also expanded. In addition, the management of neutropenic fever has improved significantly through the development and routine implementation of sepsis pathways. These updated consensus guidelines review recent evidence for the use of antibacterial prophylaxis in adults and children receiving cancer therapies associated with neutropenia. Recommendations presented in these guidelines were based on evaluating current evidence for the benefits and harms of antibacterial prophylaxis while considering the current Australian and New Zealand healthcare setting. In most circumstances, the potential harm of antibiotic resistance, adverse effects of antibiotics and disruption to the microbiome, outweighed the benefit of reducing the incidence of infection, without a benefit in mortality.},
}

Humans
*Anti-Bacterial Agents/therapeutic use
*Antibiotic Prophylaxis/standards/methods
Australia/epidemiology
Neoplasms/drug therapy
*Neutropenia/drug therapy/chemically induced

@article {pmid41521394,
year = {2026},
author = {O'Keefe, GE and Navarro, SL and Zheng, Z and Randolph, TW and Shelton, M and Elizaga, N and Qiu, Q and Nagana, GGA and Raftery, D},
title = {Metabolic profiles in adults with trauma receiving enteral nutrition support: A metabolomic cohort study.},
journal = {JPEN. Journal of parenteral and enteral nutrition},
volume = {},
number = {},
pages = {},
doi = {10.1002/jpen.70051},
pmid = {41521394},
issn = {1941-2444},
support = {R01GM127790/NH/NIH HHS/United States ; T32 GM121290/NH/NIH HHS/United States ; //NIDDK P30 DK035816 (Nutrition and Obesity Research Center)/ ; },
abstract = {BACKGROUND: We aimed to identify metabolic changes after injury and potential mechanisms whereby nutrition support may influence metabolites and pathways. We analyzed 45 metabolites in 67 trauma patients.

METHODS: We performed a metabolomic cohort study in critically ill adults with trauma using nuclear magnetic resonance to quantify 45 metabolites in plasma. We divided the cohort into two groups based on the median amount of protein intake calculated by averaging over the first 7 days of nutrition support. Using linear mixed models, we tested the hypotheses that metabolite concentrations would differ over time and the rate of change is altered by the amount of enteral protein intake.

RESULTS: Five metabolites in each of the low (median = 0.6 [IQR, 0.4-0.8] gm/kg/day) and high (1.5 [1.1-1.7] gm/kg/day) protein intake groups were different by day 3 compared with baseline. Twenty metabolites in the low-protein intake group and 14 metabolites in the high-protein intake group were different by day 7 compared with baseline. There was no evidence that the rate of metabolite change over time differs by protein intake group. Quantitative enrichment analysis indicated that branched chain amino acid (BCAA) catabolism was one of the most altered pathways in both groups.

CONCLUSION: In critically ill trauma patients, metabolites, particularly those linked with BCAA metabolism, are altered over time but not influenced by the amount of enteral protein intake during the first week.},
}

@article {pmid40911901,
year = {2026},
author = {Dela Cruz, FS and Stewart, EA and Surdez, D and Daley, JD and Soragni, A and Tomazou, EM and Alvarez-Perez, J and Feinberg, TY and Amatruda, JF and Ganapathi, SS and Ohm, JE and Heske, CM and Cohen-Gogo, S and Pesic, D and Nash, JO and Shlien, A and Roundhill, EA and Burchill, SA and Crompton, BD and Lawlor, ER and Loeb, DM and Delattre, O and Mora, J and Scotlandi, K and Reed, DR and Grohar, PJ and Grünewald, TGP and Kovar, H and Bailey, KM},
title = {Advancing Preclinical Biology for Ewing Sarcoma: An International Effort.},
journal = {Molecular cancer therapeutics},
volume = {25},
number = {1},
pages = {48-70},
pmid = {40911901},
issn = {1538-8514},
mesh = {*Sarcoma, Ewing/pathology ; Humans ; Animals ; *Bone Neoplasms/pathology ; Mice ; Disease Models, Animal ; Xenograft Model Antitumor Assays ; },
abstract = {Ewing sarcoma is an aggressive bone and soft-tissue cancer affecting adolescents and young adults. In vitro and in vivo models of Ewing sarcoma have been instrumental in advancing our understanding of Ewing sarcoma biology and essential in evaluating potential therapies, particularly for metastatic or relapsed disease for which effective treatment options remain limited. Through an international collaborative effort between the Children's Oncology Group Bone Tumor Committee and the Euro Ewing Consortium, we review the current landscape of preclinical modeling used in Ewing sarcoma research encompassing both in vitro (cell lines and tumor organoids) and in vivo (mouse and nonmammalian xenografts) model systems. We discuss factors that can influence experimental results, provide testing considerations for both in vitro and in vivo studies, and descriptions of existing preclinical data repositories. We highlight current needs in Ewing sarcoma modeling and the importance of enhanced international cooperative research and patient advocacy efforts which will be critical in expanding our resources of biologically relevant Ewing sarcoma models to enable translation of preclinical findings into effective therapeutic strategies for patients with Ewing sarcoma.},
}

*Sarcoma, Ewing/pathology
Humans
Animals
*Bone Neoplasms/pathology
Mice
Disease Models, Animal
Xenograft Model Antitumor Assays

@article {pmid41521011,
year = {2026},
author = {Kanzaria, A and Arora, S and Naik, A and Dhanushkodi, N and Ho, CC and Kaur, N and Zhang, J and Ren, X and Fromm, JR and Shadman, M and Smith, S and Gopal, A and Roncador, G and Holland, E and Naresh, KN},
title = {Biomarkers Informed by Single-Cell and Spatial Transcriptomics - Biomarkers for Grade 3 Follicular Lymphoma.},
journal = {Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc},
volume = {},
number = {},
pages = {100958},
doi = {10.1016/j.modpat.2026.100958},
pmid = {41521011},
issn = {1530-0285},
abstract = {Follicular lymphoma (FL) patients have variable outcomes, underscoring the need for biomarkers for improved risk stratification. Current FL grading systems, based on subjective centroblast counts, suffer from poor reproducibility, despite evidence linking grade 3 FL to worse prognosis. We aimed to identify objective biomarkers for centroblasts and centrocytes to improve FL prognostication. We reanalyzed publicly available spatial and single-cell transcriptomic data from normal germinal centers (GCs) and FL samples. Reanalysis revealed distinct gene expression profiles: AICDA (AID) and CXCR4 highly expressed in GC dark zone cells (centroblasts), and CD40 and TFRC (CD71) in light zone cells (centrocytes). Single-cell RNA sequencing of FL samples further showed AID and CXCR4 overexpression in malignant Grade 3A cells and CD40 and CD71 in grade 1-2 cells. We validated these findings using immunohistochemistry (IHC) (single and multiplex) on tonsils and 59 FL specimens (42 Grade 1-2, 17 Grade 3). Grade 3 FL showed significantly higher expression of AID, CD71, and Ki67 compared to grade 1-2; with CXCR4 approaching significance. Receiver operating characteristic (ROC) curve analysis identified optimal cut-offs for AID (1.54%), CXCR4 (21.9%), Ki67 (21.6%), and CD71 (7.57%) to distinguish grade 3 from grade 1-2 FL, with AID showing the best discriminatory ability. Crucially, AID expression evaluation showed reproducibility across two different digital algorithms and two independent visual observers. Furthermore, we observed a trend toward shorter disease-specific survival (DSS) in patients with both FL grade 3 and high AID expression. This prognostic observation held true regardless of whether AID overexpression was assessed via digital evaluation (cut-off: 1.54%) or visual estimation (cut-off: 2%). In conclusion, AID, CXCR4, CD71, and Ki67 are promising biomarkers for objectively identifying FL grade 3, potentially enhancing the reproducibility of grading and serving as independent prognostic tools. Further clinical validation in uniformly treated FL cohorts is warranted.},
}

@article {pmid41520338,
year = {2026},
author = {Janssens, DH and Codomo, CA and Otto, DJ and Silberstein, L and Ahmad, K and Henikoff, S},
title = {Sequential RNA polymerase II activation drives human hematopoiesis.},
journal = {Cell reports},
volume = {45},
number = {1},
pages = {116802},
doi = {10.1016/j.celrep.2025.116802},
pmid = {41520338},
issn = {2211-1247},
abstract = {Promoter-proximal pausing of RNA polymerase II (Pol II) primes genes for rapid activation, yet how Pol II dynamics are temporally organized in adult stem cells to enable fast and flexible responses to environmental cues remain unknown. To address this, we developed sciCUT&Tag2in1 for joint profiling of Pol II and histone modifications in single cells. By profiling over 200,000 CD34[+] hematopoietic stem cells (HSCs) and progenitors, we identify a Pol II regulatory cascade that directs the response to granulocyte colony-stimulating factor (G-CSF)-induced inflammatory stress. HSCs are activated by elevated Pol II occupancy and reduced Polycomb repression of immune response genes. Lineage commitment proceeds through sequential modes of Pol II activation, beginning with rapid pause-and-release genes, followed by slower initiate-and-release of Polycomb-repressed targets. sciCUT&Tag2in1 defines the temporal logic of how adult stem cells use paused Pol II to enable flexible lineage decisions, providing a powerful tool for studying the intersection of development, inflammation, and disease.},
}

@article {pmid41520058,
year = {2026},
author = {Fuller, H and Agasaro, OP and Guevara, JM and Darst, BF},
title = {Pre-diagnostic circulating untargeted metabolomics and risk of overall and clinically significant prostate cancer: a systematic review and meta-analysis.},
journal = {British journal of cancer},
volume = {},
number = {},
pages = {},
pmid = {41520058},
issn = {1532-1827},
support = {P50 CA097186/CA/NCI NIH HHS/United States ; P30 CA015704/CA/NCI NIH HHS/United States ; R00 CA246063/CA/NCI NIH HHS/United States ; },
abstract = {BACKGROUND: Metabolomic dysregulation contributes to prostate cancer (PCa) pathogenesis, and studies suggest that circulating metabolites have strong potential to act as clinical biomarkers. However, evidence of associations between circulating metabolites with overall and clinically significant PCa risk has not been quantitively aggregated.

METHODS: We performed a systematic review and meta-analysis of untargeted pre-diagnostic circulating metabolomic studies across four clinically distinct outcomes: overall, low- to intermediate-risk, high- to very high-risk, and lethal PCa, each compared to controls.

RESULTS: Twelve studies were identified in the systematic review, and up to 408 metabolites were meta-analysed across the four PCa outcomes. Three, eleven, and nineteen metabolites were significantly associated with risk of overall, high- to very high-risk, and lethal PCa, respectively. Metabolites associated with high- to very high-risk PCa were significantly enriched for lipids. Limited evidence of correlation between metabolite effects across outcomes was identified, highlighting potentially unique metabolite drivers of high-risk and lethal PCa. In follow-up analyses, 13 of the significant metabolites were found to be modifiable by drugs and/or diet.

CONCLUSIONS: These findings suggest a strong potential for metabolites to inform risk of lethal PCa, which could inform risk-stratified screening strategies and facilitate the identification of targets for PCa prevention.},
}

@article {pmid41519271,
year = {2026},
author = {Nicholas, JC and Alkis, T and Bis, JC and Boerwinkle, E and Brody, JA and Clish, CB and de Vries, PS and Gao, Y and Gerzsten, RE and Guo, X and Johnson, AD and Larson, MG and Lemaitre, RN and Psaty, BM and Ramachandran, V and Reiner, AP and Rich, SS and Rodriguez, B and Rong, J and Rotter, JI and Simino, J and Smith, NL and Wilson, J and Yao, J and Morrison, AC and Yu, B and Raffield, LM},
title = {Fibrinogen-Associated Plasma Metabolites and Implications for Coagulation, Inflammation, and Vascular Diseases.},
journal = {Journal of thrombosis and haemostasis : JTH},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jtha.2025.12.016},
pmid = {41519271},
issn = {1538-7836},
abstract = {BACKGROUND: Fibrinogen is a critical coagulation factor that plays an essential role in thrombosis and is elevated in individuals with chronic inflammation. Here, we used fibrinogen as a representative quantitative measure of pro-coagulant risk and evaluated metabolites associated with fibrinogen levels through non-targeted plasma metabolomic profiling (Broad and Metabolon platforms).

METHODS: Our analysis included 10,533 individuals across six U.S. based cohorts representing diverse population groups. The cross-sectional relationship between each of 789 tested metabolites and plasma fibrinogen concentration was assessed with adjustment for relevant covariates such as age, sex, body mass index, and circulating lipoprotein levels.

RESULTS: Meta-analysis of per-cohort results revealed 270 metabolites significantly associated with fibrinogen level (FDR adjusted p-value < 0.05). Lipid species such as glycerophospholipids, sphingolipids, and fatty acyls were prevalent among significantly associated metabolites; some of these may capture effects of inflammation, as supported by sensitivity analyses adjusted for C-reactive protein. Significant associations between fibrinogen levels and serotonin, thyroxine, and sex-hormone derivatives may capture endogenous influences on fibrinogen levels. Exogenous compounds and microbial co-metabolites significantly associated with fibrinogen also implicate lifestyle and microbiome risk-factors. Only a portion of fibrinogen-associated metabolites (30%) have been associated with a cardiovascular disease outcome in a prior study, suggesting the associations discovered here may provide insights on vascular biology which case-control studies may not yet be powered to detect.

CONCLUSIONS: These findings contribute to a growing list of metabolite biomarkers that may influence coagulation and inflammation pathways and may thereby contribute to vascular risk.},
}

@article {pmid41519253,
year = {2026},
author = {Thornburgh, S and Farland, LV and Harris, HR and Sonneville, KR and Neblett, MF and Field, AE and Chavarro, JE and Missmer, SA and Gaskins, AJ},
title = {Disordered Eating Behaviors during Adolescence and Risk of Endometriosis: A Prospective Cohort Study.},
journal = {Fertility and sterility},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.fertnstert.2025.12.027},
pmid = {41519253},
issn = {1556-5653},
abstract = {OBJECTIVE: Disordered eating behaviors may impact the gynecologic health of adolescents through effects on menstrual cycle function and body size; however, few studies have evaluated these associations. This study aimed to prospectively investigate the associations between individual disordered eating behaviors during adolescence, and the risk of subsequent endometriosis diagnosis.

DESIGN: Prospective, longitudinal cohort (1996-2021).

SUBJECTS: Female participants (n = 11773) from the Growing Up Today Study.

EXPOSURE: Frequency of binge eating, laxative use, and self-induced vomiting over the past year were self-reported on repeated questionnaires during follow-up.

MAIN OUTCOME MEASURES: Physician-diagnosed endometriosis was reported on repeated questionnaires during follow-up. Multivariable logistic regression models with generalized estimating equations were used to calculate adjusted odds ratios (aORs) and 95% confidence intervals (CIs).

RESULTS: Over 25 years of follow-up, we identified 269 incident cases of endometriosis (2.3%), 190 of which were reported as laparoscopically confirmed. A total of 32% of girls reported ever binge eating, 14% reported self-induced vomiting to lose weight, and 9% reported ever using laxatives to lose weight. The odds of laparoscopically-confirmed endometriosis diagnosis was more than three-fold higher (aOR=3.07, 95% CI 1.74, 5.40) for girls who cumulatively reported self-induced vomiting more than monthly during follow-up, compared to girls who never reported self-induced vomiting. A similar effect estimate (aOR=2.41, 95% CI 1.40, 4.12 was noted for girls who reported weekly or more frequent self-induced vomiting at least once during follow-up compared to girls who reported never vomiting. Cumulative exposure to binge eating during follow-up was not associated with diagnosis of laparoscopically-confirmed endometriosis; however, girls who reported a highest ever engagement in binge eating of weekly or more had 52% lower (aOR=0.47, 95% CI 0.25, 0.90) odds of laparoscopically-confirmed endometriosis, compared to girls who reported less than weekly binge eating. Laxative use was not strongly associated with endometriosis diagnosis, although estimates were imprecise.

CONCLUSIONS: We observed that females with a greater frequency of self-induced vomiting were more likely to be diagnosed with endometriosis during follow-up, while girls with a history of frequent binge eating had a lower likelihood of endometriosis diagnosis. We found no association between laxative use and endometriosis.},
}

@article {pmid41518882,
year = {2025},
author = {Summers, C and Mallhi, K and Persinger, H and Fan, X and Gooley, TA and Dahlberg, AE and Burroughs, LM and Thakar, MS and Bhatt, NS and Petrovic, A and Hadland, B and Carpenter, PA and Baker, KS and Bleakley, M},
title = {Outcomes following hematopoietic cell transplantation for children, adolescents and young adults with relapsed acute lymphoblastic leukemia.},
journal = {Cytotherapy},
volume = {28},
number = {3},
pages = {102004},
doi = {10.1016/j.jcyt.2025.102004},
pmid = {41518882},
issn = {1477-2566},
abstract = {BACKGROUND: Allogeneic hematopoietic cell transplantation (HCT) is a common consolidation therapy for recurrent acute lymphoblastic leukemia (ALL), reducing relapse risk but causing significant morbidity, mortality, and potential impairment of growth and development in children, adolescents, and young adults (CAYA). Avoiding or delaying HCT could prevent such complications. New targeted therapies, including CD19 chimeric antigen receptor (CAR) T cells, have increased the number of recurrent ALL patients who might achieve long-term remission without HCT. However, outcomes of delaying HCT beyond second complete remission (CR2) in the modern era remain unclear.

OBJECTIVE: To compare outcomes of HCT performed in CR2 versus third or later remission (CR3+) in CAYA with ALL.

METHODS: We retrospectively reviewed CAYA who underwent first HCT for ALL in CR2 (n = 81) or CR3+ (n = 44) at our institution from 2000-2020.

RESULTS: For all patients, estimated 1-year overall survival (OS), relapse, and nonrelapse mortality (NRM) were 76%, 20.8%, and 9.6%; 3-year estimates were 69%, 30%, and 9.6%, respectively. At 3 years, OS was 77% for CR2 versus 53% for CR3+, and NRM was 6% versus 16%. Adjusted hazard ratios (HR) for CR3+ versus CR2 were: overall mortality HR 1.87 (95% CI, 1.06-3.31), relapse HR 1.28 (95% CI, 0.66-2.50), and NRM HR 2.63 (95% CI, 1.08-6.39).

CONCLUSIONS: CAYA with ALL undergoing HCT in CR3+ experienced higher NRM and worse survival compared to those transplanted in CR2. Efforts to reduce NRM in multiply relapsed patients are required.},
}

@article {pmid41515121,
year = {2025},
author = {Park, J and Kadro, ZO and Honvoh, GD and Domeniciello, AF and Ramsden, CE and Faurot, KR and Miller, VE},
title = {Associations Between Dietary Intakes of Omega-3 Fatty Acids, Blood Levels, and Pain Interference in People with Migraine: A Path Analysis of Randomized Trial Data.},
journal = {Nutrients},
volume = {18},
number = {1},
pages = {},
pmid = {41515121},
issn = {2072-6643},
support = {RO1-AT007813/AT/NCCIH NIH HHS/United States ; Intramural Program/AG/NIA NIH HHS/United States ; T32-AT003378/AT/NCCIH NIH HHS/United States ; Gift to the Department of Physical Medicine and Rehabilitation//Dr. John M. Davis/ ; },
mesh = {Humans ; *Migraine Disorders/diet therapy/blood ; Female ; Male ; *Docosahexaenoic Acids/blood/administration & dosage ; *Eicosapentaenoic Acid/blood/administration & dosage ; Adult ; *Fatty Acids, Omega-3/blood/administration & dosage ; Middle Aged ; *Diet ; *Pain ; },
abstract = {Background/Objectives: Increasing evidence supports the hypothesis that dietary intervention can improve pain among individuals with headaches, including migraine, a highly prevalent condition that can be disabling. Non-pharmacologic treatments for migraine are particularly attractive. In this secondary analysis of 182 participants enrolled in a randomized controlled trial of a dietary intervention designed to increase omega-3 (n-3) compared with a control diet, we examined the effects of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), both thought to decrease inflammatory processes. Methods: Path models with two time points (baseline and 16 weeks after randomization), were used to test the relationships between exposures of n-3 blood levels and self-reported dietary intake on outcomes of pain interference using the PROMIS pain interference scale and the Headache Impact Test (HIT-6). Model building was based on our published conceptual model. Results: Good fit was demonstrated for both models (EPA model: CFI = 0.984, RMSEA = 0.039, and SRMR = 0.045; DHA model: CFI = 0.981, RMSEA = 0.040, and SRMR = 0.040). Both EPA and DHA in the blood at 16 weeks were associated with lower levels of pain interference, but the effect for EPA was stronger (B = -0.56, p < 0.001 for EPA, and B = -0.43, p = 0.057 for DHA). Conclusions: Our findings are consistent with an indirect pathway linking diet to pain interference through blood levels of EPA and DHA in migraine.},
}

Humans
*Migraine Disorders/diet therapy/blood
Female
Male
*Docosahexaenoic Acids/blood/administration & dosage
*Eicosapentaenoic Acid/blood/administration & dosage
Adult
*Fatty Acids, Omega-3/blood/administration & dosage
Middle Aged
*Diet
*Pain

@article {pmid41514630,
year = {2025},
author = {Alban, J and Bowen, RC and Reichstein, DA and McKean, M and Lutzky, J and Weis, E and Carvajal, RD and Dulka, S and Morse, BG and Butler, MO and Rapisuwon, S and Kim, KB and Chandrasekaran, S and Warner, AB and Zager, JS and Chmielowski, B and Patel, SP and Hernandez-Aya, LF and Correa, ZM and Fecher, LA and Najjar, YG and Montazeri, K and Shoushtari, AN and Javed, A and Gombos, DS and Salama, AKS and Tsai, K and Miller, FH and Khushalani, N and Seedor, RS and Lipson, EJ and Reddy, SA and Buchbinder, E and Bhatia, S and Pavlick, A and Mehmi, I and Aaberg, T and Ikeguchi, AP and Kim, IK and Walter, SD and Singh, AD and Sullivan, RJ and Choi, JS and Williams, BK and Orloff, M and Mruthyunjaya, P and Schollenberger, MD and Gandhi, N and Harbour, JW and Chandra, S},
title = {Metastatic Uveal Melanoma Surveillance: A Delphi Panel Consensus.},
journal = {Cancers},
volume = {18},
number = {1},
pages = {},
pmid = {41514630},
issn = {2072-6694},
abstract = {BACKGROUND/OBJECTIVES: Uveal melanoma is a rare but aggressive intraocular malignancy that metastasizes in up to half of patients, most commonly to the liver, despite effective local treatment. In the absence of robust evidence, there are no standardized guidelines for post-treatment surveillance, resulting in wide variation in imaging modalities, frequency, and duration across physicians and institutions. This study aimed to develop expert consensus recommendations for surveillance strategies in patients with uveal melanoma.

METHODS: A modified Delphi method was conducted across three iterative survey rounds between September 2024 and February 2025 using an online platform. Panelists included medical oncologists, ocular oncologists, radiologists, and surgical oncologists from North America. A multidisciplinary steering committee developed statements addressing risk-based surveillance using both molecular and clinical prognostic factors, including gene expression profiling (GEP) and PRAME status. Consensus was defined a priori as ≥70% of panelists rating a statement 7-9 on a 9-point Likert scale.

RESULTS: Forty-nine experts were invited, and 41 completed at least one survey round. The panel represented 17 U.S. states, Washington, D.C., and two Canadian provinces. Twelve statements reached stable consensus, including recommendations for imaging modality, frequency, and duration in intermediate- and high-risk patients. Although there was agreement that low-risk patients warrant surveillance, no consensus was reached on the optimal approach for this group.

CONCLUSIONS: This is the first study to provide consensus-based guidance incorporating GEP and PRAME status into surveillance recommendations for uveal melanoma, offering a standardized framework to guide clinical practice and future research.},
}

@article {pmid41514580,
year = {2025},
author = {Pettenger-Willey, CM and Laszlo, GS and Gang, M and Cole, FM and Godwin, CD and Erraiss, S and Chanana, P and Kehret, AR and Li, J and Barton, JW and Yochim, MM and Rodríguez-Arbolí, E and Walter, RB},
title = {DNA Damage Sensing and TP53 Function as Modulators of Sensitivity to Calicheamicin-Based Antibody-Drug Conjugates for Acute Leukemia.},
journal = {Cancers},
volume = {18},
number = {1},
pages = {},
pmid = {41514580},
issn = {2072-6694},
support = {N/A//Pfizer/ ; U54-DK106829/DK/NIDDK NIH HHS/United States ; T32-HL007093//National Heart Lung and Blood Institute/ ; },
abstract = {BACKGROUND/OBJECTIVES: Approved for treatment of acute leukemia, gemtuzumab ozogamicin (GO) and inotuzumab ozogamicin (InO) are antibody-drug conjugates (ADCs) that deliver a toxic calicheamicin (CLM) derivative. The resistance mechanisms to GO/InO remain incompletely understood.

METHODS: We performed a genome-wide clustered regularly interspaced short palindromic repeat (CRISPR)/Cas9 screen for CLM sensitivity genes, and then performed confirmatory cytotoxicity assays.

RESULTS: Several DNA damage pathway regulation genes were identified, most notably TP53. Across 13 acute leukemia cell lines, the six TP53-mutant cell lines (TP53[MUT]) were indeed 10- to 1000-fold less sensitive to CLM than the seven TP53[WT] cell lines. In five TP53[WT/KO] syngeneic cell line pairs we generated, TP53[KO] cells were significantly less sensitive to CLM than their TP53[WT] counterparts. In TP53[WT] but not TP53[MUT] cells, the MDM2 inhibitor and p53 activator, idasanutlin, enhanced CLM cytotoxicity, demonstrating that decoupling of cells from MDM2-p53 regulation sensitizes leukemia cells to CLM. The ATM inhibitors AZD1390 and lartesertib also significantly enhanced CLM efficacy but did so independent of the TP53 status. In contrast, neither an ATR inhibitor, Chk1/Chk2 inhibitor, Chk2 inhibitor, or a PARP inhibitor significantly impacted CLM-induced cytotoxicity across the thirteen cell lines. Together, our studies identify ATM, MDM2, and TP53-which are in the same cellular response to DNA damage pathway-as key modulators of CLM-induced cytotoxicity in acute leukemia cells.

CONCLUSIONS: These results support further evaluation of combination therapies with corresponding small-molecule inhibitors (currently pursued for therapy of other cancers) toward clinical testing as novel strategies to increase the efficacy of CLM-based ADCs such as GO and InO.},
}

@article {pmid41513413,
year = {2026},
author = {Segawa, I and Ortblad, KF and Kadama, H and Natukunda, D and Muwonge, TR and Laker, EAO and Nsubuga, R and Akello, S and Tamale, WJ and Kiragga, A and Mujugira, A},
title = {Optimising community pharmacy PrEP delivery for cisgender female sex workers in Uganda: Protocol for a mixed-methods study.},
journal = {BMJ open},
volume = {16},
number = {1},
pages = {e111220},
doi = {10.1136/bmjopen-2025-111220},
pmid = {41513413},
issn = {2044-6055},
mesh = {Humans ; Uganda/epidemiology ; *Sex Workers/statistics & numerical data ; Female ; *HIV Infections/prevention & control ; *Pre-Exposure Prophylaxis/methods ; *Health Services Accessibility ; *Community Pharmacy Services/organization & administration ; Pharmacies ; Research Design ; },
abstract = {INTRODUCTION: Pre-exposure prophylaxis (PrEP) use among cisgender female sex workers (FSWs), a population at disproportionately high HIV acquisition risk in Uganda, remains suboptimal. Uptake and continued use are constrained by barriers, such as limited clinical hours, long distances to access facility-based PrEP services, and high mobility among FSWs. Community pharmacies may offer a more accessible PrEP delivery model due to extended operating hours and convenient locations. This study aims to evaluate the accessibility and capacity of pharmacies in Kampala, Uganda, to serve as potential sites for PrEP delivery.

METHODS AND ANALYSIS: We will conduct a concurrent mixed-methods study combining geospatial mapping, structured surveys, a discrete choice experiment (DCE), and in-depth interviews (IDIs). First, the study will compare the reach and accessibility of PrEP services through community pharmacies versus public healthcare facilities. To highlight PrEP service reach, we will use geospatial analysis to map pharmacies, PrEP clinics, FSW hotspots (i.e., areas where sex is exchanged), and HIV incidence. We will also calculate a PrEP facility needs ratio (number of PrEP facilities/HIV incidence) for each of Kampala's administrative divisions and estimate travel distance and time to access PrEP services using cost-distance analysis. Perceived accessibility of PrEP services will be assessed through FSW surveys (n=50) and IDIs (n=20-30), guided by Levesque's framework. Then, we will evaluate pharmacy capacity via surveys (n=274) and IDIs (n=20-30), exploring infrastructure, resources, and staff perspectives, informed by the Consolidated Framework for Implementation Research. Additionally, a DCE will be embedded in the pharmacy survey to elicit staff preferences for delivery approaches and analysed using mixed logit models. Finally, we will integrate quantitative and qualitative findings to provide a broad assessment of whether pharmacies are suitable venues for PrEP delivery to FSWs in Kampala. Enrolment will begin by April 2026 for FSWs and July 2026 for pharmacy staff.

ETHICS AND DISSEMINATION: Ethical approval has been obtained from the Infectious Diseases Institute Research Ethics Committee (IDI-REC-2025-175) and the Uganda National Council for Science and Technology (HS6178ES). Written informed consent will be obtained from all participants. We will disseminate study findings through stakeholder meetings, scientific conferences, and peer-reviewed publications.},
}

Humans
Uganda/epidemiology
*Sex Workers/statistics & numerical data
Female
*HIV Infections/prevention & control
*Pre-Exposure Prophylaxis/methods
*Health Services Accessibility
*Community Pharmacy Services/organization & administration
Pharmacies
Research Design

@article {pmid41509490,
year = {2025},
author = {Liu, D and Song, B and Li, Z and Zhang, S and Fabiha, T and Zhao, J and Inoki, A and Piccand, J and Soh, CL and Dixon, G and Zhong, A and Hu, N and Luo, R and Ozlusen, B and Menon, V and Zhou, T and Qiu, X and Gradwohl, G and Yang, D and Dey, K and Sun, W and Li, W and Huangfu, D},
title = {A stem cell knockout village reveals lineage rewiring and a non-canonical islet cell fate in monogenic diabetes.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {41509490},
issn = {2692-8205},
abstract = {Genetics studies have identified a core set of regulators essential for pancreatic β cell development, many of which are mutated in monogenic diabetes. However, how these mutations alter developmental trajectories to produce pathological cell states remains elusive. Here we introduce a knockout village framework that enables longitudinal scRNA-seq profiling of 79 human pluripotent stem cell mutant lines targeting 30 developmental regulators, including 15 diabetes genes, across five islet differentiation stages. We show that loss of lineage regulators impairs β cell formation in a stage-specific manner and rewires developmental trajectories towards competing lineages. Notably, several monogenic diabetes gene mutations drive a shift from β cells to enterochromaffin (EC)-like cells, a recently recognized non-canonical islet cell fate. These EC-like cells exhibit incomplete activation of hormone regulation programs, along with elevated neuron signatures. Leveraging the diversity of cell fate outcomes across mutants, we predicted and experimentally validated ISL1 as a key downstream effector of PDX1 and PAX6 that safeguards β cell identity against an EC-like fate. Together, our findings reveal cell fate rewiring as a widespread, previously underappreciated pathological mechanism in monogenic diabetes and establish a scalable platform for uncovering developmental vulnerabilities in human genetic disorders.},
}

@article {pmid41509443,
year = {2025},
author = {Yanagi, KS and Chen, BJ and Kunjo, SO and Topalidou, I and Lehrbach, N},
title = {Lysine deficiency within a conserved lysine desert is critical for EEL-1/HUWE1 to support ubiquitin proteasome system function.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {41509443},
issn = {2692-8205},
abstract = {The ubiquitin proteasome system (UPS) is the primary mechanism for targeted protein degradation in eukaryotic cells. Dysfunction of this system is a driver of human disease and a hallmark of aging and late-onset neurodegenerative disorders. Understanding the mechanisms that ensure robust protein turnover may provide new avenues for treatment in these contexts. E3 ubiquitin ligases play critical roles in supplying ubiquitinated substrates to the proteasome, with HUWE1 being an enormous, versatile, and highly conserved member of this family. Here, we show that the C. elegans HUWE1 ortholog, EEL-1, contributes to robust protein turnover during challenges to the proteolytic capacity of the proteasome. We demonstrate that the ability of EEL-1/HUWE1 to safeguard protein turnover requires ubiquitin-binding domains within the substrate-binding arena and the HECT-type ubiquitin ligase activity, supporting a model in which EEL-1 ensures degradation by increasing ubiquitination of pre-ubiquitinated substrates. EEL-1 contains extensive lysine-deficient regions, found at conserved locations in its substrate-binding arena. Through unbiased mutagenesis screening and precise engineering of the EEL-1 protein, we uncover that introducing lysine residues into these regions is detrimental to UPS function. Together, our findings indicate a central and evolutionarily ancient role for EEL-1/HUWE1 in maintaining optimal UPS function and support targeting this E3 for therapeutic manipulation.},
}

@article {pmid41512237,
year = {2026},
author = {Castellino, SM and Li, H and Herrera, AF and LeBlanc, M and Parsons, SK and Unger, JM and Punnett, A and Hodgson, D and Keller, FG and Drachtman, RA and Lamble, A and Forlenza, CJ and Doan, A and Rutherford, SC and Evens, AM and Little, RF and Smith, MA and Hoppe, BS and Song, JY and Smith, SM and Friedberg, JW and Kelly, KM},
title = {Three-Year Follow-Up of Nivolumab-AVD Versus Brentuximab Vedotin-AVD in Adolescents With Advanced-Stage Classic Hodgkin Lymphoma on S1826.},
journal = {Journal of clinical oncology : official journal of the American Society of Clinical Oncology},
volume = {},
number = {},
pages = {JCO2500203},
doi = {10.1200/JCO-25-00203},
pmid = {41512237},
issn = {1527-7755},
abstract = {We present a subset analysis on the adolescent cohort of the S1826 randomized phase three trial, comparing nivolumab, doxorubicin, vinblastine, dacarbazine (N-AVD) to brentuximab vedotin-AVD (BV-AVD) in newly diagnosed advanced-stage (AS, stages III and IV) classic Hodgkin lymphoma (cHL). Among 994 patients enrolled, 24% (n = 240) were age 12-17 years. The 3-year progression-free survival (PFS) was significantly higher in the N-AVD group (93% [95% CI, 87 to 96]) compared with the BV-AVD group (82% [95% CI, 73 to 88]; hazard ratio, 0.37 [95% CI, 0.17 to 0.80]). One N-AVD and two BV-AVD patients received protocol-specified residual site radiotherapy (RT). Rates of febrile neutropenia and sepsis were low in both groups. Severe immune-related adverse events were infrequent, although thyroid dysfunction was seen in 7% with N-AVD. Sensory neuropathy (grade ≥2) was more frequent with BV-AVD (14% v 7%) by clinician report. Although premature discontinuation of therapy was reported in 12 N-AVD patients and four BV-AVD patients, no PFS events were noted in the N-AVD group. Patient-reported outcomes indicated less toxicity with N-AVD. N-AVD demonstrated high 3-year PFS in adolescents with AS cHL, with minimal RT use. S1826 exemplifies the benefits of harmonized clinical trial protocols, resulting in timely access to novel agents for adolescents.},
}

@article {pmid41512041,
year = {2026},
author = {Gao, J and Brusselmans, M and Carvalho, LM and Suchard, MA and Baele, G and Matsen, FA},
title = {Biological causes and impacts of rugged tree landscapes in phylodynamic inference.},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
volume = {123},
number = {2},
pages = {e2510938123},
doi = {10.1073/pnas.2510938123},
pmid = {41512041},
issn = {1091-6490},
support = {R01 AI162611/AI/NIAID NIH HHS/United States ; R01 AI153044/AI/NIAID NIH HHS/United States ; S10OD028685//Fred Hutchinson Cancer Center (FHCRC)/ ; G0E1420N//Fonds Wetenschappelijk Onderzoek (FWO)/ ; G098321N//Fonds Wetenschappelijk Onderzoek (FWO)/ ; 101094685//EC | ERC | HORIZON EUROPE European Research Council (ERC)/ ; },
mesh = {*Phylogeny ; Bayes Theorem ; Genetic Variation ; Models, Genetic ; },
abstract = {Phylodynamic analysis has been instrumental in elucidating epidemiological and evolutionary dynamics of pathogens. Bayesian phylodynamics integrates out phylogenetic uncertainty, which is typically substantial in phylodynamic datasets due to limited genetic diversity. Phylodynamic inference does not, however, scale with modern datasets, partly due to difficulties in traversing tree space. Here, we characterize tree space and landscape in phylodynamic inference and assess its impacts on analysis difficulty and key biological estimates. By running extensive Bayesian analyses of 15 classic large phylodynamic datasets and carefully analyzing the posterior samples, we find that the posterior tree landscape is diffuse yet rugged, leading to widespread tree sampling problems that usually stem from sequences in a small part of the tree. We develop clade-specific diagnostics to show that a few sequences-including putative recombinants and recurrent mutants-frequently drive the ruggedness and sampling problems, although existing data-quality tests show limited power to detect them. The sampling problems can significantly impact phylodynamic inferences or distort major biological conclusions; the impact is usually stronger on "local" estimates (e.g., introduction history) associated with particular clades than on "global" parameters (e.g., demographic trajectory) governed by general tree shape. We evaluate existing Markov chain Monte Carlo diagnostics and diagnostics developed here, and offer strategies for optimizing phylodynamic analysis settings and mitigating sampling problem impacts. Our findings highlight the need and directions to develop efficient traversal over rugged tree landscapes, ultimately advancing scalable and reliable phylodynamics.},
}

*Phylogeny
Bayes Theorem
Genetic Variation
Models, Genetic

@article {pmid41510809,
year = {2025},
author = {Sutliff, NA and Chao, E and Bennett, SR and Nip, Y and Lakhdari, O and Canton, DA and Zhu, Y and Tapscott, SJ},
title = {Identification of KHDC1L, a DUX4-regulated protein, as a novel plasma biomarker in facioscapulohumeral muscular dystrophy.},
journal = {Human molecular genetics},
volume = {},
number = {},
pages = {},
doi = {10.1093/hmg/ddaf183},
pmid = {41510809},
issn = {1460-2083},
abstract = {Facioscapulohumeral muscular dystrophy (FSHD) is caused by aberrant expression of the double homeobox transcription factor DUX4 in skeletal muscle. Because direct measurement of DUX4 in FSHD muscle is technically challenging, DUX4-regulated transcripts in muscle biopsies have been used as surrogates; however, this approach is invasive, limited to a single muscle, and less suitable for repeated monitoring. Thus, we sought to identify DUX4-regulated circulating biomarkers that could integrate DUX4 activity across all affected muscles and enable more frequent measurement. We performed mass spectrometry on conditioned media from DUX4-inducible immortalized human myoblasts (MB135iDUX4) and identified a top candidate-KHDC1L, the protein product of a DUX4-regulated mRNA previously shown to correlate with DUX4 expression in muscle. Western blotting confirmed KHDC1L release into the supernatant of DUX4-expressing cells. Plasma profiling demonstrated elevated KHDC1L levels in individuals with FSHD compared to healthy controls, supporting its role as a circulating readout of DUX4 activity. These findings suggest that plasma KHDC1L is a potential pharmacodynamic marker of DUX4 activity, providing a minimally invasive tool for disease monitoring and a potential response marker to evaluate emerging FSHD therapies.},
}

@article {pmid41052404,
year = {2026},
author = {Valtis, YK and Lin, C and Nemirovsky, D and Devlin, S and Rejeski, K and Curran, KJ and Wang, X and Shah, NN and Jeyakumar, N and Miller, K and Zhang, A and Kota, VK and Al Darobi, AH and Muhsen, I and Sasine, J and Aldoss, I and Advani, AS and Reshef, R and Chen, EC and Kopmar, N and Tsai, SB and Hilal, T and Shah, BD and Faramand, R and Solh, MM and Tan, V and Bezerra, E and Battiwalla, M and Ramakrishnan, A and Mathews, J and Shaughnessy, P and Mountjoy, L and Hoeg, RT and Dykes, KC and Logan, AC and Kumaran, MV and Schwartz, M and Tracy, S and Moore, J and Odstrcil Bobillo, S and Frey, NV and Connor, M and Ladha, A and Dholaria, B and Sutherland, K and Roloff, GW and Muffly, LS and Park, JH},
title = {CAR HEMATOTOX independently predicts outcomes after CD19 CAR-T therapy for acute lymphoblastic leukemia.},
journal = {Blood advances},
volume = {10},
number = {1},
pages = {276-288},
doi = {10.1182/bloodadvances.2025017526},
pmid = {41052404},
issn = {2473-9537},
mesh = {Humans ; Male ; Female ; *Precursor Cell Lymphoblastic Leukemia-Lymphoma/therapy/mortality/diagnosis ; Middle Aged ; Adult ; *Immunotherapy, Adoptive/methods/adverse effects ; *Antigens, CD19/immunology ; Treatment Outcome ; Prognosis ; *Receptors, Chimeric Antigen/immunology ; Aged ; Young Adult ; Adolescent ; },
abstract = {Chimeric antigen receptor (CAR) T-cell (CAR-T) treatment for B-cell acute lymphoblastic leukemia (ALL) induces high initial response rates, but most patients relapse. Low disease burden (often defined as <5% blasts in the bone marrow) is associated with better outcomes. CAR HEMATOTOX (HT) is a score using prelymphodepletion hematologic and inflammatory parameters to predict outcomes in lymphoma. Here, we assess its prognostic utility in a large multicenter adult B-cell ALL cohort. Patients who received brexucabtagene autoleucel across 33 centers in North America were included as part of the Real-World Outcomes Collaborative of CAR-T in Adult ALL (ROCCA) consortium. An independent cohort of 61 patients with ALL treated with an investigational CD19 CAR-T therapy at 1 center was also described. Among 199 ROCCA consortium patients, 43 (22%) patients with HTlow scores had lower rates of delayed neutrophil recovery than those with HThigh scores (26% vs 52%, P = .002) and fewer severe infections (2.5% vs 18.8%, P = .011). They also had higher response rates, overall survival (OS), and event-free survival (EFS), as well as lower nonrelapse mortality and cumulative incidence of relapse. The survival differences remained significant after multivariable adjustment for disease burden and other covariates. In the investigational cohort of 61 patients, patients with HTlow scores had improved OS and EFS, as well as higher peak CAR-T expansion. In summary, CAR HT score is a prognostic factor independent of disease burden in adult ALL. HTlow score is associated with superior outcomes after CD19 CAR-Ts and higher CAR-T expansion in a single-center cohort. These trials were registered at www.clinicaltrials.gov as #NCT01044069 and #NCT01860937.},
}

Humans
Male
Female
*Precursor Cell Lymphoblastic Leukemia-Lymphoma/therapy/mortality/diagnosis
Middle Aged
Adult
*Immunotherapy, Adoptive/methods/adverse effects
*Antigens, CD19/immunology
Treatment Outcome
Prognosis
*Receptors, Chimeric Antigen/immunology
Aged
Young Adult
Adolescent

@article {pmid41509676,
year = {2026},
author = {Sloan, A and Mortezavi, M and Gerhart, J and Banerjee, A and Alami, NN and Najera, I and Ahadieh, S and Dalam, AB and Schiffer, JT and Patel, R and Johnston, C},
title = {Orolabial and Genital Herpes Clinical Trials: A Meta-analysis of Endpoints.},
journal = {Open forum infectious diseases},
volume = {13},
number = {1},
pages = {ofaf776},
pmid = {41509676},
issn = {2328-8957},
abstract = {Although several antiviral agents are licensed for the treatment of orolabial and genital herpes simplex virus infections, new therapies are needed. Trial design is challenging for these indications due to the heterogeneity of endpoints in prior trials. We conducted a systematic review and meta-analysis of randomized placebo-controlled trials published between 1995 and 2024 consisting of adults with established herpes simplex virus infection who were immunocompetent and nonpregnant. A total of 22 articles met the inclusion criteria. For episodic treatment, endpoints included time to healing, proportion with an aborted lesion, and time to cessation of symptoms. For daily suppressive therapy, endpoints included time to first recurrence, proportion recurrence-free at 1 year, and total shedding rate. We observed that over the last 30 years, clinical trials have used various endpoints with nonstandardized definitions. A reassessment of appropriate endpoints along with regulatory guidance would assist with consistent study design for evaluation of new agents.},
}

@article {pmid41509072,
year = {2025},
author = {White, AN and Ingersoll, R and Eswaraka, J and Uthamanthil, R and Roble, G and Chitty, AI and Nikolaidis, N and Vinard, A and Kraft, M and Winter, MK},
title = {Voices from the Bench: Focus Group Insights on Shared Research Resource Sustainability Amid Federal Policy Shifts.},
journal = {Journal of biomolecular techniques : JBT},
volume = {36},
number = {4},
pages = {25-34},
pmid = {41509072},
issn = {1943-4731},
mesh = {Humans ; Focus Groups ; United States ; *Biomedical Research/economics ; },
abstract = {Shared Research Resources (SRRs) are essential for sustaining research excellence, particularly in financially constrained environments. This study examines how federal policy uncertainties exacerbate existing challenges in SRR operations and management. Findings from focus groups-including over 220 leaders in academic administration and SRRs-highlight that staffing, funding, and cross-campus collaboration disproportionately impact resource-limited institutions, widening disparities in research capabilities. Evaluating SRRs' role in supporting research during financial instability is critical. Active administrative engagement in supporting SRRs helps institutions to secure funding and align priorities with institutional goals. SRRs improve operational efficiency through shared infrastructure models and standardized procurement policies, reducing duplication and optimizing resource utilization. Workforce adaptability is key to sustainability, with cross-training and strategic recruitment fostering resilience amid financial uncertainty. This study underscores the interconnected nature of funding diversification, leadership alignment, operational efficiency, workforce adaptability, and policy reform in sustaining SRR systems. This study draws on collective insights from SRR staff across all organizational levels, from technical personnel and directors to administrators and institutional leaders, to capture a comprehensive, ground-level perspective on the conditions necessary for long-term viability. Institutions that recognize SRRs as strategic partners in addressing systemic research barriers will be better positioned to foster a more equitable, efficient, and sustainable research ecosystem.},
}

Humans
Focus Groups
United States
*Biomedical Research/economics

@article {pmid41506486,
year = {2026},
author = {Gem, H and Ebadi, M and Sebastian, G and Abasaeed, R and Lloid, M and Dean, DR and Rashidi, A},
title = {Longitudinal multi-compartment oral mucositis assessment in adults undergoing myeloablative allogeneic hematopoietic cell transplantation: a contemporary prospective cohort analysis.},
journal = {Transplantation and cellular therapy},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jtct.2026.01.004},
pmid = {41506486},
issn = {2666-6367},
abstract = {BACKGROUND: Oral mucositis (OM) is a frequent, debilitating complication of myeloablative allogeneic hematopoietic cell transplantation (HCT). OM grading tools used in HCT practice rely on subjective or summary scoring, potentially missing clinically important detail.

OBJECTIVE: To test the performance of Oral Mucositis Assessment Scale (OMAS), a validated comprehensive OM assessment tool that collects granular objective findings from 7 intraoral sites, in a contemporary cohort.

STUDY DESIGN: We longitudinally evaluated site-specific OM characteristics using OMAS in 47 myeloablative allogeneic HCT recipients.

RESULTS: A total of 249 assessments were completed at baseline (pre-conditioning) and on days +7, +14, +21, +28, and +84 post-transplant. Total and site-specific scores strongly correlated with patient-controlled analgesia use. Day +7 involvement of floor of mouth (P = 0.013), soft palate (P = 0.008), and ventrolateral tongue (P = 0.003) were associated with a greater total mucositis score. OM was overall more severe in men, driven by higher scores on day +7 (P = 0.013) and in the soft palate (P = 0.013). Graft-versus-host disease prophylaxis regimens based on post-transplantation cyclophosphamide or methotrexate led to more severe day +14 OM than those based on mycophenolate mofetil (P = 0.028).

CONCLUSION: In this prospective analysis of myeloablative allogeneic HCTs in a contemporary cohort, OMAS provided clinically relevant, granular, site-specific data not captured by popular summary-based scoring systems. We expect our findings to facilitate the development of effective strategies to prevent and treat OM.},
}

@article {pmid41506266,
year = {2026},
author = {Lu, G and Zhang, S and Feng, M and Kim, E and Cho, D and Kim, JH and Caris, H and Silberstein, L and Choi, GB and Huh, JR},
title = {In vivo detection of immune responses via cytokine activity labeling.},
journal = {Cell},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.cell.2025.12.011},
pmid = {41506266},
issn = {1097-4172},
abstract = {While much is known about the identity and regulation of cytokine-producing cells, the cell types that respond to cytokines remain largely uncharacterized. To address this knowledge gap, we developed "cytokine cellular locating platforms" (CyCLoPs), a reporter system that translates cytokine receptor engagement into a genetically traceable signal. In vitro, CyCLoPs demonstrated high specificity, robust signal-to-background ratios, and broad applicability for probing diverse cytokine receptor interactions. In vivo, interleukin (IL)-17A-CyCLoPs reporter mice enabled the identification of IL-17A-responsive intestinal epithelial cells predominantly localized in the ileal villi following commensal bacterial colonization. Interferon-gamma (IFN-γ)-CyCLoPs reporter mice allowed for the detection of IFN-γ-exposed CD8[+] T cells within tumors, which expressed CD36, CD38, and leptin receptor and displayed gene signatures associated with reduced effector function. Collectively, CyCLoPs offers a platform for the direct visualization and characterization of cytokine-induced cellular responses and provides a tool for investigating how cytokines orchestrate distinct immunological outcomes in health and disease.},
}