@article {pmid40812311,
year = {2025},
author = {Jagota, M and Hsu, C and Mazumder, T and Sung, K and DeWitt, WS and Listgarten, J and Matsen Iv, FA and Ye, CJ and Song, YS},
title = {Learning antibody sequence constraints from allelic inclusion.},
journal = {Cell systems},
volume = {},
number = {},
pages = {101368},
doi = {10.1016/j.cels.2025.101368},
pmid = {40812311},
issn = {2405-4720},
abstract = {Although antibody sequences are highly diverse, they are constrained by requirements for expression and limited off-target reactivity. Describing which sequences violate such constraints has proven to be difficult. Here, we introduce a machine-learning framework to leverage a previously underutilized source of data for this problem. We use human single-cell sequencing data to find instances of allelic inclusion, a rare event where B cells express two different antibody light chains as mRNA. Previous studies suggest that one of these chains is either autoreactive or non-expressing as protein. We train machine-learning models to identify abnormal sequences associated with allelic inclusion. The resulting models generalize to predict antibody properties including polyreactivity, surface expression, and mutation usage, outperforming methods that do not use allelic inclusion data. We also investigate similar selection forces on the heavy chain in mice and observe that surrogate light-chain pairing has a large impact on heavy-chain diversity.},
}

@article {pmid40811854,
year = {2025},
author = {Maynard, LH and Cavanaugh, EJ and Zhu, H and Starke, CE and Doherty, SM and Einhaus, TK and Pérez-Osorio, AC and Stensland, L and Blair, C and Roche, AM and Everett, JK and Murnane, RD and Hoffman, ME and Nelson, V and Herrin, SA and Littlewood, C and Camou, K and Wilson, E and Wessel, C and Bushman, F and Jerome, KR and Kiem, HP and Peterson, CW},
title = {Pooled CAR-T screening in nonhuman primates identifies designs with enhanced proliferation, trafficking, and persistence.},
journal = {Blood},
volume = {},
number = {},
pages = {},
doi = {10.1182/blood.2025028683},
pmid = {40811854},
issn = {1528-0020},
abstract = {Chimeric antigen receptor T (CAR-T) cell therapy has revolutionized treatment for B-cell malignancies, yet over 60% of patients relapse within one year, often due to insufficient CAR-T persistence. While mouse and primary cell models have been instrumental in advancing CAR-T therapy, they frequently fail to predict clinical outcomes, underscoring the need for more translationally relevant models. To address this limitation, we conducted the first systematic evaluation of CAR structure-function relationships in an immunocompetent nonhuman primate (NHP) model. We engineered an array of 20 CD20-targeted CARs with distinct combinations of hinge, transmembrane, and costimulatory domains. Following ex vivo characterization, we administered pooled autologous CAR-T arrays to three NHPs and tracked CAR abundance longitudinally using a novel digital droplet PCR assay. Ex vivo, CAR-T cells incorporating the MyD88-CD40 costimulatory domain exhibited markedly distinct functional profiles, including increased activation, unique cytokine secretion, tonic signaling, and resistance to exhaustion. In vivo, MyD88-CD40 CARs expanded dramatically, comprising up to 100% of peripheral CAR-T cells and significantly outperforming canonical CD28- and 4-1BB-based CARs. This expansion was associated with robust B-cell depletion across all animals. MyD88-CD40 CARs, particularly those with a CD28 hinge and transmembrane domain, demonstrated superior trafficking to secondary lymphoid tissues and persistence through study endpoint, unlike other CARs which waned by day 28. Our findings highlight the value of NHP models for screening CAR designs and identify MyD88-CD40 CARs as candidates with unmatched potency. The unique functional attributes conferred by this domain may provide key insights into features that drive enhanced CAR-T cell activity.},
}

@article {pmid40811818,
year = {2025},
author = {Greenbaum, U and Hashmi, H and Elsawy, M and Kim, S and Moskop, A and Oloyede, T and Awan, FT and Bachanova, V and Badar, T and Bar, M and Barba, P and Beitinjaneh, AM and Cashen, AF and Dholaria, B and Farooq, U and Foglesong, J and Ganguly, S and Hematti, P and Hill, LC and Jain, MD and Jain, T and Kebriaei, P and Kittai, AS and Locke, FL and Lulla, PD and McGuirk, JP and Mead, E and Mussetti, A and Nishihori, T and Olson, AL and Pennisi, M and Perales, MA and Ramakrishnan Geethakumari, P and Riedell, PA and Saber, W and Shouval, R and Shpall, EJ and Magalhaes-Silverman, M and Strouse, CS and Turtle, CJ and Valluripalli, A and Wudhikarn, K and Pasquini, MC and Ahmed, S and Sorror, ML},
title = {New Comorbidity Index Associated with Survival After Chimeric Antigen Receptor T Cell Therapy for Large B-Cell Lymphoma.},
journal = {Blood advances},
volume = {},
number = {},
pages = {},
doi = {10.1182/bloodadvances.2024015599},
pmid = {40811818},
issn = {2473-9537},
abstract = {The cumulative impact of baseline comorbidities on outcomes of chimeric antigen receptor T cell (CAR-T) therapy is not well-established. Therefore, we developed and validated a Cellular Therapy Comorbidity Index (CT-CI) to predict outcomes following CD19-directed CAR-T therapy for large B-cell lymphoma (LBCL). Patients aged 18 or older receiving commercial CAR-T therapy for LBCL during 2017-2020 were selected from the CIBMTR registry. Patients were randomly assigned to training or validation cohorts. Comorbidities given weighted scores comprised the CT-CI, which was then validated for overall survival (OS) prognostication. A total of 1916 patients from 97 medical centers were included, with a median age of 64 years (19-91). About 70% of patients had comorbidities, such as cardiac disease (12%); diabetes (14%); hepatic dysfunction (mild, 8%; moderate to severe, 2%); psychiatric disturbance (18%); and pulmonary dysfunction (moderate, 15%; severe, 12%). The CT-CI was calculated, stratified patients in 3 categories, and was associated with increased mortality. Patients with higher CT-CI scores had worse OS (CT-CI 1: hazard ratio [HR], 1.37; 95% CI, 1.16-1.62; P < .001. CT-CI 2: HR, 1.49; 95% CI, 1.17-1.89; P = .001. CT-CI ≥ 3: HR, 2.55; 95% CI, 1.90-3.42; P < .001). Higher CT-CI scores predicted treatment-related mortality and relapse. There was no correlation between the CT-CI score and CAR-T-related toxicities. The novel CT-CI score stratifies the effect of patient comorbidities on survival after CAR-T therapy and can be used for clinical decision-making and treatment selection in high-risk populations. However, comorbidities and fear of increased toxicity should not preclude patients from this effective therapy.},
}

@article {pmid40811667,
year = {2025},
author = {Jatt, LP and Gillespie, KM and Van, P and Hoffman, SL and Jackson, LA and Murphy, SC and Heath, JR and Kublin, JG},
title = {Manuscript title: Cytokines Associated With Moderate and Severe Adverse Events During a Sporozoite Malaria Vaccine Trial with Controlled Human Malaria Infection.},
journal = {The Journal of infectious diseases},
volume = {},
number = {},
pages = {},
doi = {10.1093/infdis/jiaf435},
pmid = {40811667},
issn = {1537-6613},
abstract = {Ensuring the safety and efficacy of candidate vaccines is critical. Although mechanisms underpinning protective immune responses to malaria vaccines are frequently investigated, immune responses correlating with moderate and severe adverse events are rarely examined. Here, we leverage a malaria vaccine trial with a higher-than-expected adverse event rate and frequent sampling to investigate cytokine profiles associated with adverse events. We found that Interleukin-6 was elevated on days in which individuals experienced moderate and severe adverse events. More research on immune responses associated with adverse events is warranted in order to identify biomarkers associated with systemic reactogenicity and accelerate vaccine development.},
}

@article {pmid40811558,
year = {2025},
author = {Shenoy, MK and Rico, DM and Lorant, AK and Touré, H and Gordon, S and Milburn, LJ and Schwensen, JS and Cabán, ME and Koch, MA},
title = {Breast milk IgG engages the mouse neonatal immune system to instruct responses to gut antigens.},
journal = {Science (New York, N.Y.)},
volume = {389},
number = {6761},
pages = {eado5294},
doi = {10.1126/science.ado5294},
pmid = {40811558},
issn = {1095-9203},
abstract = {Maternal antibodies fundamentally regulate gut immunity in the developing infant, yet the mechanisms underlying this process remain elusive. We found that maternal immunoglobulin G (IgG), ingested in the first week of life, restrained microbiota-dependent adaptive immune responses weeks later, after weaning. This activity was linked to maternal antibodies that could bind bacteria in the neonatal gut and the ability of microbe-IgG complexes to engage Fc and complement-dependent effector functions in offspring. Ingestion of microbiota-specific maternal IgG also limited aberrant neonatal responses to dietary antigens encountered at weaning. These discoveries suggest that maternal IgG engages the immune system of offspring in early postnatal life to tune mucosal responses and reinforce intestinal homeostasis in the face of dynamic shifts in food and bacterial antigens during development.},
}

@article {pmid40811246,
year = {2025},
author = {Fang, A and Kumar, L and Creevy, KE and Promislow, DEL and Ma, J and , },
title = {Constructing the first comorbidity networks in companion dogs in the Dog Aging Project.},
journal = {PLoS computational biology},
volume = {21},
number = {8},
pages = {e1012728},
pmid = {40811246},
issn = {1553-7358},
abstract = {Comorbidity and its association with age are of great interest in geroscience. However, there are few model organisms that are well-suited to study comorbidities that will have high relevance to humans. In this light, we turn our attention to the companion dog. The companion dog shares many morbidities with humans. Thus, a better understanding of canine comorbidity relationships could benefit both humans and dogs. We present an analysis of canine comorbidity networks from the Dog Aging Project, a large epidemiological cohort study of companion dogs in the United States. We included owner-reported health conditions that occurred in at least 60 dogs (n = 160) and included only dogs that had at least one of those health conditions (n = 26,614). We constructed an undirected comorbidity network using a Poisson binomial test, adjusting for age, sex, sterilization status, breed background (i.e., purebred vs. mixed-breed), and weight. The comorbidity network reveals well-documented comorbidities, such as diabetes with cataracts and blindness, and hypertension with chronic kidney disease (CKD). In addition, this network also supports less well-studied comorbidity relationships, such as proteinuria with anemia. A directed comorbidity network accounting for time of reported condition onset suggests that diabetes precedes cataracts, elbow/hip dysplasia before osteoarthritis, and keratoconjunctivitis sicca before corneal ulcer, which are consistent with the canine literature. Analysis of age-stratified networks reveals that global centrality measures increase with age and are the highest in the Senior group compared to the Young Adult and Mature Adult groups. Only the Senior group identified the association between hypertension and CKD. Our results suggest that comorbidity network analysis is a promising method to enhance clinical knowledge and canine healthcare management.},
}

@article {pmid40766360,
year = {2025},
author = {Dosey, A and Dadonaite, B and Gillespie, RA and Leaf, EM and Vukovich, MJ and McGowan, J and Grey, E and Muramatsu, H and Jun, RHJ and Pardi, N and Kanekiyo, M and Bloom, JD and King, NP},
title = {Stabilization of H5 highly pathogenic avian influenza hemagglutinin improves vaccine-elicited neutralizing antibody responses.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {40766360},
issn = {2692-8205},
support = {P01 AI167966/AI/NIAID NIH HHS/United States ; R01 AI141707/AI/NIAID NIH HHS/United States ; U19 AI181881/AI/NIAID NIH HHS/United States ; },
abstract = {Transmission of highly pathogenic avian influenza from H5 clade 2.3.4.4b has expanded in recent years to infect large populations of birds and mammals, heightening the risk of a human pandemic. Influenza viruses adapted to transmission in birds and some other animals tend to have a less stable hemagglutinin (HA) than seasonal influenza viruses, enabling membrane fusion at comparatively high pH levels. Here, we combine five mutations within H5 HA that dramatically increase its melting temperature and promote stable closure of the HA trimer. Structural analysis by cryo-electron microscopy revealed that the stabilizing mutations create several new hydrophobic interactions, while maintaining local HA structure. We found that vaccinating mice with stabilized H5 HA immunogens resulted in higher hemagglutination inhibition and neutralization titers than non-stabilized comparators. Epitope mapping of vaccine-elicited polyclonal antibody responses using negative stain electron microscopy and deep mutational scanning showed that site E on the side of the HA receptor binding domain was immunodominant across all groups; however, the stabilized immunogens shifted responses toward the receptor binding site (RBS), eliciting a higher proportion of neutralizing antibodies. These findings highlight that H5 HA-stabilizing mutations enhance the quality of antibody responses across different vaccine formats, underscoring their potential to improve pandemic preparedness vaccines targeting viruses from this widely circulating clade.},
}

@article {pmid40810606,
year = {2025},
author = {Ryser, MD and Holloway, ST and Morsomme, R and Ryan, A and Apostolidou, S and Gentry-Maharaj, A and Gogebakan, KC and Lange, J and Xu, J and Menon, U and Etzioni, R},
title = {Estimating the Opportunity for Early Detection of Ovarian Cancer Using Individual-Patient Data from a Large Randomized Controlled Trial.},
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-25-0498},
pmid = {40810606},
issn = {1538-7755},
abstract = {BACKGROUND: The UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS) did not detect a reduction in ovarian cancer (OC) mortality with either multimodal screening (MMS) or transvaginal ultrasound screening (USS) compared to no screening. The trial data provide an invaluable resource to quantify the opportunity for interception in OC.

METHODS: We used Bayesian inference to estimate OC natural history based on individual screening and cancer diagnosis records from UKCTOCS, a randomized controlled OC screening trial conducted in England, Wales, and Northern Ireland. The trial included 202,638 women aged 50 to 74 years with no family history of OC, randomized in a 1:1:2 ratio to annual MMS (serum CA125 interpreted using the Risk of Ovarian Cancer Algorithm), annual USS, or no screening. The current analysis included 199,499 women, with 674,806 screens and 2,025 cancer diagnoses.

RESULTS: Among high-grade serous cancers (HGSCs), the estimated preclinical detectable phase (PCDP) was 1.7 years (95% credible interval [CI], 1.3-2.2), compared with 7.8 years (95% CI, 5.7-10.6) for non-HGSCs. The PCDP depended on screening modality: for HGSCs, it was longer in the MMS arm (2.2 years) compared with the USS arm (0.8 years), whereas for non-HGSCs, it was shorter in the MMS arm (2.7 years) compared with the USS arm (8.2 years).

CONCLUSIONS: The interception opportunity for OC strongly depends on histological subtype and screening modality.

IMPACT: Achieving a clinically significant benefit of OC early detection will require prolonging the interception window through judicious combination of first- and second-line tests.},
}

@article {pmid40809738,
year = {2025},
author = {Ye, T and He, Q and Chen, S and Zhang, B},
title = {Role of placebo samples in observational studies.},
journal = {Journal of causal inference},
volume = {13},
number = {1},
pages = {},
pmid = {40809738},
issn = {2193-3677},
abstract = {In an observational study, it is common to leverage known null effects to detect bias. One such strategy is to set aside a placebo sample - a subset of data immune from the hypothesized cause-and-effect relationship. Existence of an effect in the placebo sample raises concerns about unmeasured confounding bias while absence of it helps corroborate the causal conclusion. This paper describes a framework for using a placebo sample to detect and remove bias. We state the identification assumptions and develop estimation and inference methods based on outcome regression, inverse probability weighting, and doubly-robust approaches. Simulation studies investigate the finite-sample performance of the proposed methods. We illustrate the methods using an empirical study of the effect of the earned income tax credit on infant health.},
}

@article {pmid40809030,
year = {2025},
author = {Garfall, AL and Banerjee, R and Frenzel, L and Khandanpour, C and Lin, Y and Ottoni, E and Rifkin, R and Rockwell, S and Rodriguez, C and Villefort, H and Zamagni, E},
title = {A roadmap to implementing outpatient administration of bispecific antibodies in multiple myeloma.},
journal = {Frontiers in oncology},
volume = {15},
number = {},
pages = {1630146},
pmid = {40809030},
issn = {2234-943X},
abstract = {INTRODUCTION: Bispecific antibodies (BsAbs) are novel immunotherapy agents for the treatment of relapsed/refractory multiple myeloma (RRMM). Currently, 3 BsAbs (teclistamab, talquetamab, and elranatamab) are approved for the treatment of RRMM. Administering BsAbs in different practice settings is crucial to improving treatment access and patient outcomes. This report provides actionable guidance to implement safe and effective administration of BsAbs for patients with RRMM in outpatient and community settings.

METHODS: Three clinician advisory workshops were held in the United States, Europe, and Latin America to discuss key factors to operationalize BsAb use in outpatient and community settings, focusing on the critical phases of practice setup, treatment initiation, and ongoing management.

RESULTS: BsAb administration in outpatient and community settings requires careful planning, a well-prepared multidisciplinary team (MDT) of healthcare professionals, and clear protocols, including MDT composition, roles/responsibilities, capacity planning, patient selection criteria, step-up dosing procedure, admission processes, patient/caregiver education requirements, and adverse event (AE) monitoring/management. Comprehensive MDT training on protocols and preparedness to manage AEs is essential. Patients initiating outpatient BsAb therapy should have a reliable caregiver, access to a hospital, controlled comorbidities, and no active infections. Ensuring patients and caregivers understand the benefits, risks, and expectations of BsAb therapy is vital for successful treatment and a positive patient experience.

CONCLUSION: Administering BsAbs in outpatient and community settings can be done safely and effectively with appropriate planning and protocols. Enabling safe and effective BsAb administration in these settings is essential to ensure more patients with RRMM have access to treatment and improved outcomes.},
}

@article {pmid40805242,
year = {2025},
author = {Amonoo, HL and Wolfe, ED and Keane, EP and Larizza, IS and Boardman, AC and Healy, BC and Traeger, LN and Cutler, C and Lee, SJ and Greer, JA and El-Jawahri, A},
title = {Medication Adherence in Patients Undergoing Allogeneic Hematopoietic Stem Cell Transplantation.},
journal = {Cancers},
volume = {17},
number = {15},
pages = {},
doi = {10.3390/cancers17152546},
pmid = {40805242},
issn = {2072-6694},
support = {K08CA251654/CA/NCI NIH HHS/United States ; n/a//Robert Wood Johnson and American Society of Hematology Harold Amos Medical Faculty Development Award/ ; n/a//Doris Duke Foundation Clinician-Scientist Development Award/ ; },
abstract = {Introduction: Medication adherence is essential for treatment and recovery following hematopoietic stem cell transplantation (HSCT). However, limited data exist on the most effective methods to measure adherence and the factors influencing it in HSCT patients. Materials and Methods: A prospective longitudinal study assessed immunosuppressant medication adherence in 150 patients with hematologic malignancies undergoing allogeneic HSCT. Adherence was assessed using pill counts, immunosuppressant medication levels, patient-reported medication logs, and the Medication Adherence Response Scale-5 (MARS-5) at 30, 100, and 180 days post-HSCT. We evaluated adherence rates, agreement between methods, and sociodemographic and clinical predictors. From patient-reported logs, we calculated dose adherence (comparing reported doses to expected doses) and timing adherence (comparing medication intake within ±3 h of the prescribed time). Kappa analysis assessed agreement among methods. Results: Of 190 eligible patients, 150 (78.9%) enrolled. The mean age was 57.5 years (SD = 13.5); 41.3% (n = 62) were female, 85.3% (n = 128) were non-Hispanic White, and 73.3% (n = 110) were married or living with a partner. Medication adherence varied across the three timepoints and by measurement type: 52-64% (pill counts), 18-24% (medication levels), 96-98% (medication log dose adherence), 83-84% (medication log timing adherence), and 97-98% (MARS-5). There was minimal agreement between measures (Kappa range: 0.008-0.12). Conclusions: Despite the feasibility of leveraging objective and patient-reported measures to assess medication adherence in HSCT patients, there was little agreement between these measures. Patient-reported measures showed high adherence, while objective measures like pill counts and medication levels revealed more modest adherence. The complexity of medication regimens likely contributes to this discrepancy. A rigorous approach to understanding medication adherence in the HSCT population may entail both objective and subjective measures of medication adherence.},
}

@article {pmid40805227,
year = {2025},
author = {Sarfraz, Z and Jayram, D and Ozair, A and Hodgson, L and Bellur, S and Maharaj, A and Venur, VA and Mukherjee, S and Ahluwalia, MS},
title = {Survival in Patients with Colorectal Cancer and Isolated Brain Metastases: Temporal Trends and Prognostic Factors from the National Cancer Database (2010-2020).},
journal = {Cancers},
volume = {17},
number = {15},
pages = {},
doi = {10.3390/cancers17152531},
pmid = {40805227},
issn = {2072-6694},
abstract = {Background: The development of brain metastases (BM) is a relatively uncommon but significantly adverse event in the spread of colorectal cancer (CRC). Although management of CRC BM has improved with advances in imaging and systemic therapies, clinical outcomes remain poor. Methods: This retrospective cohort study used the U.S. National Cancer Database to evaluate survival outcomes, treatment patterns, and prognostic factors in CRC patients diagnosed with BM between 2010 and 2020. Patients with isolated brain-only metastases formed the primary analytic cohort, while those with additional extracranial metastases were included for descriptive comparison. Multivariable Cox proportional hazards and logistic regression models were used to assess factors associated with of survival. Proportional hazards assumptions were tested using Schoenfeld residuals. Accelerated failure time models were also employed. Results: From a cohort of 1,040,877 individuals with CRC, 795 had metastatic disease present along with relevant data, of which 296 had isolated BM. Median overall survival (mOS) in BM-only metastatic disease group was 7.82 months (95% CI: 5.82-9.66). The longest survival was observed among patients treated with stereotactic radiosurgery combined with systemic therapy (SRS+Sys), with a median OS of 23.26 months (95% CI: 17.51-41.95) and a 3-year survival rate of 35.8%. In adjusted Cox models, SRS, systemic therapy, and definitive surgery of the primary site were each independently associated with reduced hazard of death. Rectal cancer patients had longer survival than those with colon primaries (mOS: 10.35 vs. 6.08 months). Age, comorbidity burden, and insurance status were not associated with survival in adjusted analyses. Conclusions: SRS+Sys was associated with longer survival compared to other treatment strategies. However, treatment selection is highly dependent on individual clinical factors such as performance status, comorbidities, and disease extent; therefore, these findings must be interpreted with caution Future prospective studies incorporating molecular and biomarker data are warranted to better guide care in this rare and high-risk group.},
}

@article {pmid40803815,
year = {2025},
author = {Naresh, KN and Karube, K and Borges, A and Cheuk, W and Gujral, S and Sayed, S and Sohani, A and Lazzi, S and Ott, G and Du, MQ and Leoncini, L and Chan, JKC},
title = {Fifth edition WHO classification: mature B-cell neoplasms.},
journal = {Journal of clinical pathology},
volume = {},
number = {},
pages = {},
doi = {10.1136/jcp-2025-210260},
pmid = {40803815},
issn = {1472-4146},
abstract = {We present a review of mature B-cell neoplasms as described in the fifth edition of the WHO classification of haematolymphoid tumours (WHO-HAEM5). Entities have expanded, and definitions are increasingly reliant on genomic and other technologies. However, the WHO-HAEM5 employs a hierarchical structure with family (class)-level definitions that group several specific entities. This approach enables the assignment of a family-level diagnosis when criteria for specific entities cannot be met due to resource constraints. To facilitate application in resource-limited settings, WHO-HAEM5 divides diagnostic criteria into 'essential' and desirable criteria for most entities. This review focuses on changes and updates in B-cell lymphoma classification, providing guidance on how to apply the WHO classification in resource-limited settings.},
}

@article {pmid40803814,
year = {2025},
author = {Love, JE and Naresh, KN},
title = {Splenic EBV-positive inflammatory follicular dendritic cell sarcoma with fibroblastic/myoid immunophenotype in a patient with EBV-negative diffuse large B cell lymphoma.},
journal = {Journal of clinical pathology},
volume = {},
number = {},
pages = {},
doi = {10.1136/jcp-2025-210303},
pmid = {40803814},
issn = {1472-4146},
}

@article {pmid40802906,
year = {2025},
author = {Roschewski, M and Kurtz, DM and Westin, JR and Lynch, RC and Gopal, AK and Alig, SK and Sworder, BJ and Cherng, HJ and Kuffer, C and Blair, D and Brown, K and Goldstein, JS and Schultz, A and Close, S and Chabon, JJ and Diehn, M and Wilson, WH and Alizadeh, AA},
title = {Remission Assessment by Circulating Tumor DNA in Large B-cell Lymphoma.},
journal = {Journal of clinical oncology : official journal of the American Society of Clinical Oncology},
volume = {},
number = {},
pages = {101200JCO2501534},
doi = {10.1200/JCO-25-01534},
pmid = {40802906},
issn = {1527-7755},
abstract = {PURPOSE: Large B-cell lymphomas (LBCL) are curable, but patients with residual disease after therapy invariably experience progression. Ultrasensitive methods to detect circulating tumor DNA (ctDNA) as minimal measurable residual disease (MRD) may improve the determination of remission.

METHODS: We integrated data from five prospective studies of frontline anthracycline-based chemotherapy in patients with LBCL. Tumor-specific phased variants were identified from pretreatment samples and monitored at landmark timepoints. Serial plasma specimens were blindly analyzed for detectable ctDNA as MRD. MRD status was compared to conventional response criteria for prognosis of progression-free survival (PFS).

RESULTS: We studied ctDNA-MRD in 137 patients by monitoring 409 plasma specimens over time. Detectable ctDNA rates decreased during therapy with 55% and 78% of patients achieving undetectable ctDNA after 2 cycles and at end of therapy, respectively. After a median follow-up of 37 months, the 2-year PFS for patients with detectable vs undetectable ctDNA after 2 cycles was 67% vs 96% (p=0.0025, hazard ratio 6.9) and after therapy was 29% vs 97% (p<0.0001, hazard ratio 28.7), respectively. Ninety-two (94%) patients with undetectable ctDNA at end of therapy remained alive without progression, while 19 (68%) patients with detectable ctDNA progressed or died. MRD status at end of therapy had greater prognostic utility than conventional lymphoma response criteria using PET scans (hazard ratio 3.6 for positive PET, and 28.3 for detectable ctDNA).

CONCLUSION: Ultrasensitive circulating tumor DNA detection after frontline LBCL therapy is more prognostic than conventional radiographic response criteria. A refined definition of remission with ctDNA-MRD may improve clinical and psychological outcomes for patients with LBCL (Funded by the National Cancer Institute and others; ClinicalTrials.gov numbers, NCT04002947; NCT00398177; NCT02529852; NCT04231877; NCT04134936).},
}

@article {pmid40802741,
year = {2025},
author = {Radtke, S and Fields, E and Swing, K and Kanestrom, G and Yen, JS and Pande, D and Enstrom, MR and Humbert, O and Weiss, MJ and Liu, DR and Newby, GA and Kiem, HP},
title = {Engraftment and persistence of HBB base-edited hematopoietic stem cells in nonhuman primates.},
journal = {Science translational medicine},
volume = {17},
number = {811},
pages = {eadn2601},
doi = {10.1126/scitranslmed.adn2601},
pmid = {40802741},
issn = {1946-6242},
abstract = {Sickle cell disease (SCD) is caused by a single nucleotide change in the β-globin gene that adenine base editors can convert to the nonpathogenic Makassar β-globin variant. Here, we evaluated the long-term efficiency and off-target editing potential of autologous Makassar base editing in three rhesus macaques as a step toward human translation. Base editing of CD34[+]CD90[+] hematopoietic stem cells (HSCs) at the Makassar locus reached greater than 60% efficiency using a bystander nucleotide as a proxy for the sickle cell target in cells from healthy macaques. No impact on myeloid and erythroid colony formation was seen, and clonal analysis revealed that >90% of HSCs were edited, >20% with biallelic editing. After transplantation of autologous gene-edited HSCs, all three macaques rapidly recovered neutrophils, red blood cells, and platelets with stable editing of 25.6%, on average, observed across nucleated blood cells. Similarly, the bone marrow stem cell compartment maintained over 20% of cells harboring mono- or biallelic edits. Off-target editing was assessed at over 900 candidate sites, with editing observed at eight sites, but no selection for or impact of these edits was observed throughout engraftment. These data support further translation of base editing of autologous HSCs for the treatment of patients with SCD.},
}

@article {pmid40802264,
year = {2025},
author = {Turner, NA and Hamasaki, T and Doernberg, SB and Lodise, TP and King, HA and Ghazaryan, V and Cosgrove, SE and Jenkins, TC and Liu, C and Sharma, S and Zaharoff, S and Wahid, L and Renard, VJ and Cook, P and Raad, I and Hachem, R and Chaftari, AM and Sims, M and DeMarco, C and Miller, LG and McCarthy, MW and Morse, CG and Lucasti, C and Forrest, GN and Cherabuddi, K and Polk, C and Fazili, T and Rupp, ME and Thompson, GR and Kim, K and Strnad, L and Schnee, AE and McKinnell, JA and Ramesh, M and Silveira, FP and McCarty, TP and Lee, TC and McDonald, EG and Paolino, K and Wiegand, K and Wall, A and Riccobene, T and Patel, R and Rappo, U and Evans, S and Chambers, HF and Fowler, VG and Holland, TL and , },
title = {Dalbavancin for Treatment of Staphylococcus aureus Bacteremia: The DOTS Randomized Clinical Trial.},
journal = {JAMA},
volume = {},
number = {},
pages = {},
doi = {10.1001/jama.2025.12543},
pmid = {40802264},
issn = {1538-3598},
abstract = {IMPORTANCE: Dalbavancin is a long-acting intravenous lipoglycopeptide that may be effective for treatment of complicated Staphylococcus aureus bacteremia without requiring long-term intravenous access.

OBJECTIVE: To evaluate the efficacy and safety of dalbavancin vs standard therapy for completion of treatment of complicated S aureus bacteremia.

Open-label, assessor-masked, randomized clinical trial conducted from April 2021 to December 2023 at 23 medical centers in the US (n = 22) and Canada (n = 1). Participant follow-up lasted 70 days (180 days for participants with osteomyelitis); date of final follow-up was December 1, 2023. Hospitalized adults with complicated S aureus bacteremia who achieved blood culture clearance following at least 72 hours but no more than 10 days of initial antibacterial therapy were included. Participants were excluded if they had central nervous system infection, retained infected prosthetic material, left-sided endocarditis, or severe immune compromise.

INTERVENTIONS: Participants were randomly assigned to receive either 2 doses of intravenous dalbavancin (n = 100; 1500 mg on days 1 and 8) or 4 to 8 total weeks of standard intravenous therapy (n = 100; cefazolin or antistaphylococcal penicillin if methicillin susceptible; vancomycin or daptomycin if methicillin resistant).

MAIN OUTCOMES AND MEASURES: The primary outcome was the desirability of outcome ranking (DOOR) at day 70, which involved 5 components (clinical success, infectious complications, safety complications, mortality, and health-related quality of life) and was assessed for superiority (achieved if the 95% CI for the probability of dalbavancin having a superior DOOR was >50%). Secondary outcomes included clinical efficacy at day 70 (prespecified noninferiority margin of 20%) and safety.

RESULTS: Of 200 participants randomized (mean [SD] age, 56 [16.2] years; 62 females [31%]), 167 (84%) survived to day 70 and had an efficacy assessment. Participants without a day 70 efficacy assessment were treated as clinical failures in the analyses. The probability of a more desirable day 70 outcome with dalbavancin vs standard therapy was 47.7% (95% CI, 39.8% to 55.7%). Regarding secondary outcomes, clinical efficacy was documented in 73 of 100 for dalbavancin and 72 of 100 for standard therapy (difference, 1.0% [95% CI, -11.5% to 13.5%]), meeting the noninferiority criterion. Serious adverse events were reported in 40 of 100 participants who received dalbavancin and 34 of 100 participants who received standard therapy; treatment-related adverse events were uncommon in both groups.

CONCLUSIONS AND RELEVANCE: Among adult participants with complicated S aureus bacteremia who achieved blood culture clearance, dalbavancin was not superior to standard therapy by desirability of outcome ranking. When considered with other efficacy and safety outcomes these findings may help inform use of dalbavancin in clinical practice.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04775953.},
}

@article {pmid40801398,
year = {2025},
author = {Childers, CP and Foe, LM and Mujumdar, V and Mabry, CD and Selzer, DJ and Senkowski, CK and Ko, CY and Tsai, TC},
title = {Longitudinal Trends in Efficiency and Complexity of Surgical Procedures: Analysis of 1.7 Million Operations Between 2019 and 2023.},
journal = {Journal of the American College of Surgeons},
volume = {},
number = {},
pages = {},
doi = {10.1097/XCS.0000000000001588},
pmid = {40801398},
issn = {1879-1190},
abstract = {BACKGROUND: CMS has proposed reducing the work RVU valuations for most surgical procedures by 2.5% through an efficiency adjustment based on the assumption that surgical work and operative length have decreased over time. Whether the length and complexity of surgical procedures has decreased or increased is unknown. Empirical data on trends in surgical length and complexity are needed to guide evidence-based regulations by federal policymakers.

STUDY DESIGN: The National Surgical Quality Improvement Program registry was analyzed in 2019 and 2023. Analysis was performed at the CPT level and limited to codes with at least 1,000 underlying cases. The primary outcome was surgical efficiency defined as skin-to-skin operative time. Secondary outcomes were measures of patient complexity including preoperative risk factors (e.g., age, comorbidities) and 30-day morbidity and mortality.

RESULTS: The sample included 1,704,311 operations across 249 CPT codes and 11 surgical specialties. Collectively, these codes accounted for $3.2B in fee-for-service Medicare spending in 2023. Overall, operative times increased by 3.1% (CI 3.0-3.3%, p<0.001) in 2023 compared to 2019, or 0.8%/year (CI 0.7-0.8%/year, p<0.001). At the procedure level, 90% of CPT codes had longer or similar operative times in 2023 compared to 2019. Statistically, all measures of complexity also increased over the study time period, without a change in operative mortality.

CONCLUSIONS: For the majority of surgical procedures, operative times have stayed the same or increased from 2019 to 2023. Patient complexity also correspondingly increased. The rationale for an efficiency adjustment to the Medicare physician fee schedule for surgical procedures is not supported by objective data from a national surgical registry.},
}

@article {pmid40798950,
year = {2025},
author = {Fouda, GG and Singh, A and Nelson, A and Janes, H and Martin, T and Levy, O and Wu, D and Zou, F and Jean-Philippe, P and De Paris, K and Van Rompay, KKA and Permar, SR},
title = {Integration of Preclinical and Clinical Vaccine Safety and Immunogenicity Testing for Development of a Pediatric HIV Vaccine to Achieve Protective HIV Immunity Prior to Adolescence.},
journal = {Current HIV research},
volume = {},
number = {},
pages = {},
doi = {10.2174/011570162X366522250721113420},
pmid = {40798950},
issn = {1873-4251},
abstract = {An optimal HIV vaccine should provide protective immunity before sexual debut to prevent infection in adolescents and young adults, including acute infections in women of childbearing age. Such a vaccine will likely require multiple sequential immunization doses and would therefore be ideally initiated in childhood. Many of the world's most successful vaccines are initiated in childhood for the induction of lifelong immunity and/or immunity that can be boosted later in life as part of the WHO Expanded Program on Immunization (EPI). Thus, the EPI vaccine framework provides an infrastructure that could be leveraged for the implementation of a multidose HIV immunization regimen. Early childhood also provides a window of time in which there is minimal HIV exposure risk, and the plasticity of the early life immune landscape may present advantages for the elicitation of broadly neutralizing Antibodies (bnAbs), a primary target for HIV vaccination. Sequential vaccination with adjuvanted immunogens targeting spe-cific bnAb lineages is a promising HIV vaccine strategy, and several vaccine candidates are cur-rently being tested in adult clinical trials. It will be critical also to evaluate the most promising immunogens and adjuvants in pediatric settings. Preclinical studies, including in vitro and in sil-ico modelling as well as studies in animal models, will be essential to guide the design of future pediatric vaccine trials. This review summarizes current advances in bnAb germline targeting immunization. It provides the rationale for a better integration of preclinical and clinical vaccine studies to facilitate the development of a vaccine that achieves protective immunity in preadoles-cence.},
}

@article {pmid40796223,
year = {2025},
author = {Grignani, G and Rutkowski, P and Lebbé, C and Guida, M and Gaudy-Marqueste, C and Spagnolo, F and Burgess, M and Morano, F and Montaudié, H and Depenni, R and Spada, F and Yeung, CCS and Pulini, J and Cornfeld, M and Tian, C and Bhatia, S},
title = {Phase II study of retifanlimab in patients with recurrent locally advanced or metastatic Merkel cell carcinoma (POD1UM-201).},
journal = {Journal for immunotherapy of cancer},
volume = {13},
number = {8},
pages = {},
doi = {10.1136/jitc-2025-012478},
pmid = {40796223},
issn = {2051-1426},
abstract = {BACKGROUND: POD1UM-201, an open-label, single-arm, phase II multiregional study, evaluated efficacy and tolerability of retifanlimab, a humanized monoclonal antibody targeting programmed cell death protein-1 (PD-1) in chemotherapy-naive patients with recurrent locally advanced or metastatic Merkel cell carcinoma (MCC).

METHODS: Patients were enrolled across 34 sites in the USA, Canada, and Europe. Eligible patients were ≥18 years with confirmed recurrent advanced locoregional or metastatic MCC not amenable to surgery or radiation therapy, had not received previous systemic treatment, had measurable disease, and Eastern Cooperative Oncology Group performance status 0-1. Retifanlimab 500 mg was administered intravenously every 4 weeks (Q4W) for up to 2 years. The primary endpoint was objective response rate (ORR). Key secondary endpoints included duration of response (DOR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and safety.

RESULTS: A total of 101 patients were enrolled between February 12, 2019, and June 16, 2021, with a median duration of follow-up for response of 22.2 (range: 1.1-55.3) months. ORR was 54.5% (95% CI: 44.2% to 64.4%; n=55), including 18 patients (17.8%) with complete responses (CRs) and 37 (36.6%) with partial responses (PRs). DCR was 60.4% (95% CI: 50.2% to 70.0%; n=61). Median DOR was not reached (95% CI: 14.0 months to not estimable (NE)) in patients who achieved CR and was 25.3 months (95% CI: 14.2 months to NE) in those with PR. With a median follow-up of 9.3 (range: 0.0-57.1) months, the estimated median PFS was 16.0 months (95% CI: 9.0 months to 32.2). Median OS was not reached with 63% of patients alive at 3 years. The safety profile was representative of the PD-(ligand)1 inhibitor class, with grade 3 immune-related adverse events occurring in 11 patients (10.9%).

CONCLUSIONS: Retifanlimab 500 mg Q4W led to frequent and durable responses in chemotherapy-naive patients with advanced MCC with an acceptable safety profile. Retifanlimab represents a new immunotherapy option for patients with locally advanced or metastatic MCC.

TRIAL REGISTRATION NUMBER: NCT03599713; EudraCT 2018-001627-39.},
}

@article {pmid40796174,
year = {2025},
author = {Sevilla-González, M and Hanson, PA and Islam, J and Hsu, S and Tsoukas, MA and Marliss, EB and Reiner, AP and Gravel, M and Kooperberg, C and Clish, CB and Manning, AK and Sladek, R and Meigs, JB and Burgos, SA},
title = {Compartment-Specific Metabolic Alterations to Insulin Reflect Adiposity-Driven Variation and Predict Type 2 Diabetes.},
journal = {The Journal of clinical endocrinology and metabolism},
volume = {},
number = {},
pages = {},
doi = {10.1210/clinem/dgaf454},
pmid = {40796174},
issn = {1945-7197},
abstract = {CONTEXT: The metabolic mechanisms underlying insulin resistance (IR) are not fully understood. Metabolomic profiling can reveal compartment-specific variations and identify individuals at risk for type 2 diabetes (T2D).

OBJECTIVE: To characterize insulin-induced metabolomic changes during a hyperinsulinemic-euglycemic clamp and evaluate a derived risk score's predictive value for T2D.

Clamp studies were conducted in 80 adults (38 with T2D, 42 without) to measure plasma and muscle metabolites in fasting and hyperinsulinemic states. An IR metabolomic score was developed and tested in a prospective case-control study (367 cases, 910 controls) from the Women's Health Initiative (28.5-year follow-up).

MAIN OUTCOME MEASURES: Metabolite changes during hyperinsulinemia and incident T2D.

RESULTS: Hyperinsulinemia altered 79.5% of plasma metabolites (notably fatty acids, lactate, pyruvate) and 15.8% of muscle metabolites (e.g., branched-chain and aromatic amino acids). T2D was associated with higher triglycerides and lower tricarboxylic acid intermediates during clamp. Adiposity amplified insulin-induced increases in plasma lipids. The risk score predicted incident T2D (HR 1.20 per SD; 95% CI: 1.09-1.32; P = 7.4 × 10⁻⁴).

CONCLUSIONS: Compartment-specific metabolic responses to insulin are shaped by adiposity and predict future T2D risk, supporting use of metabolomic signatures for early identification and prevention.},
}

@article {pmid40795788,
year = {2025},
author = {van der Heijden, MS and Powles, T and Gupta, S and Loriot, Y and Galsky, MD and Valderrama, BP and Sridhar, SS and Yu, EY and Iyer, G and Kikuchi, E and Castellano, D and Hoffman-Censits, J and Drakaki, A and Mar, N and Maroto Rey, JP and Vulsteke, C and Arafat, W and Duran, I and Dawson, NA and Swami, U and Gorla, S and Moreno, BH and Yu, X and Lu, YT and Bedke, J},
title = {Exploratory subgroup analyses of EV-302: a phase III global study to evaluate enfortumab vedotin in combination with pembrolizumab versus chemotherapy in previously untreated locally advanced or metastatic urothelial carcinoma.},
journal = {ESMO open},
volume = {10},
number = {8},
pages = {105544},
doi = {10.1016/j.esmoop.2025.105544},
pmid = {40795788},
issn = {2059-7029},
abstract = {BACKGROUND: In the phase III EV-302 study (NCT04223856), enfortumab vedotin (EV) plus pembrolizumab (P) demonstrated superior efficacy and safety versus platinum-based chemotherapy in patients with previously untreated locally advanced/metastatic urothelial cancer (la/mUC). We report the efficacy of EV+P in prespecified subgroups, including those defined by cisplatin eligibility status, the presence or absence of liver metastases, and metastatic disease sites.

METHODS: Patients with previously untreated la/mUC were randomly assigned 1 : 1 to receive either EV 1.25 mg/kg and pembrolizumab 200 mg, or gemcitabine plus cisplatin or carboplatin, all intravenously. The two primary endpoints were progression-free survival (PFS) and overall survival (OS). Confirmed objective response rate was one of the secondary endpoints.

RESULTS: Overall, 886 patients were randomized: 442 to EV+P and 444 to chemotherapy. Baseline characteristics were balanced across treatment groups. Efficacy and safety data for the intention-to-treat (ITT) population, along with PFS and OS data for cisplatin-eligible and -ineligible patients, were previously published (Powles et al. N Eng J Med, 2024). In this analysis, EV+P showed benefit across prespecified subgroups that was consistent with the ITT population. OS benefit in the EV+P arm versus chemotherapy was seen across all subgroups, including patients with liver metastases (OS 19.1 versus 10.1 months), patients without liver metastases [OS not estimable (NE) versus 17.9 months], patients with visceral metastases (OS 25.6 versus 13.6 months), and in patients with lymph node-only disease (OS NE versus 27.5 months). In addition, confirmed objective response rate and PFS benefit with EV+P versus chemotherapy was seen across all examined subgroups.

CONCLUSION: Along with previously published safety data, EV+P demonstrated benefit compared with chemotherapy across all prespecified subgroups, consistent with the ITT population and supporting EV+P as the standard of care for first-line treatment of la/mUC.},
}

@article {pmid40795197,
year = {2025},
author = {Paturi, S and Banerjee, R},
title = {Step Count, Step Aside: Newer Physical Activity Metrics to Predict Survival in Oncology.},
journal = {JCO clinical cancer informatics},
volume = {9},
number = {},
pages = {e2500197},
doi = {10.1200/CCI-25-00197},
pmid = {40795197},
issn = {2473-4276},
}

@article {pmid40794593,
year = {2025},
author = {Matsen, FA and Sung, K and Johnson, MM and Dumm, W and Rich, D and Starr, T and Song, YS and Bradley, P and Fukuyama, J and Haddox, HK},
title = {A sitewise model of natural selection on individual antibodies via a transformer-encoder.},
journal = {Molecular biology and evolution},
volume = {},
number = {},
pages = {},
doi = {10.1093/molbev/msaf186},
pmid = {40794593},
issn = {1537-1719},
abstract = {During affinity maturation, antibodies are selected for their ability to fold and to bind a target antigen between rounds of somatic hypermutation. Previous work has identified patterns of selection in antibodies using B cell repertoire sequencing data. However, this work is constrained by needing to group many sequences or sites to make aggregate predictions. In this paper, we develop a transformer-encoder selection model of maximum resolution: given a single antibody sequence, it predicts the strength of selection on each amino acid site. Specifically, the model predicts for each site whether evolution will be slower than expected relative to a model of the neutral mutation process (purifying selection) or faster than expected (diversifying selection). We show that the model does an excellent job of modeling the process of natural selection on held out data, and does not need to be enormous or trained on vast amounts of data to perform well. The patterns of purifying vs diversifying natural selection do not neatly partition into the complementarity-determining vs framework regions: for example, there are many sites in framework that experience strong diversifying selection. There is a weak correlation between selection factors and solvent accessibility. When considering evolutionary shifts down a tree of antibody evolution, affinity maturation generally shifts sites towards purifying natural selection, however this effect depends on the region, with the biggest shifts toward purifying selection happening in the third complementarity-determining region. We observe distinct evolution between gene families but a limited relationship between germline diversity and selection strength.},
}

@article {pmid40792429,
year = {2025},
author = {Zhou, P and Mills, CB and Dong, ZM and Barber, BR and Beronja, S},
title = {Barcoded Orthotopic Patient-Derived Head & Neck Squamous Cell Carcinoma Model Demonstrating Clonal Stability and Maintenance of Cancer Driver Mutational Landscape.},
journal = {Cancer medicine},
volume = {14},
number = {15},
pages = {e71137},
pmid = {40792429},
issn = {2045-7634},
support = {//Fred Hutchinson Cancer Research Center/ ; //Dick and Loraine Burger Pilot Funding/ ; //AAO-HNSF Resident Research Grant/ ; },
mesh = {Humans ; Animals ; Mice ; *Squamous Cell Carcinoma of Head and Neck/genetics/pathology ; *Head and Neck Neoplasms/genetics/pathology ; *Mutation ; Disease Models, Animal ; Female ; Xenograft Model Antitumor Assays ; Mice, SCID ; Exome Sequencing ; Male ; *DNA Barcoding, Taxonomic ; },
abstract = {OBJECTIVE: To illustrate a new barcoded orthotopic patient-derived xenograft (PDX) mouse model where one can investigate phenotypic effects of single-cell level gene manipulation in a pooled format. To address some concerns of current PDX mouse models of head and neck squamous cell carcinoma (HNSCC): (1) genomic evolution with passage by generating high-purity cancer cells, which can also be utilized for other downstream applications, including cell culture-based studies, and (2) cost-effectiveness of current PDX models.

METHODS: Two-millimeter tumor cubes from nine patients were implanted into immunodeficient mouse flanks subcutaneously. Purified tumor cells were obtained from subcutaneous xenografts. Various numbers of purified tumor cells were then injected into the lingual tissue of immunodeficient mice, and the lowest amount of cells needed to achieve a 100% orthotopic engraftment rate were identified. Clonal stability was tested using a lentiviral barcoding system. The orthotopic PDXs' genetic landscapes were characterized using whole exome sequencing.

RESULTS: This approach yielded an overall engraftment rate of 88.9%. The purification process increased cancer cell purity from 34% to 92%. Lingual injection of 100,000 purified tumor cells achieved a 100% orthotopic engraftment rate from purified subcutaneous PDX tumor cells while maintaining clonal and genetic stability.

CONCLUSION: Our study presents a barcoded orthotopic patient-derived xenograft model for head and neck squamous cell carcinoma with clonal stability. This model provides a way to study phenotypic effects of single cell level gene manipulation in a pooled format. The method can be adapted for in vitro work as well.},
}

Humans
Animals
Mice
*Squamous Cell Carcinoma of Head and Neck/genetics/pathology
*Head and Neck Neoplasms/genetics/pathology
*Mutation
Disease Models, Animal
Female
Xenograft Model Antitumor Assays
Mice, SCID
Exome Sequencing
Male
*DNA Barcoding, Taxonomic

@article {pmid40792015,
year = {2025},
author = {Raychaudhuri, S and Othus, M and Percival, MM and Garcia-Manero, G and Appelbaum, FR and Erba, HP and Appelbaum, JS},
title = {Treatment discontinuation due to toxicity for patients with acute myeloid leukemia receiving intensive chemotherapy.},
journal = {Blood neoplasia},
volume = {2},
number = {3},
pages = {100129},
pmid = {40792015},
issn = {2950-3280},
}

@article {pmid40792014,
year = {2025},
author = {DaSilva, B and Darwin, A and Zhang, A and Vyas, RD and Russell, K and Gilbert, JS and Tan, V and Feldt, S and Johnston, H and Liang, EC and DuVall, AS and Liedtke, M and Stock, W and Cassaday, RD and Schwartz, M and Leonard, JT and Muffly, LS and Luskin, MR},
title = {Real-world performance of the CALGB 10403 regimen in young adults in the United States.},
journal = {Blood neoplasia},
volume = {2},
number = {3},
pages = {100111},
pmid = {40792014},
issn = {2950-3280},
abstract = {The Cancer and Leukemia Group B 10403 (C10403) trial prospectively demonstrated the safety and efficacy of administering an asparaginase-containing pediatric regimen for the treatment of adolescents and young adults (AYAs) with acute lymphoblastic leukemia. Since its implementation as standard of care, it is unknown how the C10403 regimen performs beyond the clinical trial setting. To bridge this knowledge gap, we designed a multicenter retrospective cohort study to examine the safety, efficacy, and challenges of completing C10403 in the "real world." From October 2012 through June 2020, a total of 139 patients began induction as per the C10403 regimen across 6 US academic cancer centers. The median age was 26 years (range, 17-39), 69% were male, 55% were non-Hispanic White, and 27% were Hispanic. Among them, 122 patients (88%) achieved complete remission or complete remission with incomplete count recovery (CR/CRi) with C10403, 48 (35%) completed maintenance therapy, and 47 (34%) changed postremission regimens while in CR/CRi. The 3-year event-free survival (EFS) was 66% (95% confidence interval [CI], 55-74), and the 3-year overall survival (OS) was 81% (95% CI, 74-87). Four deaths occurred while on C10403 treatment: 1 during induction; and 3 later in the treatment course. The most common grade 3 or 4 adverse events during induction included alanine aminotransferase elevation (22%) and sepsis (14%). B-cell immunophenotype (hazard ratio [HR], 2.45; 95% CI, 1.09-5.48), Philadelphia chromosome-like genetics (HR, 3.05; 95% CI, 1.25-7.44), and Hispanic ethnicity (HR, 2.00; 95% CI, 1.06-3.78) were associated with worse EFS in univariate analyses. Overall, these real-world results are comparable to those of the C10403 trial. Further improvements are needed to enhance outcomes and regimen tolerability in the AYA population.},
}

@article {pmid40789739,
year = {2025},
author = {Tachiki, L and Moshiri, Y and Hippe, DS and Gong, E and Zawacki, L and Pulliam, T and Lachance, K and Church, C and Fu, A and Huynh, E and Remington, AJ and Harikrishnan, N and Bierma, M and Doolittle-Amieva, C and Akaike, T and Park, SY and Alexander, NA and Zaba, L and Bhatia, S and Nghiem, PT},
title = {Risk of disease progression after discontinuing immunotherapy in 105 patients with Merkel cell carcinoma who responded to PD-1 pathway blockade.},
journal = {Journal for immunotherapy of cancer},
volume = {13},
number = {8},
pages = {},
doi = {10.1136/jitc-2025-012123},
pmid = {40789739},
issn = {2051-1426},
mesh = {Humans ; *Carcinoma, Merkel Cell/drug therapy/pathology/mortality ; Male ; Female ; Disease Progression ; *Immune Checkpoint Inhibitors/therapeutic use/pharmacology ; Aged ; Retrospective Studies ; Middle Aged ; Aged, 80 and over ; *Skin Neoplasms/drug therapy/pathology ; *Immunotherapy/methods ; *Programmed Cell Death 1 Receptor/antagonists & inhibitors ; },
abstract = {BACKGROUND: Immune checkpoint inhibitors (ICIs) are the preferred systemic therapy for most patients with advanced Merkel cell carcinoma (MCC). However, the optimal duration of treatment for patients responding to ICI is unclear. Emerging data from retrospective analyses indicate a higher risk of MCC progression after ICI discontinuation, as compared with continuing ICI.

METHODS: We performed a retrospective cohort study to evaluate the rate of progressive disease (PD) after treatment discontinuation in patients with advanced MCC who experienced objective responses to first-line ICI. We evaluated whether the risk of PD was associated with the reason for treatment discontinuation (elective vs due to toxicity) and depth of response (complete vs partial response (CR vs PR)).

RESULTS: Among 105 responders, 58 discontinued ICI (median treatment duration: 12 months), and 47 continued ICI (median treatment duration: 20 months) at data cut-off. With a median follow-up of 34 months from ICI initiation, 33% of the entire cohort experienced disease progression at 2 years. 2 years after ICI initiation, 39% of patients who discontinued ICI had disease progression, compared with 14% of patients who continued ICI (HR=2.34 (95% CI: 1.07 to 5.12), p=0.034). Among patients who discontinued ICI, those with PR had a numerically higher rate of progression compared with patients with CR at 2 years after ICI discontinuation (56% vs 29%, respectively; HR=1.74 (95% CI: 0.72 to 4.20), p=0.22). Patients who discontinued due to toxicity had numerically higher rates of progression at 2 years (N=28) compared with patients who discontinued electively (N=30) (45% vs 31%, respectively; HR=2.08 (95% CI: 0.79 to 5.46), p=0.14). Among responders who stayed on ICI and had not progressed by 1 year, those who electively discontinued ICI had a high chance of remaining progression-free at 2 years (89%), similar to those who continued ICI (96%, p=0.59).

CONCLUSIONS: This study highlights the high progression risk following ICI discontinuation in advanced MCC, especially among patients with non-CRs or those discontinuing early. While elective discontinuation may be appropriate after durable CRs (response≥1 year), greater caution is warranted in other settings.},
}

Humans
*Carcinoma, Merkel Cell/drug therapy/pathology/mortality
Male
Female
Disease Progression
*Immune Checkpoint Inhibitors/therapeutic use/pharmacology
Aged
Retrospective Studies
Middle Aged
Aged, 80 and over
*Skin Neoplasms/drug therapy/pathology
*Immunotherapy/methods
*Programmed Cell Death 1 Receptor/antagonists & inhibitors

@article {pmid40789102,
year = {2025},
author = {Bhandari, R and Chen, Y and Chow, EJ and Howell, RM and Kenney, LB and Krull, KR and Leisenring, W and Nathan, PC and Neglia, JP and Ness, KK and Oeffinger, KC and Snyder, C and Turcotte, LM and Wong, FL and Yasui, Y and Armstrong, GT and Armenian, SH},
title = {Health Outcomes Beyond Age 50 Years in Survivors of Childhood Cancer: A Report From the Childhood Cancer Survivor Study.},
journal = {Journal of clinical oncology : official journal of the American Society of Clinical Oncology},
volume = {},
number = {},
pages = {JCO2500385},
pmid = {40789102},
issn = {1527-7755},
support = {K12 CA001727/CA/NCI NIH HHS/United States ; U24 CA055727/CA/NCI NIH HHS/United States ; },
abstract = {PURPOSE: There are limited data on the risk for mortality and health outcomes among the increasing population of older (age >50 years) survivors of childhood cancer during this later stage in life when there is an expected increase in aging-related morbidities.

METHODS: We assessed cause-specific mortality, incident new cancers, chronic health conditions (CHCs), frailty, and health status among survivors from the Childhood Cancer Survivor Study, conditional on surviving to 50 years. We calculated conditional survival rates, standardized mortality ratios (SMRs), and, for incident new cancers, cumulative burden, standardized incidence ratios (SIRs), and relative rates (RRs), compared with the general US population. RRs for CHCs and prevalence ratios for frailty and health status outcomes were calculated for survivors compared with siblings. Piecewise exponential regression identified risk factors.

RESULTS: Among 7,490 childhood cancer survivors alive at age 50 years, subsequent 5-, 10-, and 15-year mortality risks were 8%, 18%, and 32%, respectively; overall SMR was 3.2 (95% CI, 3.0 to 3.4). SMRs were highest for death due to new cancer (SMR = 4.7; 95% CI, 4.2 to 5.2). In subset analysis, survivors without radiation therapy (RT) exposure had similar new cancer rates as the general population. The population attributable fraction of new cancers to RT was 40%. Survivors had >2-fold risk of severe, life-threatening, or fatal CHCs (any: RR, 2.6 [95% CI, 2.2 to 3.1]; multiple: RR, 3.3 [95% CI, 2.5 to 4.4]), specifically among survivors with history of RT exposure, compared with siblings. We identified no associations between chemotherapy and late health outcomes.

CONCLUSION: Older survivors of childhood cancer continue to have an elevated burden of premature mortality, new cancers, and adverse health outcomes as they age. The increased risk for cancer and CHCs among these older survivors is associated with RT, but not chemotherapy, exposure.},
}

@article {pmid40766425,
year = {2025},
author = {Chambwe, N and Kennedy, SR and Kohrn, BF and Lazarchuk, P and Leutert, M and Qin, G and Tercan, B and Sanchez-Contreras, M and Tang, W and Graber, JJ and Paddison, PJ and Villén, J and Shmulevich, I and Monnat, RJ},
title = {Cellular heterogeneity and therapeutic response profiling of human IDH+ glioma stem cell cultures.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {40766425},
issn = {2692-8205},
abstract = {Glioblastoma stem cell (GSC) cultures are initiated from glioblastoma (GBM) surgical resection tissue. They can capture and propagate key GBM primary tumor molecular and cellular features. We have deeply characterized four isocitrate dehydrogenase (IDH)-expressing (or IDH+) GSC cultures from unrelated adults to serve as cellular models for the majority of adult primary GBM. We demonstrate that GSC cultures can be continuously propagated in defined, serum-free media and 5% oxygen without requiring specialized growth substrates; have well-defined genomic and mtDNA variants and gene/protein expression profiles; and highly reproducible dose-survival curves when treated with the GBM standard-of-care therapies of ionizing radiation (IR) and temozolomide (TMZ). We also illustrate how expressed lentiviral barcodes, mtDNA variants and single cell gene expression profiling can be used to define and track cellular heterogeneity over 40 days after IR treatment. These well-characterized IDH+ GSC cultures can support many high throughput in vitro assay formats, including xenograft, organoid and other GBM disease modeling protocols. They should prove a useful resource to better understand GBM biology, and to identify new and more effective GBM therapies and treatment regimens.},
}

@article {pmid40789098,
year = {2025},
author = {Johns, TS and Estrella, MM and Hébert, J and Franceschini, N and Larson, JC and Boulware, LE and Snetselaar, L and Golestaneh, L and Shadyab, AH and Shivappa, N and Mossavar-Rahmani, Y and Melamed, ML},
title = {Dietary Inflammatory Potential and the Risk of Incident Kidney Failure in the Women's Health Initiative.},
journal = {Kidney360},
volume = {},
number = {},
pages = {},
doi = {10.34067/KID.0000000801},
pmid = {40789098},
issn = {2641-7650},
abstract = {BACKGROUND: Diet affects inflammation and kidney health, but few studies have investigated dietary inflammatory potential in CKD progression, particularly in women. We aim to examine this association in the Women's Health Initiative (WHI).

METHODS: We conducted a non-concurrent prospective cohort study among WHI participants enrolled in the clinical trials and observational study (1993-1998) without baseline CKD and with available dietary intake assessments, Medicare data, and creatinine measurements at enrollment. The inflammatory potential of diets was assessed using the dietary inflammatory index (DII®), an acultural tool that quantifies diets from anti-inflammatory to pro-inflammatory. Scores were categorized into quartiles, with Q1 (reference group) and Q4 indicating the least and most inflammatory diets, respectively. Incident kidney failure (CKD stage G5, ESKD, or transplantation) was identified using diagnosis codes in Medicare claims from enrollment through 12/31/2019. We performed multivariable Cox proportional hazards regression and modeled death as a competing risk to determine the risk of incident kidney failure.

RESULTS: Among the 17,334 women included in our study, the baseline mean age was 64.9 years (standard deviation 7.1); 33.5% self-identified as Black, 8.8% as Hispanic, 38% had hypertension, and 6.8% had diabetes mellitus. Baseline mean estimated glomerular filtration rate (eGFR) was 87.2 ml/min/1.73m2. Over a mean follow-up of 11.2 years, 1852 women (10.7%) developed kidney failure. Compared to Q1, women with dietary patterns in Q4 had a 18% higher risk (95% confidence interval 1.03-1.37; p-trend=0.01) of developing kidney failure after adjusting for age, race/ethnicity, education, region, comorbidities, medications, smoking, energy intake, physical activity, eGFR, and body mass index. Competing risk models yielded similar results.

CONCLUSIONS: A pro-inflammatory diet (e.g., enriched in processed foods, refined sugars, and red meat) was associated with incident kidney failure in postmenopausal women without baseline CKD. Clinical trials are needed to assess the impact of an anti-inflammatory dietary pattern on CKD risk and progression.},
}

@article {pmid40788762,
year = {2025},
author = {Khyzha, N and Ahmad, K and Henikoff, S},
title = {Protocol for the spatiotemporal profiling of RNA within nuclear compartments in human cell lines using SLAM-RT&Tag.},
journal = {STAR protocols},
volume = {6},
number = {3},
pages = {104017},
doi = {10.1016/j.xpro.2025.104017},
pmid = {40788762},
issn = {2666-1667},
abstract = {Measuring RNA residence time within nuclear compartments provides insight into their roles as either storage sites or transient processing hubs. This protocol describes SLAM-RT&Tag, a genomic technique that integrates RNA metabolic labeling with RT&Tag, an RNA proximity labeling method. We detail steps for RNA labeling, library preparation, and computational quantification of T-to-C conversion events to infer RNA dynamics within nuclear compartments in human cell lines. For complete details on the use and execution of this protocol, please refer to Khyzha et al.[1].},
}

@article {pmid40785644,
year = {2025},
author = {Gauthier, J and Ahn, KW and Patel, J and Lian, Q and Badawy, S and Cairo, MS and Delgado, J and Grover, N and Haverkos, B and de Lima, M and Malone, A and Mussetti, A and Nieto, Y and Pawarode, A and Pearson, L and Solh, M and Sureda, A and Tun, AM and Wudhikarn, K and Yamshon, S and Shadman, M and Turtle, CJ and Hamadani, M and Herrera, AF},
title = {CD19 CAR T-Cell Therapy for Primary Mediastinal Large B-Cell Lymphoma: A CIBMTR Analysis.},
journal = {American journal of hematology},
volume = {},
number = {},
pages = {},
doi = {10.1002/ajh.70033},
pmid = {40785644},
issn = {1096-8652},
support = {U24CA076518/CA/NCI NIH HHS/United States ; HHSH250201700006C/HRSA/HRSA HHS/United States ; N00014-20-1-2705//Office of Naval Research/ ; N00014-20-1-2832//Office of Naval Research/ ; },
abstract = {T cells engineered with CD19-directed chimeric antigen receptors (CD19 CAR) T cells have become standard treatment for patients with high risk, relapsed or refractory (R/R) large B-cell lymphomas (LBCL). However, outcomes in patients with rare subsets of LBCL, such as primary mediastinal large B-cell lymphoma (PBMCL), have not been well characterized. The impact of prior immune checkpoint inhibitor (ICI) treatment, commonly used to treat R/R PMBCL, is also unknown. To address these gaps, we retrospectively analyzed CIBMTR registry data including PMBCL patients undergoing CD19 CAR T-cell therapy per standard-of-care. A total of 135 PMBCL adults from 66 centers were included. Median age at the time of CAR T-cell therapy was 32. Thirty-nine patients (28.9%) had received an ICI prior to CAR T-cell therapy. The best overall and complete response (CR) rates after CD19 CAR T-cell therapy were 79% and 67.7%, respectively. The 2-year progression-free (PFS) and overall survival (OS) were 58.6% (95% CI, 49.7-67.3) and 80.8% (95% CI, 72.6-87.8), respectively. The 2-year cumulative incidence (CI) of relapse and non-relapse mortality (NRM) were 36% (95% CI, 27.8-44.7) and 5.4% (95% CI, 1.9-10.5), respectively. We observed grade ≥ 3 CRS and ICANS in 6.1% and 14.7%, respectively. Prior ICI exposure was associated with lower 2-year CI of relapse (ICI-exposed, 21.7%; ICI-naïve, 41.6%; p = 0.03) and higher 2-year NRM (ICI-exposed, 11.7%; ICI-naïve, 2.8%; p = 0.03). We could not confirm statistically different PFS (p = 0.19) or OS (p = 0.26) between ICI-exposed and ICI-naïve patients. CD19 CAR T-cell therapy led to high rates of durable responses in PMBCL patients with low rates of severe toxicities.},
}

@article {pmid40784763,
year = {2025},
author = {Puschel, K and Arancibia, V and Rioseco, A and Paz, S and Soto, MG and Martinez, J and Faundez, M and Acevedo, F and Di Biase, F and Emery, J and León, A and Are, C and Thompson, B},
title = {Challenges of cancer survivorship care in Chile: a longitudinal study comparing the quality of care and quality of life for cancer survivors in a primary care network and a cancer centre in Chile.},
journal = {BMJ open},
volume = {15},
number = {8},
pages = {e097015},
pmid = {40784763},
issn = {2044-6055},
mesh = {Humans ; *Quality of Life ; Chile/epidemiology ; Female ; *Cancer Survivors/psychology/statistics & numerical data ; Male ; *Primary Health Care/standards ; Middle Aged ; *Quality of Health Care ; Retrospective Studies ; Longitudinal Studies ; Aged ; Adult ; *Survivorship ; *Cancer Care Facilities ; *Colorectal Neoplasms/therapy/psychology ; *Breast Neoplasms/therapy/psychology ; },
abstract = {OBJECTIVE: The rapid growth in the cancer survivor population in Chile and Latin America raises new challenges in addressing their care needs. This study assesses the health status and compares the quality of care and quality of life in cancer survivors at a primary care network and a private cancer centre in Santiago, Chile.

DESIGN: Retrospective cohort study.

SETTING: Three primary care clinics and one cancer centre in Chile.

PARTICIPANTS: All breast and colorectal cancer patients identified from a primary care retrospective cohort of 61 174 were followed from 2018 to 2023 and compared with an equivalent sample of patients from a university cancer centre identified during the same period.

OUTCOME MEASURES: Quality of care was assessed based on American Cancer Society standards, while quality of life was measured using the EuroQol 5 Dimensions-5 Levels survey instrument.

RESULTS: A total of 420 cancer survivors participated in the study; 208 from primary care and 212 from the cancer centre. All participants received substandard care. Patients in primary care had lower educational levels and higher rates of comorbidity. They reported a lower quality of life score (72.22 vs 78.43, p<0.001), a higher prevalence of chronic pain (37.02% vs 25.6%, p=0.016) and more severe mental health symptoms (19.89% vs 10.05%, p=0.03). Differences in educational level and cancer stage at diagnosis explained the observed disparities in chronic pain and mental health disorders between the two populations. Primary care patients received more psychosocial care (OR=2.29; 95% CI: 1.55 to 3.39), cardiovascular assessment (OR=2.66; 95% CI:2.17 to 3.26) and psychosocial evaluations (OR: 9.07; 95% CI:4.75 to 17.32).

CONCLUSION: Cancer survivors face a significant disease burden and receive substandard care in Chile. As the primary source of care for this population, primary care is challenged to better integrate with speciality care to develop an effective shared care model for cancer survivors.},
}

Humans
*Quality of Life
Chile/epidemiology
Female
*Cancer Survivors/psychology/statistics & numerical data
Male
*Primary Health Care/standards
Middle Aged
*Quality of Health Care
Retrospective Studies
Longitudinal Studies
Aged
Adult
*Survivorship
*Cancer Care Facilities
*Colorectal Neoplasms/therapy/psychology
*Breast Neoplasms/therapy/psychology

@article {pmid40781843,
year = {2025},
author = {Zhang, QS and Kang, J and Lybarger, K and Glenn, MC and Sponseller, P and Blau, KH and Ford, E},
title = {Semi-automated topic identification for radiation oncology safety event reports using natural language processing and statistical modeling.},
journal = {Medical physics},
volume = {52},
number = {8},
pages = {e17936},
doi = {10.1002/mp.17936},
pmid = {40781843},
issn = {2473-4209},
mesh = {*Natural Language Processing ; *Radiation Oncology ; *Models, Statistical ; Automation ; Humans ; *Safety ; Bayes Theorem ; },
abstract = {BACKGROUND: Incident learning provides valuable narrative text about safety and quality, but the large-volume unstructured data is difficult to analyze.

PURPOSE: We present a semi-automated method to categorize safety-related event reports and validate it using Radiation Oncology reports.

METHODS: We analyzed English text from 7174 safety-related event reports in a Radiation Oncology department, dated between 2012 and 2021. Units of text called "tokens" were preprocessed for meaningful content, resulting in 4216 tokens. 6760 reports had at least one filtered token. We fit a correlated topic model (CTM) with K = 50 topics, estimating Bayesian posterior probability distributions over tokens and proportions of each report that were about each topic. To validate the model by assessing for expert agreement on meaningful topic labels for topics, five experts independently assigned topic labels to topics by reading the top-10 most probable tokens per topic and tokens' posterior probabilities ("top-10 tokens" approach), and by separately reading any reports that were estimated to be at least 90% about a topic ("case-reports" approach). Consensus topic labels (CTLs) such as "Brachytherapy" or "Orders" were assigned to topics.

RESULTS: Of 50 modeled topics, 37 (74%) had a majority agreement of experts on the CTL assignment, supporting the model's validity. 36 topics had a CTL assigned to them via the top-10 tokens approach. Of 50 topics, 20 had at least one report that was ≥ 90% about the topic such that the case-reports approach applied. 18 of the 20 had a CTL assigned via that approach. Of 55 CTLs assigned, seven were not found by prior labeling of reports' topics during review of reports over the years.

CONCLUSIONS: We demonstrated a semi-automated method to categorize Radiation Oncology safety-related event reports by topic, offering an expedited alternative to a person reading many reports and enabling the identification of topics not discovered by reading individual reports.},
}

*Natural Language Processing
*Radiation Oncology
*Models, Statistical
Automation
Humans
*Safety
Bayes Theorem

@article {pmid40781345,
year = {2025},
author = {Alson, JG and Doll, KM and Hempstead, BH and Barr, L and Lavallee, DC and Sage, L and Moore, A and Ramsey, SD and Wolff, EM and Comstock, BA and Monsell, SE and Katz, R and Gamble, CR and Beavis, AL and Watat, M and , },
title = {Advancing equity in cancer research through principled partnership: stakeholder engagement practices in The Social Interventions for Support during Treatment for Endometrial cancer and Recurrence (SISTER) Study.},
journal = {Research involvement and engagement},
volume = {11},
number = {1},
pages = {95},
pmid = {40781345},
issn = {2056-7529},
support = {AD-2020C1-19210//Patient Centered Outcomes Research In/ ; AD-2020C1-19210//Patient Centered Outcomes Research In/ ; AD-2020C1-19210//Patient Centered Outcomes Research In/ ; AD-2020C1-19210//Patient Centered Outcomes Research In/ ; AD-2020C1-19210//Patient Centered Outcomes Research In/ ; AD-2020C1-19210//Patient Centered Outcomes Research In/ ; AD-2020C1-19210//Patient Centered Outcomes Research In/ ; AD-2020C1-19210//Patient Centered Outcomes Research In/ ; AD-2020C1-19210//Patient Centered Outcomes Research In/ ; AD-2020C1-19210//Patient Centered Outcomes Research In/ ; AD-2020C1-19210//Patient Centered Outcomes Research In/ ; },
abstract = {BACKGROUND: In cancer, lack of social support is associated with reduced survival. Peer support interventions have reduced social isolation among Black women with cancer but have yet to be adapted for Black people diagnosed with endometrial cancer - a growing, high-need demographic that has been historically excluded from community-engaged research. Our research team at the University of Washington addressed this gap by working within an established community partnership to develop a pragmatic randomized controlled trial to adapt and test social support interventions among Black women with EC - the Social Interventions for Support during Treatment of Endometrial Cancer and Recurrence (SISTER) Study. The goal of this commentary is to describe the stakeholder engagement practices used in the conceptualization and start-up of the SISTER Study.

MAIN TEXT: The research team, including Black endometrial cancer survivors, developed a grant proposal, grounded in engagement values derived from the Patient-Centered Outcomes Research Institute[®] and the Public Health Critical Race Praxis. The team implemented values-aligned stakeholder engagement activities, including the creation of an advisory board charter, structuring meetings and roles, incorporating stakeholder input into study material and protocols, establishing an external advisory board, and developing an engagement evaluation plan. Overall, we learned that it is possible to design and operationalize a community-engaged pragmatic randomized controlled trial in alignment with a racial equity social justice research methodology and patient-centered outcomes research engagement practices. We describe other lessons learned, including operational challenges to implementing our engagement practices and our approaches to addressing these challenges, and promising practices to replicate in future studies or partnerships.

CONCLUSION: The SISTER Study is an example of establishing principled methods of stakeholder engagement within an area of study and population that has been underrepresented in stakeholder-engaged research. The engagement practices within the SISTER Study can inform community-academic partnership practices in health equity research.},
}

@article {pmid40781068,
year = {2025},
author = {Kelnhofer-Millevolte, LE and Smith, JR and Nguyen, DH and Wilson, LS and Lewis, HC and Arnold, EA and Brinkley, MR and Shin, K and Ahn, JH and Kim, ET and Kulej, K and Geballe, AP and Ramachandran, S and Avgousti, DC},
title = {Human cytomegalovirus induces neuronal gene expression through IE1 for viral maturation.},
journal = {Nature communications},
volume = {16},
number = {1},
pages = {7316},
pmid = {40781068},
issn = {2041-1723},
support = {GM133441//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; AI145945//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; GM133434//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; },
mesh = {Humans ; *Cytomegalovirus/physiology/genetics/metabolism ; *Immediate-Early Proteins/metabolism/genetics ; Histones/metabolism/genetics ; *Neurons/metabolism/virology ; *Cytomegalovirus Infections/virology/genetics/metabolism ; *Virus Assembly/genetics ; Host-Pathogen Interactions/genetics ; Gene Expression Regulation ; },
abstract = {Viral invasion of the host cell causes some of the most dramatic changes in biology. Human cytomegalovirus (HCMV) extensively remodels host cells, altering nuclear shape and generating a cytoplasmic viral-induced assembly compartment (vIAC). How these striking morphology changes occur in the context of host gene regulation is still emerging. Histone variant macroH2A1 is both important for maintaining nuclear integrity and functions to promote herpes simplex virus infection. Therefore, we hypothesized it may also function in cytomegalovirus infection. Here, we discovered that macroH2A1 is necessary for HCMV-induced cellular reorganization and formation of infectious progeny. Using RNA-seq in infected cells, we find that while all viral genes are highly expressed in the absence of macroH2A1, many HCMV-induced host genes are not. Remarkably, hundreds of these HCMV-induced macroH2A1-dependent host genes are associated with a neuronal signature. Further, we find that HCMV immediate early protein, IE1, is both necessary and sufficient to induce these neuronal genes, providing a mechanism of activation. Together, our findings demonstrate that HCMV hijacks a dormant neuronal secretory pathway through chromatin manipulation for efficient virion maturation.},
}

Humans
*Cytomegalovirus/physiology/genetics/metabolism
*Immediate-Early Proteins/metabolism/genetics
Histones/metabolism/genetics
*Neurons/metabolism/virology
*Cytomegalovirus Infections/virology/genetics/metabolism
*Virus Assembly/genetics
Host-Pathogen Interactions/genetics
Gene Expression Regulation

@article {pmid40779734,
year = {2025},
author = {Wang, L and Xu, H and Simons, RL and Beach, SRH and Lei, MK and Ong, ML and Philibert, RA and Mielke, MM and Sun, Y and Lu, Y and Chiang, CWK and Darst, BF and Ye, K},
title = {Associations of Longitudinal Changes in Blood Biomarkers of Dementia With the Proportion of Genetically Inferred African Ancestry.},
journal = {Neurology},
volume = {105},
number = {5},
pages = {e213976},
doi = {10.1212/WNL.0000000000213976},
pmid = {40779734},
issn = {1526-632X},
mesh = {Aged ; Aged, 80 and over ; Female ; Humans ; Male ; Middle Aged ; Alzheimer Disease/blood/genetics ; Biomarkers/blood ; *Black or African American/genetics ; Cross-Sectional Studies ; *Dementia/blood/genetics/ethnology ; *Glial Fibrillary Acidic Protein/blood ; Longitudinal Studies ; *Neurofilament Proteins/blood ; *tau Proteins/blood ; },
abstract = {BACKGROUND AND OBJECTIVES: African American individuals have a higher risk of Alzheimer disease (AD) and related dementia (ADRD) than non-Hispanic White individuals. Some cross-sectional studies with self-reported race and ethnicity have reported racial differences in circulating ADRD biomarkers, including phosphorylated tau181 (p-Tau181), glial fibrillary acidic protein (GFAP), and neurofilament light (NfL). We aimed to examine the associations of genetically inferred African ancestry proportion with the longitudinal changes in these biomarkers and to evaluate the associations of previously identified ADRD-related genetic factors in European cohorts with these biomarkers in an African American cohort.

METHODS: This study used longitudinal data from the Family and Community Health Study, which was initiated in 1996, recruited and followed 889 African American families residing in Georgia and Iowa. Circulating p-Tau181, GFAP, and NfL were measured in serum samples collected in 2008 (wave 5) and 2019 (wave 8). Closely related individuals, genetically inferred to be third-degree relatives or closer, were excluded. Genetic ancestry proportions were inferred using the ADMIXTURE analysis. Multivariable regression analyses were performed to test the associations of African ancestry proportion with cross-sectional biomarker levels and their longitudinal changes over 11 years. We also tested the associations of selected genetic variants, polygenic scores, and APOE ε4 status with these biomarkers.

RESULTS: Our cross-sectional sample included 573 participants (mean age = 55.1 years; 69% female), whereas our longitudinal sample included 225 (57.2 years; 80% female). African ancestry proportion was not associated with cross-sectional biomarker levels but was inversely associated with the longitudinal change in p-Tau181 (β = -14.50 pg/mL, p = 0.02). The significant inverse association was robust to adjustment for age, sex, APOE ε4, socioeconomic status, physical activity, smoking, subjective cognitive decline, and various cardiovascular risk factors and comorbidities. Finally, genetic factors associated with AD and biomarkers in European cohorts were not associated with the 3 biomarkers in our African American cohort.

DISCUSSION: We found suggestive evidence that a higher African ancestry proportion is associated with an attenuated increase in the blood p-Tau181 level over time. More research is needed to characterize the longitudinal dynamics of ADRD biomarkers across ancestry and the driving biological or sociocultural factors.},
}

Aged
Aged, 80 and over
Female
Humans
Male
Middle Aged
Alzheimer Disease/blood/genetics
Biomarkers/blood
*Black or African American/genetics
Cross-Sectional Studies
*Dementia/blood/genetics/ethnology
*Glial Fibrillary Acidic Protein/blood
Longitudinal Studies
*Neurofilament Proteins/blood
*tau Proteins/blood

@article {pmid40779330,
year = {2025},
author = {Wang, Q and Duerr, A and Gao, F},
title = {Addressing Population Heterogeneity for HIV Incidence Estimation Based on Recency Test.},
journal = {Statistics in medicine},
volume = {44},
number = {18-19},
pages = {e70216},
doi = {10.1002/sim.70216},
pmid = {40779330},
issn = {1097-0258},
support = {R01AI177078/NH/NIH HHS/United States ; R01DA032106/NH/NIH HHS/United States ; R37AI029168/NH/NIH HHS/United States ; ISR-US-20-10990//Gilead/ ; },
mesh = {Humans ; *HIV Infections/epidemiology ; Incidence ; Cross-Sectional Studies ; Computer Simulation ; Models, Statistical ; },
abstract = {Cross-sectional HIV incidence estimation leverages recency test results to determine the HIV incidence of a population of interest, where recency test uses biomarker profiles to infer whether an HIV-positive individual was "recently" infected. This approach possesses an obvious advantage over the conventional cohort follow-up method since it avoids longitudinal follow-up and repeated HIV testing. In this manuscript, we consider the extension of cross-sectional incidence estimation to estimate the incidence of a different target population, addressing potential population heterogeneity. We propose a general framework that incorporates two scenarios: one when the target population is a subset of the population with cross-sectional recency testing data and the other with an external target population. In addition, we propose estimators to incorporate HIV subtypes, a special type of covariate that modifies the properties of recency tests, into our framework. Through simulation studies and a data application, we demonstrate the performance of the proposed methods. We conclude with a discussion on sensitivity analysis and future work to improve our framework.},
}

Humans
*HIV Infections/epidemiology
Incidence
Cross-Sectional Studies
Computer Simulation
Models, Statistical

@article {pmid40779102,
year = {2025},
author = {Ramos, M and Shepherd, L and Sheffield, NC and Mahmoud, A and Pagès, H and Wokaty, A and Righelli, D and Risso, D and Davis, S and Oh, S and Waldron, L and Morgan, M and Carey, V},
title = {Bioconductor's Computational Ecosystem for Genomic Data Science in Cancer.},
journal = {Methods in molecular biology (Clifton, N.J.)},
volume = {2932},
number = {},
pages = {1-46},
pmid = {40779102},
issn = {1940-6029},
mesh = {*Neoplasms/genetics ; *Genomics/methods ; Humans ; *Software ; *Computational Biology/methods ; Databases, Genetic ; *Data Science/methods ; },
abstract = {The Bioconductor project enters its third decade with over two thousand packages for genomic data science, over 100,000 annotation and experiment resources, and a global system for convenient distribution to researchers. Over 60,000 PubMed Central citations and terabytes of content shipped per month attest to the impact of the project on cancer genomic data science. This report provides an overview of cancer genomics resources in Bioconductor. After an overview of Bioconductor project principles, we address exploration of institutionally curated cancer genomics data such as TCGA. We then review genomic annotation and ontology resources relevant to cancer and then briefly survey analytical workflows addressing specific topics in cancer genomics. Concluding sections cover how new software and data resources are brought into the ecosystem and how the project is tackling needs for training of the research workforce. Bioconductor's strategies for supporting methods developers and researchers in cancer genomics are evolving along with experimental and computational technologies. All the tools described in this report are backed by regularly maintained learning resources that can be used locally or in cloud computing environments.},
}

*Neoplasms/genetics
*Genomics/methods
Humans
*Software
*Computational Biology/methods
Databases, Genetic
*Data Science/methods

@article {pmid40778818,
year = {2025},
author = {Neill, NJ and Satpathy, S and Krug, K and Meena, JK and Ramesh Babu, N and Calderon, C and Reed, D and Weber, MJ and Dobrolecki, LE and Lewis, A and Sallas, C and Anurag, M and Holloway, KR and Huang, C and Vasaikar, S and Cardenas, MF and Kim, BJ and Chan, DW and Avanessian, SC and Tyagi, S and Orellana, M and Mao, S and Li, H and Gong, F and Kurley, SJ and Meerbrey, KL and Olson, CM and Nair, A and Sun, T and Chung, HC and Bowling, EA and Wang, JH and Zhang, P and Xiao, P and Yang, D and Stossi, F and Polley, MC and Saltzman, AB and Mundt, F and Mani, DR and Gillette, MA and Hilsenbeck, SG and Miles, G and Gutierrez, C and Osborne, CK and Lin, CY and Gray, NS and Sun, J and Wheeler, DA and Perou, CM and Malovannaya, A and Lewis, MT and Zhang, B and Ellis, MJ and Carr, SA and Westbrook, TF},
title = {Integrative proteogenomics and forward genetics reveals a novel mitotic vulnerability in triple-negative breast cancer.},
journal = {Cancer discovery},
volume = {},
number = {},
pages = {},
doi = {10.1158/2159-8290.CD-23-1173},
pmid = {40778818},
issn = {2159-8290},
abstract = {Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer with few effective targeted therapies. Taxanes and other microtubule-targeting agents (MTAs) are frontline chemotherapies for TNBC; however, the molecular pathways that cause TNBC taxane sensitivity are largely unknown, preventing selection of taxane-responsive patients and development of more selective therapeutic strategies. In this study, we identified tumor-selective vulnerabilities in TNBC harboring inactivation of the tumor suppressor PTPN12 by integrating proteogenomic characterization and synthetic lethality screening. We discovered that PTPN12 inactivation drives mitotic defects through aberrant hyperactivation of the ubiquitin ligase complex APCFZR1, a critical regulator of the cell cycle. Consistent with the mitotic stress caused by PTPN12 inactivation in TNBC cell lines, tumors harboring loss of PTPN12 exhibit heightened sensitivity to taxane chemotherapy. Collectively, this data suggests that PTPN12 inactivation may drive chromosomal instability and favorable MTA response in TNBC; two prominent features of the disease with unclear mechanistic etiology.},
}

@article {pmid40778675,
year = {2025},
author = {Razzo, BM and Midha, S and Portuguese, AJ and Grajales-Cruz, AF and De Menezes Silva Corraes, A and Costello, P and Liu, Y and Sperling, AS and Nadeem, O and Dima, D and Banerjee, R and Cowan, AJ and Afrough, A and Anderson, LD and Lieberman-Cribbin, A and Kaur, G and Goyal, A and Atrash, S and Ferreri, CJ and Voorhees, PM and Pasvolsky, O and Lee, HC and Patel, KK and Julian, KL and Forsberg, PA and Herr, MM and Chhabra, S and Parrondo, RD and Lin, Y and Chen, A and Susanibar-Adaniya, SP and Khouri, J and Raza, S and Anwer, F and Vazquez-Martinez, M and Castaneda Puglianini, O and Sborov, DW and Davis, JA and Rossi, A and Shune, L and Bhurtel, J and Hwang, WT and Hansen, DK and Sidana, S and Garfall, AL and Richard, S},
title = {Real-World Experience with Teclistamab for Relapsed/Refractory Multiple Myeloma from the US Myeloma Immunotherapy Consortium.},
journal = {Blood cancer discovery},
volume = {},
number = {},
pages = {OF1-OF11},
doi = {10.1158/2643-3230.BCD-24-0354},
pmid = {40778675},
issn = {2643-3249},
support = {T32CA009615//Center for Cancer Research (CCR)/ ; //Leukemia and Lymphoma Society (LLS)/ ; },
abstract = {UNLABELLED: Teclistamab is an anti-CD3-/B-cell maturation antigen (BCMA) bispecific antibody approved for use in relapsed/refractory multiple myeloma. We undertook a retrospective study of postapproval, real-world outcomes with teclistamab in the US Multiple Myeloma Immunotherapy Consortium. Among 509 patients, 89% would have been ineligible for the MajesTEC-1 trial, primarily due to prior BCMA-directed therapy, cytopenias, or diminished performance status. Cytokine release syndrome occurred in 54% (1.4% grade ≥3) and immune effector cell-associated neurotoxicity syndrome in 11% (2.2% grade ≥3), with no fatal events. Infections occurred in 42% and contributed to death in 5%. Partial response (PR) or better was achieved in 53% and very good PR or better in 45%. With 10.1 months of median follow-up, the estimated median progression-free survival (PFS) was 5.8 months and 12-month overall survival was 61%. Independent predictors of less than very good PR and shorter PFS included BCMA-directed chimeric antigen receptor T-cell therapy in the previous 9 months, high disease burden, lymphopenia, and elevated ferritin.

SIGNIFICANCE: T cell-engaging bispecific antibodies such as teclistamab represent an important new treatment modality for multiple myeloma and other blood cancers. This study evaluates the real-world safety and efficacy of teclistamab, including its activity in populations not represented in the initial phase I/II study, and identifies clinical variables associated with treatment response.},
}

@article {pmid40778089,
year = {2025},
author = {Thonglert, K and Greer, MD and Schaub, SK and Bowen, SR and Menghini, AM and Nyflot, MJ and Grassberger, C and Tsai, J and Zaki, P and Kim, EY and Wong, T and Apisarnthanarax, S},
title = {Simultaneous integrated boost and protection proton beam therapy approach for hepatocellular carcinoma.},
journal = {Clinical and translational radiation oncology},
volume = {54},
number = {},
pages = {101008},
pmid = {40778089},
issn = {2405-6308},
abstract = {PURPOSE: Although simultaneous integrated boost and protection with proton beam therapy (SIB-PBT) facilitates tumor dose escalation while maintaining organ-at-risk (OAR) dose constraints, clinical outcomes are limited. This study assessed the safety and efficacy of using the SIB-PBT technique in hepatocellular carcinoma (HCC) patients.

METHODS: We reviewed 47 patients with HCC who underwent SIB-PBT between 2014-2021. The radiation dose ranged from 36-67.5 Gy(RBE) in 15 fractions. SIB-PBT was used for the following reasons: minimize high-dose exposure to organs-at-risk (OARs) (n = 22, 47 %), treat targets with different dose levels (n = 6, 13 %), or both (n = 19, 40 %). Survival, local control, and toxicities were assessed using Kaplan-Meier, Fine-Gray cumulative incidence, and descriptive statistics, respectively.

RESULTS: Forty-one patients (87 %) had tumors located ≤2 cm from luminal gastrointestinal (GI) OARs. The median tumor diameter was 9.2 cm (range, 2.0-21.5 cm). The median EQD2 D50%, D95% and D99% of gross tumor volume were 79.8 (range, 51.1-85.9), 66.7 (range, 36.9-84.6) and 50.2 (range, 34.1-83.6) Gy(RBE)10, respectively. Most patients (91 %) received a D0.5 cc of <45 Gy(RBE) to luminal GI OARs. At a median follow-up of 22 months (range, 0.8-77.0 months), the 2-year cumulative incidence of local failure was 12 %. The 2-year progression-free survival and overall survival rates were 12 % (95 % CI 4.7-23.4 %), and 49 % (95 % CI, 33.2-63.2 %), respectively. One patient experienced grade 3 acute nausea/vomiting. No GI bleeding/ulcers or grade 4 + toxicity were observed. CP + 2 occurred in 5 patients.

CONCLUSION: SIB-PBT enables OAR protection along with heterogeneous tumor dose escalation and is a safe and effective treatment for HCC tumors.},
}

@article {pmid40766464,
year = {2025},
author = {Holland, M and Ahmed, M and Young, JM and McFadyen, S and Drurey, JR and Ostrowski, EA and Levin, TC},
title = {Hypermutable hotspot enables the rapid evolution of self/non-self recognition genes in Dictyostelium.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {40766464},
issn = {2692-8205},
support = {R01 GM074108/GM/NIGMS NIH HHS/United States ; R35 GM150681/GM/NIGMS NIH HHS/United States ; },
abstract = {Cells require highly polymorphic receptors to perform accurate self/non-self recognition. In the amoeba Dicytostelium discoideum, polymorphic TgrB1 & TgrC1 proteins are used to bind sister cells and exclude cheaters, but it remains unknown how cells continually generate this extreme genetic diversity. Here, we created a collection of chromosome-length, whole genome sequences from 10 Dictyostelium discoideum isolates and sister species to understand the evolution of the large tgr gene family. Our dataset includes AX2-214, a widely used D. discoideum lab strain, as well as complete genomes for two Chlamydia-like endosymbionts harbored within amoebae. We find that tgrB1 and C1 lie in a hypermutational hotspot, with haplotypes that undergo repeated intralocus recombination, duplications, transpositions, and inversions. These structural dynamics are highly localized adjacent to tgrB and C, resulting in the gain and loss of dozens of genes. The tgrBC genes themselves frequently duplicate and recombine, leading to the rapid generation of unique tgrBC repertoires. In the broader tgr gene family, some genes (e.g. tgrN) are single copy and syntenic across all the genomes, whereas others (e.g. tgrA) prolifically duplicate at similar rates to Dictyostelium transposons. Thus, the tgr genes are among the most rapidly evolving families genome-wide. We propose that the intense diversification within the tgrBC locus can help explain how these genes acquire such extreme levels of polymorphism, with parallels to the MHC immune genes in mammals and other allorecognition systems. This collection of amoeba genomes is also an ideal dataset for comparative genomics and molecular evolution in Amoebozoa.},
}

@article {pmid40766138,
year = {2025},
author = {Harmon, LM and Hattig, ZS and Huang, YP and Beckford, C and Farrar, J and Pollard, JA and Zarnegar-Lumley, S and Ma, X and Ries, RE and Meshinchi, S and Godley, LA and Triche, TJ},
title = {Germline Variant Burden Warrants Universal Genetic Testing in Pediatric Myeloid Leukemia.},
journal = {medRxiv : the preprint server for health sciences},
volume = {},
number = {},
pages = {},
pmid = {40766138},
support = {F99 CA294248/CA/NCI NIH HHS/United States ; R03 CA290259/CA/NCI NIH HHS/United States ; },
abstract = {Causal germline genetic variants are frequently detected in young (under age 40) patients presenting with myelodysplastic syndromes (MDS) or bone marrow failure (BMF), where progression to acute myeloid leukemia (AML) contributes substantially to mortality in these patients. We reasoned that de novo pediatric AML, which shares clinical and biological characteristics, might also share germline genetic risk variants. We investigated germline variants in a large cohort (n=365) of pediatric AML patients with whole-genome sequencing (WGS), 29 with matched marrow-derived stromal cells, and 336 with matched remission marrow samples. Variants were deemed "likely germline" based on variant allele frequency (VAF) across available samples. Following American College of Medical Genetics and Genomics (ACMG) and Association of Molecular Pathology (AMP) guidelines, we annotated pathogenic/likely pathogenic (P/LP) variants in 555 genes linked to leukemia risk. P/LP variants were identified in 5.5% (95% CI: (3.3%,7.9%)) of patients in genes linked to familial myeloid malignancy and an additional 3.3% (95% CI: (1.6%,5.2%)) of patients in genes conferring risk to lymphoid malignancy or solid tumors. The large cohort enabled burden testing, which we employed by comparing loss-of-function variants between patients and 2504 control subjects from the 1000 Genomes Project. There was a 6.9-fold (95% CI: (3.1,14.9)) increase in loss-of-function variants in genes implicated in myeloid malignancy risk, a 2.4-fold (95% CI: (1.7,3.2)) increase in candidate risk genes, and a 1.6-fold (95% CI: (1.1,2.3)) increase in randomly-selected genes. We then assembled cohorts totaling 4,622 pediatric and adult patients with acute leukemia or MDS from 10 published studies, and compared P/LP variant burdens across age and diagnosis. The prevalence of germline variants in myeloid malignancies across age groups exceeds 5% consistently and with high confidence. Because the National Comprehensive Cancer Network recommends that all patients receive screening if their pre-test germline variant probability exceeds 5%, our results support germline genetic variant testing as an integral component of diagnostic work-up for myeloid malignancies, including donor selection for stem cell transplantation.},
}

@article {pmid40775447,
year = {2025},
author = {Chang, YH and Bresnahan, ST and Taylor Head, S and Harrison, TA and Yu, Y and Huff, CD and Pasaniuc, B and Lindström, S and Bhattacharya, A},
title = {Isoform-level analyses of 6 cancers uncover extensive genetic risk mechanisms undetected at the gene-level.},
journal = {British journal of cancer},
volume = {},
number = {},
pages = {},
pmid = {40775447},
issn = {1532-1827},
support = {CA293419//U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)/ ; },
abstract = {BACKGROUND: Integrating genome-wide association study (GWAS) and transcriptomic datasets can identify mediators for genetic risk of cancer. Traditional methods often are insufficient as they rely on total gene expression measures and overlook alternative splicing, which generates different transcript-isoforms with potentially distinct effects.

METHODS: We integrate multi-tissue isoform expression data from the Genotype Tissue-Expression Project with GWAS summary statistics (all N > ~20,000 cases) to identify isoform- and gene-level associations with six cancers (breast, endometrial, colorectal, lung, ovarian, prostate) and six related cancer subtype classifications (N = 12 total).

RESULTS: Directly modeling isoforms using transcriptome-wide association studies (isoTWAS) significantly improves discovery of genetic associations compared to gene-level approaches, identifying 164% more significant associations (6163 vs. 2336) with isoTWAS-prioritized genes enriched 4-fold for evolutionarily-constrained genes. isoTWAS tags transcriptomic associations at 52% more independent GWAS loci across the six cancers. Isoform expression mediates an estimated 63% greater proportion of cancer risk SNP heritability compared to gene expression. We highlight several isoTWAS associations that demonstrate GWAS colocalization at the isoform level but not at the gene level, including CLPTM1L (lung cancer), LAMC1 (colorectal), and BABAM1 (breast).

CONCLUSION: These results underscore the importance of modeling isoforms to maximize discovery of genetic risk mechanisms for cancers.},
}

@article {pmid40774832,
year = {2025},
author = {Sheppard, DP and Psutka, SP and Hunter, H},
title = {Prehabilitation: Cognitive considerations.},
journal = {Urologic oncology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.urolonc.2025.06.017},
pmid = {40774832},
issn = {1873-2496},
abstract = {Urologic cancers and their treatments confer risk for cognitive dysfunction, which can have significant impact on quality of life and overall well-being during survivorship. Current approaches to ameliorate cognitive dysfunction in urologic and other cancers emphasize post-treatment rehabilitation methods of cognitive compensatory strategies or training-based restorative practice. Prehabilitation involves supporting resilience prior to treatment initiation and has demonstrated promise for supporting various clinical outcomes in urologic cancers. However, there is a paucity of studies that have utilized prehabilitation approaches to support cognitive functioning, and few existing prehabilitation studies in urologic cancers have examined cognitive functioning endpoints. The objectives of this literature review are to describe: (1) common cognitive findings in urologic cancers, (2) contemporary evidence for cognitive rehabilitation in cancer populations, (3) existing cognitive prehabilitation approaches that have yet to be implemented in urologic cancers, and (4) prehabilitation efforts addressing physical activity, nutrition, and mood/mental health that could be used in the future to support and study cognitive endpoints. A model for cognitive prehabilitation is proposed to guide future research in urologic cancers.},
}

@article {pmid40774326,
year = {2025},
author = {Triplette, M and Aldrich, MC},
title = {Lung Cancer in Special Populations.},
journal = {Seminars in respiratory and critical care medicine},
volume = {},
number = {},
pages = {},
doi = {10.1055/a-2657-9494},
pmid = {40774326},
issn = {1098-9048},
abstract = {Lung cancer is the leading cause of cancer deaths worldwide, claiming more lives than other age-related and screen-detectable cancers. Cigarette smoking remains the most important risk factor. However, despite common perceptions, risk is not related solely to cigarette smoking. Several vulnerable and special populations experience a disproportionate burden of lung cancer, often complicated by overlapping medical issues, diagnostic challenges, and treatment limitations. This review highlights four populations (people with HIV, persons who are immunocompromised, lung cancer in nonsmoking women, and individuals with interstitial lung disease [ILD]) who experience unique risks that impact early detection, diagnosis, and management of lung cancer. Three of these populations are frequently underrepresented in clinical trials, yet they may be at elevated risk due to chronic inflammation, immune dysregulation, or previous medical therapies. Individuals with HIV have a significantly increased incidence of lung cancer, often presenting at younger ages and with more advanced disease. Similarly, patients who are immunocompromised following organ or stem cell transplantation are at heightened risk due to prolonged immune dysfunction and prior exposures to toxic therapies. Individuals with ILD, especially idiopathic pulmonary fibrosis (IPF), have an increased risk of developing lung cancer, which is challenging to detect with imaging given architectural distortion and even more challenging to treat given limited pulmonary reserve. We also highlight women, as there has been a striking trend of rising incidence of lung cancer among women worldwide, particularly among those who have never smoked. The intersection of these risks with traditional lung cancer risk factors like tobacco smoking highlights a critical need for increased awareness, improved risk stratification, and adapted screening strategies that take these complexities into account. In this review, we explore the epidemiology, clinical presentation, and early detection and management challenges unique to each population, underscoring the necessity of precision approaches to support individualized care.},
}

@article {pmid40773733,
year = {2025},
author = {Minalga, B and Feuer, C},
title = {Addressing Transgender Erasure in HIV Clinical Trials: The Scorecard for Transgender and Gender-Diverse Inclusion.},
journal = {American journal of public health},
volume = {},
number = {},
pages = {e1-e10},
doi = {10.2105/AJPH.2025.308134},
pmid = {40773733},
issn = {1541-0048},
abstract = {We sought to offer a structured framework for evaluating transgender and gender-diverse (TGD) inclusion in HIV clinical trials, with actionable criteria for trial design and conduct, and to quantify and characterize TGD inclusion in pivotal HIV studies as supporting evidence of the need for this framework. We devised a tool (scorecard) consisting of 14 scoreable indicators for TGD-responsive HIV research with input from global TGD communities. We tested the scorecard in a cross-sectional review of 41 randomized controlled HIV biomedical efficacy trials to measure TGD responsiveness. Studies were selected to represent the spectrum of groundbreaking HIV therapeutic and prevention studies enrolling participants in countries around the world from 1991 to 2023. We found that TGD individuals represent a reported 2532 (1.4%) of 178 893 participants in the selected HIV clinical trials. Scorecard indicators reveal a dearth of HIV research responsive to the needs of TGD communities. The lack of TGD representation in HIV clinical trials indicates a historical erasure of TGD communities with potential public health consequences. The scorecard might guide future HIV research to be more responsive to the needs of TGD people. (Am J Public Health. Published online ahead of print August 7, 2025:e1-e10. https://doi.org/10.2105/AJPH.2025.308134).},
}

@article {pmid40773709,
year = {2025},
author = {Yuen, K and Meagher, M and Mercer, J and Yilma, B and Stoppler, M and Fragkogianni, S and Mar, N and Kalebasty, AR and Gupta, S and Grivas, P and Bagrodia, A and Mckay, R and Stewart, T and Salmasi, A},
title = {Comprehensive Comparison of Somatic, Germline, and Immune Cell Profiles in Upper Tract and Bladder Urothelial Carcinoma.},
journal = {JCO precision oncology},
volume = {9},
number = {},
pages = {e2500289},
doi = {10.1200/PO-25-00289},
pmid = {40773709},
issn = {2473-4284},
mesh = {Humans ; *Urinary Bladder Neoplasms/genetics/immunology/pathology ; Retrospective Studies ; Female ; Male ; Aged ; Middle Aged ; Microsatellite Instability ; *Carcinoma, Transitional Cell/genetics/immunology ; Germ-Line Mutation ; Aged, 80 and over ; Mutation ; DNA Mismatch Repair ; *Ureteral Neoplasms/genetics/immunology ; },
abstract = {PURPOSE: Molecular characterization of anatomically distinct urothelial carcinoma in the upper tract (UTUC) and bladder (UCB) has been challenging because of the rarity of UTUC. However, recent advances in real-world data curation have facilitated the generation of larger UTUC cohorts. In this study, we investigated the somatic, germline, and immunologic landscapes of UTUC compared with UCB.

METHODS: From the Tempus Database, we retrospectively analyzed 505 UTUC and 2,416 UCB cases. Tumors were sequenced using Tempus xT DNA and xR RNA assays. Pathogenic somatic mutations, immune cell infiltration, tumor mutational burden (TMB), PD-L1, microsatellite instability (MSI), and mismatch repair (MMR) were evaluated. Potential germline alterations were assessed in 46 genes for patients with tumor/normal matched sequencing (UTUC, n = 285; UCB, n = 1,359).

RESULTS: Alterations in TERT, TP53, RB1, ERBB2, and CDKN1A were more frequent in UCB, whereas KMT2D, FGFR3, CDKN2B, KRAS, and MYC were more frequent in UTUC. Germline variants were found in 4.8% of UCB and 5.6% of UTUC, with trends toward higher Lynch syndrome-associated gene alterations (MLH1, MSH2, MSH6, PMS2) in UTUC (0.6% v 1.8%, P = .059). The prevalence of TMB ≥10 mut/Mb was higher in UCB (17% v 11%, P < .001). UCB had higher PD-L1 positivity (P = .013), whereas UTUC had more MSI-high (UTUC = 3.2% v UCB = 1%, P = .001) and MMR-deficient (P = .020) cases. CD4[+] and regulatory T-cell infiltrates were similar in both.

CONCLUSION: By comprehensive molecular characterization of UC, we observed distinct genomic alterations and tumor microenvironment patterns in UTUC and UCB. Further research is warranted to elucidate the clinical implications of these findings. We compared the genetic and immune features of upper tract and bladder cancers. Our study found key differences that could affect treatment decisions, such as specific gene changes and immune markers. These insights may help doctors personalize therapies and improve patient care.},
}

Humans
*Urinary Bladder Neoplasms/genetics/immunology/pathology
Retrospective Studies
Female
Male
Aged
Middle Aged
Microsatellite Instability
*Carcinoma, Transitional Cell/genetics/immunology
Germ-Line Mutation
Aged, 80 and over
Mutation
DNA Mismatch Repair
*Ureteral Neoplasms/genetics/immunology

@article {pmid40773210,
year = {2025},
author = {Yeh, JM and Ward, ZJ and Leisenring, W},
title = {Childhood Cancer Survivor Risk Estimates and Age, Overdispersion, and Social Context-Reply.},
journal = {JAMA oncology},
volume = {},
number = {},
pages = {},
doi = {10.1001/jamaoncol.2025.2424},
pmid = {40773210},
issn = {2374-2445},
}

@article {pmid40772965,
year = {2025},
author = {Venkatesh, H and Fong, L},
title = {CD4+ T cell dysfunction in cancer.},
journal = {The Journal of experimental medicine},
volume = {222},
number = {9},
pages = {},
doi = {10.1084/jem.20241417},
pmid = {40772965},
issn = {1540-9538},
support = {R35CA253175/NH/NIH HHS/United States ; },
mesh = {Humans ; *Neoplasms/immunology/therapy/pathology ; *CD4-Positive T-Lymphocytes/immunology ; Animals ; CD8-Positive T-Lymphocytes/immunology ; Immunotherapy ; },
abstract = {While the importance of CD8+ T cells in successful cancer immunotherapy is well-established, CD4+ T cells are increasingly recognized as key mediators of effective anti-tumor immunity. However, the mechanisms underlying the functional impairment of CD4+ T cells in tumors are not as well characterized as in CD8+ T cells. In this review, we will explore how CD4+ T cells are altered in tumor-bearing hosts, compare these changes to those observed in CD8+ T cells, and discuss how these changes impact tumor control. Approaches that counteract functional impairment in tumor-reactive CD4+ T cells may further enhance the efficacy of cancer immunotherapy.},
}

Humans
*Neoplasms/immunology/therapy/pathology
*CD4-Positive T-Lymphocytes/immunology
Animals
CD8-Positive T-Lymphocytes/immunology
Immunotherapy

@article {pmid40772634,
year = {2025},
author = {Cohen, SA and Aushev, VN and Laliotis, G and Jabbal, IS and Nagarajan, A and Wang, C and Fakih, M and Sharif, S and Alyunis, F and Tejani, MA and Alqahtani, A and Marshall, J and Chang, J and Botta, G and Manage, K and George, GV and Sharma, S and Malhotra, M and Chandana, S and Mehler, S and Somer, BG and Babadi, E and Wu, C and Hanna, D and Chidharla, A and Kasi, A and Vosoughi, E and Dayyani, F and Pedersen, K and Briski, RE and Azzi, G and Katiyar, V and Chan, A and Sharma, V and Shreenivas, A and Chakrabarti, S and Fuqua, J and Malla, M and Polite, B and Bent, AH and Rabinowitz, M and Jurdi, A and Liu, MC and Aleshin, A and Kopetz, S},
title = {Real-world Monitoring of ctDNA Reliably Predicts Cancer Recurrence and Treatment Efficacy in Patients with Resected Stages I-III Colon Cancer.},
journal = {Annals of surgery},
volume = {},
number = {},
pages = {},
doi = {10.1097/SLA.0000000000006887},
pmid = {40772634},
issn = {1528-1140},
abstract = {OBJECTIVE: In this study, we evaluate the utility of ctDNA analysis in a large cohort of patients for whom ctDNA testing was ordered commercially with real-world application.

SUMMARY BACKGROUND DATA: Circulating tumor DNA (ctDNA) has emerged as a prognostic and predictive biomarker for assessing post-surgical molecular residual disease (MRD) and response to treatment.

METHODS: A real-world data analysis was performed using commercial ctDNA testing (SignateraTM) from patients (N=795, n=5,971 plasma samples) with stage I-III colon cancer treated at multiple US institutions. The association of ctDNA detection within the MRD window, during surveillance, and the impact of ACT was correlated with patient outcomes.

RESULTS: ctDNA-positive patients during the MRD window and surveillance showed significantly shorter DFS compared to ctDNA-negative patients (hazard ratio (HR): 9.85, P<0.0001; HR: 26.91, P<0.0001). Multivariate analysis of the MRD window revealed ctDNA-positivity as the most significant factor associated with inferior DFS (adjHR: 7.7, P<0.001). MRD-positive patients who received ACT showed improved DFS compared to patients observed post-surgery (adjHR: 6.1, FDR adj P=0.0007). No ACT benefit was observed in MRD-negative patients (adj HR: 1.20, FDR adj P=0.768). On evaluating ctDNA dynamics from MRD to surveillance, patients who remained ctDNA-positive or converted from negative to positive showed a significantly inferior DFS (HR: 34.40, P<0.0001; HR: 13.65, P<0.0001) compared to persistently ctDNA-negative patients.

CONCLUSIONS: Postsurgical ctDNA detection is prognostic of relapse and potentially predictive of ACT benefit in patients with resectable colon cancer, which may enable personalized surveillance, intervention, and/or trial options, ultimately improving patient outcomes.},
}

@article {pmid40772450,
year = {2025},
author = {Webster, RT and Mirzaei, S and Bhatia, S and Srivastava, DK and Mostoufi-Moab, S and Dixon, SB and Chow, EJ and Armstrong, GT and Krull, KR and van der Plas, E},
title = {Diabetes mellitus and neurocognition: A report from the Childhood Cancer Survivor Study.},
journal = {Cancer},
volume = {131},
number = {16},
pages = {e70011},
doi = {10.1002/cncr.70011},
pmid = {40772450},
issn = {1097-0142},
support = {P30 CA021765/CA/NCI NIH HHS/United States ; U24 CA055727/CA/NCI NIH HHS/United States ; //American Lebanese Syrian Associated Charities/ ; },
mesh = {Humans ; Female ; Male ; *Cancer Survivors/psychology ; Adult ; *Neoplasms/complications/therapy ; Cardiovascular Diseases/epidemiology ; Child ; *Diabetes Mellitus/epidemiology ; Adolescent ; Young Adult ; Risk Factors ; *Cognitive Dysfunction/epidemiology/etiology ; },
abstract = {BACKGROUND: The objective of this research was to examine associations between diabetes mellitus (DM) and neurocognitive impairment in survivors of childhood cancer while exploring mechanistic associations with treatment exposures and moderating associations with cardiovascular disease (CVD) and risky lifestyle factors.

METHODS: Survivors of the Childhood Cancer Survivor Study (N = 16,196; mean ± standard deviation age, 32.9 ± 7.9 years; 50.2% female; N = 615 with DM) self-reported neurocognitive functioning, risky drinking, physical inactivity, and tobacco use. Medical data were collected from chart review. Multivariable regression determined the association of DM with neurocognitive impairment while adjusting for relevant treatment exposures. Interactions between DM and treatment, risky lifestyle, and cardiovascular predictors on impairment were explored. Path analysis was used to examine the effects of treatment exposures through DM and CVD on impairment. Among survivors with DM, multivariable regressions examined predictors of neurocognitive change over time (mean, 11.21 years).

RESULTS: Survivors with DM had an increased risk of impairment relative to survivors without DM (task completion: odds ratio [OR], 1.5; 95% confidence limits [CI], 1.2-1.9; emotion regulation: OR, 1.4; 95% CI, 1.1-2.0; and organization: OR, 1.5; 95% CI, 1.1-2.0). The effects of cranial radiation on neurocognition were mediated by DM, including task completion (β = 0.02), emotion regulation (β = 0.02), memory (β = 0.01), and organization (β = 0.02; all p < .01). Among survivors with DM, CVD was associated with declines in task completion (estimate = 0.44; p < .01) and organization (estimate = 0.27; p = .03).

CONCLUSIONS: Survivors with DM are at increased risk of neurocognitive impairment. Although CVD did not exacerbate concurrent risk for impairment, it was associated with a decline in neurocognitive functioning over time in survivors with DM. Preventing/managing CVD in survivors with DM could mitigate additional neurocognitive decline.},
}

Humans
Female
Male
*Cancer Survivors/psychology
Adult
*Neoplasms/complications/therapy
Cardiovascular Diseases/epidemiology
Child
*Diabetes Mellitus/epidemiology
Adolescent
Young Adult
Risk Factors
*Cognitive Dysfunction/epidemiology/etiology

@article {pmid40770768,
year = {2025},
author = {Wu, L and Zhu, X and Liu, Y and Zhao, D and Yu, BC and Wei, Z and Lin, X and Qi, LS},
title = {Identification of replicative aging and inflammatory aging signatures via whole-genome CRISPRi screens.},
journal = {Genome biology},
volume = {26},
number = {1},
pages = {233},
pmid = {40770768},
issn = {1474-760X},
support = {R21AG077193//NIH National Institute of Aging/ ; no. 2046650//the National Science Foundation CAREER award/ ; },
mesh = {Humans ; *Cellular Senescence/genetics ; *Inflammation/genetics ; *Aging/genetics ; Genome-Wide Association Study ; Mesenchymal Stem Cells/metabolism/cytology ; *CRISPR-Cas Systems ; Genomics ; Clustered Regularly Interspaced Short Palindromic Repeats ; Genome, Human ; },
abstract = {BACKGROUND: Aging is a major risk factor for chronic diseases and cancer. Cellular aging, particularly in adult stem cells, offers a high-throughput framework for dissecting the molecular mechanisms of aging.

RESULTS: We perform multiple genome-wide CRISPR interference (CRISPRi) screenings in human primary mesenchymal stem cells derived from adipose tissue during either replicative senescence or inflammation-induced senescence. These screens reveal distinct sets of potential novel regulators specific to each senescence pathway. Combining our perturbation-based functional genomic data with 405 genome-wide association study datasets, including 50 aging-related studies, we find that the inflammatory aging signatures identified from CRISPRi screenings are significantly associated with diverse aging processes, suggesting novel molecular signatures for analyzing and predicting aging status and aging-related disease.

CONCLUSIONS: The signatures verified through comprehensive functional genomics and genetic analyses may provide new targets for modulating the aging process and enhancing the quality of cell therapy products.},
}

Humans
*Cellular Senescence/genetics
*Inflammation/genetics
*Aging/genetics
Genome-Wide Association Study
Mesenchymal Stem Cells/metabolism/cytology
*CRISPR-Cas Systems
Genomics
Clustered Regularly Interspaced Short Palindromic Repeats
Genome, Human

@article {pmid40766494,
year = {2025},
author = {Shih, RM and Arimura, Y and Konishi, HA and Funabiki, H},
title = {IMPACTS OF DNA METHYLATION ON H2A.Z DEPOSITION AND NUCLEOSOME STABILITY.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {40766494},
issn = {2692-8205},
abstract = {In eukaryotes with DNA methylation, the histone variant H2A.Z and DNA methylation are maintained in mutually exclusive sections of the genome. How this antagonism is established, however, remains an open question. Here, we examined the impacts of DNA methylation on both the intrinsic stability of H2A.Z nucleosomes and chaperone-mediated H2A.Z deposition. Cryo-EM and endonuclease accessibility analyses show that H2A.Z nucleosomes with methylated DNA are more open and accessible compared to their unmethylated counterparts. In Xenopus laevis, H2A.Z preferentially associates with unmethylated DNA in both the fibroblast cell line XTC-2 and sperm pronuclei formed in the transcriptionally silent egg extract. The proportion of H2A.Z that colocalizes with methylated DNA, however, is higher in sperm pronuclei than in XTC-2. By monitoring nucleosome assembly on synthetic DNA constructs in Xenopus egg extracts, we find that the H2A.Z bias for unmethylated substrates is dependent on the SRCAP complex, the major H2A.Z deposition chaperone. Consistently, recruitment of the SRCAP complex to DNA is suppressed by DNA methylation. Altogether, we propose that the SRCAP complex is the major determinant for preferential H2A.Z enrichment on unmethylated DNA, whereas DNA methylation destabilizes DNA wrapping in H2A.Z-containing nucleosomes.},
}

@article {pmid40769720,
year = {2025},
author = {Nicoletti, C and Massenet, J and Pintado-Urbanc, AP and Connor, LJ and Nicolau, M and Sundar, S and Xu, M and Schmitt, A and Zhang, W and Fang, Z and Chan, TCI and Wang, YX and Tapscott, SJ and Cheung, TH and Simon, MD and Caputo, L and Puri, PL},
title = {MYOD represses gene expression from non-E-box motifs.},
journal = {Genes & development},
volume = {},
number = {},
pages = {},
doi = {10.1101/gad.352708.125},
pmid = {40769720},
issn = {1549-5477},
abstract = {We report here on the identification of a previously unrecognized property of MYOD as a repressor of gene expression via E-box-independent chromatin binding during the process of somatic cell trans-differentiation into skeletal muscle. When ectopically expressed in proliferating human fibroblasts or endogenously induced in activated muscle stem cells (MuSCs), MYOD was detected at accessible regulatory elements of expressed genes, invariably leading to reduced chromatin accessibility and gene repression. At variance with conventional E-box-driven increased chromatin accessibility and H3K27 acetylation at previously silent loci of MYOD-activated genes, MYOD-mediated chromatin compaction and repression of transcription was associated with high occurrence of non-E-box motifs and did not lead to reduced levels of H3K27ac but coincided with reduced levels of H4 acetyl-methyl lysine modification (Kacme). Using MYOD mutants, we dissected the molecular mechanism of MYOD-mediated repression, whereby repression of mitogen-responsive and growth factor-responsive genes occurred via promoter binding, which requires a conserved domain within the first helix; conversely, repression of cell of origin/alternative lineage genes occurred via binding and decommissioning of distal regulatory elements such as superenhancers (SEs), required either the N-terminal activation domain or the two chromatin remodeling domains, and coincided with reduced strength of CTCF-mediated chromatin interactions. These data extend MYOD biological properties beyond the current dogma that restricts MYOD function to a monotone transcriptional activator. They also reveal an unprecedented functional versatility arising from alternative chromatin recruitment through E-box or non-E-box sequences, whereby genetic determinants dictate differential usage of MYOD functional domains.},
}

@article {pmid40769632,
year = {2025},
author = {Arter, ZL and Park, C and Deng, L},
title = {MET Tyrosine Kinase Domain Mutations in NSCLC: Expanding the Landscape of Acquired Resistance in Oncogene-Driven Tumors.},
journal = {Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer},
volume = {20},
number = {8},
pages = {998-1000},
doi = {10.1016/j.jtho.2025.05.001},
pmid = {40769632},
issn = {1556-1380},
}

@article {pmid40769150,
year = {2025},
author = {Durfey, SL and Kapnadak, SG and Pena, T and Willmering, MM and Godwin, JD and Teresi, ME and Heltshe, SL and Vo, AT and Villacreses, RA and Aliukonyte, I and Boyken, L and Stroik, MR and Morgan, SJ and Wang, GM and Betts, HL and Zhang, S and Goss, CH and Clancy, JP and Aitken, ML and Steele, C and Feder, AF and Esther, CR and Tiddens, HAWM and Woods, JC and Stoltz, DA and Singh, PK},
title = {Pseudomonas infections persisting after CFTR modulators are widespread throughout the lungs and drive lung inflammation.},
journal = {Cell host & microbe},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.chom.2025.07.009},
pmid = {40769150},
issn = {1934-6069},
abstract = {Cystic fibrosis transmembrane conductance regulator (CFTR) modulators improve the physiological defect causing cystic fibrosis, but the lungs of most people remain infected and inflamed. A leading hypothesis implicates damaged segments as the cause of persistent infection and predicts that mildly diseased segments within an individual's lungs will clear after treatment, whereas severely diseased segments will not. Our findings contradict this hypothesis. We used bronchoscopy to sample the least- and most-damaged lung segments in Pseudomonas aeruginosa (Pa)-infected individuals before modulators and returned to these same segments after 1.5 years. Surprisingly, we find an "all-or-none" infection clearance response: the most-diseased segments clear if any other lung segment in that person clears, and the least-diseased segments remain infected if others in that person do. Furthermore, neutrophilic inflammation completely resolves where Pa clears but remains elevated where Pa persists. These data indicate that post-modulator infections are not limited to severely diseased segments and that Pa infections drive persistent lung inflammation after modulators.},
}

@article {pmid40769077,
year = {2025},
author = {Goya, S and Nunley, EB and Longley, PC and Mathis, JR and Varela, CG and Kim, DY and Nurik, M and Naccache, SN and Greninger, AL},
title = {Phylodynamics of human metapneumovirus and evidence for a duplication-deletion model in G gene variant evolution.},
journal = {Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology},
volume = {180},
number = {},
pages = {105848},
doi = {10.1016/j.jcv.2025.105848},
pmid = {40769077},
issn = {1873-5967},
abstract = {BACKGROUND: In December 2024, human metapneumovirus (hMPV) gained global attention amid rising cases in Chinese hospitals, prompting a World Health, Organization (WHO) statement indicating case numbers remained within expected ranges. To assess whether a variant of public health concern was emerging and to examine global hMPV phylodynamics, we conducted a genomic surveillance study in western Washington State.

STUDY DESIGN: We sequenced hMPV genomes from inpatient and outpatient samples collected between 2021 and 2025 in western Washington State and constructed phylogenomic and phylodynamic trees.

RESULTS: We obtained 60 hMPV-A and 39 hMPV-B genomes, including 13 from November 2024 to January 2025. Following COVID-19 pandemic disruptions, hMPV seasonality returned to typical patterns after 2023. Genomic analysis showed hMPV-A predominance since 2022-23, with co-circulation of A2b1, A2b2, B1, and B2 sublineages. The A2b2 sublineage was most prevalent and all genomes carried a 111-nt G gene duplication. Phylogenetic evidence suggests the 111-nt variant evolved from a prior 180-nt duplication via a 69-nt deletion rather than through independent duplication events. Most sublineages showed multiple co-circulating clades, except A2b1. Phylodynamics showed recovery of global diversity after pandemic-related declines and a higher evolutionary rate in hMPV-A compared to hMPV-B. No distinct evolutionary features of heightened concern were detected.

CONCLUSIONS: Despite recent concerns, our findings indicate that hMPV circulation in, the USA follows expected seasonal patterns, with ongoing introductions of diverse viral variants from preexisting sublineages rather than emergence of a novel variant. Continued genomic surveillance is essential, particularly as vaccine development progresses.},
}

@article {pmid40767935,
year = {2025},
author = {Brennan, MA and Plichta, JK and Rozenblit, M and Flanagan, MR},
title = {Surgeon Attitudes on the Management of de novo Oligometastatic Breast Cancer.},
journal = {Annals of surgical oncology},
volume = {},
number = {},
pages = {},
pmid = {40767935},
issn = {1534-4681},
}

@article {pmid40767528,
year = {2025},
author = {Lee, HJ and Gulati, R and Sayar, E and Patel, RA and Itagi, P and Richards, HM and Persse, T and Arora, S and Coleman, I and Adil, M and Schuster, SL and Shokri, F and Wright, JL and Yu, EY and True, LD and Chambers, M and Hawley, JE and Cheng, HH and Schweizer, MT and Grivas, P and Nelson, PS and Montgomery, RB and Hsieh, AC and Vakar-Lopez, F and Morrissey, C and Lam, HM and Ha, G and Tretiakova, MS and Haffner, MC and Raychaudhuri, R},
title = {Patterns of HER2 Expression in Metastatic Prostate and Urothelial Cancers: Implications for HER2-Targeted Therapies.},
journal = {Cancer research communications},
volume = {},
number = {},
pages = {},
doi = {10.1158/2767-9764.CRC-25-0069},
pmid = {40767528},
issn = {2767-9764},
abstract = {HER2 is an oncogenic driver in multiple cancers and a predictive biomarker for HER2-targeted therapies. While HER2-directed therapies like fam-trastuzumab deruxtecan (T-DXd) are approved for HER2-positive breast and other solid tumors, the landscape of HER2 expression in advanced prostate cancer (PC) and urothelial carcinoma (UC) remains inadequately characterized. We evaluated HER2 protein expression in metastatic PC and UC using a validated immunohistochemistry assay on tissue microarrays constructed from the University of Washington Tissue Acquisition Necropsy Program. HER2 expression was scored using standardized gastric cancer criteria. Genomic analysis of ERBB2 alterations was conducted on a subset of samples. HER2 expression heterogeneity and its relationship with other surface markers were also evaluated. In the PC cohort (n=52 patients, 1-19 tumors per patient), HER2 expression was low, with no 3+ expression observed and only 5 (10%) patients exhibiting 2+ expression. Low-level ERBB2 copy number gains was observed in some tumors but did not correlate with HER2 protein expression (p=0.2). In UC (n=20, 2-6 tumors per patient), HER2 expression was more frequent, with ≥2+ expression observed in 6 (30%) cases and 3+ expression observed in 3 (15%) cases in at least one tumor. UC samples showed less heterogeneity, with more consistent expression across metastases. HER2 over-expression is rare and heterogeneous in metastatic PC, limiting its utility as a therapeutic target. HER2 expression is more prevalent and uniform in UC. These findings underscore the importance of comprehensive HER2 assessment in advanced UC and suggests success of HER2-directed therapies in PC will require careful case selection.},
}

@article {pmid40765894,
year = {2025},
author = {Naifeh, JA and Edwards, ER and Bentley, KH and Gildea, SM and Kennedy, CJ and King, AJ and Kleiman, EM and Luedtke, A and Nassif, TH and Nock, MK and Sampson, NA and Zainal, NH and Stein, MB and Capaldi, VF and Ursano, RJ and Kessler, RC},
title = {Predicting suicide attempts among US Army soldiers using information available at the time of periodic health assessments.},
journal = {Nature. Mental health},
volume = {3},
number = {2},
pages = {242-252},
pmid = {40765894},
issn = {2731-6076},
support = {U01 MH087981/MH/NIMH NIH HHS/United States ; },
abstract = {The value of population screening for suicide risk remains unclear. The U.S. Army's annual medical examination, the Periodic Health Assessment (PHA), screens for suicidality and other mental and physical health problems. This 2014-2019 cohort study used PHA and Army administrative data (n=1,042,796 PHAs from 452,473 soldiers) to develop a model to predict 6-month nonfatal and fatal suicide attempts (SAs). The model was designed to establish eligibility for a planned high-risk SA prevention intervention. The PHA suicide risk screening questions had limited value, as 95% of SAs occurred among soldiers who denied suicidality. However, a simple lasso penalized regression model that included a wide range of administrative predictors had good test sample discrimination (0.794 [SE=0.009] area under the receiver operating characteristic curve) and calibration (0.0001 integrated calibration index). The 25% of soldiers at highest predicted risk accounted for 69.5% of 6-month SAs, supporting use of the model to target preventive interventions.},
}

@article {pmid40765672,
year = {2025},
author = {Heit, M and Cohen, SA},
title = {Contemporary Use of ctDNA for the Colorectal Surgeon.},
journal = {Clinics in colon and rectal surgery},
volume = {38},
number = {5},
pages = {334-338},
pmid = {40765672},
issn = {1531-0043},
abstract = {While advances in treatment and diagnostics have improved prognosis in colorectal cancer (CRC), room for advancement remains, highlighting the importance of improving tools for early detection and treatment guidance. Current national guidelines rely on stage-based treatment recommendations but fail to identify patients with lower stage disease who have a higher likelihood of recurrence or those for whom additional therapy may not be beneficial. Circulating tumor DNA (ctDNA) is an emerging noninvasive blood-based assay, which can inform cancer status as a single time point and/or longitudinal biomarker. ctDNA can be used for the diagnosis of cancer, detection of minimal/molecular residual disease, molecular profiling, and assessing treatment response. In patients for whom operative management is indicated, detectable ctDNA is associated with worse survival outcomes. This review highlights the expanding field of ctDNA in CRC, underlining pivotal data and areas with the need for more research that are key for colorectal surgeons to understand.},
}

@article {pmid40764319,
year = {2025},
author = {Wilcox-King, A and Wan, YH and Scharffenberger, SC and Chhan, CB and Davis, AR and Homad, LJ and Seydoux, E and MacPhee, KJ and Siddaramaiah, LK and Melo, M and Dosenovic, P and Irvine, DJ and Hyrien, O and Stamatatos, L and McGuire, AT},
title = {Priming VRC01-precursor B cells with non-envelope immunogens disfavors boosting with HIV-1 envelope.},
journal = {NPJ vaccines},
volume = {10},
number = {1},
pages = {185},
pmid = {40764319},
issn = {2059-0105},
support = {P01AI138212//National Institute of Allergy and Infectious Diseases/ ; P01AI138212//National Institute of Allergy and Infectious Diseases/ ; P01AI138212//National Institute of Allergy and Infectious Diseases/ ; P01AI138212//National Institute of Allergy and Infectious Diseases/ ; P01AI138212//National Institute of Allergy and Infectious Diseases/ ; P01AI138212//National Institute of Allergy and Infectious Diseases/ ; P01AI138212//National Institute of Allergy and Infectious Diseases/ ; P01AI138212//National Institute of Allergy and Infectious Diseases/ ; P01AI138212//National Institute of Allergy and Infectious Diseases/ ; P01AI138212//National Institute of Allergy and Infectious Diseases/ ; UM1AI144462//National Institute of Allergy and Infectious Diseases/ ; P01AI138212//National Institute of Allergy and Infectious Diseases/ ; P01AI138212//National Institute of Allergy and Infectious Diseases/ ; INV-032929/GATES/Gates Foundation/United States ; INV-032929/GATES/Gates Foundation/United States ; },
abstract = {VRC01-class antibodies are a genetically restricted class of antibodies capable of potently neutralizing diverse strains of HIV-1. Unmutated VRC01 precursors fail to recognize recombinant HIV-1 Envelope (Env) proteins, which necessitated the development of germline targeting vaccine immunogens capable of initiating VRC01-class B cell response. Among these, we developed an anti-idiotypic monoclonal antibody (ai-mAb)-derived VRC01 class targeting immunogen. Because it is distinct from Env, we speculated that the ai-mAb will selectively engage naive VRC01 class B cells while limiting B cell responses directed at off-target epitopes on Env during prime-boost regimens. Here, we evaluated the serum and B cell responses to ai-mAb prime/Env boost, and Env-prime/Env boost regimens in a murine adoptive transfer model where VRC01 precursor B cells are present at physiological levels. We found that the Env-Env regimen led to the greatest expansion of on-target VRC01 B cells, drove larger VRC01-class GC responses, and elicited higher titers of circulating antibodies despite also eliciting substantial off-target Env-specific responses. Single-cell sorting experiments revealed that the ai-mAb was driving off-track somatic mutations. IgG transfer experiments demonstrated that circulating off-target antibodies provide a positive feedback mechanism that potentiates on-target B cell responses. Collectively, the results suggest that non-Env immunogens are not ideal for priming VRC01-class B cells, where sequential boosting with Env will be required to drive maturation of neutralizing breadth.},
}

@article {pmid40764177,
year = {2025},
author = {Raychaudhuri, R and Khaki, AR and Redman, MW and Baker, KK and Ng, K and Chen, X and Mao, J and Woo, B and Lin, A and Hannochka, A and Conrad, N and Kahugu, M and Panlasigui, P and Haffner, MC and Hsieh, AC and Lam, HM and Vakar-Lopez, F and Yezefski, T and Schweizer, MT and Montgomery, RB and Yu, EY and Dash, A and Psutka, SP and Lin, DW and Schade, GR and Gore, JL and Wright, JL and Grivas, P},
title = {Neoadjuvant Pembrolizumab and Accelerated Methotrexate, Vinblastine, Doxorubicin, and Cisplatin in Nonurothelial Histologic Subtypes of Muscle-invasive Bladder Cancer: A Phase 2 Trial.},
journal = {European urology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.eururo.2025.07.002},
pmid = {40764177},
issn = {1873-7560},
abstract = {Muscle-invasive bladder cancer (MIBC) with histologic subtypes represents a clinical challenge because of poor responses to conventional therapies and under-representation in clinical trials. This single-center phase 2 trial evaluated the combination of neoadjuvant pembrolizumab and accelerated methotrexate, vinblastine, doxorubicin, and cisplatin (aMVAC) chemotherapy in patients with pure or predominant nonurothelial histologies. Seventeen patients were enrolled, with squamous differentiation being the most common variant. The primary endpoint, a pathologic complete response (pCR), was achieved in nine of 17 patients (53%), with an additional patient achieving ypTisN0 (downstaging rate 59%) and another achieving a clinical complete response. Grade ≥3 toxicities were observed in 47% of patients, primarily attributable to aMVAC. At median follow-up of 35 mo (range 11-48) the estimated 2-yr event-free survival (EFS) and overall survival rates were 64% (95% confidence interval 32-84%) and 79% (95% confidence interval 47-93%), respectively. Preliminary biomarker analysis did not reveal significant correlations between immune-cell subsets at baseline and pCR or EFS. These findings suggest that chemoimmunotherapy is a very promising approach for MIBC with histology subtypes. Larger studies are warranted to further refine therapeutic strategies.},
}

@article {pmid40763299,
year = {2025},
author = {Gauderman, WJ and Fu, Y and Queme, B and Kawaguchi, E and Wang, Y and Morrison, J and Brenner, H and Chan, A and Gruber, SB and Keku, T and Li, L and Moreno, V and Pellatt, AJ and Peters, U and Samadder, NJ and Schmit, SL and Ulrich, CM and Um, C and Wu, A and Lewinger, JP and Drew, DA and Mi, H},
title = {Pathway polygenic risk scores (pPRS) for the analysis of gene-environment interaction.},
journal = {PLoS genetics},
volume = {21},
number = {8},
pages = {e1011543},
doi = {10.1371/journal.pgen.1011543},
pmid = {40763299},
issn = {1553-7404},
abstract = {A polygenic risk score (PRS) is used to quantify the combined disease risk of many genetic variants. For complex human traits there is interest in determining whether the PRS modifies, i.e. interacts with, important environmental (E) risk factors. Detection of a PRS by environment (PRS x E) interaction may provide clues to underlying biology and can be useful in developing targeted prevention strategies for modifiable risk factors. The standard PRS may include a subset of variants that interact with E but a much larger subset of variants that affect disease without regard to E. This latter subset will dilute the underlying signal in former subset, leading to reduced power to detect PRS x E interaction. We explore the use of pathway-defined PRS (pPRS) scores, using state of the art tools to annotate subsets of variants to genomic pathways. We demonstrate via simulation that testing targeted pPRS x E interaction can yield substantially greater power than testing overall PRS x E interaction. We also analyze a large study (N = 78,253) of colorectal cancer (CRC) where E = non-steroidal anti-inflammatory drugs (NSAIDs), a well-established protective exposure. While no evidence of overall PRS x NSAIDs interaction (p = 0.41) is observed, a significant pPRS x NSAIDs interaction (p = 0.0003) is identified based on SNPs within the TGF-β/ gonadotropin releasing hormone receptor (GRHR) pathway. NSAIDS is protective (OR=0.84) for those at the 5th percentile of the TGF-β/GRHR pPRS (low genetic risk, OR), but significantly more protective (OR=0.70) for those at the 95th percentile (high genetic risk). From a biological perspective, this suggests that NSAIDs may act to reduce CRC risk specifically through genes in these pathways. From a population health perspective, our result suggests that focusing on genes within these pathways may be effective at identifying those for whom NSAIDs-based CRC-prevention efforts may be most effective.},
}

@article {pmid40763029,
year = {2025},
author = {McGuire, DJ and Akondy, RS and Yang, S and Edupuganti, S and Nagar, S and Michael, G and De Rosa, SC and Newell, EW and Farber, DL and Kissick, HT and McElrath, MJ and Ahmed, R},
title = {Regulation of CD45 isoforms during human effector and memory CD8 T cell differentiation: Implications for T cell nomenclature.},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
volume = {122},
number = {32},
pages = {e2322982122},
doi = {10.1073/pnas.2322982122},
pmid = {40763029},
issn = {1091-6490},
support = {U19 AI057266/AI/NIAID NIH HHS/United States ; U19 AI057266-S1//HHS | NIH | NIAID | Division of Intramural Research (DIR, NIAID)/ ; },
mesh = {Humans ; *Leukocyte Common Antigens/immunology/metabolism/genetics ; *CD8-Positive T-Lymphocytes/immunology/cytology/metabolism ; *Immunologic Memory/immunology ; *Cell Differentiation/immunology ; Protein Isoforms/immunology ; *Memory T Cells/immunology ; Receptors, CCR7 ; SARS-CoV-2/immunology ; Yellow Fever Vaccine/immunology ; COVID-19/immunology ; Yellow fever virus/immunology ; },
abstract = {This study examines the expression of CD45 isoforms on human yellow fever virus vaccine (YFV-17D) specific CD8 T cells longitudinally after vaccination. As expected, effector CD8 T cells at day 14 express CD45RO but within 4 to 6 wk these virus-specific CD8 T cells become CD45RA positive and remain CD45RA for >10 y. The journey for these YFV-specific CD8 T cells goes from naive (CD45RA+ CCR7+) to effector/effector memory (CD45RO+ CCR7-) to Temra (CD45RA+ CCR7-) to stem-cell memory (CD45RA+ CCR7+). These YFV-specific CD8 T cells rarely acquire the canonical Tcm phenotype (CD45RO+ CCR7+). This CD45RO to RA switch coincides with clearance of YFV, so we hypothesized that antigen may be playing a role in regulating CD45 expression. We addressed this issue by ex vivo analysis and provide evidence that this switch is indeed regulated by antigen. Sorted YFV-specific CD45RO effector CD8 T cells reexpress CD45RA when cultured ex vivo in the absence of antigen and retain CD45RO in the presence of cognate peptide. We also extended these ex vivo analysis to human cytomegalovirus (CMV)-specific CD8 T cells and show that CD45RO cells transition to CD45RA in the absence of antigen and CD45RA cells become CD45RO when stimulated with CMV peptide. We then show that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike-specific CD8 T cells can repeatedly undergo the same CD45RA to RO to RA transition in vivo after the SARS-CoV-2 mRNA vaccination. Again, the canonical Tcm phenotype spike-specific memory CD8 T cells were not readily detectable. These studies warrant a reevaluation of how human memory CD8 T cells are defined.},
}

Humans
*Leukocyte Common Antigens/immunology/metabolism/genetics
*CD8-Positive T-Lymphocytes/immunology/cytology/metabolism
*Immunologic Memory/immunology
*Cell Differentiation/immunology
Protein Isoforms/immunology
*Memory T Cells/immunology
Receptors, CCR7
SARS-CoV-2/immunology
Yellow Fever Vaccine/immunology
COVID-19/immunology
Yellow fever virus/immunology

@article {pmid40762835,
year = {2025},
author = {Duffy, AM and Goenka, A and Azeem, MI and Taz, A and Potdar, SV and Scott, SA and Marin, E and Kaufman, JL and Hofmeister, CC and Joseph, NS and Gupta, VA and Lonial, S and Nooka, AK and Dhodapkar, MV and Dhodapkar, KM},
title = {Early CD4+ T-cell proliferative burst and chronic T-cell engagement impact myeloma outcomes following T-cell engager therapy.},
journal = {The Journal of clinical investigation},
volume = {},
number = {},
pages = {},
doi = {10.1172/JCI192927},
pmid = {40762835},
issn = {1558-8238},
}

@article {pmid40762207,
year = {2025},
author = {Thiruvengadam, SK and Ahn, KW and Patel, J and Lian, Q and Hertzberg, M and Epperla, N and Metheny, L and Hong, S and Jain, T and Aljurf, M and Beitinjaneh, A and Vaughn, J and Gopal, A and Iqbal, M and Wirk, B and Manjappa, S and Oliver, C and Mohty, R and Shadman, M and Turtle, C and Hamadani, M and Herrera, AF},
title = {CD19 Directed CAR T Therapy for Transformed Follicular Lymphoma: A CIBMTR Analysis.},
journal = {American journal of hematology},
volume = {},
number = {},
pages = {},
doi = {10.1002/ajh.70027},
pmid = {40762207},
issn = {1096-8652},
abstract = {Transformed follicular lymphoma (tFL) is typically associated with chemotherapy resistance and a poor prognosis. There are limited data regarding outcomes after CD19-directed chimeric antigen receptor T-cell (CAR T) therapy in relapsed/refractory (R/R) tFL. A total of 923 adult patients with R/R tFL who received commercial CD19 CAR T therapy between 2017 and 2023 were identified in the Center for International Blood and Marrow Transplant Research registry. Median age was 64 years (range: 30-86) and median prior lines of therapy was 4 (range: 1-18). Most patients (78%) received axicabtagene ciloleucel, with 67% of patients having resistant disease at the time of CAR T infusion. At a median follow-up of 25 months (range: 1-72) from CAR T infusion, the 2-year overall survival (OS) was 57% (95% CI: 53-60) and progression-free survival (PFS) was 43% (95% CI: 40-47). The 2-year cumulative incidences of relapse or progression (rel/prog) and non-relapse mortality (NRM) were 47% (95% CI: 44-51) and 9% (95% CI: 7-11), respectively. The overall response rate to CAR T was 76%, with a complete response rate of 63%. Grade ≥ 3 cytokine release syndrome (CRS) was observed in 7.1% and grade ≥ 3 immune effector cell-associated neurologic syndrome (ICANS) in 21.6% of patients. Multivariable analysis suggested that resistant disease status at the time of CAR T, use of bridging therapy, and high comorbidity index ≥ 3 were associated with inferior PFS and OS. Older age ≥ 60 significantly increased the risk of NRM. Our study suggests that CD19 CAR T is effective and safe for tFL.},
}

@article {pmid40759764,
year = {2025},
author = {Talbert, PB and Henikoff, S},
title = {Centromeres drive and take a break.},
journal = {Chromosome research : an international journal on the molecular, supramolecular and evolutionary aspects of chromosome biology},
volume = {33},
number = {1},
pages = {17},
pmid = {40759764},
issn = {1573-6849},
mesh = {*Centromere/genetics/metabolism ; Animals ; Humans ; DNA Replication ; Chromosomal Proteins, Non-Histone/genetics/metabolism ; DNA, Satellite/genetics ; Meiosis ; Kinetochores/metabolism ; Evolution, Molecular ; },
abstract = {The identification of CENPA, CENPB, and CENPC by Earnshaw and Rothfield 40 years ago has revealed the remarkable diversity and complexity of centromeres and confirmed most seed plants and animals have centromeres comprised of complex satellite arrays. The rapid evolution of centromeres and positive selection on CENPA and CENPC led to the centromere drive model, in which competition between tandem satellite arrays of differing size and centromere strength for inclusion in the egg of animals or megaspore of seed plants during female meiosis drives rapid evolution of centromeres and kinetochore proteins. Here we review recent work showing that non-B-form DNA structures in satellite centromeres make them sites of frequent replication fork stalling, and that repair of collapsed forks by break-induced replication rather than unequal sister chromatid exchange is likely the primary mode of satellite expansion and contraction, providing the variation in satellite copy number that is the raw material of centromere drive. Centromere breaks at replication, rather than errors at mitosis, can account for most centromere misdivisions that underlie aneuploidies in cancer.},
}

*Centromere/genetics/metabolism
Animals
Humans
DNA Replication
Chromosomal Proteins, Non-Histone/genetics/metabolism
DNA, Satellite/genetics
Meiosis
Kinetochores/metabolism
Evolution, Molecular

@article {pmid40758946,
year = {2025},
author = {Nilius, H and Sinitsa, E and Studt, JD and Tsakiris, DA and Greinacher, A and Mendez, A and Schmidt, AE and Wuillemin, WA and Gerber, B and Vishnu, P and Graf, L and Kremer Hovinga, JA and Bakchoul, T and Nagler, M},
title = {Outcomes of Patients with Suspected Heparin-Induced Thrombocytopenia in a Contemporary Multicenter Cohort.},
journal = {Blood advances},
volume = {},
number = {},
pages = {},
doi = {10.1182/bloodadvances.2025016639},
pmid = {40758946},
issn = {2473-9537},
abstract = {Managing patients with suspected heparin-induced thrombocytopenia (HIT) poses significant clinical challenges. Limited evidence exists on how management decisions impact clinical outcomes, leading to treatment recommendations based on low-certainty evidence. This study aimed to evaluate the treatment strategies and clinical outcomes of patients with suspected heparin-induced thrombocytopenia (HIT) in a contemporary multicenter cohort. We conducted a prospective, multicenter cohort study including consecutive patients with suspected HIT from 11 centers. Patients were stratified into three groups: (a) HIT confirmed, (b) HIT-negative but heparin/PF4 antibody-positive, and (c) HIT-negative without antibodies. Clinical and laboratory data were systematically collected. HIT was diagnosed using the washed-platelet heparin-induced platelet activation (HIPA) test as the reference standard. Among 1,393 patients (46% female, median age 67), HIT was confirmed in 119 (8.5%). Most patients were in intensive care (37%) or had undergone cardiac surgery (32%). Argatroban was the predominant treatment (70%), and platelet recovery occurred in 77% of HIT patients. Among patients with HIT, subsequent venous thromboembolism occurred in 23%, arterial thromboembolism in 9%, major bleeding in 12.6%, and mortality in 18%, with no significant differences between anticoagulants. Treatment with argatroban, bivalirudin, or direct oral anticoagulants (DOACs) significantly reduced arterial thromboembolism risk. Outcomes did not differ between HIT-negative patients with or without heparin/PF4 antibodies. HIT, as well as the mere suspicion of HIT, remains a serious condition with a high risk of adverse outcomes, including death. Our findings provide further evidence supporting the effectiveness of DOACs, argatroban, and bivalirudin in reducing arterial thromboembolism risk.},
}

@article {pmid40758858,
year = {2025},
author = {Vasconcelos, AG and Johnson, M and Cai, Y and Hsu, L and Franceschini, N and Auer, PL and Kooperberg, C and Raffield, LM and Reiner, AP},
title = {Methylation profile of individuals with sickle cell trait.},
journal = {Epigenetics},
volume = {20},
number = {1},
pages = {2539234},
pmid = {40758858},
issn = {1559-2308},
mesh = {Humans ; *DNA Methylation ; *Sickle Cell Trait/genetics ; Female ; Male ; Adult ; Black or African American/genetics ; Middle Aged ; CpG Islands ; Epigenesis, Genetic ; Genome-Wide Association Study ; beta-Globins/genetics ; Epigenome ; White ; },
abstract = {Sickle cell trait (SCT) is due to heterozygosity for the β-globin sickle cell mutation. SCT recently has been associated with increased risk of various adverse health outcomes. DNA methylation (DNAm) is one potential mechanism by which SCT may impact disease risk. To identify DNAm sites associated with SCT, we conducted an epigenome-wide association (EWAS) meta-analysis using whole blood Illumina EPIC array data available in a total of 3,677 African American participants (including 1,071 with SCT) from the Women's Health Initiative and Jackson Heart Study. We identified 103 differentially methylated CpGs and 119 differentially methylated regions associated with SCT. The strongest signals were hypermethylated cis loci within predicted regulatory elements within or near the β-globin gene cluster on chromosome 11. Beyond the globin locus, SCT-associated DMPs were enriched in genes involved in redox regulation and oxidative stress. We also demonstrate an association of SCT with differences in biological age and epigenetic age acceleration, though the pattern and strength of association differ according to the epigenetic clock used. Specifically, more recent epigenetic clocks that incorporate clinical phenotypes or laboratory biomarkers related to adverse health outcomes are associated with accelerated aging among individuals with SCT compared to African American controls. Our results lay the groundwork for future study of the role of DNAm in biologic aging and related health outcomes among individuals with SCT.},
}

Humans
*DNA Methylation
*Sickle Cell Trait/genetics
Female
Male
Adult
Black or African American/genetics
Middle Aged
CpG Islands
Epigenesis, Genetic
Genome-Wide Association Study
beta-Globins/genetics
Epigenome
White

@article {pmid40758381,
year = {2025},
author = {Kumar, R and Hwang, S and Antony, M and Valenzuela, RFP and Kumar, M},
title = {Musculoskeletal Myeloid Sarcoma: Clinical, Imaging, Management, and Outcomes in 41 Adult Patients.},
journal = {Journal of computer assisted tomography},
volume = {},
number = {},
pages = {},
doi = {10.1097/RCT.0000000000001788},
pmid = {40758381},
issn = {1532-3145},
abstract = {OBJECTIVE: To analyze symptoms, imaging features, management, and outcomes of musculoskeletal myeloid sarcoma in adult leukemic patients.

MATERIALS AND METHODS: This is a retrospective analysis of clinical symptoms, imaging features, management, and outcomes in 41 adult leukemic patients with biopsy-proven myeloid sarcomas of bones and muscles.

RESULTS: Nineteen patients had acute, and 15 had chronic myeloid leukemia. Additional 5 previously treated leukemia patients included 1 with chronic myeloid leukemia, 3 with myelofibrosis, and 1 with myelodysplastic syndrome. The remaining 2 patients had isolated myeloid sarcoma with normal marrow without a history of hematologic disorder. Twenty-nine patients had bone tumors only, 3 muscle tumors only, 8 both bone and soft tissue tumors, and 1 intraarticular synovial tumor of an ankle. Of the 71 focal bone tumors, 68 were lytic and 3 were sclerotic. In addition, diffuse sclerotic bone lesions were present in 1 patient, and diffuse mixed lytic/sclerotic bone lesions in 2 patients. Most tumors were asymptomatic and were discovered incidentally on imaging. Local pain, mass, and pathologic fractures were the most common complaints when present. Vertebral bone and paravertebral soft tissue tumors caused neurological symptoms. Muscle tumors became symptomatic when they involved adjoining bone, nerve, or spinal cord. Only 3 among 13 muscle tumors presented as palpable masses. The imaging features of these musculoskeletal tumors were nonspecific. On MRI, both muscle and lytic bone MSs were hypo-to-iso-intense on T1WI, hyperintense on fat-suppressed T2WI, and enhanced on post-contrast fat-suppressed T1WI. A synovial myeloid sarcoma of the ankle showed diffusely thickened synovium on MRI. F-18 FDG PET-CT was helpful in the detection, monitoring of treatment response, and post-treatment surveillance in 5 patients. All patients were treated with cytarabine-based systemic anti-leukemic treatment and optional radiation, surgical resection, bone marrow transplant, and/or a combination of these. The known mean survival time of 35 dead patients after the appearance of musculoskeletal MS was 12.1 months.

CONCLUSIONS: Musculoskeletal myeloid sarcoma, which can occasionally precede it, is a rare complication of AML. Most tumors are asymptomatic. Imaging, particularly MRI and 18-F FDG PET-CT, plays a crucial role in detecting and monitoring treatment response, as well as post-treatment surveillance. The disease has poor clinical outcomes and short-term survival.},
}

@article {pmid40757857,
year = {2025},
author = {Shi, Z and Tsuge, M and Collier, N and Takeuchi, Y and Uchida, T and Rutter, CM and Teraoka, Y and Uprichard, SL and Ishida, Y and Tateno, C and Ozik, J and Dahari, H and Chayama, K},
title = {Modeling of hepatitis B virus infection spread in primary human hepatocytes.},
journal = {Journal of virology},
volume = {},
number = {},
pages = {e0092725},
doi = {10.1128/jvi.00927-25},
pmid = {40757857},
issn = {1098-5514},
abstract = {Chronic hepatitis B virus (HBV) infection poses a significant global health threat, causing severe liver diseases including cirrhosis and hepatocellular carcinoma. We characterized HBV DNA kinetics in primary human hepatocytes (PHHs) over 32 days post-inoculation (p.i.) and modified our in-vivo agent-based modeling (ABM) to gain insights into the HBV lifecycle and spread in vitro. Parallel PHH cultures were mock-treated or treated with HBV entry inhibitor Myr-preS1 (6.25 µg/mL) was initiated 24 h p.i. In untreated PHH, three viral DNA kinetic patterns were identified: (i) an initial decline, followed by (ii) rapid amplification and (iii) slower amplification/accumulation. In the presence of Myr-preS1, viral DNA and infected cell numbers in phase 3 were effectively blocked, with minimal to no increase. This suggests that phase 2 represents viral amplification in initially infected cells, while phase 3 corresponds to viral spread to naïve cells. The ABM reproduced well the HBV kinetic patterns observed and predicted that the viral eclipse phase lasts between 18 and 38 h. After the eclipse phase, the viral production rate increased over time, starting with a slow production cycle of 1 virion per day, which gradually accelerated to 1 virion per hour after 3 days. Approximately 4 days later, virion production reached a steady state production rate of 4 virions/h. The estimated median efficacy of Myr-preS1 in blocking HBV spread was 91% (range: 90-92%). The HBV kinetics and the predicted estimates of the HBV eclipse phase duration and HBV production cycles in PHH are similar to those predicted in uPA/SCID mice with human livers.IMPORTANCEWhile primary human hepatocytes (PHHs) are the most physiologically relevant culture system for studying HBV infection in vitro, a comprehensive understanding of HBV infection kinetics and spread in PHH is lacking. In this study, we characterize HBV viral kinetics and modify our in vivo agent-based modeling (ABM) to provide quantitative insights into the HBV production cycle and viral spread in PHH. The ABM provides an estimate of the HBV eclipse phase duration, HBV production cycles, and Myr-preS1 efficacy in blocking HBV spread in PHH. The results resemble those predicted in uPA/SCID mice with human livers, demonstrating that estimated HBV infection kinetic parameters in PHH in vitro mirror those observed in the in vivo HBV infection chimeric mouse model.},
}

@article {pmid40757627,
year = {2025},
author = {Truong, L and Adams, AK and Bishop, S and Dupuis, V and Garza, L and Quigley, T and Hassell, L and Drain, PK and Ibarra, G and Sorrell, AW and Warne, T and Gregor, C and Webber, E and Ko, LK},
title = {"It's not about me. It's about what's best for my community": Factors impacting COVID-19 vaccine uptake among Native Americans and Latinos from two agricultural communities.},
journal = {The Journal of rural health : official journal of the American Rural Health Association and the National Rural Health Care Association},
volume = {41},
number = {3},
pages = {e70057},
doi = {10.1111/jrh.70057},
pmid = {40757627},
issn = {1748-0361},
support = {/GM/NIGMS NIH HHS/United States ; /TR/NCATS NIH HHS/United States ; },
mesh = {Humans ; *COVID-19 Vaccines/administration & dosage/therapeutic use ; *COVID-19/prevention & control/ethnology ; Male ; Female ; Adult ; Focus Groups ; Middle Aged ; *Rural Population/statistics & numerical data ; *Hispanic or Latino/psychology/statistics & numerical data ; Montana/epidemiology ; Washington/epidemiology ; SARS-CoV-2 ; Aged ; *Patient Acceptance of Health Care/ethnology ; *Indians, North American/psychology/statistics & numerical data ; Qualitative Research ; White ; },
abstract = {PURPOSE: While SARS-CoV-2 significantly impacts rural Native American and Latino communities, COVID-19 vaccines offer an effective and safe mitigation strategy. Vaccine uptake is disproportionately lower in rural communities than in urban communities across the nation. This study examined barriers and motivators of COVID-19 vaccine uptake in two Native American and Latino rural agricultural communities in eastern Washington and Montana.

METHODS: We conducted 28 key informant interviews with trusted community members and six community focus groups with 39 participants from May 2021 to June 2021. Participants were from the Yakima Valley (WA) and Flathead Reservation (MT). The Social Cognitive Theory and Social Context Framework informed development of the interview and focus group moderator guides. We used deductive and inductive approach to code transcripts and thematic analysis to generate themes.

FINDINGS: Barriers to COVID-19 vaccine uptake were misconceptions about COVID-19 vaccines shaped by misinformation, politicization of vaccines, historical trauma and mistrust in government, and structural barriers in rural agricultural communities. Having access to accurate and understandable COVID-19 vaccine information and receiving information from trusted sources were motivators of COVID-19 vaccine uptake. Protecting families, children, elders, and the community, and striving to return to normal life were also noted as motivators.

CONCLUSIONS: Understanding the community's perceptions and experiences around the COVID-19 vaccine is critical for successful implementation of strategies to increase vaccine uptake during future public health emergencies. Strategies for vaccine uptake among communities in the Flathead Reservation and Yakima Valley need to address barriers and highlight motivators of COVID-19 vaccine uptake.},
}

Humans
*COVID-19 Vaccines/administration & dosage/therapeutic use
*COVID-19/prevention & control/ethnology
Male
Female
Adult
Focus Groups
Middle Aged
*Rural Population/statistics & numerical data
*Hispanic or Latino/psychology/statistics & numerical data
Montana/epidemiology
Washington/epidemiology
SARS-CoV-2
Aged
*Patient Acceptance of Health Care/ethnology
*Indians, North American/psychology/statistics & numerical data
Qualitative Research
White

@article {pmid40754387,
year = {2025},
author = {Moosavi, D and Mullens, DA and Davidson, LA and Fan, YY and Goldsby, JS and Ivanov, IV and Levy, L and Kahsai, OJ and Curtis, KR and Raftery, D and Purcell, HJ and Mather, E and Ammar, H and Randolph, T and Issaka, RB and Navarro, SL and Lampe, JW and Hullar, MA and Chapkin, RS},
title = {Gut microbial community and host intestinal gene expression with combined fish oil and soluble corn fiber compared with corn oil and maltodextrin: A randomized crossover trial in healthy older individuals.},
journal = {The American journal of clinical nutrition},
volume = {122},
number = {2},
pages = {396-412},
doi = {10.1016/j.ajcnut.2025.04.031},
pmid = {40754387},
issn = {1938-3207},
mesh = {Humans ; *Fish Oils/pharmacology/administration & dosage ; *Gastrointestinal Microbiome/drug effects ; Middle Aged ; Cross-Over Studies ; Aged ; Male ; *Polysaccharides/pharmacology/administration & dosage ; Female ; *Dietary Fiber/administration & dosage/pharmacology ; *Corn Oil/administration & dosage/pharmacology ; Feces/microbiology ; *Intestines/microbiology/drug effects ; },
abstract = {BACKGROUND: Concurrent consumption of dietary fiber and n-3 polyunsaturated fatty acids reduces colon tumor formation. However, their combined effects on colorectal cancer risk remain unexplored in human trials.

OBJECTIVES: This study investigated the synergistic effects of fish oil (FO) and fermentable fiber on the gut transcriptional profiles and microbiome composition in older adults.

METHODS: In a randomized controlled crossover pilot study, 30 adults (ages 50-75 y), received fermentable fiber (33 g/d soluble corn fiber; SCF) plus eicosapentaenoic acid and docosahexaenoic acid (EPA + DHA as FO, 7.7 g/d) or a comparator (similar doses of maltodextrin plus corn oil; MD + CO) for 30 d, followed by a 60-d washout period before crossing over to the alternate intervention. Serum phospholipid fatty acids, stool exfoliome [ribonucleic acid sequencing (RNAseq)], microbiome (16S ribosomal ribonucleic acid gene sequencing), butyrate kinase (but) gene abundance (digital droplet polymerase chain reaction), and fecal short-chain fatty acids were analyzed. Linear mixed models were used for the majority of outcome analyses. Differential expression and pathway enrichment analyses were applied to RNAseq data, whereas microbiome diversity was assessed using α and β diversity.

RESULTS: Serum EPA and DHA concentrations were higher after SCF + FO than MD + CO supplementation [EPA: β = 0.51; 95% confidence interval: 0.31, 0.72; DHA: β = 0.18; 95% confidence interval: 0.10, 0.27; P < 0.0001]. Analysis of host gut transcriptional networks revealed that SCF + FO supplementation inhibited the glucose-insulin receptor-phosphatidylinositol-3 kinase-signaling axis. Microbiome analysis revealed significant intervention differences in β-diversity (F = 4.4, R[2] = 0.08, P = 0.001), and 27 of 73 genera analyzed, several known short-chain fatty acid producers, differed between the 2 interventions (false discovery rate <0.05). Abundance of the but gene from Roseburia sp (P < 0.001) and the genera Roseburia (P = 0.006) were lower in the SCF + FO compared to MD + CO intervention, although fecal butyrate concentrations did not differ.

CONCLUSIONS: Thirty-day supplementation of SCF + FO compared with MD + CO showed significant shifts in intestinal cell pathways relevant to colorectal cancer with concomitant differences in gut microbial community structure and butyrate-producing taxa.},
}

Humans
*Fish Oils/pharmacology/administration & dosage
*Gastrointestinal Microbiome/drug effects
Middle Aged
Cross-Over Studies
Aged
Male
*Polysaccharides/pharmacology/administration & dosage
Female
*Dietary Fiber/administration & dosage/pharmacology
*Corn Oil/administration & dosage/pharmacology
Feces/microbiology
*Intestines/microbiology/drug effects

@article {pmid40754223,
year = {2025},
author = {Nadiminti, KV and Ahn, KW and Patel, J and Lian, Q and Bezerra, E and Chen, A and Ganguly, S and Gergis, U and Hashmi, H and Kharfan-Dabaja, MA and Kuruvilla, J and Lekakis, L and Locke, FL and Murthy, H and Mousthafa, MA and Perales, MA and Pophali, P and Riedell, PA and Shah, NN and Wang, T and Pasquini, M and Hamadani, M and Turtle, CJ and Herrera, AF and Shadman, M},
title = {Chimeric Antigen Receptor T-cell Therapy for Richter Transformation: A CIBMTR analysis.},
journal = {Transplantation and cellular therapy},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jtct.2025.07.021},
pmid = {40754223},
issn = {2666-6367},
abstract = {Relapsed and/or refractory Richter transformation (RT) is generally associated with poor response to available therapies and short survival time. As RT patients were excluded from participating in the pivotal studies of chimeric antigen receptor T cell therapy (CAR-T) for large B-cell lymphoma, there is paucity of information about the efficacy of CAR-T in RT. Therefore, through the Center for International Blood and Marrow Transplant Research (CIBMTR) registry, we analyzed data from 140 RT patients who received anti-CD19 CAR-T between 2018 and 2023. Patients had received a median of 3 lines of therapy for RT (range:1-8), with nearly 43% being exposed to a Bruton's tyrosine kinase inhibitor and/or venetoclax. Axicabtagene ciloleucel (axi-cel) (65%) and tisagenlecleucel (tisa-cel) (28%) were the commonly prescribed products. Grade ≥3 cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome occurred in 9.4 % and 20%, respectively. After a median follow-up of 25 months (range: 1.8-61.5) from CAR-T infusion, 2-year progression-free and overall survival were 32.5% (95%CI, 24-41) and 46.6% (95%CI, 38-58), respectively. The 2-year cumulative incidence of relapse and non-relapse mortality were 58.8% (95% CI, 50 - 67), and 8.7% (95% CI, 4 - 14%), respectively. Poor performance status and refractory disease before CAR-T infusion were predictive of inferior survival and disease progression. Our results show that anti-CD19 CAR-T can function as an effective treatment modality for a proportion of RT patients.},
}

@article {pmid40754035,
year = {2025},
author = {Jafari, O and Ma, S and Lam, BD and Jiang, JY and Zhou, E and Ranjan, M and Ryu, J and Bandyo, R and Maghsoudi, A and Peng, B and Amos, CI and Oluyomi, A and Fillmore, NR and La, J and Li, A},
title = {Development and Validation of VTE-BERT Natural Language Processing Model for Venous Thromboembolism.},
journal = {Journal of thrombosis and haemostasis : JTH},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jtha.2025.07.021},
pmid = {40754035},
issn = {1538-7836},
abstract = {BACKGROUND: Accurate and rapid phenotyping of venous thromboembolism (VTE) in longitudinal studies is important. A natural language processing (NLP) tool externally validated in representative patients is lacking.

METHODS: We designed a novel NLP platform, NLPMed, to assist thrombosis researchers with data preprocessing, phenotype annotation, language model finetuning, and NLP application. Utilizing clinical notes, discharge summaries, and radiology reports in patients with cancer from two healthcare institutions, we finetuned Bio_ClinicalBERT to develop VTE-BERT. The new model was trained to detect acute VTE events and their anatomical locations longitudinally. We internally and externally validated the model's performance in two randomly sampled cohorts of patients with advanced cancer.

RESULTS: The training cohort consisted of 715 patients and 14,013 annotated notes with ≥1 VTE keyword from the Harris Health System (HHS). The internal validation cohort included 400 additional patients with 7,190 VTE keyword-containing notes from HHS. The external validation cohort included 400 patients with 7,371 VTE keyword-containing notes from the National Veterans Affairs Healthcare System. VTE-BERT was trained until it reached a precision of 95% and recall of 98% on the patient level. Using independent datasets, the model achieved precision and recall of 95% and 91% in internal validation and of 85% and 92% in external validation.

CONCLUSIONS: We trained and externally validated an efficient NLP model to detect incident VTE events longitudinally. We believe its adoption will accelerate thrombosis research by improving VTE detection at scale and decreasing the time and expense involved with manual chart review in big data epidemiological studies.},
}

@article {pmid40753019,
year = {2025},
author = {Selukar, S and Yin, V and Othus, M},
title = {Synthetic control arms and other uses of external data in clinical trials for hematological malignancies.},
journal = {Blood reviews},
volume = {},
number = {},
pages = {101324},
doi = {10.1016/j.blre.2025.101324},
pmid = {40753019},
issn = {1532-1681},
abstract = {Clinical trialists have been debating the use of data external to the study for decades. In this review, we develop concepts for interested readers to consider the use of external data in clinical trials, and we provide perspectives on the real-world usage of external data in phase 2 and 3 clinical trials for hematological malignancies across US academic cancer clinical trial networks. Only a minority of these studies have included external data (beyond use in establishing outcome benchmarks) in recent years, but improvements in data sharing and advances in methodologies may lead to more sources of potentially high-quality data for the broader clinical trials community. Identifying appropriate external data specific to the clinical trial and developing plans to adequately address differences between study and external data will remain key considerations for including external data in clinical trials.},
}

@article {pmid40709277,
year = {2025},
author = {Cao, J and Ferguson, M and Sun, J and Shen, M and Small, R and Hippe, DS and Zhao, X and Zhang, D and Watase, H and Yuan, C and Gao, P and DeMarco, JK and Nicosia, RF and Wang, Y and Li, H and Li, Z and Wang, Y and Kohler, T and Hatsukami, T and Sui, B},
title = {Composition of Carotid Plaques Differs Between Chinese and United States Patients: A Histology Study.},
journal = {Research square},
volume = {},
number = {},
pages = {},
pmid = {40709277},
issn = {2693-5015},
abstract = {BACKGROUND: The clinical manifestations of cerebrovascular disease are known to differ between the Chinese and United States (U.S.) populations as do the plaque features on imaging.

OBJECTIVES: The aim of this study was to investigate and compare the histological features of excised carotid plaques from Chinese and U.S. patients.

METHODS: Carotid endarterectomy specimens collected from two prospective studies were included. The entire plaque was serially sectioned (10 μm thickness) at 0.5-1 mm intervals. Hematoxylin and eosin staining and Mallory's trichrome staining were performed. The morphology and components of the plaques were measured and compared between the two groups.

RESULTS: A total of 1,152 histological sections from 75 Chinese patients and 1,843 sections from 111 U.S. patients were analyzed. The Chinese group had significantly smaller minimum lumen diameters (median: 1.1 vs. 1.3 mm, p=0.046) and a larger percent wall volume (median: 74% vs. 70%, p=0.018) than the U.S. group. After adjusting for confounding factors, carotid plaques in the Chinese population were more likely to have more lipid pools (β=10.0%, 95%CI: 4.9 to 15.9%), more recent intraplaque hemorrhage (IPH; β=8.4%, 95%CI: 4.5 to 12.7%), and less late IPH (β=-8.2%, 95%CI: -11.3 to -5.4), and fewer fibrous cap disruptions (45% vs. 67%, p=0.061). Chinese plaques were more homogeneous and had a higher percentage of plaques with features of xanthomas than did U.S. plaques (20% vs 2.7%, p<0.001).

CONCLUSIONS: The histology of Chinese plaques differs significantly from that of U.S. plaques, suggesting substantial differences in the pathophysiology of atherosclerotic cerebrovascular disease between Chinese and North American populations, which could enhance the gap in racial pathology comparison, indicating a need for a different management approach.},
}

@article {pmid40672332,
year = {2025},
author = {Williamson, C and Moodley, C and Magaret, CA and Giorgi, EE and Rolland, M and Westfall, DH and Yssel, A and Deng, W and Rossenkhan, R and Mkhize, NN and Chen, L and Zhao, H and Bhattacharya, T and Pankow, A and Murrell, B and York, T and Gwashu-Nyangiwe, A and Ndabambi, N and Thebus, R and Cohen, P and Lambson, B and Kaldine, H and Bhebhe, S and Juraska, M and Bai, H and deCamp, AC and Ludwig, J and Molitor, C and Beaume, N and Matten, D and Huang, Y and Zhang, L and Reeves, DB and Mayer, B and Karuna, ST and Hural, JA and Morris, L and Montefiori, D and Bumgarner, RE and Moore, PL and Edlefsen, PT and Edupuganti, S and Mgodi, N and McElrath, MJ and Cohen, MS and Corey, L and Gilbert, PB and Mullins, JI},
title = {Influence of the broadly neutralizing antibody VRC01 on HIV breakthrough virus populations in antibody-mediated prevention trials.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {40672332},
issn = {2692-8205},
abstract = {In the HIV antibody mediated prevention (AMP) trials, the broadly neutralizing antibody VRC01 demonstrated protective efficacy against new diagnoses with susceptible HIV strains. To understand how VRC01 shaped breakthrough infections, we performed deep sequencing on 172 participants in the placebo and treatment arms, generating 63,444 gag-Δpol (2.5 kb) and 53,088 rev-env-Δnef (3 kb) sequences. Sequences were classified into transmitted founder lineages (TFLs), and infections with multiple distinct lineages were determined. Multilineage infections were detected in ~38% of participants in both the African (HVTN 703/HPTN 081) and Americas/Europe (HVTN 704/HPTN 085) cohorts, regardless of placebo or treatment group, or cohort. The high levels of multilineage infections could be attributed to minor lineages (<5% abundance) identified in 20% of participants. Infection with VRC01 discordant viruses (IC80s >3-fold different) was observed in 40% of multilineage infections, with a trend toward greater intra-host neutralization differences with increasing VRC01 dose (Jonckheere-Terpstra test, p=0.072). In six VRC01 treated participants who acquired both sensitive (IC80<1μg/ml) and resistant viruses (IC80>3μg/ml), the sensitive lineages declined over time. Recombination was pervasive, observed in 63% of multilineage infections at the time of HIV diagnosis. In one treated participant infected with VRC01 discordant lineages, recombinant viruses preferentially inherited the resistance mutation (binomial p=0.004). In conclusion, our in-depth analysis of breakthrough viruses in the AMP trials revealed a high frequency of multilineage infections, including infections with viruses with different VRC01 sensitivities. This analysis also highlights the role of recombination in shaping intra-host viral evolution and facilitating escape from VRC01.},
}

@article {pmid40752589,
year = {2025},
author = {Ng, SK and Flaherty, PW and Ancheta, M and Tindbaek, KA and Sekhon, MK and Huang, JJ and Portuguese, AJ and Albittar, A and Kopmar, NE and Cowan, AJ and Shadman, M and Hirayama, AV and Till, BG and Cassaday, RD and Turtle, CJ and Liu, C and Xie, H and Leisenring, WM and Gauthier, J and Liang, EC and Hill, JA},
title = {Opportunities to improve antibiotic stewardship, and identification of blood biomarkers associated with bacteremia following CAR-T cell therapy.},
journal = {Transplantation and cellular therapy},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jtct.2025.07.022},
pmid = {40752589},
issn = {2666-6367},
abstract = {BACKGROUND: Cytokine release syndrome (CRS) is frequent after chimeric antigen receptor T-cell therapy (CAR-T). CRS and bacteremia share clinical features, making it difficult to distinguish between the two and deliver targeted treatment. As a result, most patients with CRS receive empiric broad-spectrum antibiotics that may adversely impact long-term outcomes.

OBJECTIVES: The objectives of this study were to identify blood biomarkers that distinguish between CRS and bacteremia in the first month after CAR-T. We also describe the utilization of empiric antibiotics to identify opportunities for improved antimicrobial stewardship.

STUDY DESIGN: We identified patients who received CAR-T for hematologic malignancies between July 2013 and April 2024. We calculated the cumulative incidences of CRS and bacteremia within 30 days post-CAR-T. In a matched case control analysis, where three patients with CRS and no bacteremia (controls) were matched to each patient with bacteremia (cases), we described the clinical characteristics of CRS, bacteremia, and antibiotic exposure. We then assessed the levels and kinetics of six biomarkers (C-reactive protein [CRP], interleukin-6, ferritin, fibrinogen, lactate dehydrogenase, and D-dimer) for their ability to discriminate between bacteremia and CRS using Mann-Whitney U tests and generalized estimating equation (GEE) models.

RESULTS: Among 694 CAR-T recipients, 517 (75%; 95% confidence interval [CI], 71-78%) developed CRS. Bacteremia occurred in 19 patients with a cumulative incidence of 2.7% (95% CI, 1.7-4.2%) within 30 days and 1.4% (95% CI, 0.7-2.6%) within 14 days of CAR-T. The median time from blood culture to positive result was one day (interquartile range [IQR], 1-1). Among the 57 matched controls, CRS occurred a median of four days (IQR, 1-5) post-CAR-T, all were hospitalized for fevers, and 92% of CRS events were treated with empiric antibiotics for a median of seven days (IQR, 5-8). As a result, for every patient with bacteremia treated with antibiotics within the first 14 days, an estimated 52 patients with CRS and no serious bacterial infection received empiric antibiotics. The levels and kinetics of biomarkers were similar among cases and controls within 14 days after CAR-T. Beyond day +14, CRP, D-dimer, and ferritin levels were significantly higher among patients with bacteremia and distinguished cases from controls with moderate discrimination (area under the curve of 0.77, 0.77, and 0.81, respectively). In addition, increasing CRP and fibrinogen ≥ 14 days post-CAR-T were significantly associated with bacteremia (odds ratio [OR], 1.46; 95% CI, 1.07-2.01 and OR, 4.32; 95% CI, 1.28-14.61 per 0.25 log10 increase in biomarker level per day, respectively).

CONCLUSION: We demonstrate that most CAR-T recipients who developed CRS received empiric broad-spectrum antibiotics, but bacteremia was rare. Although blood biomarkers were unable to distinguish between CRS and bacteremia early after CAR-T, higher CRP, D-dimer, and ferritin and rising levels of CRP and fibrinogen ≥14 days post-CAR-T were associated with bacteremia and can facilitate earlier targeted interventions. These data highlight opportunities for improved antibiotic stewardship in the context of CRS, which is critical given the association between broad-spectrum antibiotic exposure, gut microbiome dysbiosis, and worse outcomes after CAR-T.},
}

@article {pmid40751436,
year = {2025},
author = {Samandari, T and Achola, M and Hutter, JN and Mboya, G and Otieno, W and Kee, JJ and Huang, Y and Aponte, JJ and Ockenhouse, CF and Lee, CK and Polakowski, L and Yacovone, M and Tapley, A and Dadabhai, S and Mkhize, NN and Kaldine, H and Bhebhe, S and Moore, PL and Hural, J and Garrett, N and Kublin, JG},
title = {Plasmodium falciparum Parasitemia Does Not Diminish Neutralizing Antibody Responses After mRNA COVID-19 Booster Vaccination in HIV-infected Adults.},
journal = {The Journal of infectious diseases},
volume = {},
number = {},
pages = {},
doi = {10.1093/infdis/jiaf398},
pmid = {40751436},
issn = {1537-6613},
abstract = {mRNA vaccines have emerged as powerful tools for the prevention of infectious diseases, but subclinical malaria may reduce vaccine immunogenicity. We evaluated neutralizing antibody responses in asymptomatic HIV-infected adults with and without PCR-confirmed Plasmodium falciparum who received either monovalent mRNA-1273 or bivalent mRNA-1273.222 (WA-1 and BA.4/5) booster vaccines. In previous studies, a 50% pseudovirus inhibitory dose neutralizing antibody (ID50) titer of 1,000 correlated with 96% efficacy in preventing COVID-19. We observed ID50 geometric mean titers >22,000 in both parasitemic and non-parasitemic participants one month after boosting. We conclude that COVID-19 mRNA vaccine antibody responses are unimpaired by concurrent asymptomatic parasitemia.},
}

@article {pmid40750774,
year = {2025},
author = {Domingo-Domènech, E and Pro, B and Illidge, T and Horwitz, S and Trumper, L and Iyer, S and Advani, R and Bartlett, NL and Christensen, JH and Kim, WS and Feldman, T and Choi, I and Gritti, G and Belada, D and Shustov, A and Illes, A and Zinzani, PL and Hüttmann, A and Trneny, M and Le Gouill, S and Jagadeesh, D and Friedberg, JW and Little, M and Dong, C and Fanale, M and Fenton, K and Savage, KJ},
title = {Brentuximab vedotin plus chemotherapy for the treatment of front-line systemic anaplastic large cell lymphoma: subgroup analysis of the ECHELON-2 study at 5 years' follow-up.},
journal = {Blood cancer journal},
volume = {15},
number = {1},
pages = {129},
pmid = {40750774},
issn = {2044-5385},
mesh = {Humans ; *Brentuximab Vedotin/administration & dosage/therapeutic use/adverse effects ; *Lymphoma, Large-Cell, Anaplastic/drug therapy/mortality/pathology ; *Antineoplastic Combined Chemotherapy Protocols/therapeutic use/adverse effects ; Follow-Up Studies ; Female ; Male ; Middle Aged ; Aged ; Adult ; Treatment Outcome ; },
abstract = {ClinicalTrials.gov number: NCT01777152.},
}

Humans
*Brentuximab Vedotin/administration & dosage/therapeutic use/adverse effects
*Lymphoma, Large-Cell, Anaplastic/drug therapy/mortality/pathology
*Antineoplastic Combined Chemotherapy Protocols/therapeutic use/adverse effects
Follow-Up Studies
Female
Male
Middle Aged
Aged
Adult
Treatment Outcome

@article {pmid40750760,
year = {2025},
author = {Golmohammadi, M and Raza, S and Albayyadhi, M and Sholehrasa, H and Khouri, J and Williams, L and Hansen, DK and Moradi, A and Xu, X and Albliwi, M and Ali, AH and Dima, D and Anwer, F and Paul, B and Jaberi-Douraki, M},
title = {Comprehensive assessment of adverse event profiles associated with bispecific antibodies in multiple myeloma.},
journal = {Blood cancer journal},
volume = {15},
number = {1},
pages = {130},
pmid = {40750760},
issn = {2044-5385},
mesh = {Humans ; *Multiple Myeloma/drug therapy ; *Antibodies, Bispecific/adverse effects/therapeutic use ; B-Cell Maturation Antigen/immunology ; Male ; *Antineoplastic Agents, Immunological/adverse effects/therapeutic use ; Female ; Aged ; },
abstract = {Bispecific antibodies (BsAbs) have shown promise in the management of relapsed/refractory multiple myeloma (MM). Despite its efficacy, this class of drugs is associated with significant toxicities. In this study, we conducted a pooled analysis of the available clinical trials on BsAbs for the treatment of MM, including full publications and abstracts until April 2025. BsAbs were classified into two groups: B-cell maturation antigen (BCMA), and GPRC5D/FcRH5 BsAbs. Welch's t-test was performed to compare the safety profiles of each agent. For clustering, we used principal component analysis (PCA). Our study analyzed 22 trials involving 2374 patients with MM from early 2023 to April 2025. Among these, 1276 patients received BCMA BsAbs, 841 treated with GPRC5D/FcRH5 BsAbs, 157 received teclistamab + talquetamab, and 65 patients received a talquetamab + daratumumab, and 35 patients received talquetamab + pomalidomide. The median follow-up for all groups was 11.83 months. Among all-grade hematologic adverse events (AEs), neutropenia occurred in 40.4%, anemia in 39.2%, thrombocytopenia in 21.4%, lymphopenia in 19.2%, infections in 45.8%, and cytokine release syndrome (CRS) in 65%. For grade 3/4 AEs, infections occurred in 20.3%, CRS in 1.5%, neutropenia in 35.2%, anemia in 24.5%%, thrombocytopenia in 13.5%, and lymphopenia in 17.7%. CRS and the need for tocilizumab were significantly less frequent with BCMA BsAbs vs GPRC5D/FcRH5 BsAbs, (P < 0.002). Skillings Mack (Generalized Friedman's) findings emphasized substantial distinctions between BCMA and GPRC5D/FcRH5×CD3 in both overall and severe grade 3/4 AEs (p ≤ 0.0002). PCA revealed agents with all grades and grade 3/4 showed similar clustering patterns except for three agents. Overall, our findings demonstrated the excellent efficacy on the use of BsAbs in MM; however, these agents have been linked to a unique AE profile. GPRC5D/FcRH5 are associated with less grade 3/4 hematologic toxicity whereas BCMA BsAbs were associated with lower grade 3/4 CRS rates, compared to GPRC5D/FcRH5. These insights are crucial for guiding treatment decisions and developing strategies to improve patient outcomes.},
}

Humans
*Multiple Myeloma/drug therapy
*Antibodies, Bispecific/adverse effects/therapeutic use
B-Cell Maturation Antigen/immunology
Male
*Antineoplastic Agents, Immunological/adverse effects/therapeutic use
Female
Aged

@article {pmid40749169,
year = {2025},
author = {Dhakal, B and Akhtar, OS and Fandrei, D and Jensen, A and Banerjee, R and Pan, D and Richard, S and Friend, R and Rees, MJ and Costello, P and Vazquez Martinez, MA and Pasvolsky, O and Wagner, CB and Davis, JA and Castaneda Puglianini, OA and Reshef, R and Afrough, A and Dima, D and Bhutani, M and Nadeem, O and Parrondo, RD and Freeman, CL and Mikkilineni, L and Raza, S and Anderson, LD and Kapoor, P and Hosoya, H and Chhabra, S and Grajales-Cruz, A and Gaballa, MR and Midha, S and Alsina, M and Sborov, DW and Patel, KK and Lin, Y and Ferreri, CJ and Gagelmann, N and Kumar, AD and Hansen, DK and Cowan, AJ and Costa, LJ and Merz, M and Sidana, S},
title = {Sequential Targeting in Multiple Myeloma: Talquetamab, a GPRC5D bispecific antibody, as a Bridge to BCMA CAR-T cell therapy.},
journal = {Blood},
volume = {},
number = {},
pages = {},
doi = {10.1182/blood.2025029773},
pmid = {40749169},
issn = {1528-0020},
abstract = {Ciltacabtagene autoleucel (cilta-cel) and idecabtagene vicleucel (ide-cel), two BCMA-directed chimeric antigen receptor T cell (CAR-T) therapies, have transformed outcomes for relapsed/refractory multiple myeloma (RRMM); however, the 6-8 weeks manufacturing time risks disease progression or death in up to 10% of patients, highlighting the need for effective bridging strategies. Talquetamab, a GPRC5D-targeting bispecific antibody, represents a promising option. We performed a multi-institutional retrospective analysis across 20 centers (18 US, 2 Germany) evaluating talquetamab as a bridging therapy prior to cilta-cel or ide-cel. Among 134 patients receiving talquetamab, 119 proceeded to CAR-T (n=98 cilta-cel, n=21 ide-cel). Reasons for not proceeding (n=15) included progression (n=7), manufacturing failure (n=6), or patient decision (n=2). Median age was 65 years; patients had received a median 5 prior lines of therapy. High-risk cytogenetics and extramedullary disease were present in 44% and 41% respectively. Notably, 85% would not have met CARTITUDE-1/KarMMa eligibility criteria. Talquetamab was administered for a median 23 days (82% at 0.8 mg/kg biweekly). Toxicity was manageable: no grade ≥3 CRS, 2% grade 3 ICANS and grade 1-2 Talq unique toxicities (70% oral, 38% skin, 17% nail; 60% resolved). Talquetamab achieved 71% response rate. Post CAR-T 88% responded (54% complete response), with low-grade toxicities (2 grade≥3 CRS, 1 grade 3 ICANS and 5% grade≥3 infections). Two cases of facial palsy and one AML occurred. Talquetamab correlated with sustained soluble BCMA decline and peak CAR-T expansion around day 14. Talquetamab bridging appears safe enabling the majority of difficult to treat patients to successfully proceed to BCMA CAR-T therapy.},
}

@article {pmid40749165,
year = {2025},
author = {McManus, D and Copsel, SN and Pfeiffer, BJ and Wolf, D and Barreras, H and Ma, S and Khodor, A and Komai, S and Burgos da Silva, M and Hazime, H and Gallardo, M and Lime, SGR and van den Brink, MRM and Park, JH and Abreu, MT and Hill, GR and Perez, VL and Levy, RB},
title = {Pretransplant targeting of TNFRSF25 and CD25 stimulates recipient Tregs in target tissues, ameliorating GVHD post-HSCT.},
journal = {Blood},
volume = {},
number = {},
pages = {},
doi = {10.1182/blood.2025028418},
pmid = {40749165},
issn = {1528-0020},
abstract = {The current approach to minimize transplant-associated complications, including graft-versus-host disease (GVHD) includes long-term pharmacological immune suppression frequently accompanied by unwanted side effects. Advances in targeted immunotherapies regulating alloantigen responses in the recipient continue to reduce the need for pan-immunosuppression. Here, in vivo targeting of the TNF superfamily receptor TNFRSF25 and the high affinity IL-2 receptor with a TL1A-Ig fusion protein and low dose IL-2, respectively was used to pre-treat recipient mice prior to allogeneic-HSCT (aHSCT). Pre-treatment induced Treg expansion persisting 1-2 weeks post-HSCT leading to diminished GVHD and improved transplant outcomes. Expansion was accompanied by an increase in the frequency of stable and active Tregs creating a suppressive tissue environment in the colon, liver and eye. Importantly, pre-treatment supported epithelial cell function/integrity, a diverse microbiome including reduction of pathologic bacteria outgrowth and promotion of butyrate producing bacteria, while maintaining physiologic levels of obligate/facultative anaerobes. Notably, using a sphingosine 1-phosphate receptor agonist to sequester T cells in lymphoid tissues, it was found that the increased tissue Treg frequency included resident CD69+CD103+FoxP3+ hepatic Tregs. In contrast to infusion of donor Treg cells, the strategy developed here resulted in the presence of immunosuppressive target tissue environments in the recipient prior to the receipt of donor allo-reactive T cells and successful perseveration of GVL responses. We posit strategies that circumvent the need of producing large numbers of Tregs ex-vivo through manipulating this recipient compartment in vivo, can provide translational approaches to improve aHSCT outcomes.},
}

@article {pmid40748320,
year = {2025},
author = {Ziller, SG and Blew, RM and Roe, DJ and Odegaard, A and Chen, Z and Caan, BJ and Luo, J and Manson, JE and Neuhouser, ML and Rohan, TE and Bea, JW},
title = {Dual-energy X-ray absorptiometry derived adiposity and colorectal cancer incidence and mortality in postmenopausal women.},
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-25-0581},
pmid = {40748320},
issn = {1538-7755},
abstract = {BACKGROUND: Determine if dual-energy X-ray absorptiometry (DXA) derived adiposity was associated with colorectal cancer (CRC) incidence and mortality in postmenopausal women from the Women's Health Initiative (WHI) DXA Cohort.

METHODS: Whole-body DXA scans estimated adiposity. Women with cancer history (except non-melanoma skin cancer) or missing baseline DXA were excluded. For 27 years of follow-up, outcomes and death were adjudicated. Descriptive statistics by CRC status were calculated. Fine and Gray's competing risks regression was used to estimate sub-hazard ratios (SHR) and 95% confidence intervals (CI). Observation time was from enrollment to first CRC event or competing risk (other cancer, other cause of death); women without cancer at last follow-up were censored. Covariates included sociodemographic, clinical, and study characteristics.

RESULTS: After exclusions, 9,950 women were included, with 191 first-incident CRC and 88 CRC-related deaths identified. At baseline, mean (±SD) age was 63.3 (±7.4) years, and body mass index was 28.2 (±5.7) kg/m2. In adjusted models, baseline continuous abdominal visceral adipose tissue (VAT) (per 100cm2) and android fat (per kg) were significantly associated with a higher risk of first-incident CRC: SHR (95% CI) 1.23 (1.04-1.45) and 1.15 (1.01-1.31), respectively. There were no significant associations between adiposity and CRC mortality.

CONCLUSIONS: Higher amounts of abdominal VAT and android fat were associated with a higher risk of CRC incidence in postmenopausal women.

IMPACT: Associations between VAT and CRC, independent of BMI, support clinical assessment of body composition across weight categories. A head-to-head comparison of VAT and BMI for CRC prediction is recommended in future research.},
}

@article {pmid40748144,
year = {2025},
author = {Flamand, L and Arbuckle, J and Bonnafous, P and Descamps, V and Hill, JA and Jarrett, R and Jerome, K and Kaufer, BB and Koide, R and Komaroff, AL and Medveczky, P and Miura, H and Mori, Y and Parrish, N and Pellett, PE and Wood, M and Yoshikawa, T and Zerr, DM},
title = {Endogenous human herpesviruses 6A/B.},
journal = {Journal of virology},
volume = {},
number = {},
pages = {e0105425},
doi = {10.1128/jvi.01054-25},
pmid = {40748144},
issn = {1098-5514},
abstract = {Human herpesviruses 6A and 6B (HHV-6A/B) can integrate into the germline, resulting in inherited viral DNA-now proposed to be called "endogenous HHV-6A/B (eHHV-6A/B)." Present in 0.2-3% of humans, this integrated DNA is passed to offspring and may reactivate, posing health risks such as angina or lupus. To reduce confusion caused by varied terminology, researchers advocate using "eHHV-6A/B" for inherited forms and reserving "chromosomally integrated" for somatic integrations only.},
}

@article {pmid40748049,
year = {2025},
author = {Xia, B and Kim, AR and Liu, F and Han, M and Stoneburner, E and Makdissi, S and Di Cara, F and Mohr, SE and Ring, A and Perrimon, N},
title = {Phage-displayed synthetic library and screening platform for nanobody discovery.},
journal = {eLife},
volume = {14},
number = {},
pages = {},
pmid = {40748049},
issn = {2050-084X},
support = {NIH NIGMS P41 GM132087/NH/NIH HHS/United States ; NIH 5R24OD035556/NH/NIH HHS/United States ; 2021R1A6A3A14039622//National Research Foundation/ ; },
mesh = {*Single-Domain Antibodies/isolation & purification/immunology/genetics ; Animals ; *Peptide Library ; Cell Surface Display Techniques ; Drosophila Proteins/immunology ; Drosophila ; },
abstract = {Nanobodies, single-domain antibodies derived from camelid heavy-chain antibodies, are known for their high affinity, stability, and small size, which make them useful in biological research and therapeutic applications. However, traditional nanobody generation methods rely on camelid immunization, which can be costly and time-consuming, restricting their practical feasibility. In this study, we present a phage-displayed synthetic library for nanobody discovery. To validate this approach, we screened nanobodies targeting various Drosophila secreted proteins. The nanobodies identified were suitable for applications such as immunostaining and immunoblotting, supporting the phage-displayed synthetic library as a versatile platform for nanobody development. To address the challenge of limited accessibility to high-quality synthetic libraries, this library is openly available for non-profit use.},
}

*Single-Domain Antibodies/isolation & purification/immunology/genetics
Animals
*Peptide Library
Cell Surface Display Techniques
Drosophila Proteins/immunology
Drosophila

@article {pmid40746155,
year = {2025},
author = {Dong, M and Thakral, A and Byrne, KS and Bosse, Y and Zhou, H and Zhang, Y and Atkins, J and Haycock, P and Brown, MC and Murison, K and Timens, W and Sin, DD and Kothari, J and Gabriel, AAG and Zaridze, D and Savic, M and Lissowska, J and Świątkowska, B and Janout, V and Holcatova, I and Mukeria, A and Fernandez-Tardon, G and Davies, MPA and Triplette, M and Schabath, MB and Andrew, AS and Chen, C and Taylor, F and Field, JK and Tardon, A and Shete, SS and Brennan, P and Landi, MT and McKay, J and Amos, CI and Lin, X and Christiani, DC and Hung, RJ and Liu, G and Xu, W},
title = {Genome-wide association study of early-stage non-small cell lung cancer prognosis: a pooled analysis in the International Lung Cancer Consortium.},
journal = {Carcinogenesis},
volume = {},
number = {},
pages = {},
doi = {10.1093/carcin/bgaf031},
pmid = {40746155},
issn = {1460-2180},
abstract = {Lung cancer is the leading cause of cancer mortality. To investigate genetic determinants for prognosis among patients diagnosed with early-stage non-small cell lung cancer (NSCLC), we conducted the first large-scale genome-wide association prognostic study using data from the International Lung Cancer Consortium (ILCCO) through a two-phase analysis. Phase 1 includes the discovery of genome-wide association studies analysis using a multivariable Cox PH model on 3428 NSCLC patients of European ancestry from 10 ILCCO participating studies to identify genetic variants associated with overall survival and validation analysis for genome-wide significant variants (P-value ≤5 × 10-8) using the Cancer Genome Atlas (TCGA). Phase 2 aims to identify causal variants using functional analyses of genome-wide significant and suggestive variants (P-value ≤1 × 10-5), including variant-epigenetic functional annotation (FAVOR), CHIP-seq data, variant-gene expression association, and colocalization analysis. We identified two significant variants; of those, a locus at 9q21.31 (rs117979484) was significant at the genome-wide level (P = 3.67 × 10-8) and validated in TCGA (P = 0.03). Three suggestive variants were found to have a putative epigenetic function: intronic variants rs149281784 (BCL7B gene) and rs148031766 (POM121 gene) both located at 7q11.23 and in moderate linkage disequilibrium with each other; and variant rs2471630 (SRCIN1 gene; 17q12). Specifically, variants rs149281784 and rs148031766 have potential regulatory roles in the transcriptional activation of the BCL7B gene and POM121 gene. Exploratory survival analyses in the squamous cell carcinomas subgroup also identified a significant variant, rs138467404 (GRHL-2 gene; 8q22.3) at a genome-wide level (P = 4.75 × 10-8) and validated by TCGA (P = 0.02). These new findings indicate potential novel pathways associated with early-stage NSCLC prognosis. Future research may validate additional genome-wide suggestive variants as being relevant for lung cancer outcomes.},
}

@article {pmid40742241,
year = {2025},
author = {Graham, LS and Yu, EY},
title = {Early and Precise: Treating HRR Alterations in Hormone-Sensitive Prostate Cancer.},
journal = {Clinical cancer research : an official journal of the American Association for Cancer Research},
volume = {},
number = {},
pages = {},
doi = {10.1158/1078-0432.CCR-25-2359},
pmid = {40742241},
issn = {1557-3265},
abstract = {Patients with prostate cancer and HRR alterations face worse outcomes. Early use of PARP inhibitors, especially in BRCA-mutated cancers is promising. However, optimal timing, sequencing, and benefits for non-BRCA alterations remain unclear, underscoring the need for well-designed clinical trials and personalized treatment discussions.},
}

@article {pmid40742180,
year = {2025},
author = {Tang, G and Carr, AV and Perez, C and Ramos Sarmiento, K and Levy, L and Lampe, JW and Diener, C and Gibbons, SM},
title = {Metagenomic estimation of absolute bacterial biomass in the mammalian gut through host-derived read normalization.},
journal = {mSystems},
volume = {},
number = {},
pages = {e0098425},
doi = {10.1128/msystems.00984-25},
pmid = {40742180},
issn = {2379-5077},
abstract = {Absolute bacterial biomass estimation in the human gut is crucial for understanding microbiome dynamics and host-microbe interactions. Current methods for quantifying bacterial biomass in stool, such as flow cytometry, quantitative polymerase chain reaction (qPCR), or spike-ins, can be labor-intensive, costly, and confounded by factors like water content, DNA extraction efficiency, PCR inhibitors, and other technical challenges that add bias and noise. We propose a simple, cost-effective approach that circumvents some of these technical challenges: directly estimating bacterial biomass from metagenomes using bacterial-to-host (B:H) read count ratios. We compared B:H ratios to the standard methods outlined above, demonstrating that B:H ratios are useful proxies for bacterial biomass in stool and possibly in other host-associated substrates. B:H ratios in stool were correlated with bacterial-to-diet (B:D) read count ratios, but B:D ratios exhibited a substantial number of outlier points. Host read depletion methods reduced the total number of human reads in a given sample, but B:H ratios were strongly correlated before and after host read depletion, indicating that host read depletion did not reduce the utility of B:H ratios. B:H ratios showed expected variation between health and disease states and were generally stable in healthy individuals over time. Finally, we showed how B:H and B:D ratios can be used to track antibiotic treatment response and recovery. B:H ratios offer a convenient alternative to other absolute biomass quantification methods, without the need for additional measurements, experimental design considerations, or machine learning, enabling robust absolute biomass estimates directly from stool metagenomic data.IMPORTANCEIn this study, we asked whether normalization by host reads alone was sufficient to estimate absolute bacterial biomass directly from stool metagenomic data, without the need for synthetic spike-ins, additional experimental biomass measurements, or training data. The approach assumes that the contribution of host DNA to stool is more constant or stable than biologically relevant fluctuations in bacterial biomass. We find that host read normalization is an effective method for detecting variation in gut bacterial biomass. Absolute bacterial biomass is a key metric that often gets left out of gut microbiome studies, and empowering researchers to include this measure more broadly in their metagenomic analyses should serve to improve our understanding of host-microbiota interactions.},
}

@article {pmid40740737,
year = {2025},
author = {Bulosan, H and Nunez, YC and Wu, B and George, E and Cogen, AL},
title = {A patient with a purple, edematous great toe.},
journal = {JAAD case reports},
volume = {62},
number = {},
pages = {113-115},
pmid = {40740737},
issn = {2352-5126},
}

@article {pmid40740502,
year = {2025},
author = {Nolan, CT and Campbell, I and Farrell-Sherman, A and Briones Ortiz, BA and Yang, C and Naish, KA and Di Stilio, VS and Kaldy, JE and Donoghue, C and Ruesink, JL and Imaizumi, T},
title = {Florigen and antiflorigen gene expression correlates with reproductive state in a marine angiosperm, Zostera marina.},
journal = {iScience},
volume = {28},
number = {8},
pages = {113082},
pmid = {40740502},
issn = {2589-0042},
abstract = {Florigen and antiflorigen genes within the phosphatidylethanolamine-binding protein (PEBP) family regulate flowering in angiosperms. In eelgrass (Zostera marina), an estuarine foundation species, flowering, and seed production are crucial for population resilience. Yet, the molecular mechanism underpinning flowering remains unknown. Among 13 PEBP genes in Z. marina (ZmaPEBP), we showed that four genes (ZmaFT2, ZmaFT4, ZmaFT9, and ZmaTFL1a) altered flowering time when overexpressed in Arabidopsis. We analyzed gene expression in different tissues and throughout the growth season from perennial and annual populations in Willapa Bay and Yaquina Bay, USA. Across six sites exhibiting different degrees of population genetic structure, ZmaFT2 and ZmaFT4 were expressed in leaves of vegetative and reproductive shoots and in rhizomes of reproductive shoots. ZmaFT9 was solely expressed in leaves of vegetative shoots, while ZmaTFL1a levels increased after flowering shoots developed. Our results suggest that ZmaFT2 and ZmaFT4 may promote flowering, while ZmaFT9 may inhibit flowering in eelgrass.},
}

@article {pmid40739416,
year = {2025},
author = {Shin, MB and Vu, T and Masud, M and Duran, MC and Escoffery, NC and Bishop, S and Winer, RL and Ko, LK},
title = {Evaluation of an implementation support program for rural communities using a two-tiered, embedded framework.},
journal = {Cancer causes & control : CCC},
volume = {},
number = {},
pages = {},
pmid = {40739416},
issn = {1573-7225},
support = {U48 DP006398 and U48 DP006377//Division of Cancer Prevention and Control, the National Center for Chronic Disease Prevention and Health Promotion of the Centers for Disease Control and Prevention, U.S. Department of Health and Human Services/ ; UL1 TR002319/TR/NCATS NIH HHS/United States ; },
abstract = {PURPOSE: Evaluate the impact of Implementation Studio (the "Studio") on community-based organizations' (CBOs) EBI implementation, including changes in breast and colorectal (CRC) cancer screening status among Hispanic/Latino/a EBI recipients.

METHODS: A two-tiered, embedded framework consisted of 1) surveys (n = 38) comparing up-to-date breast and CRC screening status among EBI recipients pre/post-EBI delivery (Tier 1); and semi-structured interviews (n = 13 total; n = 7 leaders, n = 6 community health workers) with CBO staff assessing EBI implementation outcomes using rapid qualitative analysis methods (Tier 2) guided by Proctor's Implementation Research Outcomes Framework. Surveys and interviews were conducted in Spanish/English by phone/virtually September 2022-September 2023.

RESULTS: Up-to-date screening status increased by 16.6% for breast and 19.3% for CRC screening pre/post-EBI implementation, albeit not statistically significant overall (p = 0.168). CBOs reported that implementing EBIs cultivated their confidence and enhanced CBOs' workforce capacity (acceptability). CHWs (the primary EBI implementers) proficiently used the Studio tools to adapt the EBIs to improve fit and implement them in the rural Hispanic/Latino/a communities (appropriateness). Remote delivery increased the EBI accessibility for the community (feasibility). Key drivers of costs were CHWs' time to adapt and implement EBIs (costs). CBOs expressed the need to address clients' social needs to maintain EBI's impact (sustainability).

CONCLUSION: CBOs successfully implemented CHW-led EBIs, and their efforts increased up-to-date cancer screening among rural Hispanic/Latino/a community members. These findings demonstrate that Studio is a promising strategy for building CBOs' capacity to implement EBIs and increase cancer screening.},
}

@article {pmid40739193,
year = {2025},
author = {Trejo, MJ and Floyd, JS and Massera, D and Daviglus, M and Garcia-Bedoya, O and Cai, J and Talavera, GA and Tamayo-Murillo, DE and Labovitz, D and Kaplan, R},
title = {Association of liver related biomarkers with incident cardiovascular disease and all-cause mortality in the Hispanic community health study/study of Latinos (HCHS/SOL), a population-based cohort study.},
journal = {BMC gastroenterology},
volume = {25},
number = {1},
pages = {543},
pmid = {40739193},
issn = {1471-230X},
support = {1R01DK134672/DK/NIDDK NIH HHS/United States ; N01-HC65236/HL/NHLBI NIH HHS/United States ; N01-HC65236/HL/NHLBI NIH HHS/United States ; N01-HC65233/HL/NHLBI NIH HHS/United States ; N01-HC65237/HL/NHLBI NIH HHS/United States ; N01HC65235/HL/NHLBI NIH HHS/United States ; 1R01AG085320//National Institute of Aging/ ; },
mesh = {Humans ; Male ; Female ; Middle Aged ; Adult ; *Cardiovascular Diseases/mortality/blood/ethnology/epidemiology ; Biomarkers/blood ; *Hispanic or Latino/statistics & numerical data ; *Alanine Transaminase/blood ; Aged ; *Aspartate Aminotransferases/blood ; Young Adult ; Adolescent ; Incidence ; Cohort Studies ; *Fatty Liver/blood/ethnology/complications ; United States/epidemiology ; Cause of Death ; White ; },
abstract = {BACKGROUND: Metabolic dysfunction-associated steatotic liver disease (MASLD) increases risk of cardiovascular disease (CVD). Despite the high prevalence of MASLD among Hispanic populations, there is a scarcity of research on the associations between non-invasive markers of liver disease and incident CVD and all-cause mortality. In this study we investigated the association of liver related biomarkers with CVD events and all-cause mortality in a population based Hispanic/Latino cohort.

METHODS: We included 15,216 participants from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) aged 18-74 years with no pre-existing CVD. The composite outcome combined incident CVD and all-cause mortality. Having "elevated ALT/AST" was defined as ALT > 40 IU/mL or AST > 37 IU/mL for males, and ALT or AST > 31 IU/mL for females. We estimated adjusted hazard ratios (HR) and 95% confidence intervals (CI) relating our composite outcome to elevated ALT/AST, FIB-4 and MASLD. Using interaction terms, we assessed whether the relationship between elevated ALT/AST and the composite outcome differed by MASLD status.

RESULTS: The study population was 40 years old on average, 52.7% female and had 740 CVD or all-cause mortality events. Elevated FIB-4 had the strongest association with incident CVD or all-cause mortality (comparing FIB-4 > 2.67 versus ≤ 2.67, HR:3.47; CI:2.34-5.14). Elevated AST was found to be associated with incident CVD or all-cause mortality (HR:1.53; CI:1.14-2.05). MASLD was not associated with incident CVD or all-cause mortality (HR:1.14; CI: 0.94-1.40), but it was associated with incident CVD alone (HR:1.69; CI:1.19-2.39). The relationship between elevated ALT/AST and incident or all-cause mortality was modified by MASLD, such that the strongest association between elevated ALT/AST and incident CVD or all-cause mortality was in the absence of MASLD (HR:1.95; CI:1.20-3.18).

CONCLUSIONS: Among Hispanic adults FIB-4 was strongly associated with CVD or all-cause mortality and among persons without MASLD, elevated ALT/AST were associated with CVD or all-cause mortality.},
}

Humans
Male
Female
Middle Aged
Adult
*Cardiovascular Diseases/mortality/blood/ethnology/epidemiology
Biomarkers/blood
*Hispanic or Latino/statistics & numerical data
*Alanine Transaminase/blood
Aged
*Aspartate Aminotransferases/blood
Young Adult
Adolescent
Incidence
Cohort Studies
*Fatty Liver/blood/ethnology/complications
United States/epidemiology
Cause of Death
White

@article {pmid40738478,
year = {2025},
author = {Murakami, N and Blosser, CD and Webber, AB and Gupta, G and Singh, N and Boppana, S and Master, S and Parasuraman, R and Campagnaro, EL and Java, A and Sprangers, B and Bhasin-Chhabra, B and Lum, E and Khirfan, D and Alexander, P and Molnar, MZ and Benes, B and Thakur, AK and Bumma, N and Karam, S and Hultcrantz, M and Bridoux, F and Sanchorawala, V and Leung, N and Landau, H},
title = {Management recommendations for kidney transplantation in patients with plasma cell dyscrasia.},
journal = {Kidney international},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.kint.2025.07.011},
pmid = {40738478},
issn = {1523-1755},
abstract = {Patients with plasma cell dyscrasias (PCD), including multiple myeloma, AL amyloidosis, and monoclonal gammopathy of renal significance (MGRS), face a high burden of end-stage kidney disease (ESKD), limiting survival and quality of life. While kidney transplantation offers potential benefits, it is underutilized due to high risk of recurrence and historically poor outcomes. A multidisciplinary panel of transplant nephrologists, hematologists/oncologists, and pathologists convened to evaluate contemporary evidence and evolving strategies in kidney transplant for PCD-ESKD. Advances in PCD therapies are improving survival and expanding kidney transplant eligibility. Key challenges remain, including optimizing hematologic response pre-kidney transplant, immunosuppression management to mitigate recurrence and avoid infection complications. Ongoing research and multidisciplinary collaboration are essential to refine transplant selection, integrate biomarkers for risk stratification, and develop tailored post-kidney transplant surveillance. These efforts may increase access to kidney transplant and improve outcomes for patients with PCD-ESKD.},
}

@article {pmid40737820,
year = {2025},
author = {VoPham, T and Liu, T and Cortez, M and Karasaki, S and Falkenberg, NF and Zewdie, HY and Lin, J and Nondin, C and Chao, SLS and Knowlton, T and Quennehen, B and Mendoza, JA and Ioannou, GN and Berry, K and Adamkiewicz, G and Li, CI and Hart, JE},
title = {Exposure to outdoor air pollution, wildfires, and cancer survival in the United States.},
journal = {Cancer epidemiology},
volume = {98},
number = {},
pages = {102899},
doi = {10.1016/j.canep.2025.102899},
pmid = {40737820},
issn = {1877-783X},
abstract = {BACKGROUND: Climate change has led to an increase in wildfires, a major source of air pollution, which may be particularly harmful to individuals diagnosed with cancer. The objective of this study was to examine the relationships of air pollution and wildfires with mortality risk among cancer survivors.

METHODS: Surveillance, Epidemiology, and End Results (SEER) cancer registries provided information on 7,051,014 patients diagnosed with cancer from 2000 to 2021 in the United States. Cox regression was used to calculate adjusted hazard ratios (HRs) and 95 % confidence intervals (CIs) for the associations between exposures to particulate matter < 2.5 µm (PM2.5), nitrogen dioxide (NO2), ozone (O3), and wildfires (estimated using high-resolution geospatial datasets) with all-cause and cause-specific mortality risk.

RESULTS: There were 3,452,593 deaths, including 2,369,364 from cancer, 525,409 from cardiopulmonary, and 557,820 from other causes. Among cancer survivors, higher exposure to PM2.5 and wildfires (but not NO2 or O3) were associated with increased risk for all-cause, cancer, and other mortality. The association between PM2.5 and cancer mortality was stronger in counties more heavily impacted by wildfires (HR per 10 μg/m[3] in counties with ≥ median 0.39 wildfires per year: 1.17, 95 % CI 1.04-1.33) vs. no wildfires (HR 1.06, 95 % CI 0.97-1.15) (p interaction = 0.0064).

CONCLUSIONS: Among patients diagnosed with cancer, PM2.5 air pollution, particularly in areas heavily impacted by wildfires, is associated with increased risk for mortality.},
}