@article {pmid41053004,
year = {2025},
author = {Foster, L and Anderson, LD and Chung, A and Chaulagain, CP and Pettijohn, E and Cowan, AJ and Costello, C and Larson, S and Sborov, DW and Shain, KH and Silbermann, R and Voorhees, P and Krevvata, M and Pei, H and Patel, S and Khare, V and Cortoos, A and Carson, R and Lin, TS and Badros, A},
title = {Daratumumab plus lenalidomide maintenance in newly diagnosed multiple myeloma after transplant: AURIGA subgroup analyses.},
journal = {Blood cancer journal},
volume = {15},
number = {1},
pages = {154},
pmid = {41053004},
issn = {2044-5385},
mesh = {Humans ; *Multiple Myeloma/therapy/mortality/drug therapy/diagnosis ; *Lenalidomide/administration & dosage/therapeutic use ; Female ; Male ; Middle Aged ; Aged ; *Antineoplastic Combined Chemotherapy Protocols/therapeutic use/adverse effects ; *Antibodies, Monoclonal/administration & dosage/therapeutic use ; Adult ; *Hematopoietic Stem Cell Transplantation ; Maintenance Chemotherapy ; },
abstract = {In the primary analysis (32.3-month median follow-up) of the randomized, phase 3 AURIGA study (NCT03901963), daratumumab-lenalidomide (D-R) maintenance significantly improved MRD-negative conversion rates and reduced the risk of disease progression or death by 47% versus R maintenance in anti-CD38 monoclonal antibody-naïve and post-transplant MRD-positive patients with newly diagnosed MM. Here, we present a post hoc analysis across relevant subgroups, including high-risk cytogenetic abnormalities (HRCAs) per original, revised, and modified International Myeloma Society (IMS) 2024 criteria. MRD-negative (10[-5]) conversion rates by 12 months of maintenance were higher for D-R versus R across cytogenetically high-risk subgroups per original (31.8% vs 6.7%), revised (43.8% vs 13.3%), and modified IMS 2024 (41.2% vs 0%) criteria and cytogenetically ultra-high-risk disease (≥2 revised HRCAs; 54.5% vs 0%). Similar trends in overall MRD-negative conversion rates were observed across subgroups. D-R demonstrated a trend towards improved PFS versus R (HR [95% CI]) in cytogenetically high-risk subgroups per original (0.60 [0.21-1.70]), revised (0.53 [0.21-1.31]), and modified IMS 2024 (0.45 [0.13-1.53]) criteria and cytogenetically ultra-high-risk disease (0.61 [0.17-2.25]). Similar outcomes were observed regardless of age or race, with no additional safety concerns among older (≥65 years) or Black patients. These data support the benefit of D-R maintenance regardless of age, race, and risk status.},
}

Humans
*Multiple Myeloma/therapy/mortality/drug therapy/diagnosis
*Lenalidomide/administration & dosage/therapeutic use
Female
Male
Middle Aged
Aged
*Antineoplastic Combined Chemotherapy Protocols/therapeutic use/adverse effects
*Antibodies, Monoclonal/administration & dosage/therapeutic use
Adult
*Hematopoietic Stem Cell Transplantation
Maintenance Chemotherapy

@article {pmid41052457,
year = {2025},
author = {Balogh, EP and Levit, LA and Unger, JM and Accordino, MK and Chism, DD and Kirkwood, MK and Parsons, HM and Patel, MI and Peppercorn, JM and Polite, BN and Sedrak, MS and Sharma, P and Subbiah, IM and Temel, JS and Yabroff, KR and Osarogiagbon, RU},
title = {ASCO State of Cancer Care in America Special Report 2025: Access to Cancer Clinical Trials in the United States.},
journal = {JCO oncology practice},
volume = {},
number = {},
pages = {OP2500233},
doi = {10.1200/OP-25-00233},
pmid = {41052457},
issn = {2688-1535},
abstract = {Improving patient access to cancer clinical trials is a fundamental ASCO priority because clinical cancer research is the essential link transforming biomedical discoveries into meaningful progress in cancer care and patient outcomes. Today's standard of care emerged from yesterday's clinical trials. However, numerous barriers continue to threaten patient access to cancer clinical trials. This Special Report describes the essential role clinical trials play in improving cancer care and patient outcomes, current challenges in the design and conduct of clinical trials, and steps taken by ASCO to make clinical trials more accessible, patient-centered, and embedded within the communities where people live.},
}

@article {pmid41052403,
year = {2025},
author = {Modi, D and Aljawai, YM and DeFor, TE and Bupp, C and Al Malki, MM and Bolaños-Meade, J and Gooptu, M and Jimenez Jimenez, AM and Liu, H and Mensah, F and Mielcarek, M and Shaffer, BC and Shaw, BE and Spellman, SR and Stefanski, HE and Auletta, JJ and Devine, SM and Khimani, F and Abboud, R},
title = {Matched Unrelated vs Haploidentical Donor Hematopoietic Cell Transplantation Using Post-Transplant Cyclophosphamide.},
journal = {Blood advances},
volume = {},
number = {},
pages = {},
doi = {10.1182/bloodadvances.2025017194},
pmid = {41052403},
issn = {2473-9537},
abstract = {Post-transplant cyclophosphamide (PTCy)-based graft-vs-host disease (GVHD) prophylaxis is the new standard for matched unrelated donor (MUD) hematopoietic cell transplantation (HCT). Prior studies comparing MUD and haploidentical donor HCT using PTCy were limited by size and short follow-up. We therefore performed a registry-based analysis examining the impact of donor type on HCT with PTCy. Adult patients (n=5,873) who received MUD (n=1,973) or haploidentical (n=3900) HCT with PTCy for acute leukemia (74.2%) or myelodysplastic syndrome (25.8%) reported to the CIBMTR between 2017- 2021 were included. Primary endpoints were three-year overall survival (OS) and GVHD-free, relapse-free survival (GRFS). Cox regression and sensitivity analyses were performed through adjustment of propensity scores. Haploidentical HCT had worse OS (Hazard ratio [HR] 1.15, 95% confidence interval [CI] 1.04-1.27, p=0.005) and GRFS (HR 1.19, 95% CI 1.10-1.29, p<0.001) compared to MUD HCT. Donor age was the only other consistent donor-related factor associated with survival. Results were confirmed in a sensitivity analysis adjusted for propensity scores. When the cohort was restricted to reduced intensity conditioning only or donors <30 years-old, OS did not differ between groups. Haploidentical HCT was associated with higher primary graft failure (HR 1.67; p=0.002), increased grade III-IV acute GVHD (HR 1.28; p=0.039), higher moderate/severe chronic GVHD (HR 1.47; p<0.001) and non-relapse mortality (HR 1.34; p<0.001). Grade II-IV aGVHD and relapse risk did not differ between the donor types. This large analysis showed that in adults with acute leukemia or MDS, MUD HCT was associated with improved outcomes compared to haplo HCT with PTCy-based GVHD prophylaxis.},
}

@article {pmid41052219,
year = {2025},
author = {Brokaw, A and Wallen, G and Orvis, A and Kwon, HJ and Seepersaud, R and Nguyen, S and Sharma, K and Coleman, M and Quach, P and Twentyman, J and Vornhagen, J and Jones, LA and Lin, C and Gafken, PR and Rajagopal, L},
title = {The serine protease HtrA regulates Group B Streptococcus virulence and affects the host response to infection.},
journal = {PLoS pathogens},
volume = {21},
number = {10},
pages = {e1013562},
doi = {10.1371/journal.ppat.1013562},
pmid = {41052219},
issn = {1553-7374},
abstract = {Group B Streptococcus (GBS) rectovaginally colonizes up to 20% of women worldwide and is a leading cause of invasive infections during pregnancy, contributing annually to a significant proportion of preterm births, neonatal infections, and stillbirths. Despite its reputation as a perinatal pathogen, GBS infection rates in non-pregnant adults are also increasing. While much progress has been made to understand transcriptional regulation of virulence by two-component systems, many aspects of GBS virulence regulation remain understudied. Although many bacterial pathogens utilize high temperature response A (HtrA) family serine proteases to regulate virulence and stress responses through varied mechanisms, the function of HtrA in GBS was unknown. Here, we demonstrate that HtrA is localized to the GBS membrane and regulates the abundance of endogenous surface and secreted proteins, including a subset of virulence factors. Although deletion of htrA (ΔhtrA) increased dissemination to placentas and fetuses, this strain caused significantly fewer adverse pregnancy outcomes compared to isogenic wild-type (WT). Placentas from ΔhtrA-infected dams contained more chemokines, pro-inflammatory IL-1β, and neutrophil myeloperoxidase than isogenic WT-infected placentas, suggesting that ΔhtrA GBS induces potent neutrophil chemotaxis. However, immunosuppressive IL-10 was present at increased concentration, which may in part explain the attenuation of adverse pregnancy outcomes during ΔhtrA infection. Finally, we note that recombinant GBS HtrA directly cleaves human fibronectin in vitro, highlighting that this protease may also target host substrates during infection. Together, these findings support a role for HtrA as a post-translational regulator of GBS virulence and suggest that inhibiting HtrA activity may hold therapeutic promise against GBS induced adverse pregnancy outcomes.},
}

@article {pmid41051932,
year = {2025},
author = {Jones, SMW and Aoki, RF and Alexeeff, SE and Carrell, D and Cronkite, D and Kushi, LH and Mosen, D and Strayhorn, S and Tuzzio, L and Mogk, J and Mammini, L and Kroenke, CH},
title = {Evaluation of the Electronic Health Record-Support Social Support Score in Breast Cancer: Comparison of Count and Item Response Theory Scores.},
journal = {Population health management},
volume = {},
number = {},
pages = {},
doi = {10.1177/19427891251383539},
pmid = {41051932},
issn = {1942-7905},
abstract = {In breast cancer, clinicians add data on social support to patient electronic health records (EHRs) often in free text notes, but those data may be challenging to use for population health initiatives or research purposes. We evaluated the EHR-Support score designed to summarize need for social support using data from the EHR. This study included 996 women from the Pathways study, a Kaiser Permanente Northern California cohort of women diagnosed in 2005-2013 with breast cancer. This unique data resource included both EHR data and questionnaire data on patient-reported social support. Using unstructured EHR data and natural language processing, we developed 11 concept groups (items) characterizing social support. We also used structured data to create two additional concept groups. EHR-Support scores reflecting the lack of social support were generated three ways: counting the number of negative concept groups (count score), using item response theory (IRT), and converting counts to the IRT metric (converted count scores). The count scores were only associated with two of six patient-reported measures (r's: -0.004 to -0.073). The IRT score (r's: -0.038 to -0.179) and converted count score (r's: -0.032 to -0.195) were associated with five of six patient-reported measures, indicating more need for support was associated with less patient-reported social support. The EHR-Support score is a valid and feasible measure of social support that can be used for health services research and managing population health. The converted count score may provide the best balance of validity, precision from IRT and feasibility.},
}

@article {pmid41047833,
year = {2025},
author = {Bower, JE and Radin, A and Ganz, PA and Irwin, MR and Cole, SW and Petersen, L and Asher, A and Hurvitz, SA and Crespi, CM},
title = {Inflammation and dimensions of fatigue in women with early stage breast cancer: A longitudinal examination.},
journal = {Cancer},
volume = {131},
number = {20},
pages = {e70038},
pmid = {41047833},
issn = {1097-0142},
support = {//Breast Cancer Research Foundation/ ; P30 CA016042/CA/NCI NIH HHS/United States ; R01 CA160427/CA/NCI NIH HHS/United States ; },
mesh = {Humans ; Female ; *Breast Neoplasms/complications/pathology/blood ; *Fatigue/etiology/blood ; Middle Aged ; *Inflammation/blood ; Longitudinal Studies ; C-Reactive Protein/metabolism/analysis ; Adult ; Interleukin-6/blood ; Receptors, Tumor Necrosis Factor, Type II/blood ; Tumor Necrosis Factor-alpha/blood ; Aged ; Neoplasm Staging ; },
abstract = {BACKGROUND: Fatigue is a common and long-lasting side effect of cancer. Although fatigue is a multidimensional symptom, biologic mechanisms of fatigue dimensions have not been identified.

METHODS: Women recently diagnosed with early stage breast cancer (n = 192) completed assessments before and after adjuvant therapy and at 6-month, 12-month, and 18-month posttreatment follow-up visits. At each assessment, women completed the Multidimensional Fatigue Symptom Inventory and provided blood for protein markers of inflammation (tumor necrosis factor [TNF] alpha [TNF-α], soluble tumor necrosis factor receptor type II [sTNF-RII], interleukin 6 [IL-6], and C-reactive protein [CRP]). Mixed-effect linear models examined within-person and between-person associations between inflammatory markers and dimensions of fatigue.

RESULTS: Analyses demonstrated a positive within-person association between general fatigue and TNF-α (b = 1.67; p = .037), sTNF-RII (b = 2.77; p = .002), and IL-6 (b = 0.86; p = .010) when controlling for age, race, education, body mass index, and cancer stage. Similarly, there was a positive within-person association between physical fatigue and TNF-α (b = 1.58; p = .007), sTNF-RII (b = 2.38; p < .001), and CRP (b = 0.43; p = .007). Conversely, there were negative within-person associations between emotional fatigue and TNF-α (b = -1.92; p = .004) and sTNF-RII (b = -2.10; p = .006). General and physical fatigue were positively associated with CRP at the between-person level (b = 0.82, p = .024 for general; b = 0.71; p = .012 for physical). No significant associations between mental fatigue and inflammatory makers were found.

CONCLUSIONS: The current findings identified distinct dimensions of fatigue associated with inflammatory activity in women with breast cancer and highlighted individual variability in inflammatory markers as a key predictor of fatigue symptoms.},
}

Humans
Female
*Breast Neoplasms/complications/pathology/blood
*Fatigue/etiology/blood
Middle Aged
*Inflammation/blood
Longitudinal Studies
C-Reactive Protein/metabolism/analysis
Adult
Interleukin-6/blood
Receptors, Tumor Necrosis Factor, Type II/blood
Tumor Necrosis Factor-alpha/blood
Aged
Neoplasm Staging

@article {pmid41047130,
year = {2025},
author = {Johnson, JJ and Ghosh, S and Shaw, PA and Neuhouser, ML and Lampe, JW and Tinker, LF and Prentice, RL and Tasevska, N and Freedman, LS and Boyer, BB and Hopkins, SE and Nash, SH and Votruba, SB and Krakoff, J and O'Brien, DM},
title = {The carbon isotope ratio of alanine is a biomarker of added sugar and sugar-sweetened beverage intakes: a pooled analysis of four studies.},
journal = {The American journal of clinical nutrition},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.ajcnut.2025.09.049},
pmid = {41047130},
issn = {1938-3207},
abstract = {BACKGROUND: The alanine carbon isotope ratio (Ala CIR) biomarker was positively associated with added sugar (AS) and sugar-sweetened beverage (SSB) intake in multiple studies from the USA. Association strengths varied, and Ala CIR was also correlated with protein source in certain studies.

OBJECTIVE: To examine Ala CIR associations with AS and SSB intake and animal protein ratio (animal protein/total protein, APR), and adjustment for APR, by pooling data from 4 previous studies.

METHODS: We pooled diet and biomarker data from 4 studies (n=346). These included a cross-sectional study of Yup'ik Alaska Native adults (n=62), a 12-wk randomized controlled feeding study in men (n=32), a 2-wk habitual intake controlled feeding study in postmenopausal women (n=153), and a 15-d habitual intake controlled feeding study of adults (n=99). We estimated correlations between amino acid CIRs and diet, and performed multivariable regression of Ala CIR on standardized intake variables to determine simultaneous associations with AS (g/d) or SSBs (servings/d) and APR. We included study by intake interactions to allow for heterogeneity among studies. We then ran models where leucine (Leu) CIR was included to adjust for APR.

RESULTS: There were positive correlations (95% CIs) between Ala CIR and AS intake [r=0.54 (0.46, 0.61)], log-SSB intake [r=0.63 (0.56, 0.69)], and APR [r=0.32 (0.22, 0.41)]. Study-specific slopes for the relationship between Ala CIR and AS or SSB intake were similar in models with and without adjustment for APR. Across studies, slopes ranged from 0.34 (0.08, 0.61) to 1.75 (1.29, 2.20) for AS intake in models with APR and from 0.35 (0.01, 0.68) to 1.11 (0.81, 1.40) for SSB intake in models with APR. Replacing APR with Leu CIR resulted in similar slopes between Ala CIR and AS/SSB intake.

CONCLUSIONS: The Ala CIR is a robust biomarker of AS/SSB intake. Potential associations with APR can be adjusted for using a simultaneously-measured biomarker.

(DBD study) clinicaltrials.gov/NCT01237093; (NPAAS) clinicaltrials.gov/NCT00000611.},
}

@article {pmid41046201,
year = {2025},
author = {Robesti, D and Micheli, F and Rai, SN and Fallara, G and Gallina, A and Montorsi, F and Briganti, A and Fossati, N and Grivas, P and van der Heijden, AG and Ploussard, G and Malavaud, B and Martini, A},
title = {Addressing Uneven Treatment Discontinuation Rate in the Chemotherapy Arm of the EV-302 Phase 3 Randomized Clinical Trial: Implications for Outcome Interpretation.},
journal = {Clinical genitourinary cancer},
volume = {},
number = {},
pages = {102423},
doi = {10.1016/j.clgc.2025.102423},
pmid = {41046201},
issn = {1938-0682},
abstract = {INTRODUCTION: The EV-302 trial demonstrated a very significant overall survival (OS) benefit for Enfortumab Vedotin plus Pembrolizumab (EVP) relative to standard chemotherapy (CHT) for patients with metastatic urothelial carcinoma. However, questions have been raised regarding the high rate of treatment discontinuation in the CHT arm for reasons unrelated to adverse events or progression (33% vs. 10% with EVP, P < .01), potentially resulting in loss of unaccounted information, or informative censoring, and affecting survival results interpretation.

MATERIALS AND METHODS: We performed a multistep analysis to assess the impact of differential dropout on trial outcomes. First, Kaplan-Meier (KM) curves were reconstructed from published data to estimate time-to-event outcomes. Second, a reverse KM analysis was conducted to evaluate censoring patterns in the overall population and key subgroups (PD-L1 expression; cisplatin eligibility). Third, simulation models were employed to test whether informative censoring could negatively impact survival benefit by EVP. Finally, we compared the CHT arm of EV-302 to those of other contemporary RCTs through reconstructed survival analyses and risk-of-bias assessments.

RESULTS: Overall, no significant imbalance in censoring between the treatment arms of EV-302 was found on reverse KM analysis when assessing OS (P = .73); however, a significant difference was noted for progression-free survival (PFS) (P = .002). Simulation analysis revealed that even under extreme assumptions of informative censoring, the OS benefit of EVP remained statistically significant. Comparison with historical RCTs confirmed that the CHT outcomes in EV-302 were not anomalously poor. Risk of bias was low overall, although deviations from intervention and outcome measurement were flagged for EV-302.

CONCLUSIONS: Despite the high discontinuation rate in the CHT arm, OS benefit with EVP remains robust. These findings support the reliability of EV-302 results and mitigate concerns about informative censoring, thus encouraging the use of EVP in clinical practice.},
}

@article {pmid41046057,
year = {2025},
author = {Arnold, DE and Leiding, JW and Logan, B and Marsh, RA and Griffith, LM and Grunebaum, E and Murguía-Favela, L and Mallhi, K and Chellapandian, D and Deal, CL and Lim, SS and Prasad, V and Heimall, J and Chandrakasan, S and Chen, K and Yu, LC and Seroogy, CM and Gillio, A and Bednarski, JJ and Kapoor, N and Moore, TB and Cuvelier, GDE and Touzot, F and Rayes, A and Ebens, CL and Schaefer, E and Bauchat, A and Chopek, A and Burroughs, L and Cowan, MJ and Dvorak, CC and Haddad, E and Kohn, DB and Notarangelo, LD and Pai, SY and Puck, JM and Pulsipher, MA and Torgerson, T and Malech, HL and Kang, EM and Parikh, S},
title = {Umbilical Cord Blood Transplantation Provides an Alternative for Patients with Chronic Granulomatous Disease Lacking HLA-Matched Donors: a PIDTC Report.},
journal = {Transplantation and cellular therapy},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jtct.2025.05.020},
pmid = {41046057},
issn = {2666-6367},
abstract = {BACKGROUND: Allogeneic hematopoietic cell transplantation corrects the phagocytic defect in patients with chronic granulomatous disease (CGD) and resolve infection risk and immune dysregulation. Umbilical cord blood transplantation (UCBT) is an option for patients lacking suitable HLA-matched bone marrow or peripheral blood stem cell donors. However, information related to UCBT for CGD is limited to a few small case series and limited subsets of larger cohorts where detailed information is lacking.

OBJECTIVES: To describe UCBT procedures and outcomes in patients with CGD.

STUDY DESIGN: Thirty-nine patients with CGD who underwent UCBT at Primary Immune Deficiency Treatment Consortium (PIDTC) centers between 2001 and 2019 were included.

RESULTS: All patients were male, and most (97%) had X-linked CGD due to pathogenic variants in CYBB. High infection burden (1.72/person years) and inflammatory disease (38%) were common in the year pre-UCBT. Median age at receipt of UCBT was 2.1 (range 0.3-14.0) years. Most (87%) patients received UCB from unrelated donors, and most (72%) patients received busulfan and cyclophosphamide-based conditioning. All but two (95%) patients received serotherapy with anti-thymocyte globulin or alemtuzumab. Neutrophil and platelet recovery occurred at a median of 18 (range 12-46) and 38 (range 21-186) days, respectively. Nine patients experienced early graft failure [donor myeloid chimerism <10% or receipt of second hematopoietic cell transplantation (HCT) within 100 days] for a cumulative incidence of 23.1% (95% CI 11.3-37.3). There were no cases of late graft failure (after 100 days), and median whole blood and myeloid donor chimerism of engrafted patients were >95% at all time points. One of the nine patients with early graft failure had autologous reconstitution. The remaining 8 patients underwent repeat HCT; six of the patients survived and achieved durable myeloid engraftment on long-term follow-up. Twenty-eight patients were alive at a median follow-up of 4.28 (IQR 2.66-6.08) years. Estimated 3-year overall and event-free survival were 73.7% (95% CI 56.5-84.9) and 56.2% (95% CI 39.3-70.1), respectively. No identifiable factors, including history of infection or inflammatory disease in the year prior to UCBT, year of UCBT, age at UCBT, conditioning regimen, cell dose, and recipient and donor HLA match, were associated with graft failure or survival. Infections decreased with time post-UCBT and pre-existing inflammatory disease resolved in all surviving patients CONCLUSIONS: UCBT for CGD is associated with high rates of early graft failure. Nevertheless, UCBT can provide an effective alternative for CGD patients when HLA-matched donors are not available with resolution of disease. Strategies to overcome high rates of early graft failure while optimizing conditioning regimens to minimize toxicity are needed.},
}

@article {pmid41045509,
year = {2025},
author = {Kim, D and Ding, W and Shaw, AN and Torkel, M and Turtle, CJ and Yang, P and Yang, J},
title = {Multi-view gene panel characterization for spatially resolved omics.},
journal = {Briefings in bioinformatics},
volume = {26},
number = {5},
pages = {},
pmid = {41045509},
issn = {1477-4054},
support = {//AIR@innoHK program of the Innovation and Technology Commission of Hong Kong/ ; DI2-0000000197//Chan Zuckerberg Initiative Single Cell Biology Data Insights/ ; APP2017023//National Health and Medical Research Council (NHMRC) Investigator/ ; 1173469//NHMRC Investigator/ ; //Metcalf Prize from National Stem Cell Foundation of Australia/ ; //CLEARbridge Foundation/ ; //Anthony Rothe Memorial Trust/ ; 2033771//NHMRC/ ; //Australian Commonwealth Government Research Training Program Stipend Scholarship/ ; //Children's Medical Research Institute Top up Award/ ; },
mesh = {Humans ; Algorithms ; *Gene Expression Profiling/methods ; *Transcriptome ; *Genomics/methods ; *Computational Biology/methods ; },
abstract = {Spatially resolved transcriptomics has revolutionized the study of complex tissues by enabling cellular and subcellular resolution. However, targeted spatial technologies depend on pre-selected gene panels, which are typically curated based on prior biological knowledge or specific research hypotheses. While existing methods often focus on optimizing for cell type identification, we argue that effective panel design should also account for transcriptional variation, pathway-level coverage, and minimal gene redundancy. To meet these broader criteria, we developed a two-part framework: (i) panelScope, a gene panel characterization platform that characterizes panels from multiple perspectives, allowing for holistic comparisons of gene panels for custom panel design; and (ii) panelScope-OA, a genetic algorithm that integrates these characterization metrics into a multi-loss function to automate panel optimization. We applied panelScope and panelScope-OA to characterize nine panels across four datasets. Notably, computationally constructed gene panels performed competitively in capturing major cell types when compared to our in-house manually curated panel. However, refined manual curation offered distinct advantages, particularly in capturing minor cell types. Our results demonstrate the utility of panelScope and panelScope-OA by offering quantitative and multi-dimensional insights to support the design of panels tailored to diverse research needs.},
}

Humans
Algorithms
*Gene Expression Profiling/methods
*Transcriptome
*Genomics/methods
*Computational Biology/methods

@article {pmid41001449,
year = {2025},
author = {Ssemambo, PK and Burton, M and Mirembe, BG and Nakabiito, C and Donnell, D and Beauchamp, G and Delany-Moretlwe, S and Celum, C and Velloza, J},
title = {Correlates of long-acting reversible contraceptive (LARC) use among young women in Southern Africa: a secondary analysis from HPTN 082.},
journal = {medRxiv : the preprint server for health sciences},
volume = {},
number = {},
pages = {},
pmid = {41001449},
abstract = {BACKGROUND: Long-acting reversible contraception (LARCs), including intrauterine devices (IUDs), injectables, and implants, are highly effective in preventing unintended pregnancies but LARC use rates are low among African adolescents and young women (AGYW). Understanding factors associated with LARC uptake and continuation among African AGYW may provide insights into strategies to promote LARC use.

METHODS: We conducted a secondary data analysis from the HIV Prevention Trials Network (HPTN 082) pre-exposure prophylaxis (PrEP) study, which enrolled 451 AGYW in Zimbabwe and South Africa ages 16-25 years, who reported vaginal or anal sex in the prior month, and reported PrEP interest (ClinicalTrials.gov, NCT02732730). Contraception and contraceptive counseling were offered at enrollment and visits at 4, 8, 13, 26, and 39 weeks post enrollment, with follow-up through 52 weeks. The outcome variable was any LARC use, defined as copper or hormonal IUDs, injectable contraceptives, and implants. We performed descriptive analyses and regression models to assess contraceptive use patterns and characteristics associated with LARC use and condomless sex.

RESULTS: Overall, 60% (299/499) of AGYW adopted a LARC method at enrollment and 78% (234/299) persisted on a LARC method during follow up. Among the 449 women who used contraception at enrollment and/or during follow-up, 38 (8.4%) switched between non-LARC to LARC and 34 (7.5%) discontinued contraception at some point during the study. AGYW not using a LARC at enrollment were more likely to switch contraceptive method through week 39 compared to those already using a LARC (32.7% vs. 14.7%, respectively; p-value<0.001). Factors significantly associated with choosing a LARC method were prior pregnancy [adjusted odds ratio [aOR]:2.46; 95% confidence interval [CI]: 1.59-3.79; p<0.01], and comfort talking to close friends about sexual relationships [aOR:1.82; 95% CI:1.02-3.23; p=0.04]. Consistent condom users were less likely to choose a LARC method [aOR:0.27; 95% CI:0.19-0.39; p<0.01].

CONCLUSION: Contraceptive counseling and offering LARC methods with HIV PrEP was associated with a majority of African AGYW selecting a LARC method. Peer support is important in facilitating LARC use and the high contraceptive efficacy of LARC should be discussed with AGYW using condoms for contraception. Contraceptive counseling and promotion of LARCs should be integrated with PrEP delivery for African AGYW.},
}

@article {pmid40291683,
year = {2025},
author = {Cimino, PJ and Keiser, DJ and Parrish, AG and Holland, EC and Szulzewsky, F},
title = {C-terminal fusion partner activity contributes to the oncogenic functions of YAP1::TFE3.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {40291683},
issn = {2692-8205},
support = {R35 CA253119/CA/NCI NIH HHS/United States ; },
abstract = {YAP1 gene fusions are found in a multitude of human tumors, are potent oncogenic drivers, and are the likely initiating tumorigenic events in these tumors. We and others have previously shown that a YAP1 fusion proteins exert TEAD-dependent oncogenic YAP1 activity that is resistant to inhibitory Hippo pathway signaling. However, the contributions of the C-terminal fusion partners to the oncogenic functions of YAP1 fusion proteins are understudied. Here, we used the RCAS/tv-a system to express eight different YAP1 gene fusions in vivo and observed significant differences in the latencies of tumors induced by the various YAP1 fusions. We observed that tumors induced by YAP1::TFE3 displayed a significantly different histomorphology compared to tumors induced by other YAP1 fusions or activated non-fusion YAP1. To assess the extent to which the functional TFE3 domains (DNA binding: leucine zipper (LZ) and basic-helix-loop-helix (bHLH); activation domain (AD)) contribute to the oncogenic functions of YAP1::TFE3, we generated several mutant variants and performed functional in vitro and in vivo assays. In vitro, mutation or deletion of the TFE3 DNA binding domains (LZ, bHLH) resulted in reduced TFE3 activity but increased YAP1 activity of YAP1::TFE3. In vivo, deletion of the LZ and bHLH domains did not result in a decrease in tumor incidence but induced the formation of more YAP1-like tumors that lacked prominent features of YAP1::TFE3-driven tumors. By contrast, loss of the TFE3 AD almost completely abrogated tumor formation. Our results suggest that the TFE3 domains significantly contribute to the oncogenic activity of YAP1::TFE3.},
}

@article {pmid41045472,
year = {2025},
author = {Ko, B and Rojanasopondist, P and Grady, WM},
title = {Top advances of the year: Noninvasive colorectal cancer screening tests.},
journal = {Cancer},
volume = {131},
number = {20},
pages = {e70115},
doi = {10.1002/cncr.70115},
pmid = {41045472},
issn = {1097-0142},
support = {//RACE Charities/ ; U2CCA271902//Division of Cancer Prevention, National Cancer Institute/ ; //Cottrell Family Fund/ ; },
mesh = {Humans ; *Colorectal Neoplasms/diagnosis/blood ; *Early Detection of Cancer/methods ; Feces/chemistry ; Occult Blood ; Biomarkers, Tumor/blood ; Sensitivity and Specificity ; Mass Screening/methods ; },
abstract = {Colorectal cancer (CRC) screening has been shown to be more effective in preventing deaths from this common cancer, but current methods are suboptimal. Because of limitations and barriers, interval cancers occur, and many people (25%-40%) are not compliant with colorectal cancer screening. Advances over the past year, which have led to a blood-based screening test and more accurate stool tests, address the limitations of current tests. Three clinical trials published in the past year have led to a novel blood-based test, a multitarget stool eRNA test, and an improved multitarget stool DNA test for colorectal cancer screening. The multitarget eRNA stool-based test and multitarget stool DNA test are 94.4% sensitive (87.9% specificity) and 93.5% sensitive (90.6% specificity) for CRC and 45.9% sensitive and 43.4% sensitive for advanced polyps, respectively. The blood test uses cell free DNA to detect CRC and is 83% sensitive for CRC (89.6% specificity) and 13% sensitive for advanced adenomas. These advances provide a novel effective blood-based test for CRC screening, which promises to increase compliance, and more accurate stool-based tests, which promise to lead to fewer interval CRCs.},
}

Humans
*Colorectal Neoplasms/diagnosis/blood
*Early Detection of Cancer/methods
Feces/chemistry
Occult Blood
Biomarkers, Tumor/blood
Sensitivity and Specificity
Mass Screening/methods

@article {pmid41045294,
year = {2025},
author = {Fernández-Penny, FE and Mozingo, K and Bhurgri, A and Perez, HA and Samorodnitsky, S and Lehmann, AE and Humphreys, IM and Abuzeid, WM and Jafari, A},
title = {Patient and Procedural Predictors of Early Recovery Quality After Endoscopic Endonasal Surgery.},
journal = {International forum of allergy & rhinology},
volume = {},
number = {},
pages = {},
doi = {10.1002/alr.70037},
pmid = {41045294},
issn = {2042-6984},
}

@article {pmid41043776,
year = {2025},
author = {McCurdy, SR and Solomon, SR and Shaffer, BC and He, M and Bolon, YT and Blouin, AG and Keyzner, A and Socola, FA and Ibrahim, U and Zou, J and Safah, H and Saba, N and Gadalla, S and Perales, MA and Paczesny, S and Marsh, SGE and Petersdorf, EW and Wang, T and Lee, SJ and Fuchs, EJ},
title = {Post-Transplant Cyclophosphamide Improves Survival in HLA-DPB1 Mismatched Unrelated Donor Allogeneic Transplantation.},
journal = {Transplantation and cellular therapy},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jtct.2025.09.048},
pmid = {41043776},
issn = {2666-6367},
abstract = {BACKGROUND: HLA-DPB1 mismatching is common in unrelated donor (URD) hematopoietic cell transplantation (HCT) and increases graft-versus-host disease (GVHD) when using methotrexate and tacrolimus (MTX/Tac)-based GVHD prophylaxis. Historically, national and international guidelines recommended prioritizing HLA-DPB1 matching in URD selection. The impact of HLA-DPB1 matching in URD HCT when using post-transplantation cyclophosphamide (PTCy) has been understudied.

OBJECTIVES: Our primary endpoint was the association of GVHD-prophylaxis strategy with overall survival (OS) after T cell-replete 12/12 HLA-matched or permissive or non-permissive (NP) mismatch (MM) at HLA-DPB1 (defined by the T-cell-epitope groups model) URD HCT.GVHD-free, relapse-free survival (GRFS) was our key secondary endpoint.

STUDY DESIGN: This was a retrospective cohort study using the Center for International Blood and Marrow Transplant Research (CIBMTR) database. Recipients underwent a first HCT from 2015-2020 for acute leukemia or myelodysplastic syndrome using either HLA-DPB1 NP MM (n=329), permissive MM (n=992), or 12/12 HLA-matched (n=300) URD with PTCy ± mycophenolate mofetil and/or a calcineurin inhibitor, or HLA-DPB1 NP MM (n=709), permissive MM (n=2,395), or 12/12 HLA-matched (n=911) URD with MTX/Tac.

RESULTS: HLA-DPB1 NP MM with MTX/Tac was associated with higher treatment-related mortality (TRM) (hazard ratio [HR]: 1.64, 1.08-2.49, p=0.019), lower relapse (HR: 0.73, 0.59-0.92, p=0.0073), inferior OS (HR: 1.27, 1.03 -1.57, p=0.023), and worse GRFS (HR: 1.61, 1.34-1.94, p<0.0001) when compared with PTCy. Adjusted 1-yr estimates for GRFS were 54% (95% confidence interval [CI]: 49-60%) for PTCy and 40% (CI: 37-44%) for MTX/Tac. For permissive MM URD HCT, MTX/Tac was associated with inferior GRFS (HR 1.54, CI: 1.36-1.76, p<0.0001) when compared with PTCy. When using PTCy, there were no significant differences in these outcomes for HLA-DPB1 NP MM, HLA-DPB1 permissive MM, or 12/12 HLA-matched URD HCT.

CONCLUSIONS: PTCy should be the preferred GVHD prophylaxis strategy for HLA-DPB1 MM URD HCT. Furthermore, within PTCy platforms, survival is comparable across HLA-DPB1 match and thus NP mismatching at HLA-DPB1 should not be a determinant in URD selection.},
}

@article {pmid41043723,
year = {2025},
author = {El-Serag, HB and Lopez, C and Luster, M and Reddy, KR and Parikh, N and Singal, AG and Marrero, JA and Thrift, AP and Chhatwal, J and Feng, Z and Page-Lester, S and Jin, Q and Tayob, N and Kanwal, F},
title = {HES V2.0 validation and performance compared to GALAD and ASAP in the HEDS cohort.},
journal = {Journal of hepatology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jhep.2025.09.023},
pmid = {41043723},
issn = {1600-0641},
abstract = {BACKGROUND: We previously developed Hepatocellular Carcinoma Early Detection Screening (HES) V2.0, biomarker panel (age, ALT, platelets, etiology, AFP, AFP L3, DCP and their gradient over the past one year) for early detection of HCC among patients with cirrhosis. We externally validated HES V2.0 and compared its performance to HES V1.0, GALAD, and ASAP.

METHODS: We conducted a prospective-specimen collection, retrospective-blinded-evaluation (PRoBE) cohort study in the HEDS (Hepatocellular Carcinoma Early Detection Strategy) 1,485 cirrhosis cohort (119 developed HCC). Patient- and test-level true positive rate (TPR) for HCC were calculated at 6, 12, 24 months before HCC diagnosis based on a threshold at a fixed false positive rate (FPR) of 10% and 18.1% - the latter corresponded to GALAD cut-off of -1.36.

RESULTS: HES V2.0 and GALAD had same AUROC (0.79) but different TPR/FPRs. At the FPR of 10%, HES V2.0 had 2.0%, 6.7%, and 6.0% higher TPR (sensitivity) than GALAD within 6, 12, and 24 months before HCC diagnosis (one-sided p-values 0.24, 0.025, 0.078, respectively). At 18.1% FPR, GALAD had 6% and 2% higher sensitivity than HES V2.0 within 6 and 12 months before HCC and similar sensitivity within 24 months before HCC diagnosis (all p-values >0.05).The sensitivity for HES V2.0 was 11.9% higher than HES V1.0 at 12 months (p=0.007). The sensitivity for HES V2.0 was considerably (10.9-16.3%) higher than ASAP. For patients with available labs to calculate gradients over time, the sensitivity of HES V2.0 was 3.5-8.7% higher than GALAD at all time points of testing before HCC (8.7% to 24.0% relative increase) with p<0.05 for several comparisons.

CONCLUSIONS: In a phase 3 biomarker validation study, HES V2.0 had higher sensitivity than ASAP for HCC detection, and a similar or higher sensitivity than GALAD only at 12 months before HCC diagnosis at 10% FPR and when over time gradients in AFP, AFP L3, and DCP are available.

IMPACT AND IMPLICATIONS: Hepatocellular carcinoma (HCC) remains a leading cause of cancer-related mortality, with early detection being critical for improving survival outcomes. This study provides a rigorous phase 3 validation of the HES V2.0 biomarker panel, demonstrating its superior or comparable sensitivity to established models like GALAD and ASAP in a large, diverse U.S. cirrhosis cohort. The findings are particularly impactful for clinicians and researchers focused on liver cancer surveillance, as HES V2.0 offers enhanced detection performance, especially when longitudinal biomarker data are available. These results support the integration of HES V2.0 into clinical workflows and future trials, potentially improving early HCC detection and enabling timely curative interventions for at-risk patients.},
}

@article {pmid41043413,
year = {2025},
author = {Zhang, P and Haeseleer, F and Waltner, OG and Gartlan, KH and Bhise, SS and Minnie, SA and Adams, RC and Yeh, AC and Ensbey, KS and Legg, SRW and Sekiguchi, T and Atilla, E and Nemychenkov, NS and Nelson, EL and Joshi, T and Liang, EC and Hirayama, AV and Abe, K and Koyama, M and Clouston, AD and Gauthier, J and Furlan, SN and Hill, GR},
title = {Eomesodermin[+] CD4[+] T cells are critical for curative immunotherapy outcomes.},
journal = {Immunity},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.immuni.2025.09.004},
pmid = {41043413},
issn = {1097-4180},
abstract = {Interleukin 10 (IL-10)-producing CD4[+] type-1 regulatory T cells (Tr1) promote immune tolerance during chronic infection, autoimmunity, and transplantation. However, specific Eomesodermin (Eomes)-dependent stages of Tr1 differentiation and function remain unclear. Using preclinical models of bone marrow transplantation (BMT), we demonstrated a Tr1 differentiation trajectory in vivo from Eomes[+]IL-10[-] to Eomes[+]IL-10[+] subsets with the acquisition of cytokine, cytolytic, and exhaustion features. The Eomes[+]CD4[+] fraction represented the dominant cytotoxic subset after BMT, mediating graft-versus-leukemia effects while limiting inflammation. In CD19-targeted chimeric antigen receptor (CAR) T cell immunotherapy, Eomes drove the same CD4[+] Tr1 phenotype that controlled cytolysis, while mitigating immune toxicity and promoting persistence. In individuals with high-grade B cell lymphomas that had long-term disease control after receiving commercial CD19-targeted CAR T cells, Eomes[+] Tr1 cells represented a stable population comprising 40%-80% of the CD4[+] CAR T cell population. Hence, Eomes controls both regulatory and cytotoxic programs in CD4[+] T cells, essential for curative immunotherapy outcomes.},
}

@article {pmid41043390,
year = {2025},
author = {Keogh, MC and Almouzni, G and Andrews, AJ and Armache, KJ and Arrowsmith, CH and Baek, SH and Bedford, MT and Bernstein, E and Côté, J and David, Y and Denu, JM and Fierz, B and Garcia, BA and Glass, KC and Gozani, O and Helin, K and Henikoff, S and Jensen, ON and Josefowicz, SZ and Kelleher, NL and Kutateladze, TG and Lindner, HH and Lu, C and Luger, K and Mallick, P and Musselman, CA and Muir, TW and Paša-Tolić, L and Schneider, R and Shi, X and Shi, Y and Sidoli, S and Smith, LM and Tyler, JK and Wolberger, C and Workman, JL and Strahl, BD and Young, NL},
title = {A needed nomenclature for nucleosomes.},
journal = {Molecular cell},
volume = {85},
number = {19},
pages = {3554-3561},
doi = {10.1016/j.molcel.2025.08.029},
pmid = {41043390},
issn = {1097-4164},
mesh = {*Nucleosomes/metabolism/genetics/classification ; *Protein Processing, Post-Translational ; *Histones/metabolism/genetics/classification ; Humans ; *Terminology as Topic ; Animals ; Chromatin/metabolism/genetics ; Chromatin Assembly and Disassembly ; },
abstract = {Histone post-translational modifications (PTMs) are crucial to eukaryotic genome regulation, with a range of reported functions and mechanisms of action. Though often studied individually, it has long been recognized that the modifications function by combinatorial synergy or antagonism. Interplay may involve PTMs on the same histone, within the same nucleosome (containing a histone octamer), or between nucleosomes in higher-order chromatin. Given this, the field must distinguish ever greater complexity, and the context in which it is studied, with brevity and precision. The proteoform was introduced to define individual forms of a protein by sequence and PTMs, followed by the nucleoform to describe the particular gathering of histones within an individual nucleosome. There is now a need to define specific forms of these entities in prose while providing space for experimental nuance. To this end, we introduce a nomenclature that can express discrete PTMs, proteoforms, nucleoforms, or situations where defined PTMs exist in an uncertain context. Though specifically designed for the chromatin field, adaptions of the framework could be used to describe-and thus dissect-how proteoforms are configured in functionally distinct complexes across biology.},
}

*Nucleosomes/metabolism/genetics/classification
*Protein Processing, Post-Translational
*Histones/metabolism/genetics/classification
Humans
*Terminology as Topic
Animals
Chromatin/metabolism/genetics
Chromatin Assembly and Disassembly

@article {pmid41043162,
year = {2025},
author = {Chung, K and Sotak, N},
title = {Use of Trigger Point Injections in the Management of Myofascial Pain in Patients With Temporomandibular Disorders.},
journal = {Compendium of continuing education in dentistry (Jamesburg, N.J. : 1995)},
volume = {46},
number = {8},
pages = {376-379},
pmid = {41043162},
issn = {2158-1797},
mesh = {Humans ; Aged ; *Trigger Points ; *Temporomandibular Joint Disorders/complications/drug therapy ; *Myofascial Pain Syndromes/drug therapy ; Male ; Anesthetics, Local/administration & dosage ; Injections ; },
abstract = {Myofascial pain, a prevalent condition that often involves trigger points in the craniofacial region, can significantly impair function and quality of life. This article reports on the case of a 69-year-old patient with chronic head and neck myofascial pain and limited mouth opening, which hindered dental care and obstructive sleep apnea management. Following a series of trigger point injections (TPIs), combined with pharmacologic and physical therapy, the patient experienced substantial symptom relief and improved jaw function, and was subsequently able to receive successful dental and sleep apnea treatment. The case underscores the importance of accurate diagnosis and multidisciplinary management of myofascial pain, highlighting TPI therapy as an effective, minimally invasive treatment within a multimodal care approach.},
}

Humans
Aged
*Trigger Points
*Temporomandibular Joint Disorders/complications/drug therapy
*Myofascial Pain Syndromes/drug therapy
Male
Anesthetics, Local/administration & dosage
Injections

@article {pmid41043099,
year = {2025},
author = {Ueda Oshima, M and Vo, PT and Boeckh, M and Bouvier, ME and Carpenter, PA and Mielcarek, M and Petersdorf, EW and Storb, R and Gooley, T and Sandmaier, BM},
title = {Sirolimus and Cyclosporine With Post-Transplant Cyclophosphamide or Mycophenolate Mofetil as Graft-Versus-Host Disease Prophylaxis in Unrelated Donor Hematopoietic Cell Transplantation.},
journal = {Journal of clinical oncology : official journal of the American Society of Clinical Oncology},
volume = {},
number = {},
pages = {JCO2501238},
doi = {10.1200/JCO-25-01238},
pmid = {41043099},
issn = {1527-7755},
abstract = {PURPOSE: To determine whether sirolimus (SIR) and cyclosporine (CSP) combined with post-transplantation cyclophosphamide (PTCy), after nonmyeloablative or reduced-intensity conditioning unrelated donor hematopoietic cell transplantation (HCT), would be more effective than SIR, CSP, and mycophenolate mofetil (MMF) in reducing the risk of chronic graft-versus-host disease (cGVHD) without increasing risk of recurrent malignancy.

METHODS: In a Phase II trial of HLA-matched or mismatched unrelated donor mobilized blood HCT (ClinicalTrials.gov identifier: NCT03246906), adults with hematologic malignancies ineligible for myeloablative HCT were randomly assigned 1:1 to GVHD prophylaxis with SIR/CSP/PTCy (50 mg/kg once daily on days +3, +4) or SIR/CSP/MMF. The primary end point was 1-year chronic GVHD-free relapse-free survival (CRFS).

RESULTS: One hundred forty-five patients were randomly assigned and transplanted. Median follow-up among survivors was 3.0 (range, 0.6-7.0) years. Comparing PTCy-based with non-PTCy-based immunosuppression, estimated 1-year CRFS was 73% (95% CI, 61% to 82%) versus 48% (95% CI, 36% to 59%), translating into a hazard ratio (HR) for CRFS failure of 0.46 (95% CI, 0.26 to 0.79; P = .005) for PTCy. Probabilities of acute GVHD (aGVHD) grades II-IV and III-IV, respectively, were 40% versus 42% and 6% versus 10%. One-year estimates for secondary end points were as follows: moderate-to-severe cGVHD, 3% (95% CI, 1% to 9%) versus 33% (95% CI, 22% to 44%); relapse, 15% versus 15%; progression-free survival, 75% versus 78%; survival, 86% versus 86%; and nonrelapse mortality, 10% versus 7%. The HR of ≥grade 3 infections with PTCy versus non-PTCy was 2.65 (95% CI, 1.41 to 4.97; P = .003).

CONCLUSION: After HLA-matched or mismatched unrelated donor mobilized blood HCT, replacing MMF with PTCy, when used in combination with SIR and CSP, significantly reduced risk of cGVHD, without increasing risks of aGVHD or relapse. Thus, the combination of PTCy and SIR/CSP may have synergistic cGVHD-protective effects warranting further study.},
}

@article {pmid41042747,
year = {2025},
author = {Feldacker, C and Fabens, I and Dong, TQ and Moyo, K and Makhele, C and Phohole, M and Igaba, N and Hlongwane, S and Pienaar, J and Sardini, M and Ndebele, F and Tweya, H and Holec, M and Waweru, E and Setswe, G},
title = {Strengthening evidence for text-based telehealth in post-operative care: A pragmatic study of the reach and effectiveness of two-way, text-based follow-up after voluntary medical male circumcision in South Africa.},
journal = {PloS one},
volume = {20},
number = {10},
pages = {e0314436},
pmid = {41042747},
issn = {1932-6203},
mesh = {Humans ; Male ; *Circumcision, Male/adverse effects ; South Africa ; *Telemedicine ; *Text Messaging ; Adult ; Adolescent ; *Postoperative Care/methods ; Young Adult ; Follow-Up Studies ; Middle Aged ; },
abstract = {Building upon evidence of safety and efficiency gains from a randomized control trial (RCT) in South Africa, we further scaled implementation of two-way, short message service (SMS), text-based (2wT) follow-up after voluntary medical male circumcision (VMMC). We aimed to determine if gains in adverse event (AE) identification and reduced follow-up visits could be maintained when 2wT was implemented in routine VMMC settings. A pragmatic, stepped wedge design (SWD) study was implemented across three districts in South Africa. Men ages 15 and older could opt into the 2wT telehealth follow-up approach when their facility was in the intervention period. Men in routine periods were offered the standard of care (SoC): in-person post-operative visits on days 2 and 7 as per national VMMC guidelines. 2wT participants were not required to attend any postoperative visits but could return for care if desired or referred. Two quality of care markers, safety (AE ascertainment rate) and efficiency (# in-person follow-up visits), were compared between groups. We aimed for at least 200 men per step to have 80% power to detect a change in AE rate from before to after 2wT was implemented. Secondary analysis explored response rates; client and site uptake; and AE details. Among 6842 clients in the intervention period, 2856 opted into 2wT (37.8%) across three intervention waves and two platforms (SMS or WhatsApp). Among those with post-operative follow-up, the AE ascertainment rate was higher among 2wT (0.60%) than SoC (0.13%) clients (p = 0.0018), demonstrating safety gains. On average, 2wT participants had 2.1 fewer visits compared to SoC clients (p < 0.001), demonstrating gains in follow-up efficiency. Among 2wT men, 2069/2586 (80%) responded via 2wT over 14 days, demonstrating engagement in post-operative care. Of all intervention clients, 93 2wT (3.6%) and 342 (8.0%) SoC were considered lost to follow-up. In this expansion trial, we provided additional evidence that the 2wT approach maintains the quality of post-operative care for adult VMMC clients. 2wT should be scaled to augment in-person, post-operative visits after VMMC for eligible, interested males ages 15 and older. To achieve potential impact, effort is needed to improve access and uptake to 2wT among providers and sites, expanding the 2wT approach for other acute follow-up care especially among men.},
}

Humans
Male
*Circumcision, Male/adverse effects
South Africa
*Telemedicine
*Text Messaging
Adult
Adolescent
*Postoperative Care/methods
Young Adult
Follow-Up Studies
Middle Aged

@article {pmid41001472,
year = {2025},
author = {Kerrebijn, I and Bjornsdottir, G and Arbabi, K and Urpa, L and Haapaniemi, H and Thorleifsson, G and Stefansdottir, L and Frangakis, S and Valliere, J and Kunorozva, L and Abner, E and Ji, C and Aagaard, B and Bliddal, H and Brunak, S and Bruun, MT and Didriksen, M and Erikstrup, C and Geirsson, AJ and Gudbjartsson, DF and Hansen, TF and Jonsdottir, I and Knight, S and Knowlton, KU and Mikkelsen, C and Nadauld, LD and Olafsdottir, TA and Ostrowski, SR and Pedersen, OB and Saevarsdottir, S and Skuladottir, AT and Sørensen, E and Stefansson, H and Sulem, P and Sveinsson, OA and Thorlacius, GE and Thorsteinsdottir, U and Ullum, H and Vikingsson, A and Werge, TM and , and , and , and , and , and Saxena, R and Stefansson, K and Brummett, CM and Glintborg, B and Clauw, DJ and Thorgeirsson, TE and Williams, FM and Sinnott-Armstrong, N and Ollila, HM and Wainberg, M},
title = {The genetic architecture of fibromyalgia across 2.5 million individuals.},
journal = {medRxiv : the preprint server for health sciences},
volume = {},
number = {},
pages = {},
pmid = {41001472},
support = {K08 AR082454/AR/NIAMS NIH HHS/United States ; RM1 HG010461/HG/NHGRI NIH HHS/United States ; },
abstract = {Fibromyalgia is a common and debilitating chronic pain syndrome of poorly understood etiology. Here, we conduct a multi-ancestry genome-wide association study meta-analysis across 2,563,755 individuals (54,629 cases and 2,509,126 controls) from 11 cohorts, identifying the first 26 risk loci for fibromyalgia. The strongest association was with a coding variant in HTT, the causal gene for Huntington's disease. Gene prioritization implicated the HTT regulator GPR52, as well as diverse genes with neural roles, including CAMKV, DCC, DRD2/NCAM1, MDGA2, and CELF4. Fibromyalgia heritability was exclusively enriched within brain tissues and neural cell types. Fibromyalgia showed strong, positive genetic correlation with a wide range of chronic pain, psychiatric, and somatic disorders, including genetic correlations above 0.7 with low back pain, post-traumatic stress disorder and irritable bowel syndrome. Despite large sex differences in fibromyalgia prevalence, the genetic architecture of fibromyalgia was nearly identical between males and females. This work provides the first robust genetic evidence defining fibromyalgia as a central nervous system disorder, thereby establishing a biological framework for its complex pathophysiology and extensive clinical comorbidities.},
}

@article {pmid41000947,
year = {2025},
author = {Kanaan, SB and Underwood, JG and Gladden, RG and Fan, E and Bhise, SS and Thakar, MS and Jaeger-Ruckstuhl, CA and Stevens, J and Gray, AN and Riddell, SR and Bleakley, M and Meshinchi, S and Furlan, SN},
title = {Quantifying HLA transcripts by genotype in chimeric mixtures at single-cell resolution.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {41000947},
issn = {2692-8205},
abstract = {Gene products from the highly variable major histocompatibility locus, including HLA, are essential for self-recognition and immune surveillance of malignancy. Following allogeneic hematopoietic cell transplantation (alloHCT), genetic and epigenetic alterations in HLA can drive disease recurrence, making precise HLA assessment critical for determining future therapy. However, current methods lack the sensitivity to quantify HLA transcripts at the single-cell level, limiting their clinical utility. We introduce scrHLA-typing, a novel technique that accurately identifies and quantifies HLA transcripts in single cells using long-read sequencing. When applied to samples from patients with post-transplant relapse, scrHLA-typing successfully detected HLA allele-specific expression, across a range of levels of donor-recipient chimerism, at clinically actionable levels. By characterizing allele expression in residual leukemia cells, our assay identified differences in expression patterns among patients. This capability highlights scrHLA-typing's potential to improve risk stratification and guide the selection of appropriate salvage therapies, enhancing personalized treatment strategies after relapse.},
}

@article {pmid41000687,
year = {2025},
author = {Wick, BJ and Kluesner, MG and Slipek, NJ and Skeate, JG and Niemeyer, EM and Webber, BR and Moriarity, BS},
title = {Installation of Dominant-Negative Mutations in FAS and TGFβR2 via Base Editing in Primary T Cells.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {41000687},
issn = {2692-8205},
abstract = {Adoptive cell transfer (ACT) of engineered T cells is effective against B-cell malignancies but has faltered against solid tumors due to the immunosuppressive tumor microenvironment (TME). FASL and TGFβ are key mediators of T cell dysfunction in the TME and overexpressing dominant negative (dn) forms of their receptors in T cells increases anti-tumor efficacy in solid tumor models. However, an approach which directly targets the endogenous genes would be more amenable to multiplex editing and reduce competition with WT alleles. Here, we employ base editing (BE) in primary human T cells to install naturally occurring dominant negative FAS and TGFβR2 mutations. In vitro survival and proliferation assays demonstrate that BE T cells are resistant to pro-apoptotic and anti-proliferative effects of FAS and TGFβ signaling. CAR-T cells with BE-installed dn TGFβR2 or dn FAS exhibit improvements in cytotoxicity, while dn TGFβR2 CAR T demonstrate increased persistence and reduced expression of phenotypic markers of exhaustion compared to controls. Moreover, BE-engineered dn CAR T outperform lentiviral-engineered cDNA over expression counterparts in several functional assays. Considering the efficiency of BE and its amenability for multiplex editing, our novel approach lends itself to engineering strategies necessary to overcome T cell dysfunction in solid tumors.},
}

@article {pmid40291684,
year = {2025},
author = {Vick, SC and Domenjo-Vila, E and Frutoso, M and Glabman, RA and Warrier, LS and Hughes, SM and Kirby, AC and Fialkow, MF and Hladik, F and Prlic, M and Lund, JM},
title = {Mucosal tissue NK cells tune their function between optimal anti-pathogen activity and tissue protection.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {40291684},
issn = {2692-8205},
support = {K99 AI180649/AI/NIAID NIH HHS/United States ; R01 AI141435/AI/NIAID NIH HHS/United States ; },
abstract = {Preserving barrier integrity is of great importance in mucosal tissues while simultaneously defending against inflammatory threats and exposures to pathogens. NK cells at barrier sites are essential for viral control during infections such as herpes simplex virus 2 (HSV-2) but must also balance pathogen response with tissue protection. We have characterized human tissue NK cells in the vaginal tissue (VT) as having distinct effector and tissue protective functions. Using scRNA-seq and high-parameter flow cytometry, we uncovered a unique signature for VT NK cells, indicating a reduced effector phenotype with increased factors related to tissue residency and immunoregulation at steady state. Despite their functionally quiescent nature, these cells were able to respond robustly to inflammatory signals, suggesting they are poised for pathogen response. We found that the gene signatures between mouse and human NK cells were remarkably similar, demonstrating the feasibility of using a mouse model to probe distinct NK cell functions during mucosal infection. In mice, VT NK cells responded robustly to acute HSV-2 infection and retained an enhanced recall potential after viral clearance. They also secreted tissue repair factors and played a role in restricting tissue damage following viral infection. Our data, using both human tissues and a mouse model, reveal an unexpected role of mucosal tissue NK cells in the VT in balancing host protection with tissue repair in the context of localized mucosal tissue infection.},
}

@article {pmid41042680,
year = {2025},
author = {Srinivasan, S and Strenk, SM and Beamer, MA and Fiedler, TL and Proll, S and Acevedo-Oquendo, GR and Bonura, GM and Nagana Gowda, GA and Raftery, D and Hillier, SL and Fredricks, DN},
title = {Umbribacter vaginalis gen. nov., sp. nov.: novel bacterium isolated from the human vagina.},
journal = {International journal of systematic and evolutionary microbiology},
volume = {75},
number = {10},
pages = {},
pmid = {41042680},
issn = {1466-5034},
mesh = {*Phylogeny ; Female ; RNA, Ribosomal, 16S/genetics ; Humans ; *Vagina/microbiology ; Fatty Acids/analysis/chemistry ; DNA, Bacterial/genetics ; Bacterial Typing Techniques ; Base Composition ; *Vaginosis, Bacterial/microbiology ; Sequence Analysis, DNA ; Adult ; },
abstract = {Gram-variable obligately anaerobic novel bacteria DNF00809 and PR-HUZ-602407-17 were isolated from vaginal fluid samples from women with bacterial vaginosis (BV) in two independent studies conducted in different laboratories. They each displayed ≥99.9% 16S rRNA gene sequence identity to the uncultured bacterial clone sequence AY738656 designated as Eggerthella-like vaginal bacterium (ELVB) and shared 100% 16S rRNA gene sequence identity with each other. Studies using molecular bacterial identification have associated ELVB sequences with BV, higher risk for human immunodeficiency virus acquisition and development of pelvic inflammatory disease in women. Given the clinical significance of this bacterium, we characterized the novel bacterium designated DNF00809[T] using biochemical, genotypic and phylogenetic analyses. DNF00809[T] was a coccobacillus that was non-motile, non-spore forming, asaccharolytic, proteolytic and indole negative. Fatty acid methyl ester analysis for DNF00809[T] indicated C14 : 0, C16 : 0, C16 : 0 dimethyl acetal and C18 : 1 cis9 to be the major fatty acids. Whole genomic DNA G+C content was 46.1 mol%. Phylogenetic and phylogenomic analyses indicate that DNF00809[T] represents a novel genus and novel species within the Eggerthellaceae family. We propose the name Umbribacter vaginalis gen. nov., sp. nov. with DNF00809[T] representing the type strain of this species (=DSM 118866[T]=CCUG77988[T]).},
}

*Phylogeny
Female
RNA, Ribosomal, 16S/genetics
Humans
*Vagina/microbiology
Fatty Acids/analysis/chemistry
DNA, Bacterial/genetics
Bacterial Typing Techniques
Base Composition
*Vaginosis, Bacterial/microbiology
Sequence Analysis, DNA
Adult

@article {pmid41042528,
year = {2025},
author = {Boiko, JR and Cooke, KR},
title = {Moving the needle on chronic GVHD of the lung.},
journal = {Blood advances},
volume = {9},
number = {19},
pages = {5038-5039},
doi = {10.1182/bloodadvances.2025017297},
pmid = {41042528},
issn = {2473-9537},
}

@article {pmid41042026,
year = {2025},
author = {Rafati, M and Wang, Y and Koppayi, AL and Savage, SA and Godley, LA and Williams, KM and Porter, C and Jones, K and Hicks, B and Spellman, SR and He, M and Atshan, R and Iwuagwu, C and Bolon, YT and Arrieta-Bolaños, E and Saultz, JN and Benjamin, CL and Lee, SJ and Saber, W and Gadalla, SM},
title = {Germline Pathogenic Variants in MUTYH Are Associated With Inferior Survival After Hematopoietic Cell Transplantation in Patients With Hematologic Malignancies or Disorders.},
journal = {American journal of hematology},
volume = {},
number = {},
pages = {},
doi = {10.1002/ajh.70093},
pmid = {41042026},
issn = {1096-8652},
support = {W81XWH-19-1-0241/CP/NCI NIH HHS/United States ; 75N910D00024/CA/NCI NIH HHS/United States ; U24CA076518//U.S. Public Health Service/ ; //Congressionally Directed Medical Research Programs/ ; },
}

@article {pmid41039543,
year = {2025},
author = {Bouras, E and Papagiannopoulos, CK and Mustafa, R and Sobieski, D and Schmit, SL and Wu, AH and Brenner, H and Li, CI and Chan, AT and Pellatt, AJ and Zheng, W and Keku, TO and Moreno, V and Um, CY and Van Guelpen, B and Phipps, AI and Pai, RK and Lewis, SJ and Martin, RM and Gunter, MJ and Peters, U and Dehghan, A and Tsilidis, KK},
title = {Investigating the relationship of plasma microRNAs and colorectal cancer risk using genetic evidence.},
journal = {BMC medicine},
volume = {23},
number = {1},
pages = {532},
pmid = {41039543},
issn = {1741-7015},
support = {C18281/A29019/CRUK_/Cancer Research UK/United Kingdom ; C18281/A29019/CRUK_/Cancer Research UK/United Kingdom ; },
mesh = {Humans ; *Colorectal Neoplasms/genetics/blood ; *MicroRNAs/blood/genetics ; Mendelian Randomization Analysis ; Male ; Genetic Predisposition to Disease ; Risk Factors ; Female ; Case-Control Studies ; Middle Aged ; },
abstract = {BACKGROUND: MicroRNAs (miRNAs) are short, single-stranded RNAs that function as post-transcriptional regulators of gene expression. Although circulating miRNAs have been linked to carcinogenesis, they have not yet been systematically investigated in relation to risk of colorectal cancer (CRC).

METHODS: We used Mendelian randomization (MR) and colocalization analyses to investigate the association of genetically predicted plasma miRNA concentrations (2083 miRNAs in 710 individuals) with risk of CRC (58,221 cases and 67,694 controls). For miRNAs associated with CRC risk, we also investigated their association with circulating plasma proteins (4907 proteins in 35,559 participants), bidirectionally, using MR. We performed pathway enrichment analysis (PEA) to explore downstream molecular pathways.

RESULTS: Associations of five miRNAs with CRC were found in MR and supported in colocalization analyses. Specifically, miR-146a-5p, miR-21-5p, and miR-4707-3p were positively, and miR-1908-5p and miR-6810-3p were inversely associated with CRC risk. Several protein associations were found for these miRNAs (range of proteins with P < 0.05: 78-796; 211 with FDR < 5%), and 11 pathways were identified in PEA, including regulation of Erb-B2 receptor tyrosine kinase 4 (miR-6810-3p) and insulin-like growth factor pathways (miR-1908-5p).

CONCLUSIONS: Our results support a potential implication of miR-146a-5p, miR-21-5p, miR-4707-3p, miR-1908-5p, and miR-6810-3p to CRC risk. However, their downstream effects should be elucidated before they can be utilized as preventive targets.},
}

Humans
*Colorectal Neoplasms/genetics/blood
*MicroRNAs/blood/genetics
Mendelian Randomization Analysis
Male
Genetic Predisposition to Disease
Risk Factors
Female
Case-Control Studies
Middle Aged

@article {pmid41038991,
year = {2025},
author = {Termini, CM},
title = {SLAM passes the haematopoietic stem cell identity test.},
journal = {Nature reviews. Molecular cell biology},
volume = {},
number = {},
pages = {},
pmid = {41038991},
issn = {1471-0080},
}

@article {pmid41037133,
year = {2025},
author = {Garzia, NA and Fest, S and Cushing-Haugen, K and Kensler, TW and Chavarro, JE and Tamimi, RM and Harris, HR},
title = {Childhood and adolescent dietary patterns and incidence of benign breast disease.},
journal = {Cancer causes & control : CCC},
volume = {},
number = {},
pages = {},
pmid = {41037133},
issn = {1573-7225},
support = {T32 CA094880/NH/NIH HHS/United States ; U01 HL145386/NH/NIH HHS/United States ; },
abstract = {PURPOSE: Childhood and adolescence may represent critical time windows for shaping future breast cancer risk. The association between early-life diet and breast cancer risk has been investigated, but few studies have examined the relation between adolescent diet and benign breast disease (BBD), an established breast cancer risk factor.

METHODS: Among 11,422 female Growing Up Today Study participants followed from 1996 to 2016 who completed food frequency questionnaires, we investigated the associations between adherence to three dietary patterns (Alternative Healthy Eating Index [AHEI], the Empirical Dietary Inflammatory Pattern [EDIP], and the Empirical Dietary Index for Hyperinsulinemia [EDIH]) at ages 10 and 14 years and self-reported BBD diagnosis. Cox proportional hazards models were used to estimates hazard ratios (HRs) and 95% confidence intervals (CIs).

RESULTS: Over 20 years of follow-up, 554 BBD cases were ascertained, with 259 biopsy-confirmed cases. Non-significant inverse associations were observed between greater adherence to the AHEI at age 10 and BBD risk (HR for fourth vs. first quartile = 0.74; 95% CI = 0.50-1.10; ptrend = 0.09), and between AHEI at age 14 and biopsy-confirmed BBD (HR for fourth vs. first quartile = 0.70; 95% CI = 0.48-1.03; ptrend = 0.10). Non-significant positive associations were observed between adherence to the EDIH at age 10 and (HR for fourth vs. first quartile = 1.49; 95% CI = 0.91-2.43; ptrend = 0.09) age 14 (HR for fourth vs. first quartile = 1.33; 95% CI = 0.97-1.82; ptrend = 0.09) and BBD risk. No associations were observed for EDIP. In secondary analyses, the association between EDIH at age 10 and BBD became statistically significant after accounting for change in dietary pattern quartile from age 10 to 14 (HR for fourth vs. first quartile = 2.14; 95% CI = 1.04-4.41). Adjustment for adult diet also strengthened associations between EDIH at age 10 and BBD risk (HR = 1.94; 95% CI = 1.12-3.37; ptrend = 0.007), and showed a significant inverse trend for AHEI (ptrend = 0.04).

CONCLUSION: These findings may suggest that greater early-life adherence to a healthier dietary pattern (AHEI) is associated with lower BBD risk, while consuming a more insulinemic dietary pattern (EDIH) may be associated with increased risk. Associations for EDIH at age 10 were statistically significant in secondary analyses accounting for dietary change and adult diet. Further research is needed to confirm these findings and clarify potential mechanisms.},
}

@article {pmid41036248,
year = {2025},
author = {Wallace, B and Dimitrov, D and Hébert-Dufresne, L and Berdahl, AM},
title = {Hotspot model shows how location-based superspreading accelerates and reshapes epidemics.},
journal = {PNAS nexus},
volume = {4},
number = {9},
pages = {pgaf299},
pmid = {41036248},
issn = {2752-6542},
abstract = {During outbreaks of many diseases, a small number of infected individuals are responsible for a disproportionately large number of new infections in what are called superspreading events (SSEs). SSEs broadly fall into four categories: (i) a single individual is more infectious due to biological differences in their infection or (ii) their greater degree of social connection; or (iii) the disease spreads more readily in certain high-risk facilities or (iv) "opportunistic" situations such as large gatherings. Existing modeling approaches work well to understand the first two of these but are not well suited to describe the dynamics in the latter two. Here, we introduce a simple agent-based model which captures the essential features of disease spreading more readily at high-risk locations or gatherings, which we call "hotspots." In our model, disease spreads and people recover as in a standard Susceptible, Infected, Recovered model, but agents are also characterized by individual probability of visiting the hotspot where disease spreads much more readily, providing an additional risk structure to the population. We use this model to investigate how an outbreak's probability, peak, and final size all vary under different risk heterogeneity assumptions. We show how some particular distributions of risk-taking behavior across the population heighten these effects. We complement our simulations with analytic results that provide theoretical bases for all of our numerical results and allow for robust interpretation and prediction.},
}

@article {pmid41035891,
year = {2025},
author = {Lawore, DC and Jena, S and Berard, AR and Birse, K and Lamont, A and Mackelprang, RD and Noel-Romas, L and Perner, M and Hou, X and Irungu, E and Mugo, N and Knodel, S and Muwonge, TR and Katabira, E and Hughes, SM and Levy, C and Calienes, FL and Hladik, F and Lingappa, JR and Burgener, AD and Green, LN and Brubaker, DK},
title = {Computational microbiome pharmacology analysis elucidates the anti-cancer potential of vaginal microbes and metabolites.},
journal = {Frontiers in microbiology},
volume = {16},
number = {},
pages = {1602217},
pmid = {41035891},
issn = {1664-302X},
abstract = {The vaginal microbiome's role in risk, progression, and treatment of female cancers has been widely explored. Yet, there remains a need to develop methods to understand the interaction of microbiome factors with host cells and to characterize their potential therapeutic functions. To address this challenge, we developed a systems biology framework we term the Pharmacobiome for microbiome pharmacology analysis. The Pharmacobiome framework evaluates similarities between microbes, microbial byproducts, and known drugs based on their impact on host transcriptomic cellular signatures. Here, we apply our framework to characterization of the Anti-Gynecologic Cancer Vaginal Pharmacobiome. Using published vaginal microbiome multi-omics data from the Partners PrEP clinical trial, we constructed vaginal epithelial gene signatures associated with each profiled vaginal microbe and metabolite. We compared these microbiome-associated host gene signatures to post-drug perturbation host gene signatures related to 35 FDA-approved anti-cancer drugs from the Library of Integrated Network-based Cellular Signatures database to identify vaginal microbes and metabolites with high statistical and functional similarity to these drugs. We found that select lactobacilli particularly L. crispatus and their metabolites, such as taurine, can regulate host gene expression in ways similar to certain anti-cancer drugs. Additionally, we experimentally tested our model prediction that taurine, a metabolite produced by L. crispatus, kills cancerous breast and endometrial cancer cells. Our study shows that the Pharmacobiome is a robust framework for characterizing the anti-cancer therapeutic potential of vaginal microbiome factors with generalizability to other cancers, microbiomes, and diseases.},
}

@article {pmid41034423,
year = {2025},
author = {Setiawan, T and Muhammad, JA and Marcellina, N and Wirawan, LM and Jun, N and Sari, IN and Oehler, VG and Kim, DW and Kwon, HY},
title = {Regulation of metabolic adaptation and leukemia progression by MUSASHI2-DEPTOR-KIF11 axis.},
journal = {Leukemia},
volume = {},
number = {},
pages = {},
pmid = {41034423},
issn = {1476-5551},
support = {2023R1A2C1003952//National Research Foundation of Korea (NRF)/ ; RS-2024-00437643//Korea Health Industry Development Institute (KHIDI)/ ; },
abstract = {Amino acid homeostasis is critical for leukemic cell survival, with the mTOR pathway playing a central role in sensing and responding to nutrient availability. DEPTOR, a component and negative regulator of mTOR complexes, has been extensively studied in solid tumors and multiple myeloma, but its role in acute myeloid leukemia (AML) remains unclear. Here, we identify DEPTOR as a key regulator of leukemia progression through its interaction with KIF11. DEPTOR expression is transcriptionally induced by ATF4 and post-transcriptionally stabilized by MSI2, which binds to DEPTOR mRNA and prevents its degradation. DEPTOR is highly expressed in leukemia stem cells (LSCs) and is associated with poor clinical outcomes. Functionally, DEPTOR loss impairs leukemogenesis in both AML and blast phase chronic myeloid leukemia (bpCML) models, without affecting normal hematopoietic stem cells. Mechanistically, DEPTOR stabilizes KIF11 by preventing its ubiquitination and proteasomal degradation, thereby ensuring proper mTORC1 localization and metabolic adaptation during nutrient stress. Collectively, our findings establish the MSI2/DEPTOR/KIF11 axis as a critical driver of leukemogenesis and a promising therapeutic target for aggressive myeloid leukemias.},
}

@article {pmid41034193,
year = {2025},
author = {Guo, B and Cai, Y and Kim, D and Smit, RAJ and Wang, Z and Iyer, KR and Hilliard, AT and Haessler, J and Tao, R and Broadaway, KA and Wang, Y and Pozdeyev, N and Stæger, FF and Yang, C and Vanderwerff, B and Patki, AD and Stalbow, L and Lin, M and Rafaels, N and Shortt, J and Wiley, L and Stanislawski, M and Pattee, J and Davis, L and Straub, PS and Shuey, MM and Cox, NJ and Lee, NR and Jørgensen, ME and Bjerregaard, P and Larsen, C and Hansen, T and Moltke, I and Meigs, JB and Stram, DO and Yin, X and Zhou, X and Chang, KM and Clarke, SL and Guarischi-Sousa, R and Lankester, J and Tsao, PS and Buyske, S and Graff, M and Raffield, LM and Sun, Q and Wilkens, LR and Carlson, CS and Easton, CB and Liu, S and Manson, JE and Marchand, LL and Haiman, CA and Mohlke, KL and Gordon-Larsen, P and Albrechtsen, A and Boehnke, M and Rich, SS and Manichaikul, A and Rotter, JI and Yousri, NA and Irvin, RM and , and , and Gignoux, C and North, KE and Loos, RJF and Assimes, TL and Peters, U and Kooperberg, C and Raghavan, S and Highland, HM and Darst, BF},
title = {Polygenic risk score for type 2 diabetes shows context-dependent effects across populations.},
journal = {Nature communications},
volume = {16},
number = {1},
pages = {8632},
pmid = {41034193},
issn = {2041-1723},
support = {R01HL143885//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; R01HD30880//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; R01HL151152//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; R01DK139598//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; R01HL142302//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; R01HL143885//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; R01HL163262//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; R01DK122503//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; R01HL151152//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; R01HL156991//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; R01DK123019//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; UM1DK078616//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; R00CA246063//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; R03CA287235//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; U01CA261339//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; R01HL174378//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; U54HG013243//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; PPM2-0226-170020//Qatar National Research Fund (QNRF)/ ; NPRP11S-0114-180299//Qatar National Research Fund (QNRF)/ ; NNF20OC0059313//Novo Nordisk Fonden (Novo Nordisk Foundation)/ ; NNF18CC0034900//Novo Nordisk Fonden (Novo Nordisk Foundation)/ ; P50CA097186//U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)/ ; P30CA015704//U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)/ ; },
mesh = {Humans ; *Diabetes Mellitus, Type 2/genetics/epidemiology ; *Multifactorial Inheritance/genetics ; Male ; Female ; *Genetic Predisposition to Disease ; Middle Aged ; Genome-Wide Association Study ; Risk Factors ; Aged ; Adult ; Polymorphism, Single Nucleotide ; Case-Control Studies ; Genetic Risk Score ; },
abstract = {Polygenic risk scores hold prognostic value for identifying individuals at higher risk of type 2 diabetes. However, further characterization is needed to understand the generalizability of type 2 diabetes polygenic risk scores in diverse populations across various contexts. We systematically characterize a multi-ancestry type 2 diabetes polygenic risk score among 244,637 cases and 637,891 controls across diverse populations from the Population Architecture Genomics and Epidemiology Study and 13 additional biobanks and cohorts. Polygenic risk score performance is context dependent, with better performance in those who are younger, male, without hypertension, and not obese or overweight. Additionally, the polygenic risk score is associated with various diabetes-related cardiometabolic traits and type 2 diabetes complications, suggesting its utility for stratifying risk of complications and identifying shared genetic architecture between type 2 diabetes and other diseases. These findings highlight the need to account for context when evaluating polygenic risk score as a tool for type 2 diabetes risk prognostication and the potentially generalizable associations of type 2 diabetes polygenic risk score with diabetes-related traits, despite differential performance in type 2 diabetes prediction across diverse populations. Our study provides a comprehensive resource to characterize a type 2 diabetes polygenic risk score.},
}

Humans
*Diabetes Mellitus, Type 2/genetics/epidemiology
*Multifactorial Inheritance/genetics
Male
Female
*Genetic Predisposition to Disease
Middle Aged
Genome-Wide Association Study
Risk Factors
Aged
Adult
Polymorphism, Single Nucleotide
Case-Control Studies
Genetic Risk Score

@article {pmid41033921,
year = {2025},
author = {Kishan, AU and Juarez Casillas, JE and Sargos, P and Kalbasi, TR and Chabaud, S and Brihoum, M and Sachdeva, A and Nikitas, JN and Ma, TM and Karasik, D and Ballas, LK and Lock, D and Valle, L and Taparra, K and Reiter, RE and Saigal, C and Chamie, K and Donin, N and Chin, AI and Rettig, M and Nickols, NG and Sun, Y and Spratt, D and Lamb, JM and Cao, M and Pommier, P and Steinberg, ML},
title = {Stereotactic Intensity-modulated Radiotherapy After Radical Prostatectomy (SCIMITAR): 4-Year Outcomes of a Phase 2 Clinical Trial.},
journal = {European urology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.eururo.2025.09.4149},
pmid = {41033921},
issn = {1873-7560},
abstract = {In the phase 2 SCIMITAR trial, stereotactic body radiotherapy (SBRT; 30-34 Gy in 5 fractions) was delivered to the prostatic fossa after radical prostatectomy in 100 patients requiring postoperative RT, with or without nodal RT and androgen deprivation therapy (ADT). The primary endpoint was 4-yr biochemical recurrence (BCR)-free survival (BCR-FS), with events defined as BCR (prostate-specific antigen ≥0.2 ng/ml above nadir), salvage ADT, or death. Outcomes were compared to individual patient data (IPD) from a phase 3 trial of conventionally fractionated RT (CFRT) using inverse probability of treatment weighting and Fine-Gray models. At median follow-up of 53 mo, the 4-yr BCR-FS rate was 60% (95% confidence interval [CI] 50-70%). The IPD analysis revealed that for men not receiving ADT, the risk of BCR was lower with SBRT than with CFRT (subdistribution hazard ratio [sHR] 0.49, 95% CI 0.29-0.84; p = 0.008). For men receiving ADT, there was no significant difference in BCR risk between SBRT and CFRT (sHR 1.58, 95% CI 0.81-3.11; p = 0.18), although the asymmetrically broad 95%CI and directionality of the point estimate suggest that a higher BCR risk with SBRT cannot be ruled out. The 4-yr cumulative incidence rates for late grade ≥2 gastrointestinal and genitourinary toxicities were 6.6% and 32%, respectively. At 48 mo, the proportion of patients reporting a decline of more than two times the minimal clinically important difference in urinary incontinence, urinary irritative/obstructive, bowel, and sexual domains was 23%, 6.7%, 13%, and 9.7%, respectively. SBRT to the prostatic fossa appears to be safe and effective through 4 yr.},
}

@article {pmid41032739,
year = {2025},
author = {Owens, CA and Ludmir, EB and Liu, Q and Qiu, W and Gupta, AC and Smith, SA and Rigaud, B and Brock, KK and Bates, JE and Meyers, TG and Paulino, AC and Peterson, CB and Kry, SF and Teepen, JC and Ronckers, CM and Neglia, JP and Leisenring, WM and Oeffinger, KC and Nathan, PC and Turcotte, LM and Hodgson, DC and Hudson, MM and Robison, LL and Moskowitz, CS and Armstrong, GT and Henderson, TO and Yasui, Y and Howell, RM},
title = {Colorectal-Specific Radiation Dose and Chemotherapy Risk for Subsequent Colorectal Malignancies in Childhood Cancer Survivors: A Childhood Cancer Survivor Study (CCSS) Report.},
journal = {Journal of clinical oncology : official journal of the American Society of Clinical Oncology},
volume = {},
number = {},
pages = {JCO2500531},
doi = {10.1200/JCO-25-00531},
pmid = {41032739},
issn = {1527-7755},
abstract = {PURPOSE: Among childhood cancer survivors, we evaluated not previously explored relationships between colorectal subsequent malignant neoplasm (SMN) incidence and colorectum-specific radiation dose metrics currently used in radiation therapy (RT) planning and expanded upon previously reported chemotherapy associations.

METHODS: The Childhood Cancer Survivor Study (CCSS) includes 5-year survivors of childhood cancer diagnosed between 1970 and 1999. RT was assessed as mean colorectal dose (MCD) and the percent volume (VX Gy) receiving ≥5, 10, 20, 30, and 40 Gy. Chemotherapy was assessed as cumulative doses for procarbazine and platinum agents, cyclophosphamide-equivalent doses for alkylating agents, and doxorubicin-equivalent doses for anthracyclines. Piecewise-exponential models and excess rate ratio (ERR) models evaluated dose-response relationships for the incidence of colorectal SMNs. Reference groups were those not receiving the assessed treatment(s).

RESULTS: Among 25,723 survivors (median follow-up = 28.5 years; range = 5.0-48.9), 104 colorectal SMNs were identified. A dose-response relationship was observed between MCD and colorectal SMN rates; incidence rate ratios (IRRs) for 10 to <20 Gy and ≥20 Gy were 3.6 (95% CI, 1.9 to 6.9) and 8.3 (95% CI, 3.9 to 17.8), respectively. When ≥20% of the colorectum volume was irradiated, IRRs increased with increasing volume. The V20 Gy IRRs were 3.8 (95% CI, 1.9 to 7.6), 4.9 (95% CI, 2.0 to 12.0), and 8.7 (95% CI, 3.5 to 21.6) for irradiated volumes of 20% to <40%, 40% to <80%, and ≥80%, respectively. The IRR was 1.8 (95% CI, 1.0 to 3.0) for doxorubicin-equivalent dose ≥250 mg/m[2], 3.7 (95% CI, 2.2 to 6.4) for cyclophosphamide-equivalent dose ≥6,000 mg/m[2], and 4.5 (95% CI, 2.0 to 10.1) for platinum dose ≥450 mg/m[2]. For procarbazine dose, the IRR was 6.3 (95% CI, 3.0 to 13.2) for 4,200 to <7,036 mg/m[2] and 9.0 (95% CI, 4.3 to 18.9) for ≥7,036 mg/m[2]. In the absence of RT, colorectal SMN rates increased with exposure to any platinum-based agent (IRR, 3.8 [95% CI, 1.1 to 12.7]), alkylator (IRR, 4.8 [95% CI, 1.6 to 14.4]), or procarbazine (IRR, 16.9 [95% CI, 5.9 to 48.8]). Colorectal SMN rates increased linearly with procarbazine dose (ERR per 1,000 mg/m[2] = 73.0 [95% CI, 26.4% to 119.6%]) and MCD (ERR per 1 Gy = 20.8 [95% CI, 9.0% to 32.5%]). Quadratic ERR models did not improve data fit compared with linear ERR models.

CONCLUSION: These RT and chemotherapy dose-response relationships can better inform contemporary RT planning for pediatric patients and surveillance guidelines for high-risk survivors.},
}

@article {pmid41032722,
year = {2025},
author = {Curtis, DJ and Reynolds, J and Hill, GR},
title = {Cyclophosphamide and Cyclosporin for GVHD Prevention. Reply.},
journal = {The New England journal of medicine},
volume = {393},
number = {13},
pages = {1350-1351},
doi = {10.1056/NEJMc2511563},
pmid = {41032722},
issn = {1533-4406},
}

@article {pmid41032518,
year = {2025},
author = {Corey, L},
title = {Operation Warp Speed offers a roadmap for improving the efficiency of bench to bedside medical advances.},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
volume = {122},
number = {40},
pages = {e2502975122},
doi = {10.1073/pnas.2502975122},
pmid = {41032518},
issn = {1091-6490},
support = {UM1 AI068614-14//HHS | NIH | National Institute of Allergy and Infectious Diseases (NIAID)/ ; },
}

@article {pmid41032288,
year = {2025},
author = {Blechter, B and Wang, X and Dai, J and Karsonaki, C and Shi, J and Shiraishi, K and Choi, J and Matsuo, K and Chen, TY and Hung, RJ and Chen, K and Shu, XO and Kim, YT and Choudhury, PP and Williams, J and Landi, MT and Lin, D and Zheng, W and Yin, Z and Zhou, B and Wang, J and Seow, WJ and Song, L and Chang, IS and Hu, W and Chien, LH and Cai, Q and Hong, YC and Kim, HN and Wu, YL and Wong, MP and Richardson, BD and Li, S and Zhang, T and Breeze, C and Wang, Z and Bassig, BA and Kim, JH and Albanes, D and Wong Sm, JY and Shin, MH and Chung, LP and Yang, Y and Zheng, H and Dai, H and Yatabe, Y and Zhang, XC and Kim, YC and Caporaso, NE and Chang, J and Ho, JCM and Daigo, Y and Momozawa, Y and Kamatani, Y and Kobayashi, M and Okubo, K and Honda, T and Hosgood, HD and Kunitoh, H and Watanabe, SI and Miyagi, Y and Matsumoto, S and Horinouchi, H and Tsuboi, M and Hamamoto, R and Goto, K and Takahashi, A and Goto, A and Minamiya, Y and Hara, M and Nishida, Y and Takeuchi, K and Wakai, K and Matsuda, K and Murakami, Y and Shimizu, K and Suzuki, H and Saito, M and Ohtaki, Y and Tanaka, K and Wu, T and Wei, F and Machiela, MJ and Kim, YH and Oh, IJ and Lee, VHF and Chang, GC and Chen, KY and Su, WC and Chen, YM and Seow, A and Park, JY and Kweon, SS and Gao, YT and Liu, J and Schwartz, AG and Houlston, R and Gorlov, IP and Wu, X and Yang, P and Lam, S and Tardon, A and Chen, C and Bojesen, SE and Johansson, M and Risch, A and Bickeböller, H and Ji, BT and Wichmann, HE and Christiani, DC and Rennert, G and Arnold, SM and Brennan, P and McKay, J and Field, JK and Davies, MPA and Shete, SS and Le Marchand, L and Liu, G and Andrew, AS and Kiemeney, LA and Zienolddiny-Narui, S and Grankvist, K and Cox, A and Taylor, F and Yuan, JM and Lazarus, P and Schabath, MB and Aldrich, MC and Jeon, HS and Jiang, SS and Chen, CH and Hsiao, CF and Hu, Z and Burdett, L and Yeager, M and Hutchinson, A and Hicks, B and Liu, J and Berndt, SI and Wu, W and Wang, J and Li, Y and Choi, JE and Park, KH and Sung, SW and Kang, CH and Wang, WC and Xu, J and Guan, P and Tan, W and Yu, CJ and Yang, G and Sihoe, ADL and Choi, YY and Park, IK and Hung, HH and Vermeulen, RCH and Cheng, I and Wu, J and Tsai, FY and Chan, JKC and Li, J and Lin, HC and Liu, J and Song, B and Sawada, N and Yamaji, T and Wyatt, K and Ma, H and Zhu, M and Wang, Y and Qi, T and Li, X and Ren, Y and Chao, A and Iwasaki, M and Zhu, J and Wu, G and Chen, CY and ScD, CC and Yang, PC and Stevens, VL and Fraumeni, JF and Lin, K and Walters, RG and Chen, Z and Chatterjee, N and Gorlova, OY and Amos, CI and Shen, H and Hsiung, CA and Chanock, SJ and Rothman, N and Kohno, T and Lan, Q and Zhang, H},
title = {Stratifying lung adenocarcinoma risk with multi-ancestry polygenic risk scores in East Asian never-smokers.},
journal = {Journal of the National Cancer Institute},
volume = {},
number = {},
pages = {},
doi = {10.1093/jnci/djaf272},
pmid = {41032288},
issn = {1460-2105},
abstract = {BACKGROUND: Lung adenocarcinoma (LUAD) in never-smokers is a major public health burden, especially among East Asian women. Polygenic risk scores (PRSs) are promising for risk stratification but are primarily developed in European-ancestry populations. We aimed to develop and validate single- and multi-ancestry PRSs for East Asian never-smokers to improve LUAD risk prediction.

METHODS: PRSs were developed using genome-wide association study summary statistics from East Asian (8,002 cases; 20,782 controls) and European (2,058 cases; 5,575 controls) populations. Single-ancestry models included PRS-25, PRS-CT, and LDpred2; multi-ancestry models included LDpred2+PRS-EUR128, PRS-CSx, and CT-SLEB. Performance was evaluated in independent East Asian data from the Female Lung Cancer Consortium (FLCCA) and externally validated in the Nanjing Lung Cancer Cohort (NJLCC). We assessed predictive accuracy via AUC, with 10-year and (age 30-80) absolute risks estimates.

RESULTS: The best multi-ancestry PRS, using East Asian and European data via CT-SLEB (clumping and thresholding, super learning, empirical Bayes), outperformed the best East Asian-only PRS (LDpred2; AUC = 0.629, 95% CI:0.618,0.641), achieving an AUC of 0.640 (95% CI : 0.629,0.653) and odds ratio of 1.71 (95% CI : 1.61,1.82) per SD increase. NJLCC Validation confirmed robust performance (AUC =0.649, 95% CI: 0.623, 0.676). The top 20% PRS group had a 3.92-fold higher LUAD risk than the bottom 20%. Further, the top 5% PRS group reached a 6.69% lifetime absolute risk. Notably, this group reached the average population 10-year LUAD risk at age 50 (0.42%) by age 41, nine years earlier.

CONCLUSIONS: Multi-ancestry PRS approaches enhance LUAD risk stratification in East Asian never-smokers, with consistent external validation, suggesting future clinical utility.},
}

@article {pmid41031719,
year = {2025},
author = {Nizam, A and Nguyen, CB and Li, J and Zabor, EC and Msaouel, P and Jiang, CY and Alhalabi, O and Oh, E and Davidsohn, MP and Epstein, IB and Bakaloudi, DR and Talukder, R and Jindal, T and Taylor, AK and Glover, MJ and Khaki, AR and Lemke, E and Mabey, H and Abuqayas, B and Jang, A and Brown, JR and Evans, ST and Pywell, C and Basu, A and Bilen, MA and Barata, PC and Zakharia, Y and Milowsky, MI and Kilari, D and Hoimes, CJ and Shah, SA and Emamekhoo, H and Davis, NB and Gupta, S and Grivas, P and Bellmunt, J and Campbell, MT and Alva, AS and Koshkin, VS},
title = {Treatment-Related Adverse Events and Associated Outcomes in Patients With Advanced Urothelial Carcinoma Treated With Enfortumab Vedotin: Analysis of the UNITE Study.},
journal = {Cancer medicine},
volume = {14},
number = {19},
pages = {e71284},
pmid = {41031719},
issn = {2045-7634},
mesh = {Humans ; Male ; Female ; Aged ; Retrospective Studies ; Middle Aged ; *Antibodies, Monoclonal/adverse effects ; Aged, 80 and over ; *Immunoconjugates/adverse effects/therapeutic use/administration & dosage ; *Urologic Neoplasms/drug therapy/mortality/pathology ; *Carcinoma, Transitional Cell/drug therapy/mortality/pathology ; Treatment Outcome ; *Antineoplastic Agents, Immunological/adverse effects ; *Urinary Bladder Neoplasms/drug therapy/mortality/pathology ; },
abstract = {INTRODUCTION: Enfortumab vedotin-ejfv (EV), an antibody-drug conjugate approved for advanced urothelial carcinoma (aUC), has limited real-world safety data and no validated predictive biomarkers. Retrospective studies suggest higher objective response rates (ORR) among patients developing EV-related dermatologic toxicities, but survival implications remain unclear. This analysis assessed the safety of EV monotherapy and the impact of dermatologic and neurologic toxicities on efficacy outcomes in a multi-institutional cohort.

MATERIALS AND METHODS: UNITE is a multicenter, retrospective study across 16 US sites of patients with aUC treated with targeted agents, including EV. Primary endpoints were the incidence of EV treatment-related adverse events (TRAEs, any grade) and TRAE-related treatment modifications. Secondary endpoints included a comparison of ORR, progression-free survival (PFS), and overall survival (OS) between patients with and without dermatologic toxicities and neuropathy. To reduce immortal time bias, Cox regression models incorporated TRAEs as time-dependent covariates to adjust for EV treatment duration as well as Eastern Cooperative Oncology Group performance status (ECOG PS), hemoglobin, and liver metastases.

RESULTS: Between 2018 and 2023, 485 patients with aUC received > 1 dose of EV monotherapy. Most (67%) received > 2 prior therapy lines. Any grade TRAEs occurred in 77%, most frequently neuropathy (36%) and dermatologic toxicities (27%); 57% required treatment modification and 21% discontinued EV, primarily due to neuropathy (9%) and fatigue (3%). Patients with dermatologic toxicities and neuropathy had higher ORR (56% vs. 42%; p = 0.007 and 64% vs. 35%; p < 0.0001, respectively). Neuropathy was independently associated with improved OS (HR 0.66; 95% CI 0.50-0.87; p = 0.002); dermatologic TRAEs were not associated with PFS or OS benefit.

CONCLUSIONS: EV safety outside clinical trials was consistent with prior reports, with no new signals. Treatment modifications were most often due to neuropathy, dermatologic toxicities, and fatigue. Both dermatologic toxicities and neuropathy correlated with higher ORR, but only neuropathy was independently associated with improved OS.},
}

Humans
Male
Female
Aged
Retrospective Studies
Middle Aged
*Antibodies, Monoclonal/adverse effects
Aged, 80 and over
*Immunoconjugates/adverse effects/therapeutic use/administration & dosage
*Urologic Neoplasms/drug therapy/mortality/pathology
*Carcinoma, Transitional Cell/drug therapy/mortality/pathology
Treatment Outcome
*Antineoplastic Agents, Immunological/adverse effects
*Urinary Bladder Neoplasms/drug therapy/mortality/pathology

@article {pmid41031512,
year = {2025},
author = {Chalitsios, CV and Markozannes, G and Aglago, EK and Berndt, SI and Buchanan, DD and Campbell, PT and Cao, Y and Chan, AT and Dimou, N and Drew, DA and French, AJ and Georgeson, P and Giannakis, M and Gruber, SB and Gunter, MJ and Harrison, TA and Hoffmeister, M and Hsu, L and Huang, WY and Hullar, MA and Huyghe, JR and Lynch, BM and Moreno, V and Murphy, N and Newton, CC and Nowak, JA and Obón-Santacana, M and Ogino, S and Qu, C and Schmit, SL and Steinfelder, RS and Sun, W and Thomas, CE and Toland, AE and Trinh, QM and Ugai, T and Um, CY and Van Guelpen, B and Zaidi, SH and Schoen, RE and Woods, MO and Brenner, H and Andreson, L and Pellatt, AJ and Peters, U and Phipps, AI and Tsilidis, KK},
title = {Physical activity and molecular subtypes of colorectal cancer: a pooled observational analysis and mendelian randomisation study.},
journal = {JNCI cancer spectrum},
volume = {},
number = {},
pages = {},
doi = {10.1093/jncics/pkaf095},
pmid = {41031512},
issn = {2515-5091},
abstract = {BACKGROUND: Physical activity is associated with lower colorectal cancer (CRC) risk, but its association with molecular subtypes defined by genetic and epigenetic alterations of the disease is unclear. Such information may enhance the understanding of the mechanisms related to the benefits of physical activity.

METHODS: Pooled observational (ncases=5,386, ncontrols=6,798; nstudies=5) and genome-wide association data (ncases=8,178, ncontrols=10,472; nstudies=5) were utilised. We used multivariable logistic regression models and Mendelian randomisation (MR) to assess the association between physical activity and the risk of CRC subtypes defined by individual tumour markers (and marker combinations), namely microsatellite instability (MSI) status, CpG island methylator phenotype (CIMP) status, BRAF and KRAS mutations. We used case-only analysis to test for differences between molecular subtypes. We applied Bonferroni correction to account for multiple tests.

RESULTS: In the pooled observational analysis, higher levels of physical activity were associated with lower CRC risk (ORObs-per 1SD=0.94, 95%CI 0.90-0.97), with an association that was stronger in males (ORObs-per 1SD=0.91, 95%CI 0.87-0.96) than in females (ORObs-per 1SD=0.97, 95%CI 0.91-1.03) (Pinteraction=0.04). Higher physical activity was associated with a lower risk of CRC across all molecular subtypes, especially in males. There was no difference in the associations by subtypes by pooled observational or MR analyses. The findings did not differ by study design, anatomical site, and early or late age onset of CRC.

CONCLUSIONS: Our findings suggest that physical activity is not differentially associated with the four major molecular subtypes involved in colorectal carcinogenesis, indicating that its benefits extend broadly across colorectal cancer pathogenesis.},
}

@article {pmid41028200,
year = {2025},
author = {Cheung, KJ and Horne-Badovinac, S},
title = {Publisher Correction: Collective cell migration modes in development, tissue repair and cancer.},
journal = {Nature reviews. Molecular cell biology},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41580-025-00911-7},
pmid = {41028200},
issn = {1471-0080},
}

@article {pmid41028170,
year = {2025},
author = {Bot, A and Scharenberg, A and Friedman, K and Guey, L and Hofmeister, R and Andorko, JI and Klichinsky, M and Neumann, F and Shah, JV and Swayer, AJ and Trudeau, K and Weissman, D and Stephan, MT and Buchholz, CJ and June, CH},
title = {In vivo chimeric antigen receptor (CAR)-T cell therapy.},
journal = {Nature reviews. Drug discovery},
volume = {},
number = {},
pages = {},
pmid = {41028170},
issn = {1474-1784},
abstract = {Chimeric antigen receptor (CAR)-T cell therapy has transformed the outcomes of patients with haematological malignancies, yet its use is limited by labour-intensive manufacturing, constrained production capacity and variable clinical performance. In vivo CAR-T cell engineering, in which CAR-T cells are generated directly inside the patient's body, seeks to overcome these challenges by eliminating the need for ex vivo cell processing and complex logistics, as well as improve clinical performance. Recent advances in virology, RNA medicines and nanotechnology have catalysed a radical overhaul of this approach, which uses targeted delivery systems such as lentiviral vectors and lipid nanoparticles to introduce CAR-encoding genetic material into endogenous T cells. Early clinical studies have shown efficient transduction, sustained CAR expression and initial signs of antitumour activity, establishing proof of concept. This Review explores the underlying technologies - including RNA delivered by lipid nanoparticles and engineered viral vectors - and discusses how they are being adapted to develop more broadly applicable, scalable, safe and effective CAR-T cell therapies. By removing the need for ex vivo manipulation and chemotherapeutic conditioning, this strategy could enable the wider application of CAR-T cell therapies not just to blood cancers but to autoimmune diseases for which ex vivo CAR-T cell therapies have shown strong promise, such as systemic lupus erythematosus.},
}

@article {pmid41027579,
year = {2025},
author = {Cheng, GS and Campbell, AP and Xie, H and Ogimi, C and Waghmare, A and Kuypers, J and Nichols, WG and Carpenter, P and Corey, L and Callais, C and Sandmaier, BM and Stevens-Ayers, T and Jerome, KR and Chien, JW and Leisenring, WM and Englund, JA and Boeckh, M},
title = {Respiratory Virus Infections and Pulmonary Impairment after Allogeneic Hematopoietic Cell Transplantation.},
journal = {The Journal of infectious diseases},
volume = {},
number = {},
pages = {},
doi = {10.1093/infdis/jiaf503},
pmid = {41027579},
issn = {1537-6613},
abstract = {BACKGROUND: Respiratory virus infections (RVI) are common after hematopoietic cell transplantation (HCT), but their effect on pulmonary outcomes, including bronchiolitis obliterans syndrome (BOS), and mortality is poorly defined.

METHODS: Prospective cohort study of 471 allogeneic HCT recipients transplanted in the pre-COVID-19 pandemic era in an academic cancer center. Participants were prospectively followed for one year with serial handheld spirometry, symptom questionnaires, and multiplex 11-virus PCR. Pulmonary function testing occurred at recommended intervals. Cox proportional hazard and generalized estimating equation models were used to estimate associations between RVI and weekly spirometry with late airflow obstruction (AFO), BOS, and overall mortality.

RESULTS: The one-year cumulative incidence of at least one RVI was 62%; lower respiratory tract disease (LRTD) occurred in 7.6% of patients. Late AFO developed in 15.6% of patients and BOS in 3.9% of patients. Any symptomatic viral upper respiratory tract infections (URTI) were associated with AFO (adjusted HR [aHR] 1.87, 95% CI 1.11-3.16) and BOS (aHR 2.65, 95% CI 1.02-6.91). Individually, PIV-3 URTI were associated with AFO (aHR 2.83, 95% CI 1.01-7.97) and RSV URTI were associated with BOS (aHR 6.32, 95% CI 2.04-19.6). Short-term airflow decline was associated with AFO. Any LRTD (aHR 3.49, 95% CI 2.18-5.57), as well as symptomatic influenza URTI (aHR 2.68, 95% CI 1.52-4.72), were associated with mortality.

CONCLUSIONS: RVI after HCT, particularly those caused by RSV, PIV-3 and influenza, increase the risk of pulmonary impairment and mortality. These infections should be targeted for specific anti-viral approaches and intensified monitoring for late onset pulmonary disease.},
}

@article {pmid41027557,
year = {2025},
author = {Spellman, SR and Xu, K and Oloyede, T and Ahn, KW and Akhtar, OS and Bolon, YT and Broglie, L and Bloomquist, J and Bupp, C and Chen, M and Devine, SM and Jurdi, NE and Hamadani, M and Hengen, M and Huppler, AH and Jaglowski, S and Kuxhausen, M and Lee, SJ and Moskop, A and Page, KM and Pasquini, MC and Pérez, WS and Phelan, R and Rizzo, D and Saber, W and Stefanski, HE and Steinert, P and Tuschl, E and Visotcky, A and Vogel, R and Auletta, JJ and Shaw, BE and Allbee-Johnson, M},
title = {Corrigendum to: Current Activity Trends and Outcomes in Hematopoietic Cell Transplantation and Cellular Therapy - A Report from the CIBMTR, Transplantation and Cellular Therapy, 31:8, August 2025, 505-532; Article Number: JTCT-S-25-00377.},
journal = {Transplantation and cellular therapy},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jtct.2025.09.001},
pmid = {41027557},
issn = {2666-6367},
}

@article {pmid40924543,
year = {2025},
author = {Baele, G and Carvalho, LM and Brusselmans, M and Dudas, G and Ji, X and McCrone, JT and Lemey, P and Suchard, MA and Rambaut, A},
title = {HIPSTR: highest independent posterior subtree reconstruction in TreeAnnotator X.},
journal = {Bioinformatics (Oxford, England)},
volume = {41},
number = {10},
pages = {},
doi = {10.1093/bioinformatics/btaf488},
pmid = {40924543},
issn = {1367-4811},
support = {//Research Foundation-Flanders/ ; },
mesh = {*Software ; *Phylogeny ; *SARS-CoV-2/genetics/classification ; Bayes Theorem ; *Ebolavirus/genetics/classification ; Algorithms ; Humans ; *Computational Biology/methods ; COVID-19/virology ; },
abstract = {SUMMARY: In Bayesian phylogenetic and phylodynamic studies, it is common to summarize the posterior distribution of trees with a time-calibrated summary phylogeny. While the maximum clade credibility (MCC) tree is often used for this purpose, we here show that a novel summary tree method-the highest independent posterior subtree reconstruction, or (HIPSTR)-contains consistently higher supported clades over MCC. We also provide faster computational routines for estimating both summary trees in an updated version of TreeAnnotator X, an open-source software program that summarizes the information from a sample of trees and returns many helpful statistics such as individual clade credibilities contained in the summary tree.

RESULTS: HIPSTR and MCC reconstructions on two Ebola virus and two SARS-CoV-2 datasets show that HIPSTR yields summary trees that consistently contain clades with higher support compared to MCC trees. The MCC trees regularly fail to include several clades with very high posterior probability (≥0.95) as well as a large number of clades with moderate to high posterior probability (≥50%), whereas HIPSTR-in particular its majority-rule extension MrHIPSTR-achieves near-perfect performance in this respect. HIPSTR and MrHIPSTR also exhibit favourable computational performance over MCC in TreeAnnotator X. Comparison to the recent CCD0-MAP algorithm yielded mixed results and requires a more in-depth investigation in follow-up studies.

TreeAnnotator X is available as part of the BEAST X (v10.5.0) software package, available at https://github.com/beast-dev/beast-mcmc/releases, and on Zenodo (DOI: https://doi.org/10.5281/zenodo.4895234).},
}

*Software
*Phylogeny
*SARS-CoV-2/genetics/classification
Bayes Theorem
*Ebolavirus/genetics/classification
Algorithms
Humans
*Computational Biology/methods
COVID-19/virology

@article {pmid41027157,
year = {2025},
author = {Dominguez Islas, CP and Magaret, CA and Molitor, C and Serebryannyy, L and Narpala, S and Castro, M and Posavad, CM and Roberts, PC and Lyke, KE and Atmar, RL and Janes, H and Deming, ME},
title = {SARS-CoV-2 spike sequence-based distance as a marker of binding antibody response to COVID-19 vaccines.},
journal = {Vaccine},
volume = {65},
number = {},
pages = {127738},
doi = {10.1016/j.vaccine.2025.127738},
pmid = {41027157},
issn = {1873-2518},
abstract = {COVID-19 vaccines based on ancestral SARS-CoV-2 have proven highly effective at reducing the risk of illness, especially severe disease. Both binding and neutralizing antibodies have been demonstrated to be strong predictors of the level of vaccine efficacy (VE). Both VE and vaccine-induced antibody responses have been shown to be lower against emergent SARS-CoV-2 viruses; therefore, predicting COVID-19 VE against emergent viruses is critical for decision-making regarding the composition of new vaccines. The data needed to enable such prediction are unclear. We report on 728 individuals without prior SARS-CoV-2 infection who received primary vaccination with ancestral-virus-based mRNA and vector-based COVID-19 vaccines and who were boosted in a homologous or heterologous fashion with mRNA, vector, or protein-based COVID-19 vaccines including a bivalent B.1.351 mRNA vaccine. Post-prime and post-boost binding antibody responses were used to evaluate the extent and drivers of variability in these responses to 22 SARS-CoV-2 Spike antigens from viruses that emerged between 2020 and 2021. We evaluated how well proteomic distance between the vaccine and assay Spike antigen predicted the vaccine-induced antibody response. Following primary vaccination, antibody responses varied across Spike antigens and were, on average, 36 % lower per 10-amino acid (AA) difference between the vaccine and assay Spike antigen (95 % CI: 30 % to 43 %). The geometric mean antibody response to a given antigen was nearly perfectly predicted by the sequence-based distance of the antigen to the vaccine. Post-boost responses were less variable across antigens and weakly associated with Spike distance (17 % lower per 10-AA difference; 95 % CI: 14 % to 20 %). The high variability in binding antibodies across individuals was only partially explained by participant characteristics. Given that populations now have experienced multiple rounds of prior vaccination and infection, measurement of vaccine-induced antibody responses from representative populations will likely be needed to predict the efficacy of COVID-19 vaccines against future strains.},
}

@article {pmid41025350,
year = {2025},
author = {Jakubek, YA and Smith, AP and Leng, XI and Hall, ME and Ezzat, D and Pershad, Y and Collins, JM and Uddin, MM and Fardo, DW and Natarajan, P and Bick, AG and Kitzman, JO and Honigberg, MC and Hayden, KM and Manson, JE and Jaiswal, S and Whitsel, EA and Reiner, AP},
title = {Clonal hematopoiesis of indeterminate potential and the risk of cognitive impairment in the Women's Health Initiative Memory Study.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {21},
number = {10},
pages = {e70737},
pmid = {41025350},
issn = {1552-5279},
support = {//WHI/ ; /NH/NIH HHS/United States ; 75N92021D00001/HL/NHLBI NIH HHS/United States ; 75N92021D00002/HL/NHLBI NIH HHS/United States ; 75N92021D00003/WH/WHI NIH HHS/United States ; 75N92021D00004/WH/WHI NIH HHS/United States ; 75N92021D00005/WH/WHI NIH HHS/United States ; },
mesh = {Humans ; Female ; *Cognitive Dysfunction/genetics/epidemiology ; Aged ; *Clonal Hematopoiesis/genetics ; Risk Factors ; Women's Health ; *Dementia/genetics/epidemiology ; Aged, 80 and over ; Middle Aged ; Proportional Hazards Models ; Incidence ; },
abstract = {INTRODUCTION: Clonal hematopoiesis of indeterminate potential (CHIP) confers an increased risk of several chronic aging-related diseases. Paradoxically, CHIP was associated with lower risk of dementia in recent studies.

METHODS: We examined associations between baseline CHIP and incident mild cognitive impairment (MCI) and/or probable dementia in the Women's Health Initiative Memory Study. CHIP was detected using blood-based targeted sequencing. Cox proportional hazards models examined time to onset of cognitive impairment, adjusting for traditional risk factors.

RESULTS: Using a conventional variant allele fraction (VAF) threshold of 2%, CHIP was not associated with incident cognitive impairment. The presence of larger CHIP clone (VAF ≥ 8%) was associated with a lower incidence of adjudicated probable dementia (hazard ratio = 0.62 [95% confidence interval = 0.41 to 0.94], p = 0.025), while the association with the composite outcome MCI/probable dementia was weaker and overlapped 1.0.

DISCUSSION: The association of CHIP with lower risk of cognitive impairment in postmenopausal women may be dependent on VAF and impairment severity.

HIGHLIGHTS: The WHIMS comprises ∼5000 postmenopausal women, followed for up to 25 years. CHIP was associated with reduced risk of adjudicated probable dementia in WHIMS. Large CHIP clones (> 8% VAF), but not small clones (<8% VAF), showed an association. CHIP was not associated with MCI in the WHIMS cohort.},
}

Humans
Female
*Cognitive Dysfunction/genetics/epidemiology
Aged
*Clonal Hematopoiesis/genetics
Risk Factors
Women's Health
*Dementia/genetics/epidemiology
Aged, 80 and over
Middle Aged
Proportional Hazards Models
Incidence

@article {pmid41024277,
year = {2025},
author = {Gafken, PR and Paczesny, S},
title = {Blood proteomics for quantitative biomarkers of cellular therapies.},
journal = {Biomarker research},
volume = {13},
number = {1},
pages = {120},
pmid = {41024277},
issn = {2050-7771},
support = {P30CA015704/CA/NCI NIH HHS/United States ; R01CA168814/CA/NCI NIH HHS/United States ; R21AI178981//National Institute of Allergy and Infectious Diseases/ ; R01HL158096/HL/NHLBI NIH HHS/United States ; },
abstract = {Cellular therapies for several blood cancers particularly of lymphoid origin have made remarkable leaps forward. In parallel, blood proteomics, specifically quantitative proteomics, has been a powerful tool for identifying and quantifying protein biomarkers associated with cellular therapies, providing insights into treatment efficacy and toxicity. Both mass spectrometry (MS)-based proteomics and large-scale affinity-based platforms such as Olink and SomaScan have been increasingly implemented in research and clinical laboratories to identify and quantify candidate biomarkers in the blood. Biomarkers are used for risk stratification, early diagnosis, prognosis, and for treatment response prediction and monitoring in context of treatment efficacy and toxicity. These biomarkers might facilitate timely and selective therapeutic intervention and understand pathogenesis mechanisms of responses and adverse events. They are anticipated to undergo faster transition from bench to bedside soon. This review article summarizes recent technical progresses in clinical proteomics. The review also provides current information on validated biomarkers in the field of cellular therapies.},
}

@article {pmid41022768,
year = {2025},
author = {Liu, P and Li, JJ},
title = {mcRigor: a statistical method to enhance the rigor of metacell partitioning in single-cell data analysis.},
journal = {Nature communications},
volume = {16},
number = {1},
pages = {8602},
pmid = {41022768},
issn = {2041-1723},
support = {R35GM140888//U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS)/ ; 1846216//NSF | BIO | Division of Biological Infrastructure (DBI)/ ; 2113754//NSF | Directorate for Mathematical & Physical Sciences | Division of Mathematical Sciences (DMS)/ ; 2022-249355//Silicon Valley Community Foundation (SVCF)/ ; },
mesh = {*Single-Cell Analysis/methods ; Algorithms ; Humans ; RNA-Seq ; Reproducibility of Results ; Gene Expression Profiling/methods ; *Computational Biology/methods ; Software ; },
abstract = {In single-cell data analysis, addressing sparsity often involves aggregating the profiles of homogeneous single cells into metacells. However, existing metacell partitioning methods lack checks on the homogeneity assumption and may aggregate heterogeneous single cells, potentially biasing downstream analysis and leading to spurious discoveries. To fill this gap, we introduce mcRigor, a statistical method to detect dubious metacells, which are composed of heterogeneous single cells, and optimize the hyperparameter(s) of a metacell partitioning method. The core of mcRigor is a feature-correlation-based statistic that measures the heterogeneity of a metacell, with its null distribution derived from a double permutation scheme. As an optimizer for existing metacell partitioning methods, mcRigor has been shown to improve the reliability of discoveries in single-cell RNA-seq and multiome (RNA + ATAC) data analyses, such as uncovering differential gene co-expression modules, enhancer-gene associations, and gene temporal expression. Moreover, mcRigor enables benchmarking and selection of the most suitable metacell partitioning method with optimized hyperparameter(s) tailored to a specific dataset, ensuring reliable downstream analysis. Our results indicate that among existing metacell partitioning methods, MetaCell and SEACells consistently outperform MetaCell2 and SuperCell, albeit with the trade-off of longer runtimes.},
}

*Single-Cell Analysis/methods
Algorithms
Humans
RNA-Seq
Reproducibility of Results
Gene Expression Profiling/methods
*Computational Biology/methods
Software

@article {pmid41021636,
year = {2025},
author = {Giersch, RM and Sevigny, JK and Weinandt, SA and Mayo, C and Garrett, FES and Tindbaek, K and Yonemitsu, MA and Hart, SFM and Metzger, MJ},
title = {Variation in natural infection outcomes and cancer cell release from soft-shell clams (Mya arenaria) with bivalve transmissible neoplasia.},
journal = {PLoS pathogens},
volume = {21},
number = {9},
pages = {e1013537},
doi = {10.1371/journal.ppat.1013537},
pmid = {41021636},
issn = {1553-7374},
support = {R01 CA255712/CA/NCI NIH HHS/United States ; T32 GM007270/GM/NIGMS NIH HHS/United States ; T32 HG000035/HG/NHGRI NIH HHS/United States ; },
abstract = {Bivalve transmissible neoplasias (BTNs) are leukemia-like cancers found in at least 10 bivalve species, in which the cancer cells themselves transfer from one individual to another, spreading as an unusual form of infectious disease. Before the infectious etiology was known, there were reports of lethality and outbreaks of cancer in the soft-shell clam (Mya arenaria) on the east coast of North America. Using sensitive and specific qPCR assays, we followed the outcomes of BTN in naturally-infected soft-shell clams from Maine, USA. We observed variable outcomes, with about half of clams (9/21) progressing to high levels of cancer and death, about half exhibiting long-term non-progression (11/21), and a single animal showing regression of cancer. We also observe a significant decrease in survival in animals that progress to >10% cancer in their hemolymph, while we see no effect on survival in clams with BTN that are long-term non-progressors. As most bivalves do not physically contact each other, and BTN cells can survive in seawater, it has been proposed that BTN is spread through release of cancer cells into the water. We used qPCR to detect BTN-specific sequences in environmental DNA (eDNA) in the tanks of animals throughout this experiment. We show that BTN-specific eDNA (likely from released cancer cells) can be detected in tank water of most clams with >24% cancer in their hemolymph, but not below this level. This detection of BTN eDNA is variable and occurs in bursts, but in clams with >24% cancer, the detection of BTN eDNA correlates with progression of the cancer in the hemolymph. This study demonstrates the lethality of BTN, but the observation that about half of clams with BTN do not progress to death provides evidence suggesting that there may be a block to the progression of BTN in a large portion of clams in a population with this enzootic disease. This study also further supports the hypothesis that BTN cells transmit through seawater and provides insights into the mechanisms of the transmission dynamics.},
}

@article {pmid41021323,
year = {2025},
author = {Etzioni, R and Owens, L},
title = {Learning from prostate cancer statistics.},
journal = {CA: a cancer journal for clinicians},
volume = {},
number = {},
pages = {},
doi = {10.3322/caac.70037},
pmid = {41021323},
issn = {1542-4863},
}

@article {pmid41019149,
year = {2025},
author = {Mohty, M and Banerjee, R},
title = {Networking for a successful career in clinical hematology: a strategic approach.},
journal = {Clinical hematology international},
volume = {7},
number = {3},
pages = {20-23},
pmid = {41019149},
issn = {2590-0048},
abstract = {Networking is fundamental to career development in clinical hematology, providing avenues for knowledge exchange, collaborations, and professional growth. This manuscript examines specific strategies for networking within this specialized field, detailing effective platforms, strategies, overcoming challenges, and illustrating real-world success stories. References to key studies and expert opinions underscore the importance of building a robust professional network through in-person and online activities. An extensive review of literature highlights how networking contributes to scientific collaboration, mentorship, career opportunities, and the dissemination of cutting-edge hematological research.},
}

@article {pmid41018806,
year = {2025},
author = {Li, S and Gilbert, PB and Duan, R and Luedtke, A},
title = {Data fusion using weakly aligned sources.},
journal = {Journal of the American Statistical Association},
volume = {},
number = {},
pages = {},
pmid = {41018806},
issn = {0162-1459},
support = {DP2 LM013340/LM/NLM NIH HHS/United States ; R37 AI054165/AI/NIAID NIH HHS/United States ; UM1 AI068635/AI/NIAID NIH HHS/United States ; },
abstract = {We introduce a new data fusion method that utilizes multiple data sources to estimate a smooth, finite-dimensional parameter. Most existing methods only make use of fully aligned data sources that share common conditional distributions of one or more variables of interest. However, in many settings, the scarcity of fully aligned sources can make existing methods require unduly large sample sizes to be useful. Our approach enables the incorporation of weakly aligned data sources that are not perfectly aligned, provided their degree of misalignment is known up to finite-dimensional parameters. We quantify the additional efficiency gains achieved through the integration of these weakly aligned sources. We characterize the semiparametric efficiency bound and provide a general means to construct estimators achieving these efficiency gains. We illustrate our results by fusing data from two harmonized HIV monoclonal antibody prevention efficacy trials to study how a neutralizing antibody biomarker associates with HIV genotype.},
}

@article {pmid41018563,
year = {2025},
author = {Williamson, BD and King, D and Huang, Y},
title = {Practical Considerations for Variable Screening in the Super Learner.},
journal = {The New England Journal of Statistics in Data Science},
volume = {},
number = {},
pages = {},
pmid = {41018563},
issn = {2693-7166},
support = {S10 OD028685/OD/NIH HHS/United States ; R01 GM106177/GM/NIGMS NIH HHS/United States ; R01 CA277133/CA/NCI NIH HHS/United States ; R37 AI054165/AI/NIAID NIH HHS/United States ; U24 CA086368/CA/NCI NIH HHS/United States ; },
abstract = {Estimating a prediction function is a fundamental component of many data analyses. The super learner ensemble, a particular implementation of stacking, has desirable theoretical properties and has been used successfully in many applications. Dimension reduction can be accomplished by using variable screening algorithms (screeners), including the lasso, within the ensemble prior to fitting other prediction algorithms. However, the performance of a super learner using the lasso for dimension reduction has not been fully explored in cases where the lasso is known to perform poorly. We provide empirical results that suggest that a diverse set of candidate screeners should be used to protect against poor performance of any one screener, similar to the guidance for choosing a library of prediction algorithms for the super learner. These results are further illustrated through the analysis of HIV-1 antibody data.},
}

@article {pmid41017661,
year = {2025},
author = {Lasowski, P and Tollefson, D and Menacho, L and DePierro, J and Duerr, A},
title = {High prevalence of pain and mental health conditions amongst people well-established in HIV care: results of a cross-sectional survey in Lima, Peru.},
journal = {AIDS care},
volume = {},
number = {},
pages = {1-10},
doi = {10.1080/09540121.2025.2562242},
pmid = {41017661},
issn = {1360-0451},
abstract = {People living with HIV (PLWH) are at risk for mental health (MH) disorders and pain, but this burden is largely unknown in low/middle-income countries. From February-October 2023, we conducted a cross-sectional survey at a large HIV clinic in Lima, Peru to quantify the prevalence of MH disorders and pain amongst PLWH established in care and to explore relationships between MH and well-managed HIV. At clinic visits, PLWH were invited to complete validated measures for depression, post-traumatic stress disorder (PTSD), alcohol use disorder (AUD), and pain (PHQ-8, PCL5, AUDIT-C, and BPISF). We abstracted data on treatment and viral suppression from medical charts. We calculated the prevalence of depression (PHQ8 ≥ 10), PTSD (PCL-5 ≥ 30), AUD (AUDIT-C ≥ 4 for men, ≥ 3 for women), and pain severity/interference (none, mild, moderate, or severe). We conducted logistic regression analyses to determine associations between MH/pain and viral suppression. Among 397 participants, 32% (95% CI: 27-37%) reported AUD, 21% (17-26%) reported depression, and 13% (9.5-16%) reported PTSD; 14% (11-18%) and 12% (9.3-16%) reported moderate/severe pain intensity and interference, respectively. There were no associations between MH/pain and viral suppression. High levels of MH disorders and pain among PLWH established in care suggest screening is needed for all PLWH, even those with well-controlled HIV.},
}

@article {pmid41017648,
year = {2025},
author = {Hyde, ET and Bandoli, GE and Zou, J and Crespo, NC and Parada, H and Evenson, KR and Howard, AG and LaMonte, MJ and Stefanick, ML and Tinker, LF and Haring, B and Manson, JE and Lee, IM and LaCroix, AZ},
title = {Prospective associations between accelerometer-measured physical activity, sedentary behavior, and healthy longevity: the Women's Health Accelerometry Collaboration.},
journal = {The journals of gerontology. Series A, Biological sciences and medical sciences},
volume = {},
number = {},
pages = {},
doi = {10.1093/gerona/glaf206},
pmid = {41017648},
issn = {1758-535X},
abstract = {BACKGROUND: The influence of physical activity (PA) and sedentary behavior (SB) on survival to late age with intact mobility is unclear. This study investigated associations between accelerometer-measured daily PA, SB, and survival to age 90 birthyear with and without intact mobility in the Women's Health Accelerometry Collaboration (WHAC).

METHODS: Postmenopausal U.S. women aged 78-89 years without mobility disability were followed for an average of 6.1 years. At age 90 birthyear, participants were categorized as: (1) surviving with intact mobility, (2) surviving with mobility disability, or (3) deceased. Participants wore an accelerometer on the hip for up to 7 days at baseline from 2011-2015. Covariate-adjusted multinomial logistic regression models estimated odds ratios (ORs) of PA (light, moderate-to-vigorous [MVPA], total, steps) and SB (sitting time, mean sitting bout duration) with survival outcomes relative to dying.

RESULTS: Among 2,656 women (mean baseline age 83.1 years), 62.8% survived with intact mobility, 22.3% with mobility disability, and 15.0% died. Compared to dying before age 90, the OR (95% confidence intervals [CI]) for every 1-SD increment in accelerometer variables and survival with intact mobility were 1.36 (1.20, 1.54) for light PA, 1.69 (1.47, 1.96) for MVPA, 1.51 (1.33, 1.71) for total PA, 1.75 (1.51, 2.03) for steps, 0.70 (0.61, 0.80) for sitting time, and 0.79 (0.70, 0.89) for sitting bouts. Similar, weaker trends were present for mobility disability.

CONCLUSIONS: These findings corroborate the potential role of increasing physical activity in preserving physical functioning as an important element of healthy longevity.},
}

@article {pmid41017259,
year = {2025},
author = {Sharma, P and George, N and Srivastava, D and Chow, EJ and Alderfer, MA and Leisenring, W and Long, KA and Lown, AE and Oeffinger, KC and Zeltzer, LK and Armstrong, GT and Krull, KR and Brinkman, TM and Buchbinder, D},
title = {Psychosocial Health and Chronic Health Conditions Among Bereaved Siblings: A Report From the Childhood Cancer Survivorship Study (CCSS).},
journal = {Pediatric blood & cancer},
volume = {},
number = {},
pages = {e32076},
doi = {10.1002/pbc.32076},
pmid = {41017259},
issn = {1545-5017},
support = {CA55727/CA/NCI NIH HHS/United States ; //to St. Jude Children's Research Hospital/ ; CA21765//Cancer Center Support/ ; //American Lebanese-Syrian Associated Charities/ ; },
abstract = {OBJECTIVE: To compare psychosocial health and chronic health conditions (CHCs) in bereaved and non-bereaved adult siblings impacted by childhood cancer and to identify predictors of emotional distress and health-related quality of life among bereaved siblings.

METHODS: A total of 4558 adult siblings (733 bereaved; 3825 non-bereaved) of 5-year survivors of childhood cancer completed measures of emotional distress (Brief Symptom Inventory [BSI]-18) and health-related quality of life (Medical Outcomes Survey Short Form [SF]-36) and reported their social attainment milestones (i.e., educational attainment, employment, and marital status). CHCs' burden was classified as none/low versus medium/high/very severe. Cancer-associated complications prior to the patient's death, sibling age at bereavement, and social attainment variables were examined as predictors of emotional distress and health-related quality of life among bereaved siblings using multivariable modified Poisson regression.

RESULTS: Bereaved siblings in this sample reported excellent psychosocial health long term (e.g., depressive symptoms 6.5%, somatization 4.4%, anxiety 3.5%). Bereaved siblings had an elevated risk of depression (relative risk [RR] 1.53; 1.10-2.13, p = 0.01), reduced social quality of life (RR 1.35; 1.00-1.82, p = 0.05), diminished educational attainment, and greater CHC burden than non-bereaved siblings. No differences were observed for other subscales or social attainment outcomes. Among bereaved siblings, risk factors for depression included male sex (RR 0.42; 0.19-0.93, p = 0.05), never being married (RR 3.02; 1.45-6.28, p = 0.05), and greater CHC burden (RR 2.42; 1.18-4.99, p = 0.05). Risk factors for poor social functioning included unemployment (RR 2.24; 1.12-4.45, p = 0.05) and never being married (RR 2.16; 1.22-3.82, p = 0.05).

CONCLUSION: Bereaved siblings report excellent psychosocial health long-term and demonstrate only a marginally elevated risk of experiencing symptoms of depression and poor social quality of life compared to non-bereaved siblings.},
}

@article {pmid41016483,
year = {2025},
author = {K, R and Ac, H and K, B and Je, G and A, A and G, O and D, M and S, K and Z, N and M, F and M, S and F, F and Mh, A and P, S and Y, B and F, L and C, P and K, M and I, M and J, G and A, B and M, S and A, D and K, K and A, L and B, N and Ks, B and K, R and S, C},
title = {Late Effects After Haematopoietic Stem Cell Transplantation in patients with HLH: A Histiocyte Society, PDWP, IEWP and TCWP EBMT Study.},
journal = {The Journal of allergy and clinical immunology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jaci.2025.09.014},
pmid = {41016483},
issn = {1097-6825},
abstract = {BACKGROUND: Hematopoietic stem cell transplantation is the only curative treatment in primary hemophagocytic lymphohistiocytosis. However, hematopoietic stem cell transplantation is associated with a wide range of late effects.

OBJECTIVE: Characterization of the long-term outcome and late effects following hematopoietic stem cell transplantation in primary hemophagocytic lymphohistiocytosis.

METHODS: 274 children with pHLH from the EBMT registry who underwent allogeneic hematopoietic stem cell transplantation between 2004 and 2015 were included. Multivariable logistic regression models were performed to evaluate the adjusted impact of baseline variables on CNS and hormonal late effects, respectively.

RESULTS: A broad spectrum of late effects was identified, with neurological (31%) and hormonal (34.8%) complications being the most prevalent. Chemotherapy (HLH-94/HLH04) before hematopoietic stem cell transplantation was identified as a significant risk factor for endocrinological late effects (p=0.03), highlighting a novel aspect not previously reported. The presence of neurological abnormality at diagnosis was an independent risk factor for neurological late effects (p<0.001) as was incomplete remission status at time of HCT (p=0.04).

CONCLUSION: Hematopoietic stem cell transplantation has significantly improved survival in primary hemophagocytic lymphohistiocytosis patients, however survivors still face significant risks of late effects.},
}

@article {pmid41015745,
year = {2025},
author = {Samady, H and Drangsholt, M and Sebastian, G and Dean, D},
title = {Osteonecrosis of the jaw as a possible adverse effect of tocilizumab.},
journal = {Oral surgery, oral medicine, oral pathology and oral radiology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.oooo.2025.08.011},
pmid = {41015745},
issn = {2212-4411},
abstract = {We report the case of a 79-year-old female with a complex medical history, presenting with recurrent gingival swelling, progressive gingival hyperplasia, and osteonecrosis of the jaw potentially associated with tocilizumab. Oral complications developed in close proximity to diagnosis of chronic myelomonocytic leukemia, complicating diagnosis and management.},
}

@article {pmid41015336,
year = {2025},
author = {Shoenbill, KA and Ostroff, JS and Taylor, KL and Jafarinia, A and Minion, M and Chichester, LA and Omernik, B and McCall, M and Yeung, S and Wiseman, K and Chen, LS and Salloum, RG and Warren, G},
title = {Recommendations for Standardization of Tobacco Use Treatment Data.},
journal = {Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jtho.2025.09.1756},
pmid = {41015336},
issn = {1556-1380},
abstract = {INTRODUCTION: Although there is widespread acceptance of the importance of assessing and treating tobacco use in cancer care settings, there is much variation in the documentation and reporting of metrics relevant to tobacco treatment. The Cancer Center Cessation Initiative (C3I), as part of NCI's Cancer Moonshot, convened a Metrics Standardization Workgroup to develop a data dictionary and make recommendations for standardized quality measurement, program evaluation, and tobacco treatment program development.

METHODS: A multidisciplinary workgroup of 12 subject matter experts was convened to deliberate and standardize definitions for tobacco assessment and treatment utilization metrics. Decisions on which data elements to include were informed by clinical guidelines, literature reviews, and workgroup members' expertise. Consensus was reached when all members agreed that the proposed metric was clear, clinically relevant, and could be abstracted and reported.

RESULTS: The group considered metrics in the following categories: (1) patient identification, screening, and referral, (2) tobacco treatment process metrics, and (3) treatment outcomes. We developed a tobacco screening, referral and engagement workflow, and a data library for the following terms: patient population, screening rate, tobacco use prevalence, referral rate, reach, unsuccessful reach attempts, enrollment, treatment engagement, and counseling dose. Outcome metrics (i.e., varied "quit rate" terms) were collated and defined.

DISCUSSION: The proposed standardized data definitions can be used to improve communication and measure effectiveness for tobacco use treatment, research, operational performance, policy, quality improvement, and guideline development.},
}

@article {pmid41014345,
year = {2025},
author = {Zhao, LP and Papadopoulos, GK and McFarland, BJ and Skyler, JS and Parikh, HM and Kwok, WW and Lybrand, TP and Bondinas, GP and Moustakas, AK and Wang, R and Pyo, CW and Nelson, WC and Geraghty, DE and Lernmark, Å},
title = {Correction: Profiling associations of interactive ligand-receptors (HLA class I and KIR gene products) with the progression to type 1 diabetes among seroconverted participants.},
journal = {Diabetologia},
volume = {},
number = {},
pages = {},
doi = {10.1007/s00125-025-06557-6},
pmid = {41014345},
issn = {1432-0428},
}

@article {pmid41014159,
year = {2025},
author = {Fernandez Turizo, MJ and Velez, MA and Glenn, B and Cummings, AL and Segarra-Vazquez, B and Gorbatov, S and Park, SJ and Shen, C and Lind-Lebuffe, JP and Unger, JM and Garon, EB},
title = {Characteristics of clinical trials associated with appeal and return on investment to participants, A Review and Framework.},
journal = {The oncologist},
volume = {},
number = {},
pages = {},
doi = {10.1093/oncolo/oyaf313},
pmid = {41014159},
issn = {1549-490X},
abstract = {Despite decades of investment in clinical research infrastructure, patient participation in clinical trials remains strikingly low. In the United States, fewer than 1 in 10 adults report ever being invited to participate in a clinical trial, and among those, less than half ultimately enroll. In oncology, across all adult cancer patients, only about 8% enroll in a clinical trial, regardless of eligibility or trial availability. Active engagement of patients in cancer clinical trials substantially enhances scientific knowledge, and patient participation is required to obtain approval for novel therapeutics. Analyses focusing on evaluating if clinical trial participation improves survival for participants have yielded conflicting results. Yet, there is limited data or metrics to assess the specific attributes of oncology trials that hold greater appeal or return on investment to participants, limiting researchers' ability to determine if these factors vary across different populations. Our group demonstrated that patients with limited English proficiency were unlikely to participate in studies not sponsored by industry as compared to industry-sponsored studies. If trial participation for specific populations can differ by sponsor type, it could also differ by the trial's appeal or return on investment. While the underrepresentation of racial and ethnic minority groups in trials is attributed to multiple factors, it is possible that patients from these groups are less likely to be offered participation in studies with higher appeal or return on investment, due to systemic biases, disparities in recruitment practices and/or lack of access. In this manuscript, we propose a systematic framework for evaluating attributes of interventional oncology clinical trials, with an emphasis on the study's purpose, experimental design and investigational agent. This framework aims to pinpoint characteristics that may enhance trials' appeal or return on investment to participants and could lay a foundation for future research. This will allow investigators to assess the return on investment of appeal of studies offered across different patient populations.},
}

@article {pmid40711480,
year = {2025},
author = {Wesolowski, R and Rugo, HS and Specht, JM and Han, HS and Kabos, P and Vaishampayan, U and Wander, SA and Gogineni, K and Spira, A and Schott, AF and Abu-Khalaf, M and Mutka, SC and Suzuki, S and Sullivan, B and Gorbatchevsky, I and Layman, RM},
title = {Gedatolisib Combined with Palbociclib and Letrozole in Patients with No Prior Systemic Therapy for Hormone Receptor-Positive, HER2-Negative Advanced Breast Cancer.},
journal = {Clinical cancer research : an official journal of the American Association for Cancer Research},
volume = {31},
number = {19},
pages = {4040-4048},
doi = {10.1158/1078-0432.CCR-25-0992},
pmid = {40711480},
issn = {1557-3265},
mesh = {Humans ; Female ; *Breast Neoplasms/drug therapy/pathology/genetics/metabolism/mortality ; Letrozole/administration & dosage ; Pyridines/administration & dosage/adverse effects ; Piperazines/administration & dosage/adverse effects ; *Antineoplastic Combined Chemotherapy Protocols/therapeutic use/adverse effects/administration & dosage ; Receptor, ErbB-2/metabolism/genetics ; Middle Aged ; Receptors, Estrogen/metabolism ; Aged ; Receptors, Progesterone/metabolism ; Adult ; Aged, 80 and over ; Class I Phosphatidylinositol 3-Kinases/genetics ; },
abstract = {PURPOSE: Nonclinical evidence demonstrating that estrogen receptor, cyclin-dependent kinases 4 and 6 (CDK4/6), and PI3K/AKT/mTOR (PAM) pathways cross-promote tumor proliferation in hormone receptor-positive (HR+)/HER2- breast cancer cell lines led to the development of CDK4/6 inhibitors and agents inhibiting single PAM pathway nodes to treat HR+/HER2- advanced breast cancer. Simultaneous blockade of the estrogen receptor, CDK4/6, and PAM pathways may optimize antitumor control in the treatment-naïve advanced breast cancer setting. Gedatolisib, a pan-PI3K/mTOR inhibitor, was evaluated as first-line therapy, combined with standard-of-care palbociclib and letrozole, for patients with HR+/HER2- advanced breast cancer.

PATIENTS AND METHODS: Treatment-naïve patients from a phase Ib study with HR+/HER2- advanced breast cancer treated with gedatolisib plus palbociclib and letrozole were analyzed. The primary endpoint of the overall study was investigator-assessed objective response. Secondary endpoints included safety, duration of response, progression-free survival (PFS), and overall survival.

RESULTS: Of 41 patients, all had stage IV disease, 93% had measurable disease, 78% had visceral metastases, and 22% had detectable PIK3CA mutations. The objective response rate was 79% in patients with evaluable disease (N = 33). The median duration of response was 48 months for confirmed responders. The median PFS was 48.4 months, and the median overall survival was 77.3 months. The overall response rate and PFS were comparable in patients with and without PIK3CA mutations. Fewer than 10% discontinued treatment due to treatment-related adverse events. The most frequent grade 3/4 adverse events were neutropenia (61%), rash (39%), and oral stomatitis (29%).

CONCLUSIONS: Gedatolisib plus palbociclib and letrozole demonstrated preliminary efficacy in patients with no prior systemic therapy for advanced breast cancer. These results warrant further evaluation of gedatolisib added to standard-of-care, first-line therapy for HR+/HER2- advanced breast cancer.},
}

Humans
Female
*Breast Neoplasms/drug therapy/pathology/genetics/metabolism/mortality
Letrozole/administration & dosage
Pyridines/administration & dosage/adverse effects
Piperazines/administration & dosage/adverse effects
*Antineoplastic Combined Chemotherapy Protocols/therapeutic use/adverse effects/administration & dosage
Receptor, ErbB-2/metabolism/genetics
Middle Aged
Receptors, Estrogen/metabolism
Aged
Receptors, Progesterone/metabolism
Adult
Aged, 80 and over
Class I Phosphatidylinositol 3-Kinases/genetics

@article {pmid41012183,
year = {2025},
author = {Pallerla, S and Kallur Siddaramaiah, L and Mundsperger, P and Katinger, D and Fauland, K and Kreismayr, G and Weik, R and Arslan, O and Shen, M and Ozorowski, G and Lee, WH and Ward, AB and Baboo, S and Diedrich, JK and Yates, JR and Paulson, JC and Blumen, T and Craig, D and Swoyer, R and Yuan, M and Stamatatos, L},
title = {GMP Manufacturing and Characterization of the HIV Booster Immunogen HxB2.WT.Core-C4b for Germline Targeting Vaccine Strategies.},
journal = {Vaccines},
volume = {13},
number = {9},
pages = {},
pmid = {41012183},
issn = {2076-393X},
support = {7E11AI093022-02/NH/NIH HHS/United States ; },
abstract = {BACKGROUND/OBJECTIVES: Despite progress in antiretroviral therapy, HIV remains a major global health challenge with over one million new infections annually. An effective vaccine is urgently needed. Germline-targeting immunogens show promise in initiating broadly neutralizing antibody (bNAb) precursors. This study developed a scalable, cGMP-compliant process to manufacture the HIV vaccine booster immunogen HxB2.WT.Core-C4b, a nanoparticle designed to direct bNAb precursor maturation after priming.

METHODS: A CHO cell platform was established through single-cell cloning from a high-producing stable pool. Upstream and downstream processes were optimized for scalability and yield. Three scales were tested 10 L, 40 L, and 400 L. Key parameters (pH, temperature, feeding, metabolite profiles) were systematically refined. Analytical characterization included glycosylation profiling, electron microscopy, and antigenicity testing. Viral clearance was evaluated per ICH Q5A guidelines.

RESULTS: Optimization ensured consistent yields above 130 mg/L, with titers up to 250 mg/L. The selected clone (4E22) demonstrated strong growth, viability, and reproducibility. Glycan occupancy at 18 N-linked sites, including bNAb epitopes (N276, N332), was stable across scales. Over 70% of self-assembling nanoparticle were fully assembled at the GMP level. Antigenicity and purity met cGMP release criteria. Viral clearance achieved >13-log reduction for enveloped and >7-log for non-enveloped viruses.

CONCLUSIONS: This work establishes a robust, scalable platform for HIV nanoparticle immunogens. Consistent quality and yield across scales support clinical development of HxB2.WT.Core-C4b and provide a model for other glycosylated nanoparticle vaccines. The immunogen is being evaluated in clinical study HVTN 320 (NCT06796686), enabling early testing of next-generation vaccines designed to elicit broadly neutralizing antibodies.},
}

@article {pmid41006096,
year = {2025},
author = {Button, E and Zhang, ARY and Thamm, C and Chan, RJ and Charalambous, A and Ee, C and Merlo, G and McErlean, G and Anderson, BO and Kitson, AL},
title = {The Australian Cancer Plan through a Caring Life Course Lens: Moving from Cancer to Care by Placing the Person at the Center of Care.},
journal = {Seminars in oncology nursing},
volume = {},
number = {},
pages = {152020},
doi = {10.1016/j.soncn.2025.152020},
pmid = {41006096},
issn = {1878-3449},
abstract = {OBJECTIVE: We propose the Caring Life Course Theory (CLCT) as a lens that can inform and enrich national cancer policy and clinical practice. The purpose of this discussion paper is to highlight how a CLCT lens can inform the implementation of a national cancer control plan, using sections of the Australian Cancer Plan as examples-Optimal Care Pathways and the Australian Comprehensive Cancer Network.

METHODS: This discussion paper presents novel suggestions by drawing on CLCT concepts-care biographies, care networks, and self-care. Contrasting "current state" and "future state" vignettes are described to demonstrate how CLCT can help cancer policy move from cancer to care. Based on a robust theoretical lens, recommendations for policy and practice have been made at the micro, meso, and macro levels, with reflection on the nurses' role, and application to other national cancer control plans.

RESULTS: Optimal care pathways should include holistic assessments that incorporate broader histories at key clinical time points. The Australian Comprehensive Care Network should consider the holistic needs of people affected by cancer, and harness innovative approaches for how these needs can be met in a networked approach. In addition to clinical considerations, understanding of an individual's care biography, care network, and self-care can inform the delivery of high-quality cancer care. Implementation of these aspects of care will be led by nurses, supported by a multidisciplinary team.

CONCLUSIONS: A CLCT lens can help support implementation of the aspirational person-centered objectives described in the ACP. The potential exists for application of the CLCT approach to other national cancer control plans, including those in low-resource settings.

Nurses play a vital role in leading the implementation of person-centered dimensions of cancer control plans and core aspects of the CLCT approach.},
}

@article {pmid41005288,
year = {2025},
author = {Symonds, LK and Davidson, NE},
title = {RecOVARY? Using anti-Müllerian hormone to predict ovarian function after anti-HER2 therapy for early breast cancer.},
journal = {Journal of the National Cancer Institute},
volume = {},
number = {},
pages = {},
doi = {10.1093/jnci/djaf247},
pmid = {41005288},
issn = {1460-2105},
support = {//Breast Cancer Research Foundation/ ; },
}

@article {pmid41004543,
year = {2025},
author = {Müller, NF and Bouckaert, RR and Wu, CH and Bedford, T},
title = {MASCOT-Skyline integrates population and migration dynamics to enhance phylogeographic reconstructions.},
journal = {PLoS computational biology},
volume = {21},
number = {9},
pages = {e1013421},
doi = {10.1371/journal.pcbi.1013421},
pmid = {41004543},
issn = {1553-7358},
abstract = {The spread of infectious diseases is shaped by spatial and temporal aspects, such as host population structure or changes in the transmission rate or number of infected individuals over time. These spatiotemporal dynamics are imprinted in the genomes of pathogens and can be recovered from those genomes using phylodynamics methods. However, phylodynamic methods typically quantify either the temporal or spatial transmission dynamics, which leads to unclear biases, as one can potentially not be inferred without the other. Here, we address this challenge by introducing a structured coalescent skyline approach, MASCOT-Skyline, that allows us to jointly infer spatial and temporal transmission dynamics of infectious diseases using Markov chain Monte Carlo inference. To do so, we model the effective population size dynamics in different locations using a non-parametric function, allowing us to approximate a range of population size dynamics. We show, using a range of different viral outbreak datasets, potential issues with phylogeographic methods. We then use these viral datasets to motivate simulations of outbreaks that illuminate the nature of biases present in the different phylogeographic methods. We show that spatial and temporal dynamics should be modeled jointly, even if one seeks to recover just one of the two. Further, we showcase conditions under which we can expect phylogeographic analyses to be biased, particularly different subsampling approaches, as well as provide recommendations on when we can expect them to perform well. We implemented MASCOT-Skyline as part of the open-source software package MASCOT for the Bayesian phylodynamics platform BEAST2.},
}

@article {pmid41004338,
year = {2025},
author = {Rominger, MC and O'Brien, S and Gupta, S and Moorthi, S and McSharry, M and Kamlapurkar, S and Lowe, AR and Waldum, A and Lo, A and Duke, F and Wu, F and Headley, MB and Cromwell, E and Glabman, R and Koehne, A and Berger, AH},
title = {Mutant RIT1 cooperates with YAP to drive an EMT-like lung cancer state.},
journal = {Cell reports},
volume = {44},
number = {10},
pages = {116185},
doi = {10.1016/j.celrep.2025.116185},
pmid = {41004338},
issn = {2211-1247},
abstract = {Mutations in "Ras-like in all tissues" (RIT1) occur in up to 2% of lung adenocarcinomas and are mutually exclusive with KRAS and EGFR mutations, suggesting that RIT1 may act as a non-canonical driver oncogene in lung cancer. However, the lack of a RIT1-mutant lung cancer model has hindered the development and testing of RIT1-targeted therapeutics. Here, we report a mouse model with conditional regulation of the cancer-associated RIT1[M90I] variant. We show that autochthonous expression of RIT1[M90I] and combined inactivation of Nf2 and p53 drives an aggressive lung cancer with 100% penetrance and short latency. Oncogenic cooperation between RIT1[M90I] and p53/Nf2 loss is driven by synergistic activation of AP-1 transcription factors and can be reversed by the combined inhibition of MEK and TEAD. These data identify YAP/TEAD as a mediator of RIT1's oncogenic capability and nominate TEAD as a potential drug target in RIT1-mutant lung cancer.},
}

@article {pmid41003951,
year = {2025},
author = {Iyer, HS and Karasaki, S and Yi, L and Hswen, Y and James, P and VoPham, T},
title = {Harnessing Geospatial Artificial Intelligence (GeoAI) for Environmental Epidemiology: A Narrative Review.},
journal = {Current environmental health reports},
volume = {12},
number = {1},
pages = {34},
pmid = {41003951},
issn = {2196-5412},
support = {K01ES035734, P30ES005022/ES/NIEHS NIH HHS/United States ; T32 CA094880/CA/NCI NIH HHS/United States ; UG3OD035533//NIH Office of the Director/ ; P01AG082653/AG/NIA NIH HHS/United States ; R01 HL150119/HL/NHLBI NIH HHS/United States ; K01 DK125612/DK/NIDDK NIH HHS/United States ; },
mesh = {*Artificial Intelligence ; Humans ; *Environmental Exposure ; Geographic Information Systems ; *Environmental Health/methods ; },
abstract = {PURPOSE OF REVIEW: Geospatial analysis is an essential tool for research on the role of environmental exposures and health, and critical for understanding impacts of environmental risk factors on diseases with long latency (e.g. cardiovascular disease, dementia, cancers) as well as upstream behaviors including sleep, physical activity, and cognition. There is emerging interest in leveraging machine learning and artificial intelligence (AI) for environmental epidemiology research. In this review, we provide an accessible overview of recent advances.

RECENT FINDINGS: There have been two major recent shifts in geospatial data types and analytic methods. First, novel methods for statistical prediction, combining geospatial analysis with machine learning and artificial intelligence (GeoAI), allow for scalable geospatial exposure assessment within large population health databases (e.g. cohorts, administrative claims). Second, the widespread adoption of smartphones and wearables with global positioning systems and other sensors has allowed for passive data collection from people, and when combined with geographic information systems, enables exposure assessment at finer spatial scales and temporal resolution than ever before. Illustrative examples include refining models for predicting outdoor air pollution exposure, characterizing populations susceptible to water pollution, and use of deep learning to classify Street View image-derived measures of greenspace. While these tools and approaches may facilitate more rapid, higher quality objective exposure measures, they pose challenges with respect to participant privacy, representativeness of collected data, and curation of high quality validation sets for training of GeoAI algorithms. GeoAI approaches are beginning to be used for environmental exposure assessment and behavioral outcome ascertainment with higher spatial and temporal precision than before. Epidemiologists should continue to apply critical assessment of measurement accuracy and design validity when incorporating these new tools into their work.},
}

*Artificial Intelligence
Humans
*Environmental Exposure
Geographic Information Systems
*Environmental Health/methods

@article {pmid40999576,
year = {2025},
author = {Dela Cruz, FS and Stewart, EA and Surdez, D and Daley, JD and Soragni, A and Tomazou, EM and Alvarez-Perez, J and Feinberg, TY and Amatruda, JF and Ganapathi, SS and Ohm, JE and Heske, CM and Cohen-Gogo, S and Pesic, D and Nash, JO and Shlien, A and Roundhill, EA and Burchill, SA and Crompton, BD and Lawlor, ER and Loeb, DM and Delattre, O and Mora, J and Scotlandi, K and Reed, DR and Grohar, PJ and Grünewald, TGP and Kovar, H and Bailey, KM},
title = {Advancing Preclinical Biology for Ewing Sarcoma: An International Effort.},
journal = {Molecular cancer therapeutics},
volume = {},
number = {},
pages = {OF1-OF23},
doi = {10.1158/1535-7163.MCT-25-0428},
pmid = {40999576},
issn = {1538-8514},
abstract = {Ewing sarcoma is an aggressive bone and soft-tissue cancer affecting adolescents and young adults. In vitro and in vivo models of Ewing sarcoma have been instrumental in advancing our understanding of Ewing sarcoma biology and essential in evaluating potential therapies, particularly for metastatic or relapsed disease for which effective treatment options remain limited. Through an international collaborative effort between the Children's Oncology Group Bone Tumor Committee and the Euro Ewing Consortium, we review the current landscape of preclinical modeling used in Ewing sarcoma research encompassing both in vitro (cell lines and tumor organoids) and in vivo (mouse and nonmammalian xenografts) model systems. We discuss factors that can influence experimental results, provide testing considerations for both in vitro and in vivo studies, and descriptions of existing preclinical data repositories. We highlight current needs in Ewing sarcoma modeling and the importance of enhanced international cooperative research and patient advocacy efforts which will be critical in expanding our resources of biologically relevant Ewing sarcoma models to enable translation of preclinical findings into effective therapeutic strategies for patients with Ewing sarcoma.},
}

@article {pmid40666860,
year = {2025},
author = {Harris, ED and McGovern, M and Pernikoff, S and Ikeda, R and Kipnis, L and Hannon, W and Sobolik, EB and Gray, M and Greninger, AL and He, S and Chin, CN and Fu, TM and Pancera, M and Boonyaratanakornkit, J},
title = {DEVELOPMENT OF A POTENT MONOCLONAL ANTIBODY FOR TREATMENT OF HUMAN METAPNEUMOVIRUS INFECTIONS.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {40666860},
issn = {2692-8205},
support = {P30 CA015704/CA/NCI NIH HHS/United States ; R01 AI171186/AI/NIAID NIH HHS/United States ; },
abstract = {Human metapneumovirus (HMPV) is a major cause of respiratory infections, particularly among vulnerable populations, yet effective therapeutics remain unavailable. Monoclonal antibodies (mAbs) offer a promising approach for both treatment and prevention. Here, we describe the discovery and characterization of 4F11, a highly potent and broadly neutralizing mAb with demonstrated in vitro and in vivo efficacy against HMPV. Using cryo-electron microscopy, we defined a unique mechanism of binding HMPV employed by 4F11, which distinguishes it from previously characterized RSV and HMPV mAbs. 4F11 targets an epitope located at the apex of the prefusion F protein (site Ø) with a 1:1 stoichiometry, distinct from the 3:1 stoichiometry observed with other HMPV site Ø antibodies. Unlike other site Ø antibodies, which penetrate the glycan shield between Asn57 and Asn172, 4F11 binds vertically and directly interacts with the Asn172 glycan, representing a unique glycan-dependent mode of recognition. In vitro, 4F11 displayed high potency and broad neutralization across diverse HMPV strains. It also showed a low propensity for resistance development, with only a single escape mutation (K179E) identified, a mutation not found in any published HMPV sequence to date. Viruses rescued with the K179E escape mutation had significantly decreased fitness in vitro compared to wild-type virus. In a hamster challenge model, 4F11 significantly reduced viral loads in both the lungs and nasal turbinates. These findings highlight 4F11 as a promising candidate for therapeutic development, particularly for immunocompromised individuals and other high-risk groups.},
}

@article {pmid40661569,
year = {2025},
author = {Risse-Adams, OS and Liquori, JL and Sinnott-Armstrong, N and Musharoff, SA},
title = {Examining the Effect of Social Determinants of Health on Human Trait Heritability.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {40661569},
issn = {2692-8205},
support = {RM1 HG010461/HG/NHGRI NIH HHS/United States ; U54 CA267738/CA/NCI NIH HHS/United States ; },
abstract = {Social determinants of health (SDOH) data are often excluded from genetic models of human traits. We use individual-level data from the All of Us Research Program to assess whether SDOH survey variables alter heritability estimates. Incorporating SDOH summaries decreases heritability significantly for 4 of 18 anthropometric and metabolic traits in individuals whose self-reported race is "White" (n=67,545). There are no such significant changes in individuals whose self-reported race is "Black or African American" (n=6,538), likely reflecting reduced statistical power. Incorporating genetic principal components consistently lowers heritability estimates in both groups, whether or not SDOH summaries are included. These findings demonstrate that survey-derived SDOH summaries can change heritability estimates and should be considered along with genetic summaries.},
}

@article {pmid39484476,
year = {2025},
author = {Arora, S and Nuechterlein, N and Jensen, M and Glatzer, G and Sievers, P and Varadharajan, S and Korshunov, A and Sahm, F and Mack, SC and Taylor, MD and Gujral, T and Holland, EC},
title = {Integrated transcriptomic landscape of medulloblastoma and ependymoma reveals novel tumor subtype-specific biology.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {39484476},
issn = {2692-8205},
support = {R35 CA253119/CA/NCI NIH HHS/United States ; },
abstract = {Medulloblastoma and ependymoma are common pediatric central nervous system tumors with significant molecular and clinical heterogeneity. We collected bulk RNA sequencing data from 888 medulloblastoma and 370 ependymoma tumors to establish a comprehensive reference landscape. Following rigorous batch effect correction, normalization, and dimensionality reduction, we constructed a unified landscape to explore gene expression, signaling pathways, RNA fusions, and copy number variations. Our analysis revealed distinct clustering patterns, including two primary ependymoma compartments, EPN-E1 and EPN-E2, each with specific RNA fusions and molecular signatures. In medulloblastoma, we observed precise stratification of Group 3/4 tumors by subtype and in SHH tumors by patient age. This landscape serves as a vital resource for identifying biomarkers, refining diagnoses, and enables the mapping of new patients' bulk RNA-seq data onto the reference framework to predict biology and outcome from nearest neighbor analysis facilitate accurate disease subtype identification. The landscape is accessible via Oncoscape, an interactive platform, empowering global exploration and application.},
}

@article {pmid39464160,
year = {2025},
author = {Hsieh, YP and O'Keefe, IP and Wang, Z and Sun, W and Yang, H and Vu, LM and Ernst, RK and Dandekar, AA and Malik, HS},
title = {Magnesium depletion unleashes two unusual modes of colistin resistance with different fitness costs.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {39464160},
issn = {2692-8205},
support = {R01 AI104895/AI/NIAID NIH HHS/United States ; R35 GM152107/GM/NIGMS NIH HHS/United States ; },
abstract = {Increasing bacterial resistance to colistin, a vital last-resort antibiotic, is an urgent challenge. We previously reported that magnesium sequestration by Candida albicans enables Pseudomonas aeruginosa to become colistin-resistant. Here, we show that Mg[2+] depletion drives P. aeruginosa to evolve greater colistin resistance through genetic changes in lipid A biosynthesis-modification pathways and a putative magnesium transporter. These mutations synergize with the Mg[2+]-sensing PhoPQ two-component signaling system to remodel lipid A structures of the bacterial outer membrane in previously uncharacterized ways. One predominant mutational pathway relies on early mutations in htrB2, a non-essential gene involved in lipid A biosynthesis, which enhances resistance but compromises outer membrane integrity, resulting in fitness costs and increased susceptibility to other antibiotics. A second pathway achieves increased colistin resistance independently of htrB2 mutations without compromising membrane integrity. In both cases, reduced binding of colistin to the bacterial membrane underlies resistance. Our findings reveal that Mg[2+] scarcity unleashes two novel trajectories of colistin resistance evolution in P. aeruginosa. (160).},
}

@article {pmid41000465,
year = {2018},
author = {Mitov, KV and Yanev, NM and Hyrien, O},
title = {MULTITYPE BRANCHING PROCESSES WITH INHOMOGENEOUS POISSON IMMIGRATION.},
journal = {Advances in applied probability},
volume = {50},
number = {A},
pages = {211-228},
pmid = {41000465},
issn = {0001-8678},
support = {R01 AI069351/AI/NIAID NIH HHS/United States ; R01 AI129518/AI/NIAID NIH HHS/United States ; R01 CA134839/CA/NCI NIH HHS/United States ; R01 NS039511/NS/NINDS NIH HHS/United States ; },
abstract = {In this paper we introduce multitype branching processes with inhomogeneous Poisson immigration, and consider in detail the critical Markov case when the local intensity r(t) of the Poisson random measure is a regularly varying function. Various multitype limit distributions (conditional and unconditional) are obtained depending on the rate at which r(t) changes with time. The asymptotic behaviour of the first and second moments, and the probability of nonextinction are investigated.},
}

@article {pmid40998424,
year = {2025},
author = {White, AJ and Hart, JE and Quraishi, SM and Bookwalter, DB and Sweeney, MR and Spalt, EW and Hendryx, MS and Irvin, VL and Lane, DS and Shadyab, AH and Sealy-Jefferson, S and Neuhouser, ML and Whitsel, EA and Kaufman, JD and Laden, F and Sandler, DP},
title = {Air Pollutants and Breast Cancer Risk: A Parallel Analysis of Five Large US Prospective Cohorts.},
journal = {American journal of public health},
volume = {},
number = {},
pages = {e1-e14},
doi = {10.2105/AJPH.2025.308247},
pmid = {40998424},
issn = {1541-0048},
abstract = {Objectives. To determine whether outdoor air pollution exposure is associated with breast cancer incidence. Methods. Residential-level concentrations of nitrogen dioxide (NO2, parts per billion [ppb]), fine particulate matter (PM2.5; ≤ 2.5 μ/m[3]) and ozone (ppb) in the United States were estimated for participants of the Nurses' Health Studies, Women's Health Initiative Clinical Trials and Observational Study Cohort, and Sister Study using high-resolution spatiotemporal models. Cox proportional hazards regression estimated cohort-specific hazard ratios (HRs) and 95% confidence intervals (CIs), and a random effects model determined summary HRs, overall and by estrogen receptor (ER)/progesterone receptor (PR) subtype and census region. Results. NO2 was positively associated with overall breast cancer incidence (n = 28 811 cases; HR = 1.03; 95% CI = 1.00, 1.05), with little variation by subgroups. PM2.5 was associated with higher incidence of ER-/PR- tumors (n = 2367 cases; HR = 1.14; 95% CI = 1.04, 1.24; P-heterogeneity < .001) and with higher overall incidence in the Midwest (HR = 1.15; 95% CI = 1.01, 1.32; P-heterogeneity = .01). Ozone was not associated with overall incidence, but was associated with ER-/PR- tumors (n = 3406 cases; HR = 1.10; 95% CI = 1.00, 1.21; P-heterogeneity = .03). Conclusions. In this largest US study to date, we confirmed an association between NO2 and breast cancer, and we present novel associations of PM2.5 and ozone with ER-/PR- tumors. (Am J Public Health. Published online ahead of print September 25, 2025:e1-e14. https://doi.org/10.2105/AJPH.2025.308247).},
}

@article {pmid40998267,
year = {2025},
author = {Ardila, V and Onstad, L and Carpenter, P and Pidala, J and Kitko, C and Jurdi, NE and Lee, SJ and Hamilton, BK},
title = {Obesity Associations with Chronic Graft-Versus-Host Disease.},
journal = {Transplantation and cellular therapy},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jtct.2025.09.030},
pmid = {40998267},
issn = {2666-6367},
abstract = {BACKGROUND: Obesity is increasing in prevalence and has been linked to inflammation, leading to worse outcomes in various disease states. Pre-clinical studies have demonstrated deleterious effects of obesity on graft-versus-host disease (GVHD). Several retrospective clinical studies have investigated the impact of obesity on allogeneic hematopoietic cell transplantation (HCT); however, with varying results and more limited data on the impact on chronic GVHD.

OBJECTIVES: We aimed to investigate the association of obesity on organ involvement, severity, and response to chronic GVHD therapy in a multicenter cohort of patients with chronic GVHD, as well as its impact on overall survival (OS), non-relapse mortality (NRM), failure-free survival (FFS), and quality of life (QOL).

STUDY DESIGN: We conducted a retrospective study of patients enrolled from 2007 to 2019 in two prospective longitudinal observational studies from the Chronic GVHD Consortium. Obesity was defined as a body mass index (BMI) ≥30, as calculated based on height and weight at the time of enrollment. Grade, organ involvement, and response to chronic GVHD therapy were compared between obese (BMI ≥30) and non-obese (BMI <30) patients. Secondary outcomes included OS, NRM, FFS, and QOL measurement with the Lee symptom scale (LSS), Functional Assessment of Cancer Therapy (FACT), and Medical Outcomes Study Short Form 36 (SF-36).

RESULTS: Among 487 patients identified with newly diagnosed chronic GVHD within 3 months of study enrollment, 114 (23.4%) had BMI ≥ 30. The only significant difference between obese and non-obese patients was the presence of diabetes as a comorbidity. There were no significant differences in affected organs, grade, overall response to treatment, or organ-specific response to treatment between obese and non-obese patients. Chronic lung GVHD was more common in obese compared to non-obese patients (24.6% vs 13.9% for mild, 5.3% vs 4.8% for moderate, and 0.9% vs 0.8% for severe lung GVHD, p=0.047) however small case numbers and the lack of between group differences in OS, NRM or FFS limit this interpretation. QOL analyses revealed greater patient-reported symptom burden and worse QOL in obese patients at enrollment and after 6 months.

CONCLUSION: We found obesity is associated with worse QOL but not with chronic GVHD phenotypes, responsiveness to treatment, or survival outcomes in a multicenter cohort of allogeneic HCT recipients. Given the increasing evidence of a multi-factorial role for obesity as a modulator of immune processes, additional studies investigating more accurate measures of obesity and body composition are needed to further understand their role in chronic GVHD.},
}

@article {pmid40998264,
year = {2025},
author = {Kogler, V and Pagano, MB and Fontaine, MJ and Azimi, V and Brancamp, R and Cataife, G and Covington, M and Delaney, M and Eichbaum, Q and Jacquot, C and Kutner, JM and Lu, W and Saifee, NH and Shan, H and Thibodeaux, SR and Wali, JA and Yeh, A and Yokoyama, APH and Yunce, M and Ziman, A and , },
title = {Serologic Characteristics and Clinical Significance of Non-ABO Red Blood Cell Antibodies in Hematopoietic Stem Cell Transplant. The BEST Collaborative Study.},
journal = {Transplantation and cellular therapy},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jtct.2025.09.040},
pmid = {40998264},
issn = {2666-6367},
abstract = {BACKGROUND: ABO-incompatible hematopoietic stem cell transplant (HSCT) has a number of well-established complications including hemolysis, delayed RBC engraftment, pure red cell aplasia (PRCA), and transfusion dependence. However, the clinical significance of non-ABO RBC antibodies in allogeneic HSCT remains insufficiently explored.

OBJECTIVE: The aim of this study is to characterize the prevalence, incidence, and clinical implications of non-ABO RBC auto- and alloantibodies in the HSCT population.

STUDY DESIGN: This international, multicenter, retrospective study analyzed HSCT 2010-2021 across nine U.S. and one Brazilian academic centers. This study focused on immunohematologic findings in recipients of allogeneic HSCTs, excluding hemoglobinopathies. RBC antibodies were evaluated pre-HSCT and 100 days post-HSCT. Hemolysis was assessed by labs and confirmed by a two-physician review of the medical records. Descriptive statistics and regression analysis were performed. IRB approval and data use agreements were obtained at each center.

RESULT: Study analysis included a total of 8896 transplants. The majority of transplants utilized apheresis collections (78.0%), were matched unrelated (41.6%), involved a non-myeloablative conditioning regimen (51.2%), and were ABO-compatible (56.7%). The prevalence of non-ABO antibodies pre-HSCT, including auto-, alloantibodies, and passive transfer of anti-D, was 4.0% (n=355). The majority of these were alloantibodies (77.5%), followed by warm autoantibodies (7.3%) and both alloantibodies and warm-reactive autoantibodies (6.5%). De-novo antibody formation post-HSCT occurred in 1.5% (n=135). The most frequent pre-HSCT alloantibody specificities were in the Rh blood group system (46%), followed by Kell (17%) and Kidd (13%). The incidence of anti-D in RhD-mismatched transplant was 1% (n=8) for RhD-positive recipients with RhD-negative donors, and 0.2% (n=2) for RhD-negative recipients with RhD-positive donors. Myeloproliferative neoplasms and myelodysplastic syndromes had the highest rate of antibodies pre- and post-HSCT. Hemolysis was observed in 24 cases (antibodies present pre-HSCT) and 15 de-novo cases post-HSCT. Pure red cell aplasia was not observed in any of these cases. The presence of non-ABO RBC antibodies was associated with higher RBC transfusions, but not platelet transfusions; engraftment of neutrophils and platelets were not affected by the presence of RBC antibodies.

CONCLUSION: The current study reports on a low prevalence of RBC antibodies, including allo- and autoantibodies, in HSCT patients during the peri-transplant period, with a rate of 4% for those with pre-existing antibodies prior to transplant and 1% for the de-novo antibody formation post-transplant. They are associated with a low risk of mild to moderate hemolysis, but increased RBC transfusions. Comprehensive immunohematology data should be incorporated into HSCT databases for improved risk assessment, monitoring, and management.},
}

@article {pmid40998194,
year = {2025},
author = {Hammouda, K and Tokuyama, N and Corredor, G and Pathak, T and Dakarapu, R and Genega, E and Mian, OY and Pavicic, PG and Diaz-Montero, CM and Mirtti, T and Farré, X and Gupta, S and Madabhushi, A},
title = {AI-informed computational pathology classifier predicts outcomes across treatment modalities in muscle-invasive urothelial carcinoma.},
journal = {Cancer letters},
volume = {634},
number = {},
pages = {218059},
doi = {10.1016/j.canlet.2025.218059},
pmid = {40998194},
issn = {1872-7980},
abstract = {Urothelial carcinoma (UC) is one of the leading causes of cancer-related mortality, and effective, scalable biomarkers for treatment planning remain limited. We present UC-TIL, an artificial intelligence (AI)-based model that quantifies spatial patterns of tumor-infiltrating lymphocytes (TILs) from routine H&E-stained slides to predict survival and immunotherapy response. We analyzed 558 whole-slide images across three cohorts: TCGA (D0&1, N = 292), Emory (D2, N = 161), and TRRC2819 (D3, N = 105), spanning chemotherapy and immune checkpoint inhibitor (ICI) treatments. UC-TIL classification was associated with OS (HR = 2.11, 95 %CI:1.01-4.41, p = 0.011) and PFS (HR = 3.68, 95 %CI:1.07-12.65, p = 0.0012) in locally advanced disease (D1 and D2), with consistent results in metastatic disease (D3) (HR = 1.73, 95 %CI:1.08-2.77, p = 0.043; PFS HR = 1.73, 95 %CI:1.07-2.81, p = 0.047). In the ICI-treated D3 cohort, UC-TIL achieved AUC = 0.757 and identified non-responders with 91 % specificity. UC-TIL enables reliable risk stratification and treatment response prediction in both locally advanced and metastatic urothelial carcinoma by analyzing spatial TIL patterns from standard pathology slides. These findings position UC-TIL as a readily deployable tool to guide personalized therapy across multiple clinical settings.},
}

@article {pmid40998019,
year = {2025},
author = {Glenny, EM and Lin, T and Bandera, VM and Mirminachi, B and Khumukcham, SS and Gigic, B and Warby, CA and Aksonova, O and Coleman, MF and Carpanese, A and Busch, C and Himbert, C and Ose, J and Nix, DA and Boucher, K and Schirmacher, P and Strehli, I and Hardikar, S and Cohan, JN and Jedrzkiewicz, J and Brobeil, A and Schneider, MA and Kahlert, C and Siegel, EM and Byrd, DA and Toriola, AT and Shibata, D and Li, CI and Figueiredo, JC and Tan, AC and Roper, J and Ulrich, CM and Hursting, SD},
title = {Obesity promotes conserved inflammatory and metabolic transcriptional programs in colon tumors: Evidence from mouse models and the ColoCare Study patient cohort.},
journal = {The American journal of clinical nutrition},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.ajcnut.2025.09.031},
pmid = {40998019},
issn = {1938-3207},
abstract = {BACKGROUND: The global prevalence of obesity, an established risk and progression factor for colon cancer, is high and rising. Unfortunately, the mechanisms underlying the obesity-colon cancer association are incompletely understood, and new molecular targets enabling more effective intervention strategies to break the obesity-colon cancer link are urgently needed.

OBJECTIVE: This study integrated RNA sequencing data from mouse and human colon tumor samples, as well as human adipose samples, to rigorously establish obesity-associated transcriptomic signatures conserved between the two species.

METHODS: We employed a mouse colon cancer model with colonoscopy-guided orthotopic transplantation of syngeneic Apc-null;KrasG12D/+;Trp53-null;Smad4-null;tdTomato colon tumor organoids. Epithelial cell adhesion molecule (EpCAM)-positive cells from murine tumors, and 193 human colon tumors and 188 human mesenteric adipose tissue samples from the prospective ColoCare Study cohort underwent transcriptomic analyses.

RESULTS: Diet-induced obesity reduced survival in the mouse model of colon cancer. Integrated transcriptomic analyses of EpCAM-positive murine tumor cells and bulk human tumors revealed obesity-driven enrichment of inflammation and metabolic pathways, including upregulation of genes involved in innate immune sensing (TLR2, MYD88, IRF4) and tumor microenvironment remodeling (MMP9, TGFB1, SERPINE1). Analysis of paired mesenteric visceral adipose tissue and tumor samples from the study patients (63±13 years old, 48% female, BMI: 28.9±6.0 kg/m[2]) indicated that obesity was associated with enriched inflammatory signaling pathways through unique adipose ligand-tumor receptor interactions.

CONCLUSIONS: These results establish obesity-associated adipose tissue dysregulation as a key inter-tissue modulator of biology, with concordant cross-species effects on tumor cell-intrinsic inflammatory and metabolic programs.},
}

@article {pmid40997296,
year = {2025},
author = {Wang, ES and Montesinos, P and Foran, J and Erba, H and Rodríguez-Arbolí, E and Fedorov, K and Heiblig, M and Heidel, FH and Altman, JK and Baer, MR and Ades, L and Pettit, K and Peterlin, P and Papayannidis, C and Berthon, C and Walter, RB and Shah, MV and Balasubramanian, S and Khawandanah, M and Salamero Garcia, O and Bergeron, J and Madanat, YF and Roboz, GJ and Ulrickson, M and Redner, RL and McCloskey, J and Pigneux, A and de la Fuente Burguera, A and Mitra, A and Soifer, HS and Tabachri, M and Zhang, Z and Riches, M and Corum, D and Leoni, M and Issa, GC and Fathi, AT and , },
title = {Ziftomenib in Relapsed or Refractory NPM1-Mutated AML.},
journal = {Journal of clinical oncology : official journal of the American Society of Clinical Oncology},
volume = {},
number = {},
pages = {JCO2501694},
doi = {10.1200/JCO-25-01694},
pmid = {40997296},
issn = {1527-7755},
abstract = {PURPOSE: Ziftomenib-a potent, highly selective, oral menin inhibitor-was well tolerated and demonstrated encouraging clinical activity as monotherapy for relapsed/refractory NPM1-mutated (NPM1-m) and KMT2A-rearranged AML in the KOMET-001 phase I trial.

METHODS: In the registration-enabling phase II part of KOMET-001, patients with relapsed/refractory NPM1-m AML received ziftomenib 600 mg once daily. The primary end point was the rate of complete remission with full hematologic recovery (CR)/CR with partial hematologic recovery (CRh).

RESULTS: From January 26, 2023, to May 13, 2024, 92 patients (median age, 69 years [range, 33-84]) were treated. The primary end point was met, with a CR/CRh rate of 22% (95% CI, 14 to 32; P = .0058); 61% were negative for measurable residual disease. Overall response rate was 33% (95% CI, 23 to 43), with a median duration of 4.6 months (95% CI, 2.8 to 7.4). Prespecified subgroup analyses showed comparable CR/CRh regardless of previous therapy, including venetoclax, or type of comutations. Median overall survival was 6.6 months (95% CI, 3.6 to 8.6). Common grade ≥3 treatment-emergent adverse events were febrile neutropenia (26%), anemia (20%), and thrombocytopenia (20%). Differentiation syndrome occurred in 25% of patients (15% grade 3; no grade 4-5) and was manageable with protocol-defined mitigation. Three patients (3%) discontinued treatment because of ziftomenib-related adverse events.

CONCLUSION: Ziftomenib demonstrated significant clinical benefit and deep responses in patients with heavily pretreated, relapsed/refractory NPM1-m AML. Ziftomenib was well tolerated with a safety profile consistent with previous studies, including manageable differentiation syndrome, lack of clinically significant QTc prolongation, and low rates of myelosuppression.},
}

@article {pmid40996773,
year = {2025},
author = {Fasching, PA and Stroyakovskiy, D and Yardley, DA and Huang, CS and Crown, J and Bardia, A and Chia, S and Im, SA and Martin, M and Xu, B and Loi, S and Barrios, C and Untch, M and Moroose, R and Visco, F and Hortobagyi, GN and Slamon, DJ and Fresco, R and Zarate, JP and Li, Z and Waters, S and Hurvitz, SA},
title = {Ribociclib Plus Endocrine Therapy in Hormone Receptor-Positive/ERBB2-Negative Early Breast Cancer: 4-Year Outcomes From the NATALEE Randomized Clinical Trial.},
journal = {JAMA oncology},
volume = {},
number = {},
pages = {},
doi = {10.1001/jamaoncol.2025.3700},
pmid = {40996773},
issn = {2374-2445},
abstract = {IMPORTANCE: Ribociclib plus a nonsteroidal aromatase inhibitor (NSAI) has demonstrated a statistically significant invasive disease-free survival (iDFS) benefit over NSAI alone in patients with hormone receptor-positive/ERBB2 (formerly HER2)-negative early breast cancer. Evaluating the efficacy and safety of adjuvant ribociclib beyond the planned 3-year treatment period is critical for understanding the long-term impact on recurrences.

OBJECTIVE: To evaluate efficacy and safety of adjuvant ribociclib in an exploratory 4-year analysis of the NATALEE (New Adjuvant Trial With Ribociclib [LEE011]) randomized clinical trial, with all patients no longer receiving ribociclib treatment.

This exploratory analysis of an international, open-label, randomized phase 3 trial analyzed adjuvant treatment for premenopausal and postmenopausal women and men with hormone receptor-positive/ERBB2-negative early breast cancer. Eligible patients had anatomic stage IIA (either N0 with additional risk factors or N1 [1-3 axillary lymph nodes]), IIB, or III disease per the American Joint Committee on Cancer Staging Manual, eighth edition. The data cutoff date was April 29, 2024.

INTERVENTIONS: Patients were randomized 1:1 to receive ribociclib (400 mg once daily, days 1-21 of a 28-day cycle, over 36 months) plus NSAI (letrozole, 2.5 mg, or anastrozole, 1 mg, once daily continuously for 60 months) or NSAI alone. Men and premenopausal women also received goserelin (3.6 mg once every 28 days administered subcutaneously).

MAIN OUTCOMES AND MEASURES: The primary end point was iDFS, and secondary efficacy end points included distant disease-free survival, recurrence-free survival, and overall survival. Survival was evaluated by the Kaplan-Meier method.

RESULTS: Among 5101 patients included in the analysis (median [range] age, 52 [24-90] years; 5081 [99.6%] female), the median follow-up for iDFS was 44.2 months (range, 0-63 months). Ribociclib plus NSAI continued to show iDFS benefit over NSAI alone (hazard ratio, 0.72; 95% CI, 0.61-0.84), with 3-year iDFS rates of 90.8% vs 88.1% (difference, 2.7 percentage points) and 4-year rates of 88.5% vs 83.6% (difference, 4.9 percentage points). The efficacy benefit was consistent across subgroups and secondary end points. Overall survival data remain immature, although a trend in favor of ribociclib plus NSAI over NSAI alone was observed (hazard ratio, 0.83; 95% CI, 0.64-1.07). The incidence of adverse events has remained stable.

CONCLUSIONS AND RELEVANCE: This exploratory analysis of the NATALEE randomized clinical trial, with a median follow-up beyond the 3-year treatment duration, demonstrated consistent iDFS benefit with ribociclib plus NSAI over NSAI alone.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03701334.},
}

@article {pmid40996743,
year = {2025},
author = {Barber, B and Harris, H},
title = {Acid-Resistant Oral Microbiome on Oral Cancer Development-Reply.},
journal = {JAMA otolaryngology-- head & neck surgery},
volume = {},
number = {},
pages = {},
doi = {10.1001/jamaoto.2025.3047},
pmid = {40996743},
issn = {2168-619X},
}

@article {pmid40996319,
year = {2025},
author = {Janitz, AE and Qiu, W and Schraw, JM and Mostoufi-Moab, S and Mirabello, L and Stewart, DR and Neglia, JP and Turcotte, LM and Bhatia, S and Yasui, Y and Chow, EJ and Armstrong, GT and Lupo, PJ},
title = {Health Outcomes in Childhood Cancer Survivors with Congenital Anomalies in the Childhood Cancer Survivor Study.},
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-25-0611},
pmid = {40996319},
issn = {1538-7755},
abstract = {BACKGROUND: Congenital anomalies are associated with increased risk of childhood cancer. However, there is a knowledge gap regarding health outcomes for childhood cancer survivors with congenital anomalies.

METHODS: We included childhood cancer survivors from the Childhood Cancer Survivor Study (n=22,247) comparing survivors with and without self-reported anomalies. Using Cox regression, we estimated hazard ratios (HR) and 95% confidence intervals (CI) of chronic health conditions (CHC) classified per the Common Terminology Criteria for Adverse Events (CTCAE) from 1 (mild) to 5 (fatal) and subsequent malignant neoplasms (SMN) comparing survivors by anomaly status. We calculated age-sex-calendar year-specific mortality rates and standardized mortality ratios (SMR) for survivors compared to the US population.

RESULTS: Among survivors, 16.9% (n=3,880) reported a congenital anomaly. Survivors with anomalies had a higher rate of any CHC (grades 1-5 HR: 1.24, 95% CI: 1.18-1.31), severe CHCs (grades 3-5 HR: 1.29, 95% CI 1.19-1.40), and multiple CHCs of any grade (≥2 CHCs HR: 1.31, 95% CI 1.24-1.39; ≥3 HR: 1.42, 95% CI 1.33-1.52). Survivors with anomalies had an increased rate of soft-tissue sarcomas (HR: 1.96, 95% CI 1.12-3.44). For deaths related to the original cancer diagnosis, survivors with anomalies (compared to no anomalies) had a lower mortality rate (0.64 vs. 0.90 per 1000 person-years).

CONCLUSIONS: We identified an increased rate of CHCs and SMNs among childhood cancer survivors with anomalies and lower mortality directly related to the cancer diagnosis.

IMPACT: Future work will focus on evaluation of genetic pathways that increase the risk of CHCs and SMNs.},
}

@article {pmid40995047,
year = {2025},
author = {Moore, M and Anderson, L and Bracis, C and Swan, DA and Painter, I and Everson, E and Janes, H and Schiffer, JT and Matrajt, L and Dimitrov, D},
title = {Estimating Population Immunity and Impact of COVID-19 Vaccination in Washington State and Oregon.},
journal = {Open forum infectious diseases},
volume = {12},
number = {9},
pages = {ofaf531},
pmid = {40995047},
issn = {2328-8957},
abstract = {BACKGROUND: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccine showed high clinical efficacy against the ancestral variant, but immunological waning, emergence of new variants, and the durability of infection-induced immunity complicate the estimation of population-level effectiveness. We used mathematical modeling to calculate the proportion of hospitalizations averted by vaccination in Washington and Oregon.

METHODS: We used an age- and region-structured compartmental model of vaccine-induced and infection-induced immunity from January 2020 until December 2022. We parameterized the strength and durability of immunity via a meta-regression of vaccine efficacy. We calibrated a time-varying contact matrix to weekly hospitalizations reported by the Washington Department of Health and Oregon Health Authority. We validated our model with Centers for Disease Control and Prevention serosurveillance data. To estimate vaccine effectiveness, we created counterfactual scenarios with no vaccination either in the entire population or in select age groups.

RESULTS: We found that total hospitalizations were reduced 74% (95% credible interval [CrI], 69%-78%) and 15% (95% CrI, 9%-19%) by primary vaccination and boosters, respectively. Vaccination effectiveness was highest during the Alpha wave, averting 90% (95% CrI, 88%-93%) of hospitalizations and in people aged 65+, averting 78% (95% CrI, 73%-81%). Relative to only vaccinating individuals aged 50+, vaccination of individuals aged 18-49 averted 52% (95% CrI, 44%-58%) of hospitalizations overall and 42% (95% CrI, 35%-48%) of hospitalizations among individuals 65+.

CONCLUSIONS: The SARS-CoV-2 vaccination program in Washington and Oregon averted the majority of hospitalizations. Vaccinating individuals aged 18-49 significantly reduced hospitalization among individuals aged 65+.},
}

@article {pmid40993182,
year = {2025},
author = {Sarnowski, C and Zhang, Y and Ammous, F and Shade, LMP and DiCorpo, D and Jian, X and Arnett, DK and Austin, TR and Beiser, A and Bis, JC and Blangero, J and Boerwinkle, E and Bressler, J and Curran, JE and DeCarli, CS and Doddapaneni, H and Dupuis, J and Fardo, DW and Florez, JC and Gabriel, S and Gibbs, RA and Glahn, DC and Gupta, N and González, HM and González, KA and Hatzikotoulas, K and Hayden, KM and Heckbert, SR and Hidalgo, B and Huerta-Chagoya, A and Hughes, TM and Kardia, SLR and Kooperberg, CL and Launer, LJ and Longstreth, WT and , and , and Mandla, R and Mathias, RA and Morris, AP and Mosley, TH and Nasrallah, IM and Nyquist, P and Psaty, BM and Qi, Q and Raffield, LM and Rayner, NW and Reiner, AP and Satizabal, CL and Selvin, E and Sevilla-Gonzalez, MDR and Smith, AV and Smith, JA and Smith, K and Snively, BM and Southam, L and Sofer, T and Suzuki, K and Taylor, HJ and Udler, MS and Viaud-Martinez, KA and Wassertheil-Smoller, S and Wood, AC and Yanek, LR and Yin, X and Manning, AK and Rotter, JI and Rich, SS and Meigs, JB and Fornage, M and Seshadri, S and Morrison, AC and , and , },
title = {Association of genetic scores related to insulin resistance with neurological outcomes in ancestrally diverse cohorts from the Trans-Omics for Precision Medicine (TOPMed) program.},
journal = {Communications biology},
volume = {8},
number = {1},
pages = {1352},
pmid = {40993182},
issn = {2399-3642},
support = {R00 AG066849/AG/NIA NIH HHS/United States ; },
mesh = {Humans ; Male ; *Insulin Resistance/genetics ; Middle Aged ; Female ; Precision Medicine ; Cross-Sectional Studies ; Aged ; Metabolic Syndrome/genetics ; Adult ; },
abstract = {To better characterize the potential biological mechanisms underlying insulin resistance (IR) and dementia, we derive cross-population and population specific polygenic scores [PSs] for fasting insulin and IR-related partitioned PSs [pPSs]. We conduct a cross-sectional study of the associations of these genetic scores with neurological outcomes in >17k participants (36% men, mean age 55 yrs) from the Trans-Omics for Precision Medicine (TOPMed) program (50% Non-Hispanic White, 23% Black/African American, 21% Hispanic/Latino American, and 4% Asian American). We report significant negative associations (P < 0.002) of the cross-population (P = 1.3 × 10[-5]) and European (PEA = 3.0 × 10[-8]) fasting insulin PSs with total cranial volume, and of a metabolic syndrome European PS with general cognitive function (BEA = -0.13, PEA = 0.0002) and lateral ventricular volume (BEA = 0.09, PEA = 0.002). We identify suggestive negative associations (P < 0.007) of metabolic syndrome and obesity pPSs with general cognitive function, and of lipodystrophy pPSs with total cranial volume. A higher genetic predisposition to IR is associated with lower brain size, and a genetic predisposition to specific IR-related type 2 diabetes subtypes, such as metabolic syndrome and mechanisms of IR mediated through obesity and lipodystrophy, is potentially involved in cognitive decline.},
}

Humans
Male
*Insulin Resistance/genetics
Middle Aged
Female
Precision Medicine
Cross-Sectional Studies
Aged
Metabolic Syndrome/genetics
Adult

@article {pmid40991892,
year = {2025},
author = {Dorovini-Zis, K and Li, H and Zhe, C and Zhang, B and Small, D and Taylor, TE},
title = {Mapping the expression of endothelial adhesion receptors for Plasmodium falciparum-infected erythrocytes in fatal cerebral malaria in Malawian children.},
journal = {Journal of neuropathology and experimental neurology},
volume = {},
number = {},
pages = {},
doi = {10.1093/jnen/nlaf104},
pmid = {40991892},
issn = {1554-6578},
support = {5R01AI34969//US National Institutes of Health/ ; },
abstract = {We investigated the expression and distribution of 5 cytoadhesion receptors for the Plasmodium falciparum erythrocyte membrane protein 1 in 12 regions of post-mortem brains of 50 Malawian children, that is, 27 with the clinical and pathological diagnosis of cerebral malaria (CM) and 23 with a non-malarial cause of death. We quantified the expression of each receptor by microvascular endothelium and the colocalization of receptor-expressing microvessels with sequestered infected red blood cells (iRBC) and calculated a receptor-independent sequestration ratio. There were differences in the level of expression and regional distribution of the five receptors: ICAM-1 was the most widely expressed receptor, followed by CD36, VCAM-1, E-selectin, and thrombospondin. Receptor-expressing microvessels were most numerous in the frontal lobe and least numerous in the brainstem and cerebellum. Colocalization of receptor-expressing endothelial cells with iRBC was present in all brain regions; it was highest for ICAM-1 and CD36 and greatest in the frontal lobe. The sequestration ratios were close to 100% for all receptors across all brain regions and were similar in cerebral and extracerebral microvessels. Receptor expression and colocalization ratios were greater in the brain than in the lung, heart, liver, spleen, and subcutaneous tissue. These differences in cerebral endothelial expression of cytoadhesion receptors and their preferential regional distribution may underpin differences in iRBC sequestration and lesion development in CM. Moreover, greater expression of these receptors in the brain vs peripheral organs may explain a comparatively greater degree of iRBC sequestration in the brain.},
}

@article {pmid40991418,
year = {2025},
author = {Matsuk, VY and Khatib, TO and Marcus, LJ and Robinson, IE and Liu, Y and Pasupathy, JK and Shanmugam, M and Mouw, JK and Marcus, AI},
title = {Metabolic programming defines oxygen sensitive subpopulation hierarchies and patterning in collective invasion.},
journal = {Molecular biology of the cell},
volume = {},
number = {},
pages = {mbcE25070314},
doi = {10.1091/mbc.E25-07-0314},
pmid = {40991418},
issn = {1939-4586},
abstract = {Phenotypic heterogeneity - distinct molecular and behavioral variations within a population -significantly influences collective invasion and tumor progression. Here, we employ a molecular approach to explore how the underlying metabolic heterogeneity in non-small cell lung cancer (NSCLC) influences invasion and pack patterning. Assessing three-dimensional (3D) pack patterning revealed invasive heterogeneity across NSCLC cell lines and patient-derived samples. Flow cytometry identified IL13RA2 as a biomarker for invasive potential, enabling isolation of subpopulations with distinct invasive characteristics. By integrating a cell surface biomarker (IL13RA2±) with mitochondrial membrane potential (TMRM), we identified and isolated three distinct subpopulations. Two-dimensional (2D) analyses revealed differences in mitochondrial polarity and transcriptional programs associated with migration and oxygen-sensitivity. In 3D, these subpopulations invaded with distinct patterns, from contiguous circular packs to structured chains. Assessments under varied oxygen tension demonstrated that oxygen availability and subpopulation metabolism together influence collective invasion patterning. When recombined at ratios recapitulating the original population, both stochastic and opportunistic cooperative dynamics emerged, dependent on subpopulation composition and oxygen levels. Our molecular approach, integrating cell surface and metabolic characteristics, enables isolation of unique subpopulations and demonstrates that phenotypic and metabolic heterogeneity, population composition, and oxygen availability collectively pattern invasion packs and drive collective invasion.},
}

@article {pmid40964310,
year = {2025},
author = {Ramsey, EL and Dobersch, S and Freie, B and Hong, NH and Wu, X and Kugel, S and Eisenman, RN and Carroll, PA},
title = {MondoA mediates transcriptional coordination between the MYC network and the integrated stress response in pancreatic ductal adenocarcinoma.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {40964310},
issn = {2692-8205},
abstract = {MYC amplification contributes to poor survival and outcome in pancreatic ductal adenocarcinoma (PDAC). Here we show that in PDAC cell lines with amplified MYC, MondoA is required for viability, facilitating proliferation while suppressing apoptosis in vitro and in vivo. Transcriptional and genomic profiling demonstrates that loss of MondoA leads to altered expression of direct MondoA targets as well as MYC target genes and is accompanied by shifts in genomic occupancy of MYC, MNT, and the MondoA paralog ChREBP. This altered genomic binding by MYC network members is associated with transcriptional perturbation of multiple metabolic and stress pathways, as well as global changes in N6-methyladenosine modification (m[6]A) of mRNA. MondoA inhibition disrupts coordination between MYC network members and the Integrated Stress Response (ISR), resulting in decreased translation of ATF4 mRNA, discordant gene regulation of shared targets of MYC and ATF4 and, ultimately, apoptosis. Re-establishing ATF4 protein expression rescues the diminished viability due to loss of MondoA expression or activity, providing direct evidence of a link between deregulated MYC and the transcriptional machinery of the ISR. Lastly, we find that small-molecule inhibition of MondoA is lethal in a subset of PDAC cell lines, including patient-derived organoids, suggesting that the ability to target MYC via chemical inhibition of MondoA transcriptional activity may have broad efficacy.},
}

@article {pmid40991382,
year = {2025},
author = {Faulk, KE and Kairalla, JA and Hibbitts, E and Long-Boyle, JR and Devidas, M and August, A and Gore, L and Raetz, EA and Hunger, SP and Loh, ML and Teachey, DT and Brown, PA and Breese, EH and Kotecha, RS and Guest, E},
title = {Age-Based Pegaspargase Dosing is Safe and Achieves Therapeutic Levels in Infants with ALL: Report from COG AALL15P1.},
journal = {Blood advances},
volume = {},
number = {},
pages = {},
doi = {10.1182/bloodadvances.2025017013},
pmid = {40991382},
issn = {2473-9537},
}

@article {pmid40987290,
year = {2025},
author = {Reeves, DB and Rigau, DN and Romero, A and Zhang, H and Simonetti, FR and Varriale, J and Hoh, R and Zhang, L and Smith, KN and Montaner, LJ and Rubin, LH and Gange, SJ and Roan, NR and Tien, PC and Margolick, JB and Peluso, MJ and Deeks, SG and Schiffer, JT and Siliciano, JD and Siliciano, RF and Antar, AAR},
title = {Mild HIV-specific selective forces overlaying natural CD4+ T cell dynamics explain the clonality and decay dynamics of HIV reservoir cells.},
journal = {Cell systems},
volume = {},
number = {},
pages = {101402},
doi = {10.1016/j.cels.2025.101402},
pmid = {40987290},
issn = {2405-4720},
abstract = {To determine whether HIV persistence arises from the natural dynamics of memory (m)CD4+ T cells, we compare clonal dynamics of HIV proviruses and mCD4+ T cells from the same people living with HIV (PWH) on antiretroviral therapy and from matched HIV-seronegative people (N = 51). HIV proviruses are more clonal than mCD4+ T cells but similarly clonal to antigen-specific cells. Increasing reservoir clonality over time and differential decay of intact and defective proviruses are not explained by mCD4+ T cell kinetics alone. We develop and validate a stochastic model trained on 10 quantitative data metrics, which shows that negative selection against HIV-infected cells is necessary to explain all metrics. We estimate the strength of negative selection, finding that death of cells harboring intact and defective proviruses is infrequently (∼6% and ∼2% on average) due to HIV-specific factors. Thus, our data indicate that HIV persistence is mostly, but not entirely, driven by natural mCD4+ kinetics.},
}

@article {pmid40986647,
year = {2025},
author = {Ribi, K and Cole, BF and Fleming, GF and Walley, BA and Francis, PA and Abdi, E and Burstein, HJ and Cheng, KL and Chia, SKL and Dakhil, SR and Davidson, NE and Della-Fiorentina, SA and Frith, AE and Levine, E and Lupichuk, S and Pritchard, K and Salim, M and Stearns, V and Stewart, J and Valero, V and van der Westhuizen, A and Pagani, O and Loi, S and Colleoni, M and Gelber, RD and Goldhirsch, A and Coates, AS and Regan, MM and Bernhard, J},
title = {Prognostic value of patient-reported depression in women with hormone-responsive early breast cancer in TEXT and SOFT.},
journal = {Cancer},
volume = {131},
number = {19},
pages = {e70094},
doi = {10.1002/cncr.70094},
pmid = {40986647},
issn = {1097-0142},
support = {//Pfizer/ ; /CA/NCI NIH HHS/United States ; //European Thoracic Oncology Program and International Breast Cancer Study Group Partners Foundation/ ; },
mesh = {Adult ; Female ; Humans ; Middle Aged ; Androstadienes/administration & dosage/therapeutic use ; Antidepressive Agents/therapeutic use ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; *Breast Neoplasms/drug therapy/psychology/mortality/complications ; *Depression/drug therapy ; Disease-Free Survival ; Premenopause ; Prognosis ; Tamoxifen/therapeutic use/administration & dosage ; },
abstract = {BACKGROUND: Depression has been identified as an adverse mental health outcome in women with breast cancer (BC). Depression was investigated as a risk factor for poor survival in premenopausal women with hormone-responsive early BC treated in the TEXT (Tamoxifen and Exemestane Trial) and SOFT (Suppression of Ovarian Function Trial) trials.

METHODS: The data used were from a subset of patients who participated in TEXT or SOFT and completed the Center of Epidemiologic Studies-Depression scale. Associations between baseline depression-score categories and baseline characteristics were assessed using the Cochran-Mantel-Haenszel test controlling for antidepressant use. Multivariable proportional hazards regression models were used to test the association between baseline depression and disease-free survival (DFS) and overall survival (OS). Regression models were adjusted for factors known to be associated with outcomes, baseline antidepressant use, and early treatment cessation.

RESULTS: Forty percent (2287 of 5738) of the women enrolled in the SOFT and TEXT trials were included in this analysis (SOFT, n = 1259; TEXT, n = 1028). Twenty-seven percent of women reported mild-to-moderate or severe depression at baseline. Race (p = .001), body mass index (p = .02), family history (p = .02), and performance status (p =.007) were significantly associated with the severity of depression. Relative to the no-symptomatology group, the hazard ratios (overall p = .04) for DFS were 1.34 (95% confidence interval [CI], 1.03-1.76) for women with mild-to-moderate depression and 1.34 (95% CI, 0.96-1.87) for those with severe depression. Relative to the no-symptomatology group, the hazard ratios (overall p = .008) for OS were 1.68 for mild-to-moderate depression (95% CI, 1.15-2.44) and 1.67 for those with severe depression (95% CI, 1.05-2.66).

CONCLUSIONS: In premenopausal women with hormone-responsive early BC, depression at baseline is a risk factor for poorer DFS and OFS. Further investigation of the underlying interactive processes is needed.

TRIAL REGISTRATION: Clinicaltrials.gov NCT00066703 (SOFT) and NCT00066690 (TEXT).},
}

Adult
Female
Humans
Middle Aged
Androstadienes/administration & dosage/therapeutic use
Antidepressive Agents/therapeutic use
Antineoplastic Combined Chemotherapy Protocols/therapeutic use
*Breast Neoplasms/drug therapy/psychology/mortality/complications
*Depression/drug therapy
Disease-Free Survival
Premenopause
Prognosis
Tamoxifen/therapeutic use/administration & dosage

@article {pmid40986340,
year = {2025},
author = {Su, Y and Thelen, A and Wirth, LV and Jenkins, CM and Mak, SR and Chen, DG and Gottardo, R and Greenberg, PD},
title = {A TGF-βR/IL-2R immunomodulatory fusion protein transforms immunosuppression into T cell activation to enhance adoptive T cell therapy.},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
volume = {122},
number = {39},
pages = {e2516951122},
doi = {10.1073/pnas.2516951122},
pmid = {40986340},
issn = {1091-6490},
support = {CA18029/GF/NIH HHS/United States ; CA225517/GF/NIH HHS/United States ; DRQ-13-22//Damon Runyon Cancer Research Foundation (DRCRF)/ ; Hartwell Innovation Award//Hartwell Foundation (HARTWELL)/ ; CA015704/GF/NIH HHS/United States ; },
mesh = {Humans ; *Immunotherapy, Adoptive/methods ; *Lymphocyte Activation/immunology ; *Receptors, Transforming Growth Factor beta/genetics/immunology/metabolism ; *Recombinant Fusion Proteins/genetics/immunology ; Interleukin-2/metabolism ; Signal Transduction ; STAT5 Transcription Factor/metabolism ; CD8-Positive T-Lymphocytes/immunology ; Tumor Microenvironment/immunology ; *Receptors, Interleukin-2/genetics/immunology/metabolism ; Phosphorylation ; Transforming Growth Factor beta ; Immunosuppression Therapy ; T-Lymphocytes/immunology ; },
abstract = {Adoptive T cell therapies have shown limited efficacy against solid tumors due in part to immunosuppressive cues such as from TGF-β and insufficient survival/proliferative signals within the tumor microenvironment (TME). We engineered chimeric immunomodulatory fusion proteins (IFPs) that convert immunosuppressive TGF-β signals into proliferative/survival Interleukin 2 (IL-2) signals in T cells. Chimeric TGF-βR/IL-2R IFPs were constructed by fusing extracellular domains of the TGF-β receptor chains with intracellular domains of IL-2Rβ and IL-2Rγ to enable TGF-β binding to trigger STAT5 phosphorylation and activate the downstream IL-2 pathway. In human primary CD8[+] T cells, select IFP designs robustly induced p-STAT5 upon exposure to TGF-β1, and simultaneously reduced canonical SMAD2/3 signaling. IFP-expressing T cells proliferated and displayed enhanced viability in response to TGF-β1, effectively leveraging TGF-β-rich conditions to outcompete nontransduced cells. Transcriptomic analyses revealed that IFP signaling promoted T cell activation and allowed maintenance of stemness during culture with TGF-β. Functionally, coexpressing IFPs with a mesothelin-specific T cell receptor improved tumor killing and promoted T cell expansion in the presence of TGF-β1, highlighting both neutralization of TGF-β-mediated suppression and enhanced proliferation. TGF-βR/IL-2R IFPs appear promising for reprogramming the signals T cells receive in the TME and improving efficacy of adoptive T cell therapy in solid tumors.},
}

Humans
*Immunotherapy, Adoptive/methods
*Lymphocyte Activation/immunology
*Receptors, Transforming Growth Factor beta/genetics/immunology/metabolism
*Recombinant Fusion Proteins/genetics/immunology
Interleukin-2/metabolism
Signal Transduction
STAT5 Transcription Factor/metabolism
CD8-Positive T-Lymphocytes/immunology
Tumor Microenvironment/immunology
*Receptors, Interleukin-2/genetics/immunology/metabolism
Phosphorylation
Transforming Growth Factor beta
Immunosuppression Therapy
T-Lymphocytes/immunology

@article {pmid40985344,
year = {2025},
author = {Hausmann, O and Schobert, PP and Ose, J and Himbert, C and Pletneva, M and Jedrzkiewicz, J and Nguyen, A and Lin, T and Warby, CA and Hardikar, S and Peoples, AR and Strehli, I and Huang, LC and Cohan, JN and Pickron, B and Scaife, C and Li, CI and Grady, WM and Shibata, D and Toriola, AT and Schneider, M and Figueiredo, JC and Siegel, EM and Gigic, B and Herzig, S and Ilozumba, MN and Ulrich, CM},
title = {Associations of Biomarkers of Systemic Inflammation, Angiogenesis, and Cell-to-Cell Adhesion With Tumor Budding Among Early-Onset and Later-Onset Colorectal Cancer Patients.},
journal = {Cancer medicine},
volume = {14},
number = {18},
pages = {e71267},
pmid = {40985344},
issn = {2045-7634},
support = {//Stiftung LebensBlicke/ ; P30CA042014/CA/NCI NIH HHS/United States ; K07222060/NH/NIH HHS/United States ; R01CA189184/NH/NIH HHS/United States ; R01CA207371/NH/NIH HHS/United States ; R01CA254108/NH/NIH HHS/United States ; R03CA270473/NH/NIH HHS/United States ; U01CA206110/NH/NIH HHS/United States ; },
mesh = {Aged ; Female ; Humans ; Male ; Middle Aged ; Age of Onset ; Angiogenesis ; *Biomarkers, Tumor/blood ; Cell Adhesion ; *Colorectal Neoplasms/pathology/blood ; *Inflammation/blood ; Intercellular Adhesion Molecule-1/blood ; Neoplasm Staging ; *Neovascularization, Pathologic/blood/pathology ; Prognosis ; },
abstract = {BACKGROUND: High tumor budding and elevated systemic inflammation are adverse prognostic indicators in colorectal cancer. Its underlying mechanisms remain poorly understood. It is unclear whether systemic inflammation, angiogenesis, and cell-to-cell adhesion influence tumor budding.

METHODS: We investigated n = 132 stage I-III colorectal cancer patients recruited at Huntsman Cancer Institute enrolled in the ColoCare Study. Tumor budding was evaluated using an evidence-based scoring system, and patient sera were analyzed for nine circulating biomarkers using the Meso Scale Discovery platform. We examined associations between biomarkers and tumor budding using multivariable linear regression models adjusted for age, sex, neoadjuvant treatment, stage, and non-steroidal anti-inflammatory drug use.

RESULTS: The study population was predominantly non-Hispanic White (95%), with a mean age of 61 years; 56% were male. Most tumors were stage III (47%), located in the colon (64%), and exhibited low-grade tumor budding (58%). Soluble intercellular adhesion molecule 1 was inversely associated with tumor budding overall (M1: β = -0.57, p = 0.03), among females (M1: β = -0.81, p-value = 0.03) and later-onset (≥ 50 years) colorectal cancer (M1: β = -0.71, p-value = 0.008). C-reactive protein was positively associated with tumor budding in males (M1: β = 0.23, p = 0.001), while interleukin-8 (M1: β = 0.96, p-value = 0.01) and soluble vascular adhesion molecule 1 (M2: β = 1.48, p-value = 0.04) were positively associated with tumor budding in early-onset patients. However, these associations did not remain statistically significant after correction for multiple testing.

CONCLUSION: Overall, our findings do not provide evidence of a significant association between biomarkers of systemic inflammation, angiogenesis, and cell-to-cell adhesion with tumor budding count. We observed patterns for some biomarkers, yet none remained statistically significant after correction for multiple testing. These findings provide preliminary insights for future studies.

TRIAL REGISTRATION: ClinicalTrials.gov: NCT02328677.},
}

Aged
Female
Humans
Male
Middle Aged
Age of Onset
Angiogenesis
*Biomarkers, Tumor/blood
Cell Adhesion
*Colorectal Neoplasms/pathology/blood
*Inflammation/blood
Intercellular Adhesion Molecule-1/blood
Neoplasm Staging
*Neovascularization, Pathologic/blood/pathology
Prognosis

@article {pmid40983593,
year = {2025},
author = {Fitchett, G and Campbell, D and Chang, C and Hester, C and King, S and Peery, B and Saks, NT},
title = {Developing and implementing spiritual screening in healthcare: six successful models.},
journal = {Journal of health care chaplaincy},
volume = {},
number = {},
pages = {1-22},
doi = {10.1080/08854726.2025.2563472},
pmid = {40983593},
issn = {1528-6916},
abstract = {Healthcare chaplains recognize the importance of informed referrals for spiritual care; they are essential for spiritual care in outpatient settings. Research about the prevalence and harmful effects of religious/spiritual distress underscores the importance of effective methods for identifying patients who would benefit from spiritual care. Spiritual screening is a valuable way to help healthcare colleagues identify patients who would benefit from further assessment and spiritual care. To help spiritual care programs implement spiritual screening, in this article chaplains from six organizations with successful spiritual screening describe the development and implementation of their programs. The settings for these screening programs include hospital inpatients, oncology outpatient centers, palliative care, and population health. The descriptions include the screening questions used, how they are administered, and what it took to get them implemented. Common and unique features of these six approaches to spiritual screening are discussed along with areas for future research.},
}

@article {pmid40982684,
year = {2025},
author = {Alencar, GF and Mohamed, AO and Burnett, MG and Jean, SS and Nelson, AR and Su, Y and Voillet, V and Bates, BM and Rodgers Suarez, M and Ruskin, SL and Trieu, L and Lam, JL and Bekiranov, S and Gottardo, R and Greenberg, PD and Anderson, KG},
title = {Triple checkpoint blockade of PD-1, Tim-3, and Lag-3 enhances adoptive T cell immunotherapy in a mouse model of ovarian cancer.},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
volume = {122},
number = {39},
pages = {e2419888122},
doi = {10.1073/pnas.2419888122},
pmid = {40982684},
issn = {1091-6490},
support = {CA009657-26A1 CA266737 P30CA044579 CA018029 CA033084//HHS | NIH | National Cancer Institute (NCI)/ ; Ann and Sol Schreiber Mentored Investigator Training Grant//Ovarian Cancer Research Alliance (OCRA)/ ; no number//Parker Institute for Cancer Immunotherapy (PICI)/ ; no number//Lonza Houston (Lonza Houston, Inc.)/ ; no number//Celgene Corporation | Juno Therapeutics/ ; 5T32AI007496-29//HHS | NIH | National Institute of Allergy and Infectious Diseases (NIAID)/ ; },
mesh = {Animals ; Female ; *Ovarian Neoplasms/therapy/immunology/pathology/genetics ; Mice ; *Programmed Cell Death 1 Receptor/antagonists & inhibitors/immunology ; *Immunotherapy, Adoptive/methods ; *Hepatitis A Virus Cellular Receptor 2/antagonists & inhibitors/immunology/metabolism ; Mesothelin ; Lymphocyte Activation Gene 3 Protein ; *Immune Checkpoint Inhibitors/pharmacology ; *T-Lymphocytes/immunology ; Tumor Microenvironment/immunology ; Disease Models, Animal ; *Antigens, CD/immunology/metabolism/genetics ; Cell Line, Tumor ; Humans ; },
abstract = {The five-year survival rate for ovarian cancer patients remains below 50%, underscoring the need for innovative therapies. One promising approach involves engineering T cells to specifically target proteins uniquely overexpressed in tumors, thereby controlling tumor growth without toxicity to healthy tissues. Mesothelin (MSLN) contributes to the malignant and invasive phenotype in ovarian cancer and has limited expression in healthy cells, making it a candidate immunotherapy target. Our previous results in a mouse model of ovarian cancer demonstrated that T cells engineered to express a T cell receptor (TCR) targeting MSLN (TCRMSLN) mediated therapeutic activity, delaying tumor growth and prolonging mouse survival. However, inhibitory ligands expressed in the tumor microenvironment (TME) interacted with inhibitory receptors on activated T cells, suppressing antitumor function. We hypothesized combining engineered T cells with checkpoint blockade would enhance T cell function and improve therapeutic efficacy, but administration of monospecific antibodies targeting individual inhibitory pathways had no significant impact on T cell efficacy. By contrast, the combination of PD-1, Tim-3, and Lag-3 blockade with engineered T cells significantly improved T cell function and overall animal survival relative to treatment with antibody alone or TCRMSLN with singlet or doublet antibody combinations. Single-cell RNA sequencing revealed TCRMSLN T cells treated with the triplet antibody combination increased expression of genes involved in interferon responses and metabolic function, and reduced expression of genes associated with exhaustion. These results suggest that strategies to disrupt multiple inhibitory pathways simultaneously may be necessary for improved adoptive T cell therapy efficacy in patients.},
}

Animals
Female
*Ovarian Neoplasms/therapy/immunology/pathology/genetics
Mice
*Programmed Cell Death 1 Receptor/antagonists & inhibitors/immunology
*Immunotherapy, Adoptive/methods
*Hepatitis A Virus Cellular Receptor 2/antagonists & inhibitors/immunology/metabolism
Mesothelin
Lymphocyte Activation Gene 3 Protein
*Immune Checkpoint Inhibitors/pharmacology
*T-Lymphocytes/immunology
Tumor Microenvironment/immunology
Disease Models, Animal
*Antigens, CD/immunology/metabolism/genetics
Cell Line, Tumor
Humans

@article {pmid40982561,
year = {2025},
author = {Chen, C and Lovendahl, KN and Overbaugh, JM and Lee, KK},
title = {Interprotomer crosstalk in mosaic viral glycoprotein trimers provides insight into polyvalent immunogen co-assembly.},
journal = {PLoS pathogens},
volume = {21},
number = {9},
pages = {e1013143},
doi = {10.1371/journal.ppat.1013143},
pmid = {40982561},
issn = {1553-7374},
abstract = {SARS-CoV-2 variants have demonstrated the ability to evade immune responses, leading to waves of infection throughout the pandemic. In response, bivalent mRNA vaccines, encoding the original Wuhan-Hu-1 and emerging variants, were developed to display both spike antigens. To date, it has not been determined whether co-transfection and co-translation of different SARS-CoV-2 variants results in co-assembly of mosaic heterotrimer antigens and how this may affect trimer stability, dynamics, and antigenicity. Understanding whether such mosaic heterotrimers can form and their implications for antigen structure can provide important information to guide future polyvalent vaccine design where multiple variants of an antigen are co-formulated. To investigate this, we purified mosaic spike assemblies of both genetically close (Omicron BA.2 and XBB) and distant (Omicron BA.2 and Wuhan-Hu-1 G614) strains. We found that the stability and integrity of mosaic spike trimers were maintained without misfolding or aggregation. Glycosylation profiles likewise were preserved relative to the homotrimer counterparts. Hydrogen/deuterium-exchange mass spectrometry and biolayer-interferometry were used to investigate the mosaic spike dynamics and any impact on epitope presentation and receptor binding. The Omicron-XBB heterotrimer, sharing a common fusion subunit sequence, retained protomer-specific dynamics similar to the corresponding homotrimers in antigenically important regions. The Omicron-G614 heterotrimer, co-assembling from protomers of divergent fusion subunit sequences, likewise showed overall similar dynamics and conformations in the receptor-binding subunit compared to the homotrimers. However, the incorporation of the Wuhan-Hu-1 G614 protomer led to a stabilizing effect on the relatively unstable Omicron fusion subunit in the heterotrimer. These findings reveal structural dynamic crosstalk in mosaic trimers, suggesting a potential for enhanced immunogen display and important considerations to be aware of in the use of polyvalent nucleic acid vaccines.},
}

@article {pmid40980587,
year = {2025},
author = {Deo, R and Choudhary, MC and Glover, OT and Ignacio, RB and Boucau, J and Chew, KW and Moser, C and Currier, JS and Eron, JJ and Javan, AC and Giganti, MJ and Aga, E and Gibbs, M and Cohen, T and Streicher, K and Soboleva, K and Fletcher, CV and Daar, ES and Greninger, AL and Coombs, RW and Fischer, W and Hughes, MD and Smith, D and Wohl, DA and Barczak, AK and Li, JZ},
title = {Rapid Elimination of Culturable SARS-CoV-2 With Intramuscular or Intravenous Administration of Antiviral Monoclonal Antibody Therapy.},
journal = {Open forum infectious diseases},
volume = {12},
number = {9},
pages = {ofaf542},
pmid = {40980587},
issn = {2328-8957},
abstract = {We evaluated intramuscular (IM) versus intravenous (IV) administration of tixagevimab/cilgavimab in early COVID-19. Both routes achieved rapid elimination of culturable virus and minimal emergence of resistance. These results support IM delivery as a viable alternative to IV, with important implications for scalable deployment in future viral pandemics.},
}