@article {pmid41776157,
year = {2026},
author = {Frouard, J and Telwatte, S and Luo, X and Gill, N and Thomas, R and Arneson, D and Roychoudhury, P and Butte, AJ and Wong, JK and Hoh, R and Deeks, SG and Lee, SA and Roan, NR and Yukl, SA},
title = {HIV-seq reveals gene expression differences between HIV-transcribing cells from viremic and suppressed people with HIV.},
journal = {Nature communications},
volume = {17},
number = {1},
pages = {},
pmid = {41776157},
issn = {2041-1723},
support = {P01AI169606//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; R01DK120387//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; R01AI132128//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; R01AI147777//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; R01DK131526//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; R01AI183286//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; R21AI170166//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; UM1AI164559//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; UM1AI164567//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; UM1AI164560//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; P30AI027763//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; R01AI183666//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; R01AI194343//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; BB19-SF-009/A135087//California HIV/AIDS Research Program (CHRP)/ ; },
abstract = {HIV-transcribing cells can perpetuate chronic inflammation in ART-suppressed people with HIV (PWH) and likely contribute to viral rebound after ART interruption. However, these cells are difficult to study using single-cell RNA-seq (scRNA-seq) due to their low frequency and low levels of HIV transcripts, which are usually not polyadenylated. By spiking in capture sequences targeting conserved regions of HIV during scRNA-seq - a new method we call "HIV-seq" - we detect double the mean number of HIV reads per cell from PWH. HIV RNA+ cells are enriched among T effector memory cells during both viremia and ART suppression but exhibit a cytotoxic signature during viremia only. In contrast, HIV-transcribing cells from ART-suppressed timepoints exhibit a distinct anti-inflammatory signature involving elevated TGF-β and diminished IFN signaling. These findings demonstrate that HIV-seq is a useful tool to better understand the mechanisms by which HIV-transcribing cells can persist during ART.},
}

@article {pmid41775684,
year = {2026},
author = {Suarez-Carmona, M and Hampel, M and Zhang, XW and Pöchmann, A and Grauling-Halama, SA and Valous, NA and Charoentong, P and Ferber, D and Wissfeld, J and Höflich, A and Goriely, S and Detavernier, A and Azouz, A and Rongvaux, A and Zukunft, S and Fleming, I and Okun, JG and Baracos, V and Heikenwalder, M and Zitvogel, L and Xu, X and Xu, C and Volkmar, M and Schraivogel, D and Steinmetz, L and Hamanishi, J and Mandai, M and Gaida, M and Mokry, T and Nattenmüller, J and Sedlaczek, O and Monje, N and Schwab, R and Hasenburg, A and Mavratzas, A and Boger, RJ and Marmé, F and Schott, S and Halama, N},
title = {Harnessing lipid-driven immunometabolic pathways in omental metastases to enhance immunotherapy in patients with ovarian cancer.},
journal = {Signal transduction and targeted therapy},
volume = {11},
number = {1},
pages = {},
pmid = {41775684},
issn = {2059-3635},
support = {Zukunftsthema//Helmholtz Association/ ; ERDF 2022-2027 WAL IMAGIN SYST-IMM//Fédération Wallonie-Bruxelles (French Community of Belgium)/ ; 318346496//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; },
mesh = {Humans ; Female ; Animals ; Mice ; *Immunotherapy ; *Omentum/pathology/immunology ; *Ovarian Neoplasms/immunology/pathology/therapy/genetics ; Tumor Microenvironment/immunology/drug effects ; *Lipid Metabolism/immunology ; *Carcinoma, Ovarian Epithelial/immunology/pathology/therapy/genetics ; Tumor-Associated Macrophages/immunology ; Neoplasm Metastasis ; Signal Transduction ; },
abstract = {Immunotherapy with immune checkpoint blockade (ICB) in epithelial ovarian carcinoma (EOC) shows limited clinical benefit only for a small subset of patients. Overall response rates are low, so that overcoming immunotherapy resistance and improved stratification are key. In this study, we investigated the immunometabolic landscape of EOC with a focus on omental metastases, identifying lipid-laden macrophages as central elements for actionable therapeutic vulnerabilities and giving rise to biomarkers for improved patient stratification. Using patient-derived explants, we demonstrated a functional dichotomy inside the typically lipid-rich microenvironment of omental metastases: augmented maintenance of effector T cell function, while lipid uptake and processing by tumor-associated macrophages (TAMs) induces oxidative stress-dependent signaling programs, which drive macrophage dysfunction and immune suppression. Pharmacological modulation of lipid-driven signaling pathways through CCR5 inhibition (inflammation modulation through maraviroc) or blockade of the lipid scavenger receptor CD36 reprograms TAMs, restores T cell activity, and enhances antitumor immune responses within lipid-rich tumor niches. Mechanistically, studies in humanized mouse models reveal that maraviroc-mediated CCR5 inhibition induces transcriptional programs associated with immune activation in stressed, lipid-laden human TAMs. Consistent with these mechanistic insights, we demonstrated that the specific immunometabolic niche in omental metastases is clinically associated with responsiveness to ICB. We propose a non-invasive radiomics and machine-learning-based analysis of imaging data to assess omental involvement for patient stratification.},
}

Humans
Female
Animals
Mice
*Immunotherapy
*Omentum/pathology/immunology
*Ovarian Neoplasms/immunology/pathology/therapy/genetics
Tumor Microenvironment/immunology/drug effects
*Lipid Metabolism/immunology
*Carcinoma, Ovarian Epithelial/immunology/pathology/therapy/genetics
Tumor-Associated Macrophages/immunology
Neoplasm Metastasis
Signal Transduction

@article {pmid41775429,
year = {2026},
author = {Flores, TF and Tonorezos, ES and Bhatia, S and Brahmer, JR and Cappelli, LC and Cooper, M and Davies, M and Guild, S and Gunturu, K and Haanen, JBAG and Johnson, DB and Lacouture, ME and Leidner, R and Mitchell, S and Moledina, DG and Moslehi, J and Naidoo, J and Obeid, M and Postow, M and Puzanov, I and Reid, ME and Santomasso, BD and Schadendorf, D and Silk, AW and Sullivan, RJ and Walunas, T and Wang, Y and Ascierto, PA and Ernstoff, MS},
title = {Where is the data? Delayed and chronic irAE surveillance and management after cessation of ICIs: expert insights from SITC on survivorship care and the need for long-term data.},
journal = {Journal for immunotherapy of cancer},
volume = {14},
number = {3},
pages = {},
pmid = {41775429},
issn = {2051-1426},
abstract = {Immune checkpoint inhibitors (ICIs) have revolutionized cancer therapy, offering durable responses and prolonged survival. However, these therapies also present unique challenges, particularly with the onset of immune-related adverse events (irAEs), which can manifest during treatment either acutely and/or become chronic or emerge long after treatment cessation. Delayed, chronic, and re-emergent irAEs often require tailored survivorship care, including coordination across multiple disciplines focused on oncology, specialty care, and primary care. Despite the increased usage of ICIs, there is limited longitudinal data guiding the surveillance, diagnosis, attribution, and management of irAEs after ICI treatment. To address these gaps, the Society for Immunotherapy of Cancer convened an Expert Panel to deliberate best practices and identify research opportunities for improving post-treatment care. This paper outlines these expert insights into irAE surveillance, coordination and continuity across care transitions and settings, and clinical management strategies. The paper also underscores the importance of clinicians' understanding of irAE onset patterns, multidisciplinary coordination, and the urgent need in the field for the development of a comprehensive irAE registry. By addressing these critical gaps, the oncology community can better support the growing population of ICI-treated cancer survivors, ensuring improved quality of life and care outcomes.},
}

@article {pmid41774708,
year = {2026},
author = {Hsieh, YP and O'Keefe, IP and Wang, Z and Sun, W and Yang, H and Vu, LM and Smalley, NE and Ernst, RK and Dandekar, AA and Malik, HS},
title = {Magnesium depletion by Candida albicans unleashes two unusual modes of colistin resistance in Pseudomonas aeruginosa with different fitness costs.},
journal = {PLoS biology},
volume = {24},
number = {3},
pages = {e3003673},
doi = {10.1371/journal.pbio.3003673},
pmid = {41774708},
issn = {1545-7885},
abstract = {Increasing bacterial resistance to colistin, a vital last-resort antibiotic, is an urgent challenge. Previous studies have shown that Mg2+ depletion enables Pseudomonas aeruginosa to become resistant to colistin. Here, we show that magnesium sequestration by Candida albicans also enables P. aeruginosa to evolve a nearly hundredfold higher level of colistin resistance through genetic changes in lipid A biosynthesis-modification pathways and a putative magnesium transporter. These mutations synergize with the Mg2+-sensing PhoPQ two-component signaling system to remodel lipid A structures of the bacterial outer membrane in previously uncharacterized ways. One predominant mutational pathway involves 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 colistin binding to the bacterial membrane underlies resistance. Our findings reveal that Mg2+ scarcity triggers novel evolutionary trajectories, leading to extremely high colistin resistance in P. aeruginosa.},
}

@article {pmid41774517,
year = {2026},
author = {Crombie, JL and Ahmed, S and Frigault, MJ and Hunter, BD and Palomba, ML and Mirza, AS and Lunning, MA and Egini, O and Odstrcil Bobillo, MS and Kallam, A and Kambhampati Thiruvengadam, S and Lee, D and Dahiya, S and Hamadani, M and Herrera, AF and Lee, CJ and Patel, K and Patel, SS and Reagan, PM and Shadman, M and Bernasconi, D and Kim, S and Liu, FF and Roy, D and Pasquini, MC and Isufi, I},
title = {Real-world outcomes for lisocabtagene maraleucel in patients with relapsed or refractory large B-cell lymphoma.},
journal = {Blood},
volume = {},
number = {},
pages = {},
doi = {10.1182/blood.2025031733},
pmid = {41774517},
issn = {1528-0020},
abstract = {This study assessed real-world effectiveness and safety of lisocabtagene maraleucel (liso-cel) in patients with relapsed/refractory (R/R) large B-cell lymphoma (LBCL), including those with high-risk disease, secondary central nervous system (sCNS) involvement, comorbidities, and poor fitness, using data in the Center for International Blood and Marrow Transplant Research Registry from 5 Feb 2021 to 4 Feb 2025. Eligible patients (N=1116) received liso-cel and had ≥1 effectiveness and safety assessment after infusion, including 195 in the second-line setting, 71 with sCNS, and 257 with transformed LBCL. Median age was 71.1 years (range, 21.5‒91.2), with 72.3% ≥65 years. Within the overall population, 6.6% had Eastern Cooperative Oncology Group performance status of ≥2, 53.4% had ≥1 comorbidity, and median number of prior lines of therapy was 3 (range, 1‒16). Median study follow-up was 12.6 months (95% confidence interval [CI], 12.5‒12.8). Among effectiveness-evaluable patients (n=1109), objective response rate was 81.2% and complete response rate was 71.3%. Duration of response, progression-free survival, and overall survival rates (95% CI) at 12 months were 60.2% (56.4‒63.9), 51.2% (48.0‒54.4), and 67.6% (64.5‒70.6), respectively. Cytokine release syndrome was reported in 51.0% of patients, with grade ≥3 events in 2.5%. Immune effector cell-associated neurotoxicity syndrome was reported in 26.6% of patients, with grade ≥3 events in 9.2%. The 12-month nonrelapse mortality rate was 6.1% (95% CI, 4.6‒7.8). These real-world data reinforce the effectiveness and safety of liso-cel in this broad population of patients with R/R LBCL, including younger patients and those with high-risk disease features.},
}

@article {pmid41774512,
year = {2026},
author = {Becilli, M and Merli, P and Algeri, M and Del Bufalo, F and Pagliara, D and Bertaina, V and Agrati, C and Rosignoli, C and Cefalo, MG and Boccieri, E and Di Cecca, S and Iaffaldano, L and Lee, Y and De Angelis, B and Meshinchi, S and Quintarelli, C and Campana, D and Locatelli, F},
title = {Anti-CD7 fratricide-resistant chimeric antigen receptor T cells for relapsed/refractory acute myeloid leukemia.},
journal = {Blood},
volume = {},
number = {},
pages = {},
doi = {10.1182/blood.2025032299},
pmid = {41774512},
issn = {1528-0020},
abstract = {Autologous second-generation CD7-directed CAR T-cells, expressing an anti-CD7 protein expression blocker to prevent self-killing fratricide, were infused in three pediatric/young adult patients with relapsed/refractory CD7+ acute myeloid leukemia resulting in measurable residual disease negativity. The safety profile was favorable.},
}

@article {pmid41774321,
year = {2026},
author = {Chrostek, MR and Robinson, J and Krishnan, R and Yu, EY and Nordquist, LT and Vandross, AL and Salkeni, MA and Schehr, J and Mannino, M and Hintz, A and Caceres, J and Vatani, M and Emamekhoo, H and Nelson, P and Markey, C and Coates, E and Breitmeyer, J and Fong, L and De Bono, JS and Lang, JM and Zhao, SG},
title = {Phase I multi-center clinical and biomarker study of the dual-action androgen receptor inhibitor ONCT-534.},
journal = {Investigational new drugs},
volume = {},
number = {},
pages = {},
pmid = {41774321},
issn = {1573-0646},
support = {T32GM140935/GF/NIH HHS/United States ; P50CA269011/GF/NIH HHS/United States ; DP2 OD030734/GF/NIH HHS/United States ; },
abstract = {ONCT-534 is a dual-action androgen receptor inhibitor (DAARI) that combines AR antagonism and degradation via N-terminal domain binding, additionally targeting AR splice variants. In this study patients received ONCT-534 daily ranging from 40 to 1200 mg. The primary objectives were safety and dose-limiting toxicities (DLTs). Additional objectives included antitumor activity and AR signaling biomarkers. Adverse events (AEs) were assessed within the first 28 days for DLTs. Clinical activity was evaluated by PSA and radiographic progression per PCWG3 and RECIST v1.1. The trial was stopped early and not all patients were evaluated per protocol. Twenty-one patients received ONCT-534 across six doses. The most common AEs were anemia, back pain, and fatigue. While no DLTs were observed within 28 days, Grade 3/4 AEs occurred later in 9 patients (anemia most frequently). One patient discontinued due to treatment-related AE. No radiographic or PSA-based responses were observed; however, three patients showed PSA declines at week 4, with one achieving a PSA50 at time of study closure. Of 10 patients with baseline AR protein data, the median change was - 40.59% in AR protein levels at week 4. In the 300 mg cohort, 3 patients showed concordant decreases in AR protein and AR gene expression. Here, PSA levels correlated positively with AR target gene and AR gene expression. ONCT-534 had acceptable safety and demonstrated biological activity through AR protein degradation and AR signaling suppression in mCRPC patients. Although clinical responses weren't observed, these findings provide proof-of-concept for examining AR protein changes in patients receiving DAARIs.},
}

@article {pmid41771133,
year = {2026},
author = {Tosteson, ANA and Stout, NK and Su, YR and van Ravesteyn, NT and Lowry, KP and Abraham, L and Alagoz, O and DiFlorio-Alexander, R and de Koning, HJ and Hampton, JM and Henderson, L and Mandelblatt, JS and Onega, T and Schechter, CB and Sprague, BL and Stein, S and Trentham-Dietz, A and Miglioretti, DL and Kerlikowske, K and Lee, CI},
title = {Outcomes of Density-Targeted Supplemental Breast Magnetic Resonance Imaging Screening by Breast Cancer Risk: Long-Term Health and Economic Considerations.},
journal = {Annals of internal medicine},
volume = {},
number = {},
pages = {},
doi = {10.7326/ANNALS-25-00792},
pmid = {41771133},
issn = {1539-3704},
abstract = {BACKGROUND: Federally mandated breast density notifications motivate consideration of supplemental breast magnetic resonance imaging (MRI).

OBJECTIVE: To evaluate supplemental breast MRI strategies.

DESIGN: Simulation of women at average to 4 times higher-than-average relative risk (RR) for breast cancer incidence undergoing screening digital breast tomosynthesis (DBT) with or without supplemental MRI.

DATA SOURCES: Breast Cancer Surveillance Consortium and literature.

TARGET POPULATION: Women aged 40 years or older.

TIME HORIZON: Lifetime.

PERSPECTIVE: U.S. federal payer.

INTERVENTION: Screening with DBT with or without breast density-targeted MRI by starting age (40, 45, or 50 years) and interval (annual or biennial).

OUTCOME MEASURES: Breast cancer deaths averted, false-positive biopsy recommendations, harm-benefit ratios, and incremental cost-effectiveness ratios (ICERs).

RESULTS OF BASE-CASE ANALYSIS: Across all starting ages and intervals, DBT averted 7.4 to 10.5 breast cancer deaths per 1000 average-risk women screened and 23.2 to 33.6 per 1000 women with 4 times higher-than-average risk. Across all RR levels, DBT with supplemental MRI for women with extremely dense breasts (DBT+MRId) averted 0.1 to 0.8 additional breast cancer deaths and resulted in 22 to 186 additional false-positive biopsy recommendations. False-positive biopsies per breast cancer death averted for biennial DBT+MRId for women with 2 times higher-than-average risk were similar to those associated with DBT in average-risk women. For all risk groups, biennial DBT+MRId starting at age 50 years was more effective but less cost-effective than DBT starting at age 45 years.

The ICERs were sensitive to cancer risk, MRI costs, and false-positive biopsy rates.

LIMITATION: Subgroups considered risk and breast density only.

CONCLUSION: Supplemental MRI for women aged 40 years or older with extremely dense breasts and higher-than-average risk (RR ≥2.0) had harm-benefit ratios similar to biennial DBT alone and could be cost-effective if MRI costs and false-positive biopsy rates are reduced.

PRIMARY FUNDING SOURCE: National Cancer Institute.},
}

@article {pmid41771028,
year = {2026},
author = {Kamat, AM and Hensley, PJ and Maiorano, BA and Li, R and Psutka, SP and Mouw, KW and Horowitz, A and Gupta, S and Necchi, A},
title = {Bacillus Calmette-Guérin (BCG) and Beyond: Is Systemic Immunotherapy for BCG-Naïve Non-Muscle-Invasive Bladder Cancer Progress or Overreach?.},
journal = {Journal of clinical oncology : official journal of the American Society of Clinical Oncology},
volume = {},
number = {},
pages = {JCO2502670},
doi = {10.1200/JCO-25-02670},
pmid = {41771028},
issn = {1527-7755},
}

@article {pmid41770790,
year = {2026},
author = {Minnie, S and Ho, K and Boiko, JR and Adams, RC and Ensbey, KS and Nemychenkov, NS and Legg, SR and Schmidt, CR and Comstock, ML and Lyons, J and Sekiguchi, T and Koyama, M and Spencer, A and Green, DJ and Hill, GR},
title = {CSF-1R inhibition and lenalidomide synergize to promote myeloma control after autologous stem cell transplantation.},
journal = {Blood},
volume = {},
number = {},
pages = {},
doi = {10.1182/blood.2025030207},
pmid = {41770790},
issn = {1528-0020},
abstract = {Autologous stem cell transplantation (ASCT) with maintenance lenalidomide remains the mainstay of consolidation therapy for eligible multiple myeloma (MM) patients but preventing disease relapse remains a critical unmet need. Here we investigated whether immunosuppressive myeloid populations in bone marrow (BM) correlated with ASCT outcomes. We identified a subset of CD64+CD169+CD163+ macrophages that expressed CSF-1R, PD-L1, and CD155, and were expanded in patients who relapsed post-ASCT. Using a preclinical ASCT model with suboptimal endogenous anti-myeloma activity, we demonstrated that while neither CSF-1R inhibition nor lenalidomide monotherapy significantly improved outcomes, their combination synergistically attenuated disease progression and prolonged survival. Single-cell RNA sequencing revealed that lenalidomide expanded NK-like CD8+ T-cells but paradoxically also increased the frequency of Csf1r+ macrophages. Cell-cell communication analyses identified Csf1r+ macrophages as suppressors of these NK-like and effector-like exhausted (Tphex) CD8 T-cell populations through CD94/NKG2A and PD-L1/PD-1, respectively. CSF-1R blockade depleted these immunosuppressive macrophages, which correlated with decreased expression of inhibitory receptors and enhanced expression of activation markers in Tphex. Given the FDA approval of axatilimab for chronic GVHD, combining CSF-1R blockade with lenalidomide maintenance represents a readily testable strategy to improve progression-free survival after ASCT.},
}

@article {pmid41770651,
year = {2026},
author = {Abrams, HR and Loggers, ET and Wagner, MJ and Kim, EY and Schaub, SK and Roberts, JL and Brinkmann, E and Thompson, M and Moore, R and Johnson, R and Baroudi, M and Morin, N and Gooley, T and Cranmer, LD},
title = {A Phase 1 Study of Neoadjuvant Cabozantinib in Combination With Radiation Therapy for Sarcomas of the Extremities.},
journal = {American journal of clinical oncology},
volume = {},
number = {},
pages = {},
pmid = {41770651},
issn = {1537-453X},
abstract = {OBJECTIVES: Cabozantinib demonstrates activity in multiple soft tissue sarcoma (STS) subtypes, but use with concurrent radiation therapy (RT) has been limited by concern for risk of fistula or perforation. This phase 1 trial evaluated the safety of concurrent cabozantinib and RT as neoadjuvant therapy in patients with extremity STS.

METHODS: Adults with newly diagnosed localized extremity STS planned for neoadjuvant RT and surgical resection were eligible. Participants received radiation with 5000 to 5040 cGy with conventional fractionation and cabozantinib 40 mg or 60 mg daily. Patients were observed for dose-limiting toxicity (DLT) up to 28 days after completion of concurrent cabozantinib/RT. The primary objective was to identify a recommended phase 2 dose (RP2D) of cabozantinib for combination with RT, and secondary objectives included estimating rates of treatment-related adverse event (TRAE), margin positivity, and objective response.

RESULTS: Six patients were enrolled with histologic subtypes of undifferentiated pleomorphic sarcoma, myxofibrosarcoma, leiomyosarcoma, and myxoid liposarcoma. No DLT due to the combination of cabozantinib and radiation was observed, but 3/6 (50%) patients required dose-reduction due to TRAE of cabozantinib alone. No grade ≥3 toxicities were attributed to RT. The RP2D was cabozantinib 60 mg. Six (100%) patients demonstrated stable disease at 12 weeks, and 5 (83%) underwent R0 resection. Two (33%) patients experienced metastatic relapse, and 1 (17%) died without relapse; 3 (50%) patients survived without relapse by last contact. No local recurrences occurred.

CONCLUSIONS: In this phase 1 trial, concurrent cabozantinib/RT was feasible and demonstrated an acceptable safety profile for patients with extremity STS.},
}

@article {pmid41767406,
year = {2026},
author = {Haddox, HK and Abdel Aziz, O and Galloway, JG and Kent, J and Cooper, CR and Jennings-Shaffer, C and Dumm, W and Temple, SD and Bloom, JD and Matsen, FA},
title = {Clonal interference and changing selective pressures shape the escape of SARS-CoV-2 from hundreds of antibodies.},
journal = {Virus evolution},
volume = {12},
number = {1},
pages = {veaf104},
pmid = {41767406},
issn = {2057-1577},
abstract = {SARS-CoV-2 has evolved increased resistance to human polyclonal antibody responses. But, how it escaped individual monoclonal antibodies from these responses has not been thoroughly explored. Cao et al. used deep mutational scanning to identify mutations that allow SARS-CoV-2 to escape individual antibodies, doing so for hundreds of different antibodies. Here, we use these data to reconstruct how the virus escaped each antibody in nature. For each antibody, we predict how levels of escape changed in the global SARS-CoV-2 population over time. For many antibodies, these levels dramatically fluctuated due to escape mutations being displaced by clade-turnover events. We validate predicted patterns using pseudovirus neutralization data. Fitness effects estimated from natural sequences suggest that mutations are displaced due to clonal interference between clades and that the order in which mutations arose is shaped by changing selective pressures. Overall, this work suggests that SARS-CoV-2 evaded polyclonal responses via complex evolutionary dynamics.},
}

@article {pmid41726945,
year = {2026},
author = {Patton, RD and Netzley, A and Persse, TW and Nair, A and Galipeau, PC and Coleman, IM and Itagi, P and Chandra, P and Adil, M and Vashisth, M and Sayar, E and Hiatt, JB and Dumpit, R and Kollath, L and Demirci, RA and Ghodsi, A and Lam, HM and Morrissey, C and Iravani, A and Chen, DL and Hsieh, AC and MacPherson, D and Haffner, MC and Nelson, PS and Ha, G},
title = {Deep learning-based non-invasive profiling of tumor transcriptomes from cell-free DNA for precision oncology.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {41726945},
issn = {2692-8205},
abstract = {Circulating tumor DNA (ctDNA) profiling from liquid biopsies is increasingly adopted as a minimally invasive solution for clinical cancer diagnostic applications. Current methods for inferring gene expression from ctDNA require specialized assays or ultra-deep, targeted sequencing, which preclude transcriptome-wide profiling at single-gene resolution. Herein we jointly introduce Triton, a tool for comprehensive fragmentomic and nucleosome profiling of cell-free DNA (cfDNA), and Proteus, a multi-modal deep learning framework for predicting single gene expression, using standard depth (~30-120x) whole genome sequencing of cfDNA. By synthesizing fragmentation and inferred nucleosome positioning patterns in the promoter and gene body from Triton, Proteus reproduced expression profiles using pure ctDNA from patient-derived xenografts (PDX) with an accuracy similar to RNA-Seq technical replicates. Applying Proteus to cfDNA from four patient cohorts with matched tumor RNA-Seq, we show that the model accurately predicted the expression of specific prognostic and phenotype markers and therapeutic targets. As an analog to RNA-Seq, we further confirmed the immediate applicability of Proteus to existing tools through accurate prediction of gene pathway enrichment scores. Our results demonstrate the potential clinical utility of Triton and Proteus as non-invasive tools for precision oncology applications such as cancer monitoring and therapeutic guidance.},
}

@article {pmid41763494,
year = {2026},
author = {Lee, S and Shu, X and Derkach, A and Reiner, AS and Liang, X and Woods, M and Concannon, P and Lynch, CF and Malone, KE and Knight, JA and John, EM and Deasy, JO and Bernstein, JL and Oh, JH},
title = {Integrating genomic and non-genomic data to stratify the risk of contralateral breast cancer after radiotherapy.},
journal = {International journal of radiation oncology, biology, physics},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.ijrobp.2026.02.237},
pmid = {41763494},
issn = {1879-355X},
abstract = {PURPOSE: Women treated with radiation therapy (RT) for breast cancer have an increased risk of developing radiation-associated contralateral breast cancer (CBC). Predicting CBC events is challenging due to the complex interplay of genomic, treatment, personal, and clinical factors. This study investigated computational methods that integrate genome-wide single nucleotide polymorphisms (SNPs) and non-genomic data to develop a risk stratification model for developing CBC in women treated with RT for their first primary breast cancer.

METHODS: This study used a subset of the population-based WECARE Study that included 633 CBC cases and 1,253 individually matched unilateral breast cancer (UBC) controls who were treated with RT and had SNP data available from a genome-wide association study (GWAS). The study population was split into training, validation, and test sets for rigorous modeling and validation. Three data integration methods were compared in terms of their ability to stratify CBC risk: 1) Naive integration, 2) Sequential integration, and 3) Sequential iterative integration. A biological analysis of the final model was performed using gene set enrichment analysis (GSEA) and protein-protein interaction (PPI) analysis with gene annotation information informed by the model.

RESULTS: The best-performing integration method was the sequential iterative integration equipped with the mixed effect random forest (MERF) algorithm. This approach achieved an area under the curve of 0.64 to stratify CBC risk in the test set, representing moderate predictive power. Calibration analysis showed good agreement between the lowest and highest risk bins stratified using sorted predicted values in the test set, resulting in an odds ratio of 3.27 for both predicted and observed CBC occurrence. GSEA and PPI analysis revealed that genes with high importance scores were associated with pathways relevant to lipid and fatty acid metabolism as well as breast cancer sensitivity to tamoxifen.

CONCLUSION: The MERF approach demonstrated the potential for integrating high-dimensional genomic and low-dimensional non-genomic data to stratify CBC risk.},
}

@article {pmid41763313,
year = {2026},
author = {Kirtane, K and Kalos, M and Billups, R and Chapuis, AG and Coutinho, V and Feldman, SA and Gastman, B and Haanen, J and Hanley, PJ and Hegde, P and Hopewell, EL and Levine, BL and Locke, FL and Maus, MV and Nair, NV and Nathenson, M and Perales, MA and Rivière, I and Sikder, D and Tendler, C and Yee, C and Luke, J and O'Cearbhaill, RE},
title = {Advancing Cell Therapies for Solid Tumors: A Pathway to Overcome Biological, Operational, and Regulatory Hurdles.},
journal = {Transplantation and cellular therapy},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jtct.2026.02.054},
pmid = {41763313},
issn = {2666-6367},
abstract = {Cellular therapies have revolutionized the treatment of hematologic malignancies and are now emerging as potentially promising interventions for solid tumors. While considerable learnings can be leveraged from hematologic applications to inform the development of cell therapies in solid tumors, a number of biological and operational challenges-such as target-antigen heterogeneity; off-tumor target-mediated toxicity; immunosuppressive microenvironment; limited trafficking and persistence; tissue accessibility; and significantly larger patient populations-necessitate innovative clinical, manufacturing, regulatory, and operational strategies to deliver effective cell therapies for solid tumors. This white paper, informed by the 2025 Summit on Advancing Cell Therapy for Solid Tumors-co-sponsored by American Society for Transplantation and Cellular Therapy (ASTCT) and Society for Immunotherapy of Cancer (SITC)-proposes a framework for cellular therapy development in solid tumors, with an emphasis on logistical, operational, and regulatory considerations unique to this setting. The paper lays out an innovative, collaborative operational model to leverage collective experience and knowledge; emphasize standardization; invest in both prospective and retrospective banking of materials; engage in regulatory data-driven recalibration; engage payers before therapy begins; and establish regional manufacturing hubs and tailored accreditation pathways to support scalability and quality assurance. Operational innovations that can streamline access include hub-and-spoke clinical networks-where a central specialized facility is connected to smaller, more accessible locations-as well as early patient referrals. To safely implement new therapies, it is essential for providers to undergo enhanced training to manage cellular therapy-specific and delayed toxicities. Regulatory recalibrations-including streamlined evaluation of long-term follow-up requirements and proactive payer engagement for comprehensive reimbursement-are equally vital. Finally, cell therapy experts must lead cross-disciplinary education to ensure equitable and safe access as indications for cellular therapy expand across solid-tumor types, autoimmune diseases, and other disease types. Collaborative efforts across clinical, operational, regulatory, and policy initiatives are vital in order to unlock the full potential of cellular therapy for diverse patient populations.},
}

@article {pmid41763306,
year = {2026},
author = {Rosenthal, KJ and Felix-Sanchez, P and Forbush, K and Rhoads, N and Kang, M and Vicente, JJ and Smith, FD and Wordeman, L and Ong, SE and Cheung, KJ and Scott, JD},
title = {AKAP2 is required for assembly of cytoskeletal signaling complexes that promote growth and metastasis of triple-negative breast cancer.},
journal = {The Journal of biological chemistry},
volume = {},
number = {},
pages = {111329},
doi = {10.1016/j.jbc.2026.111329},
pmid = {41763306},
issn = {1083-351X},
abstract = {A Kinase Anchoring Proteins (AKAPs) that coordinate spatiotemporal signaling are increasingly implicated in cancer. Elevated AKAP2 protein correlates with an invasive phenotype in triple-negative breast cancer cell lines. A combination of biochemical, cellular, and omics approaches show that AKAP2 cytoskeleton and focal adhesion associated scaffolds contribute to the progression of basal-like triple-negative breast cancer. Proximity proteomics identifies AKAP2 as an element of focal adhesions in MDA-MB-231 cells. Molecular and immunofluorescent microscopy studies demonstrate that AKAP2 indirectly constrains focal adhesion kinase (FAK). Gene silencing of AKAP2 not only decreases FAK levels but also attenuates the phosphorylation of the cell motility adapter protein paxillin on Tyr118. Cell-derived xenograft studies in mice establish that AKAP2 is required for triple-negative breast cancer growth and metastasis, phenotypes that are linked to FAK action. These findings discover a new role for focal adhesion-associated AKAP2 in triple-negative breast cancer pathology.},
}

@article {pmid41761831,
year = {2026},
author = {Boeckh, M and Corey, L},
title = {Cytomegalovirus and Aging-How Can the Field Move Forward?.},
journal = {The Journal of infectious diseases},
volume = {},
number = {},
pages = {},
doi = {10.1093/infdis/jiag099},
pmid = {41761831},
issn = {1537-6613},
}

@article {pmid41760865,
year = {2026},
author = {Mandrik, O and Thomas, C and Bessey, A and Brennan, A and Carvalho, AL and Castilla-Rodríguez, I and Doroshenko, O and Hill, H and Kunst, N and Nagy, B and Payne, K and Pollard, D and Ramsey, SD and Roitberg, F and Shinkins, B and Smitht, RA and Howard, T and Whyte, S},
title = {Ten Recommendations for Modelling Cost Effectiveness of Screening: Perspectives of an International Stakeholder Group.},
journal = {PharmacoEconomics},
volume = {},
number = {},
pages = {},
pmid = {41760865},
issn = {1179-2027},
support = {189350//University of Sheffield/ ; },
abstract = {Modelling the cost effectiveness of screening interventions presents unique challenges. These relate to a lack of knowledge about underlying health states and disease progression in the absence of screening, added costs arising from incidental findings, screening recall and follow-up diagnostics, imperfect uptake, potential harms to otherwise healthy people, and impacts on resource capacity and equity. No specific but generalisable advice currently exists to help guide health economic modellers working in this area. There is a need for tailored recommendations beyond the widely used, health economic modelling frameworks. We aimed to develop a set of recommendations for modelling the cost effectiveness of screening programmes. In our iterative process, we first drafted a conceptual document outlining key issues requiring recommendations. This framework was then expanded based on additional themes identified through a survey of screening modelling experts. Next, the draft recommendations were shared with a broader international expert group, which included modellers, health economists and policy specialists. Finally, the core concepts were refined and agreed upon during a virtual stakeholder meeting. A set of ten recommendations and a checklist are presented. The document provides guidance on critical methodological requirements for modelling screening interventions. These guidelines are intended to help health economic modellers and screening policy makers working to evaluate screening interventions across a wide range of diseases and jurisdictions with clarity, rigour and consistency.},
}

@article {pmid41760378,
year = {2026},
author = {Cook, AJ and Wellman, RD and Marsh, T and Tiwari, RC and Nguyen, MD and Russek-Cohen, E and Peng, Y and Nelson, JC},
title = {Estimating Risk Differences Using Large Healthcare Data Networks for Medical Product Post-Market Safety Outcomes in a Distributed Data Setting and Allowing for Active Post-Market Surveillance.},
journal = {Statistics in medicine},
volume = {45},
number = {6-7},
pages = {e70440},
doi = {10.1002/sim.70440},
pmid = {41760378},
issn = {1097-0258},
support = {HHSF223200910006I/FD/FDA HHS/United States ; 75D30122D15428/CC/CDC HHS/United States ; },
abstract = {Risk differences allow decision makers to easily estimate the excess safety risk associated with a medical product relative to the potential benefits. However, in post-market observational surveillance studies that actively monitor (e.g., sequentially over time) for safety risk of new medical products, available methods target a relative measure (e.g., odds ratio and relative risk), which can be especially unstable in the rare event setting. These studies are typically conducted within distributed healthcare networks (e.g., Food and Drug Administration [FDA] Sentinel and Centers for Disease Control [CDC] Vaccine Safety Datalink) with patient-level data protected behind firewalls, but sharing of aggregate, deidentified data for centralized analyses. We propose an inverse probability of treatment weighting (IPTW) method that uses site-specific propensity scores to estimate site-specific risk differences that are combined to create an overall stratified risk difference estimate. This method is tailored to the rare event setting and requires minimal data sharing. The stratified IPTW approach is then extended to the active post-market surveillance setting by incorporating group sequential monitoring boundaries using a novel permutation approach. A simulation study is conducted to evaluate the performance of the new methods relative to two centralized analysis approaches, and the methods are applied to a safety surveillance study comparing the risk of febrile seizure between two vaccines using FDA Sentinel Data from three healthcare organizations.},
}

@article {pmid41758981,
year = {2026},
author = {Gill, H and Palandri, F and Ross, DM and Göthert, JR and Cochrane, T and Larsen, SR and Halpern, AB and Shortt, J and Rossetti, JM and Liang, J and Marchetti, M and Wilson, AJ and Innes, AJ and Hanna, M and Vianelli, N and Stevenson, WS and Vannucchi, AM and Kleppe, M and Flynn, J and Natsoulis, G and Harrison, CN and Rienhoff, HY},
title = {Phase 2 study of the lysine-specific demethylase 1 (LSD1) inhibitor bomedemstat for essential thrombocythemia.},
journal = {Blood advances},
volume = {},
number = {},
pages = {},
doi = {10.1182/bloodadvances.2025017575},
pmid = {41758981},
issn = {2473-9537},
abstract = {Novel treatments that can improve disease course of essential thrombocythemia (ET) are needed. In this phase 2 trial, participants with ET who required cytoreduction and had inadequate response to or were intolerant of ≥1 standard therapy received bomedemstat at a starting dose of 0.6 mg/kg per day, titrated to achieve a target platelet count (200-400×109/L). Primary end points were safety and response, defined as a platelet count ≤400×109/L without new thromboembolic events. Seventy-three participants received bomedemstat. At 24 weeks, 49 of 64 evaluable participants (77%) had a response. Durable reductions in platelet count (≤400×109/L for ≥12 weeks) were observed in 52 of 72 participants (72%). Durable reduction in white blood cell count (<10×109/L for ≥12 weeks) was observed in 61 of 72 participants (85%); of 10 participants with elevated white blood cell count at baseline, 9 had normal white blood cell count (<10×109/L) at week 24. Hemoglobin levels remained stable. After 24 weeks of treatment, a decrease in variant allele frequency of CALR, JAK2, or MPL was observed in 39 of 46 (85%) evaluable participants. By week 24, 2 of 73 participants (3%) had experienced ≥1 thrombotic event and 15 of 73 (21%) experienced ≥1 hemorrhagic event. During overall treatment period, grade 3 or 4 adverse events (AEs) occurred in 34 of 73 participants (47%). AEs led to temporary treatment interruption in 29 participants (40%) and permanent discontinuation in 11 (15%). No participants died due to AEs. Bomedemstat had clinically relevant activity and manageable safety in participants with ET. Registration: NCT04254978 (Study of Bomedemstat in Participants With Essential Thrombocythemia [IMG-7289-CTP-201/MK-3543-003]).},
}

@article {pmid41758580,
year = {2026},
author = {Cai, Y and Surapaneni, A and Vasconcelos, AG and Johnson, M and Hsu, L and Sun, W and Kooperberg, C and Yu, B and Yeo, WJ and Auer, PL and Grams, ME and Franceschini, N and Raffield, LM and Reiner, AP},
title = {Alterations of Plasma Metabolites Associated with Sickle Cell Trait.},
journal = {Clinical journal of the American Society of Nephrology : CJASN},
volume = {},
number = {},
pages = {},
doi = {10.2215/CJN.0000001015},
pmid = {41758580},
issn = {1555-905X},
abstract = {BACKGROUND: Sickle cell trait (SCT) is the heterozygous carrier state for sickle cell disease (SCD) and is common among individuals of African ancestry. While SCT is a known risk factor for chronic kidney disease and end-stage kidney disease (ESKD), the mechanisms underlying this phenotypic association have not been fully characterized. We utilized metabolomic profiling to gain insight into the pathobiology of SCT.

METHODS: We used a nontargeted metabolomics approach (Metabolon Global Discovery Panel) to measure baseline plasma levels of 851 metabolites in 986 older Black or African American women with SCT (mean age 61 ± 7 years) compared to 998 age- and race-matched controls without SCT from the prospective Women's Health Initiative (WHI) study. Age-adjusted linear regression was used to assess the association between metabolite levels and SCT. Replication was performed in an independent sample of 1,070 African American men and women (including 70 with SCT) from the Atherosclerosis Risk in Communities (ARIC) study.

RESULTS: In age-adjusted models, 69 metabolites were significantly associated with SCT in WHI after correction for multiple testing. Many of the SCT-associated metabolites are markers of kidney glomerular filtration (eGFR) and/or related to oxidative stress metabolic pathways known to be altered in SCD homozygotes. Of the 64 SCT-associated metabolites available for replication, 25 or 39% were replicated in the ARIC study. Inclusion of SCT-associated metabolites was associated with significantly better risk prediction of incident ESKD in WHI among SCT individuals compared with a baseline model adjusted for age + estimated glomerular filtration rate (eGFR).

CONCLUSIONS: We identified and replicated metabolites associated with SCT, many of which are related to eGFR and/or pathways altered in SCD (e.g., oxidative stress, membrane remodeling). These results suggest that plasma metabolomic profiling may be useful in ESKD risk stratification for individuals with SCT, meriting validation in larger cohorts.},
}

@article {pmid41752282,
year = {2026},
author = {Amissah, CM and Crump, AA and Fu, YH and Khadka, S and Contreras, J and Jones, SMW and Reeve, BB and Villalonga-Olives, E},
title = {Developing an Index to Measure Structural Racism: Methodological Process, Challenges, and Considerations.},
journal = {International journal of environmental research and public health},
volume = {23},
number = {2},
pages = {},
pmid = {41752282},
issn = {1660-4601},
support = {R01MD019029//National Institute of Health/ ; },
abstract = {Access to valid and reliable measures of structural racism is essential for addressing health inequities, yet few validated ecological-level indices exist for assessing structural racism affecting Black and Hispanic populations in the United States. Guided by the National Institute on Minority Health and Health Disparities framework, our interdisciplinary team undertook the development of an ecological-level structural racism index. In the process, we encountered substantive methodological and data-related challenges that warrant explicit documentation. This paper describes the methodological process used to identify and select indicators of structural racism, including a modified Delphi consensus process involving social epidemiologists, health inequality researchers, community members, economic inequality specialists, and psychometricians. We outline a five-step approach for extracting and harmonizing geographic-level data from publicly available sources and discuss key challenges encountered, including limited availability of granular geographic data, insufficient data documentation guidelines, inconsistent reporting frequencies, and difficulties in adapting publicly available datasets for structural racism measurement. Rather than presenting a finalized index, this paper serves as a methodological guide and cautionary account for researchers seeking to develop ecological measures of structural racism, emphasizing the importance of transparency, adaptability, and rigorous data selection in advancing public health equity research.},
}

@article {pmid41749842,
year = {2026},
author = {Chakrabarti, S and Cohen, SA and Tin, A and Dangl, A and Chung, KY and Tejani, MA and Fakih, MG and Chandana, SR and Donahue, CA and George, V and Malla, M and Aushev, VN and George, GV and Ortiz, JB and Herter, WK and Nagarajan, A and Weinberg, BA and Sharma, VR and Botta, GP and Cho, M and Azzi, G and Kasi, A and Dayyani, F and Hanna, DL and Somer, BG and Malhotra, M and Sharma, S and Jurdi, A and Liu, MC and Landmann, RG and Dasari, A},
title = {Utility of Circulating Tumor DNA to Assess Tumor Response in Patients with Locally Advanced Rectal Cancer Undergoing Neoadjuvant Therapy.},
journal = {Cancers},
volume = {18},
number = {4},
pages = {},
pmid = {41749842},
issn = {2072-6694},
abstract = {BACKGROUND: Circulating tumor (ct)DNA is a prognostic biomarker in gastrointestinal malignancies. In rectal cancer, its utility to inform perioperative management and predict recurrence, particularly in patients undergoing non-operative management (NOM), remains unclear. Studies are needed to clarify how post-neoadjuvant therapy (NAT) and post-surgical ctDNA status correlate with clinical outcomes in localized rectal cancer.

METHODS: We retrospectively analyzed ctDNA data from 220 patients with rectal cancer using a personalized tumor-informed assay (Signatera™, Natera, Inc., Austin, TX, USA). Of these, 148 (67.3%) underwent NAT followed by surgery, and 72 (32.7%) underwent NAT followed by NOM. We assessed associations between post-NAT ctDNA status and survival outcomes. In the surgical cohort, we examined associations between post-operative ctDNA status and clinical response, pathological response, survival outcomes, and NAR scores.

RESULTS: In the surgical cohort, ctDNA positivity at the post-operative MRD timepoint was a strong predictor of recurrence, with an 88.3% relapse rate compared to 11.5% in ctDNA-negative patients (p < 0.001). Among the 64 NOM patients with post-NAT ctDNA, 21.9% (14/64) were ctDNA-positive, of whom 100% (14/14) relapsed (92.9% local-only), 13 relapsed by the time of data cut-off, and one relapsed 8 months after the cut-off. Only 10% (5/50) of the ctDNA-negative NOM patients experienced local recurrence (p < 0.0001). ctDNA positivity post-NAT was associated with inferior DFS (p = 0.003).

CONCLUSION: ctDNA was a strong predictor of recurrence in rectal cancer, including in NOM settings. In NOM patients, ctDNA detected local recurrences, highlighting its potential to guide post-NAT surveillance and treatment.},
}

@article {pmid41748788,
year = {2026},
author = {Montano-Campos, JF and Adair, JE and Basu, A and Kyeyune, RB and Bayigga, L and Kityo-Mutuluuza, C and Hansen, R},
title = {Cost-effectiveness of gene therapy for sickle cell disease in Uganda: tailoring high-income evidence to Uganda's context.},
journal = {Gene therapy},
volume = {},
number = {},
pages = {},
pmid = {41748788},
issn = {1476-5462},
support = {P51OD010425//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; U42OD011123//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; R01AI167009//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; R01AI158728//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; INV002613//Bill and Melinda Gates Foundation (Bill & Melinda Gates Foundation)/ ; INV03398//Bill and Melinda Gates Foundation (Bill & Melinda Gates Foundation)/ ; },
abstract = {Blood stem cell gene therapy to treat hemoglobinopathies is beginning to transform health for small numbers of patients in the U.S. and Europe, where these conditions qualify as rare diseases. Yet hemoglobinopathies are common globally, disproportionately affecting low- and middle-income countries (LMICs), creating an ethical imperative to ensure access where disease burden is greatest. Gene therapy could have blockbuster drug potential if distributable to these regions, but cost is a major barrier. Cost-effectiveness analysis (CEA) models are seldom adapted to low-income settings, where limited data and resources constrain efforts to contextualize high-income evidence. Here, we present a novel framework to evaluate high-income country authorized gene therapies in LMIC contexts. Uganda, where sickle cell disease (SCD) imposes a major burden and no curative therapies are available, is the test case. We evaluate cost-effectiveness of gene therapy for adolescents and adults with SCD in Uganda, adapting U.S. evidence to local economic conditions. Using a three-state Markov model to estimate lifetime costs of standard-of-care in Uganda, two U.S.-based CEA models were adapted using scaling factors and applied to two authorized gene therapies for SCD, Lyfgenia™ (lovo-cel) and Casgevy® (exa-cel), assuming biologically consistent efficacy across populations. Incremental cost-effectiveness ratios (ICERs) were calculated from healthcare and societal perspectives, with internationally accepted gross domestic product-based thresholds. This study demonstrates that Casgevy could be cost-effective in Uganda at a scaled cost when societal benefits are considered. This framework enables CEAs for emerging therapies where local clinical trial data are limited, supporting local decision-makers, global funders, and manufacturers in advancing equitable access to transformative therapies in LMICs.},
}

@article {pmid41748695,
year = {2026},
author = {Jutzi, JS and Crosse, E and Kim, CJ and van Gasteren, B and Laurore, C and Rolles, B and Kramer, F and Tishena, A and Rocha, AV and Wazir, M and Weeks, LD and How, J and Stahl, M and Luskin, MR and Lindsley, RC and Pozdnyakova, O and Rai, S and Graubert, TA and Bradley, RK and Mullally, A and Marneth, AE},
title = {Mutant SRSF2-associated impaired erythropoiesis is defined by increased mTORC1 signaling due to FYN missplicing.},
journal = {Leukemia},
volume = {},
number = {},
pages = {},
pmid = {41748695},
issn = {1476-5551},
support = {W81XWH-20-1-0904//U.S. Department of Defense (United States Department of Defense)/ ; W81XWH2110909//U.S. Department of Defense (United States Department of Defense)/ ; Hypatia//Radboud Universitair Medisch Centrum (Radboudumc)/ ; 70114570//Deutsche Krebshilfe (German Cancer Aid)/ ; R01HL131835//U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)/ ; I15-0026//Starr Foundation/ ; },
abstract = {Somatic mutations in RNA splicing regulators, including the serine/arginine-rich protein SRSF2, are frequently observed in myeloid malignancies. Using mouse models and primary human samples, we investigated the impact of SRSF2 mutations on erythropoiesis. We found reduced erythropoiesis in Srsf2[P95H] versus wild-type mice upon stress-induced erythropoiesis and identified that SRSF2 mutations correlate with reduced hemoglobin in JAK2-mutant patients with myeloproliferative neoplasms (MPN). Consistent with this, Jak2[V617F]-Srsf2[P95H] versus Jak2[V617F] mice displayed reduced red blood cell counts and erythroid precursor frequencies. RNA-sequencing on erythroid precursors showed reduced expression of heme metabolism and mitotic spindle-related genes, and increased expression of mTORC1 signaling in Srsf2[P95H] versus wild-type cells. RNA splicing analyses on the same cells and on human patient samples identified aberrant FYN splicing in SRSF2[mut] cells, with increased aberrant FYNB over normal FYNT transcripts. FYNB, but not FYNT, expression resulted in reduced erythroid differentiation and increased phosphorylation of mTORC1 downstream target S6. Additionally, increased S6 phosphorylation was confirmed in primary Srsf2[P95H] erythroid cells. mTORC1 pathway inhibition using rapamycin normalized FYNB- and Srsf2[P95H]-induced impaired erythropoiesis and significantly increased erythroid colony formation of SRSF2-mutant myelodysplastic neoplasm (MDS) bone marrow cells. Our data reveal targetable molecular mechanisms of impaired erythropoiesis in SRSF2-mutant cells.},
}

@article {pmid41747891,
year = {2026},
author = {Booth, A and Hillman, S and Laumann, K and Zhao, YQ and LeBlanc, M and Chansky, K and Giri, S and Dill, J and Johnson, J and Kelley, K and Martin, L and Osarogiagbon, RU and Morris, MJ and Chiang, AC and Kozono, DE and Blanke, CD and Galanis, E and Gray, JE and Stinchcombe, TE and Aljumaily, R and Morgensztern, D and Mandrekar, SJ},
title = {PROSPECT-LUNG: A National Clinical Trials Network Trial Advancing Pragmatic Innovation in Cancer Clinical Trials.},
journal = {Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer},
volume = {},
number = {},
pages = {103650},
doi = {10.1016/j.jtho.2026.103650},
pmid = {41747891},
issn = {1556-1380},
abstract = {PURPOSE: Clinical trial designs marked by extensive data collection, restrictive eligibility, and lengthy protocols create inefficiencies, increase costs, and hinder accrual. These are further compounded by staffing shortages and operational burdens. By incorporating pragmatic features including simplified eligibility criteria, streamlined protocol, and data collection, the PROSPECT-Lung trial paves the way forward as a model for enhancing clinical trial efficiency and feasibility, while maintaining scientific rigor.

PATIENTS AND METHODS: PROSPECT-Lung (CTIU2317-A082304-S2402) is a pragmatic, phase III, open-label, randomized trial comparing 3-year real-world event-free survival and overall survival using approved perioperative and adjuvant immunotherapy-based treatment strategies in patients with resectable non-small cell lung cancer. Protocol length and data collection elements were compared with Alliance A081801, Integration of Immunotherapy into Adjuvant Therapy for Resected NSCLC: ALCHEMIST CHEMO-IO (ClinicalTrials.gov Identifier: NCT04267848), a phase III trial in the same disease setting, to quantify streamlining efforts.

RESULTS: Relative to A081801, PROSPECT-Lung achieved major reductions in trial complexity. Protocol length decreased from 88 to 30 pages (65%), and data fields per patient were reduced from 2523 to 438 (82.6%), driven by streamlined summary versus cycle-by-cycle data collection. These efficiencies translate to estimated site workload reductions from 210 hours per patient in A081801 to 36.5 hours in PROSPECT-Lung. At full accrual, this equates to more than 190,000 hours saved in chart review, data entry, documentation, and quality control.

CONCLUSION: By broadening eligibility and streamlining logistics, PROSPECT-Lung reduces burden for patients, investigators, and sites while preserving scientific integrity. This pragmatic approach, when appropriate and possible, provides a replicable model for future cancer trials, promoting efficiency, accessibility, and real-world relevance.},
}

@article {pmid41747248,
year = {2026},
author = {Kelly, MM and Dempsey, A and Ameral, V and Petrakis, BA and Reilly, ED and Quigley, K and Bricker, JB and Heffner, JL},
title = {Web-Based Acceptance and Commitment Therapy Tobacco Cessation Program for Veterans With Mental Health Disorders: Adaptation and Usability Testing.},
journal = {JMIR formative research},
volume = {10},
number = {},
pages = {e75394},
doi = {10.2196/75394},
pmid = {41747248},
issn = {2561-326X},
abstract = {BACKGROUND: US veterans with mental health disorders have high rates of smoking and low rates of smoking cessation.

OBJECTIVE: This study aims to focus on an adaptation of a web-based acceptance and commitment therapy (ACT) tobacco cessation intervention (Vet WebQuit) for veterans with mental health disorders who use tobacco and used a qualitative approach to test its usability (n=16).

METHODS: Participants were asked to walk through the site during laboratory-based usability testing and "think aloud" about the features of the intervention. A trained facilitator used semistructured interview questions to assess participants' experiences with Vet WebQuit and obtain feedback on their impressions of the site. Qualitative analyses identified themes regarding participants' experiences with the intervention, usability concerns, and recommendations for improving Vet WebQuit.

RESULTS: Overall, veterans found that the Vet WebQuit layout was simple and easy to navigate and use. Veterans reported that several features of the program were useful, including the quit plan, identification of triggers, content that targets mental health concerns (eg, dealing with anger), information on the health effects of smoking, tools for managing triggers (eg, urge surfing), and involving others in their quit plan. Veterans reported that particular features of the ACT approach for tobacco cessation were appealing to them, including the distinction between internal and external smoking triggers, the inclusion of the serenity prayer, and mindfulness exercises, which they could use as a tool reduce the intensity of cravings. Veterans reported wanting more information on the health aspects of smoking (ie, effects on breathing and lung capacity) as a way to motivate them to quit smoking. In addition, they suggested targeting specific mental health concerns that serve as triggers for smoking, including nightmares, boredom, and social isolation.

CONCLUSIONS: Overall, results from this project identified important elements of ACT digital tobacco cessation interventions for veterans with mental health disorders.},
}

@article {pmid41747197,
year = {2026},
author = {Sharp, J and Strati, P and Bhatta, S and Huang, JJ and Thomas, CJ and Elghawy, O and Reef, D and Gorzewski, AM and Wang, JS and Shouse, G and Reinert, C and Teferra, A and Toro Velez, E and Pelcovits, A and Ollila, TA and Clark, WB and Yazbeck, V and Maakaron, JE and Kamdar, M and Fitzgerald, LA and Danilov, AV and Karmali, R and Grover, NS and Barta, SK and Voorhees, TJ and Chen, AI and Shadman, M and Ahmed, S and Epperla, N},
title = {Real-World Outcomes and Toxicities of CAR-T in Relapsed/Refractory Follicular Lymphoma: A Multicenter Cohort Study.},
journal = {Blood advances},
volume = {},
number = {},
pages = {},
doi = {10.1182/bloodadvances.2025019115},
pmid = {41747197},
issn = {2473-9537},
abstract = {Chimeric antigen receptor T-cell (CAR-T) therapy revolutionized treatment of relapsed/refractory (R/R) follicular lymphoma (FL). Real-world efficacy and toxicity data are needed as clinical trial populations are often not representative. Hence, we conducted a multi-center retrospective study of patients with R/R FL undergoing commercial CAR-T with axicabtagene ciloleucel (axi-cel) or tisagenlecleucel (tisa-cel) between 2021 and 2024. Endpoints included measures of efficacy (overall response rate [ORR], complete response rate [CRR], progression-free survival [PFS], and overall survival [OS]) and toxicity (rates of cytokine release syndrome [CRS] and immune effector cell-associated neurotoxicity syndrome [ICANS]). Among 136 patients, 100 (74%) received axi-cel and 36 (26%) received tisa-cel. Axi-cel patients were younger (median age 60 vs 68 years, p=0.001) and received bendamustine lymphodepletion less often (9% vs 33%, p<0.001). Median follow up was 14.4 months (range 0.8 - 72.0 months). In the unweighted analysis, axi-cel was associated with higher ORR (96% vs 80%, p=0.007), CRR (88% vs 71%, p=0.024), and longer median PFS (30.5 months vs 11.9 months, p=0.021) compared with tisa-cel. Median OS did not differ significantly between the two products (not reached vs 23.6 months, p=0.061). Rates of CRS were comparable (75% vs 75%, p=0.99), whereas ICANS occurred more frequently with axi-cel (42% vs 17%, p=0.008). After inverse probability of treatment weighting, efficacy outcomes were largely similar between axi-cel and tisa-cel, however, axi-cel remained associated with significantly higher toxicity. In real-world settings, both axi-cel and tisa-cel demonstrated efficacy in patients with R/R FL, although PFS was inferior to that reported in clinical trials.},
}

@article {pmid41746780,
year = {2026},
author = {Shaffer, BC and Lee, SJ and Perales, MA},
title = {How I Treat: Selection of Hematopoietic Cell Donors in the Era of Post-Transplant Cyclophosphamide.},
journal = {Blood},
volume = {},
number = {},
pages = {},
doi = {10.1182/blood.2025030823},
pmid = {41746780},
issn = {1528-0020},
abstract = {Selection of a hematopoietic progenitor cell donor for allogeneic hematopoietic cell transplantation (allo HCT) is essential for treatment planning; however, the parameters that define an "optimal" donor in the modern era are not well defined. Historically, donor-recipient human leukocyte antigen (HLA) mismatching correlated strongly with risk for graft versus host disease (GVHD) and reduced survival. For this reason, donor selection was typically hierarchical: HLA matched related and unrelated donors were evaluated first, followed by HLA mismatched donors (or deferral of HCT altogether) in patients lacking an HLA matched donor. The advent of post-transplant cyclophosphamide (PTCy)-based GVHD prevention has changed this paradigm. Survival outcomes following HLA-mismatched donor HCT with PTCy, including from related haploidentical or HLA-mismatched unrelated donors, are not different than HLA matched donor recipients in recent clinical trials and retrospective studies. These encouraging results present a new challenge: In the PTCy era, how should donors be prioritized among the many potential sources available? Herein we review HLA and non-HLA parameters that inform donor selection and discuss approaches to increase donor availability. Case vignettes focusing on concepts that may be adapted to heterogenous clinical scenarios are presented.},
}

@article {pmid41746629,
year = {2026},
author = {Shadman, M and LeBlanc, M and Rimsza, L and Leonard, JP and Smith, SM and Li, H and Friedberg, JW},
title = {Treatment of Follicular Lymphoma With CHOP and Anti-CD20 Therapy: 15-Year Follow-Up of the SWOG S0016 Trial.},
journal = {JAMA oncology},
volume = {},
number = {},
pages = {},
pmid = {41746629},
issn = {2374-2445},
abstract = {IMPORTANCE: Follicular lymphoma (FL) has historically been regarded as incurable, with patients experiencing late relapses after initial chemoimmunotherapy treatment.

OBJECTIVE: To provide 15-year follow-up data from the SWOG S0016 trial that evaluated the potential for long-term remission and cure following chemoimmunotherapy with cyclophosphamide, hydroxydaunorubicin/doxorubicin, oncovin, and prednisone/prednisolone (CHOP)-based regimens.

This multicenter, intergroup study was conducted at academic and community practice locations throughout the US and enrolled patients with untreated, advanced-stage FL. Cure modeling, which involves estimating the proportion of patients cured of the disease, was conducted by incorporating background mortality rates to estimate the proportion of patients cured of FL during the S0016 trial. Patients were enrolled between May 2001 and October 2008 and followed up for a median (IQR) of 15.5 (13.6-16.9) years. The 15-year analysis was conducted in June 2025.

INTERVENTIONS: Patients were randomized to receive either rituximab plus CHOP (R-CHOP) or CHOP followed by radioimmunotherapy (CHOP-RIT).

MAIN OUTCOMES: The main outcomes were 15-year progression free survival (PFS) and overall survival (OS). Secondary outcomes included cure modeling.

RESULTS: A total of 531 eligible patients (242 female patients [46%]; median [IQR] age, 53 [45-61] years) were included in the final analysis (267 [50%] received R-CHOP and 264 [50%] CHOP-RIT). The overall 15-year OS was 70%, with no significant difference between treatment arms, and the 15-year PFS was 40% (95% CI, 36.0%-44.7%). CHOP-RIT demonstrated superior 15-year PFS (47% vs 34%; P = .004) compared with R-CHOP. Cure modeling estimated an overall cure rate of 42%, with the highest cure rates observed in patients with low Follicular Lymphoma International Prognostic Index scores and normal β2 microglobulin levels. The rate of relapse declined substantially over time, from 6.8% during the first 5 years to 0.6% between 15 to 20 years.

CONCLUSIONS AND RELEVANCE: The results of this secondary analysis suggest that a subset of patients with advanced-stage FL can achieve cure with CHOP-based chemoimmunotherapy, as relapse rates decline over time. This finding represents a paradigm shift in the understanding of and approach to FL, with implications for initial patient discussions and future research strategies.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00006721.},
}

@article {pmid41746611,
year = {2026},
author = {Andrasik, M and Broder, G and Louis, K and Baepanye, K and Kamel, L and Davis, A and Segura, P and Makhubalo, B and Leon Rhandomy, MR and Soler, J and Certo, SK and Gonzalez, R and Dawit, W and Reinstein, S and Shipman, CE and Seyama, L and Sanchez Sarmiento, H and Mpongo, NC and Swann, E and Morar, NS},
title = {Building Trust and Engaging Communities for HIV Prevention Research Globally.},
journal = {AIDS education and prevention : official publication of the International Society for AIDS Education},
volume = {38},
number = {1},
pages = {1-17},
doi = {10.1521/aeap.2026.38.1.1},
pmid = {41746611},
issn = {1943-2755},
abstract = {The HIV Vaccine Trials Network (HVTN) is the largest publicly funded international collaboration facilitating the evaluation of vaccines to prevent HIV and TB. Central to the HVTN's success is the reliance on robust community engagement methods, ensuring community participation and facilitating community awareness and knowledge of research. Community engagement is a dynamic process that requires active participation from all stakeholders to ensure success. The HVTN and its global Clinical Research Sites (CRSs) located in Africa, Latin America, and North America are known as the Network. We describe relationships across the Network, specific staff roles and responsibilities, and the myriad activities undertaken to ensure optimal community engagement. Key activities include involving active Community Advisory Boards (CABs), using community consultations, and having trained Community Engagement staff at each CRS. Operating with robust community engagement has resulted in rapid enrollment and high retention of diverse participant populations across Network studies.},
}

@article {pmid41744883,
year = {2026},
author = {Bea, JW and Ziller, SG and Decker, D and Roe, DJ and Odegaard, AO and Ochs-Balcom, HM and Lima, SM and Caan, B and Wactawski-Wende, J and Pichardo, MS and Harris, H and Chen, Z},
title = {DXA-Derived Visceral and Subcutaneous Adipose Tissue and Postmenopausal Breast Cancer Mortality.},
journal = {Current oncology (Toronto, Ont.)},
volume = {33},
number = {2},
pages = {},
pmid = {41744883},
issn = {1718-7729},
support = {R01CA253302//National Cancer Institute at the National Institutes of Health/ ; },
abstract = {BACKGROUND: Elevated abdominal adipose tissue at time of diagnosis is associated with breast cancer mortality. We sought to understand the association between abdominal adipose tissue (subcutaneous, SAT and visceral, VAT) assessed via dual-energy X-ray absorptiometry (DXA) and breast cancer mortality in the prevention setting.

METHODS: Women enrolled in the Women's Health Initiative study with baseline whole-body DXA scans were included in the study (n = 9767). Causes of death were adjudicated up to 27 years of follow-up. Competing risk models were used to examine independent associations between baseline VAT, SAT, per 100 cm[2], and breast cancer-specific deaths; findings were reported as sub-hazard ratios (SHR) and confidence intervals (CI). Time-varying analyses additionally included DXA at years 3 and 6. Covariates included demographic, lifestyle, and tumor factors.

RESULTS: Baseline VAT and SAT ranged from undetectable to 616.25 cm[2] and 55.26-952.46 cm[2], respectively. There were 738 incident breast cancer cases post-enrollment, and 87 breast cancer-related deaths. Median age at diagnosis was 62 years. In adjusted models, higher baseline VAT and SAT were significantly associated with higher risk breast cancer mortality (49% and 40%, respectively); time-varying models were similar.

CONCLUSIONS: Higher VAT and SAT were similarly associated with breast cancer mortality in this group of postmenopausal women.},
}

@article {pmid41744290,
year = {2026},
author = {Armstrong, AJ and Morris, MJ and Abida, W and Aggarwal, RR and Antonarakis, ES and Attard, G and Beltran, H and Bryce, A and Carducci, MA and Cheng, HH and Chen, DL and Chi, KN and Childs, DS and Dahut, W and Emmett, L and Fizazi, K and Gafita, A and George, DJ and Hermann, K and Hofman, MS and Hope, T and Hussain, M and Kelly, WK and Kessler, E and Kuo, PH and Lang, J and Liu, G and Marshall, CH and Morgans, AK and McKay, RR and Nanus, D and Nelson, P and Paller, C and Reichert, ZR and Ryan, CJ and Sartor, AO and Schöder, H and Schwartz, LH and Sharifi, N and Stadler, WM and Stein, M and Sternberg, CN and Szmulewitz, RZ and Tagawa, ST and Sokolova, AO and Wyatt, AW and Yamoah, K and Yu, EY and Halabi, S and Scher, HI and , },
title = {Trial Design and Objectives for Patients With Prostate Cancer: Recommendations From the Prostate Cancer Working Group 4.},
journal = {Journal of clinical oncology : official journal of the American Society of Clinical Oncology},
volume = {},
number = {},
pages = {JCO2502834},
doi = {10.1200/JCO-25-02834},
pmid = {41744290},
issn = {1527-7755},
abstract = {PURPOSE: The continuous development of new imaging approaches, molecular phenotyping, genetic subtypes, prognosis assessments, and effective therapies across a range of disease states has created a need to redefine terminology and best practices for clinical trial conduct in patients with advanced prostate cancer.

METHODS: We convened an international expert committee of diverse working groups, the Prostate Cancer Working Group 4 (PCWG4), between 2016 and 2025. Our objective was to formulate updated criteria based on emerging evidence and clinical trial data in a biomarker context to provide guidance for clinical trial design, eligibility, and end point assessments for patients with advanced prostate cancer.

RESULTS: PCWG4 redefines terminology around the disease state and previous therapies in a patient-centric context and terminology focused on androgen pathway modulation. We consider imaging, with a particular focus on positron emission tomography (PET)-defined disease. New recommendations are provided for disease state terminology, defining eligibility criteria, response and delay/prevent end points, intervals for reassessments including imaging, and patient-reported outcome determination. We provide recommendations in a biomarker-based context of use for the intended indication, reflective of patient benefit for specific interventions. We emphasize the need for development of validated PET imaging and molecular and phenotypic criteria as well as trial designs to appropriately risk stratify patients, predict and assess benefit, and measure post-treatment outcomes reliably in a trial framework.

CONCLUSION: PCWG4 updates recommendations on patient and tumor characterization, therapy development, and imaging criteria and extends guidance into earlier androgen pathway modulator-naïve/sensitive disease states to reflect an evolving, heterogeneous, and diverse patient population to optimize treatment benefits for all patients.},
}

@article {pmid41742599,
year = {2026},
author = {Marsh, SGE and Osoegawa, K and Bodmer, WF and Bontrop, RE and Carrington, MN and Erlich, HA and Heidt, S and Holdsworth, R and Mayr, WR and Maiers, M and Parham, P and Petersdorf, EW and Robinson, J and Trowsdale, J and Fernández-Viña, M},
title = {Nomenclature for Factors of the HLA System, 2026.},
journal = {HLA},
volume = {107},
number = {3},
pages = {e70595},
pmid = {41742599},
issn = {2059-2310},
}

@article {pmid41740864,
year = {2026},
author = {van den Berg, DMN and Brück, CC and Nascimento de Lima, P and Alarid-Escudero, F and Hahn, AI and Lansdorp-Vogelaar, I and , },
title = {The best screening test is the one that gets followed up on.},
journal = {Gastroenterology},
volume = {},
number = {},
pages = {},
doi = {10.1053/j.gastro.2026.02.013},
pmid = {41740864},
issn = {1528-0012},
}

@article {pmid41740461,
year = {2026},
author = {Whitaker, JA and Rebolledo, PA and Abate, G and Babu, TM and Rouphael, NG and Wald, A and El Sahly, HM and Jooss, K and Hart, MG and Makowski, M and Mu, J and Carmack, A and Archer, JI and Roberts, PC and Makhene, M and Posavad, CM and McElrath, MJ and De Rosa, SC and Coler, R and Montefiori, D and Eaton, A and Suthar, MS and Atmar, RL and Hoft, DF and , },
title = {The safety, reactogenicity, and immunogenicity of the self-amplifying mRNA COVID-19 vaccine GRT-R910 as a booster in healthy adults.},
journal = {Vaccine},
volume = {77},
number = {},
pages = {128358},
doi = {10.1016/j.vaccine.2026.128358},
pmid = {41740461},
issn = {1873-2518},
abstract = {BACKGROUND: GRT-R910 (Gritstone bio, Inc), a self-amplifying mRNA vaccine expressing SARS CoV-2 (D614G) spike protein and T-cell epitopes, was evaluated as a booster vaccine in a phase 1 study in 2021-2022.

METHODS: This open-label, dose escalation study enrolled healthy adults ≥112 days after completion of primary COVID-19 vaccination, booster of approved mRNA COVID-19 vaccine, or known SARS-CoV-2 infection. Persons aged 18-60 years received single doses of 3 or 6 μg GRT-R910 (n = 10/group). Persons >60 years of age received GRT-R910 at 3, 6, or 10 μg (n = 8-10/group). Safety and immunogenicity responses were assessed for 1 year after vaccination.

RESULTS: We enrolled 48 participants. Most participants developed mild-to-moderate systemic reactions and/or injection site tenderness. Eight of 48 (17%) had severe systemic reactions. Pseudovirus neutralizing antibody geometric mean fold rise (GMFR) responses against SARS-CoV-2 (D614G) at Day 29 and Day 181, respectively, among those ≤60 years were 5.2 (95% CI 2.1, 13.3) and 6.1 (2.8, 13.2) after 3 μg, and 3.6 (1.3, 10.4) and 2.4 (0.2, 33.0) after 6 μg. The GMFR responses among those aged >60 years were 8.1 (2.1, 31.4) and 8.2 (1.2, 57.5) after 3 μg, 2.7 (1.1, 6.7) and 1.8 (0.5, 6.7) after 6 μg, 3.3 (1.5, 7.4) and 3.3 (1.3, 8.0) after 10 μg. The 6 μg dose group in those ≤60 years, 6 μg and 10 μg dose groups in those aged >60 years had higher baseline geometric mean titers (GMTs), which, in turn may have lowered the GMFR for those groups. GMFR persistence until Day 181 in most groups indicated these boosts were associated with durable increases in GMFR. Neutralizing antibody titers assessed via focus reduction neutralization test against SARS-CoV-2 D614G largely mirrored the PsVNA findings.

CONCLUSIONS: GRT-R910 was safe but reactogenic when administered to previously vaccinated or infected adults and boosted anti-SARS-CoV-2 neutralizing antibody responses in most participants with responses that appeared durable for up to 6 months.

CLINICAL TRIAL REGISTRATION: https://clinicaltrials.gov/study/NCT04776317.

CLINICALTRIALS: gov ID NCT04776317.},
}

@article {pmid31018183,
year = {2019},
author = {Bellettiere, J and Zhang, Y and Berardi, V and Full, KM and Kerr, J and LaMonte, MJ and Evenson, KR and Hovell, M and LaCroix, AZ and Di, C},
title = {Parameterizing and validating existing algorithms for identifying out-of-bed time using hip-worn accelerometer data from older women.},
journal = {Physiological measurement},
volume = {40},
number = {7},
pages = {075008},
pmid = {31018183},
issn = {1361-6579},
support = {HHSN268201600018C/HL/NHLBI NIH HHS/United States ; R01 HL130483/HL/NHLBI NIH HHS/United States ; T32 HL079891/HL/NHLBI NIH HHS/United States ; HHSN268201600003C/HL/NHLBI NIH HHS/United States ; HHSN268201600004C/HL/NHLBI NIH HHS/United States ; HHSN268201600001C/HL/NHLBI NIH HHS/United States ; HHSN268201600002C/BC/NCI NIH HHS/United States ; R01 HL105065/HL/NHLBI NIH HHS/United States ; },
mesh = {Accelerometry/*instrumentation ; Activities of Daily Living ; Aged ; Aged, 80 and over ; *Algorithms ; *Beds ; Female ; *Hip ; Humans ; Monitoring, Physiologic/*instrumentation ; Signal Processing, Computer-Assisted ; Sleep/physiology ; },
abstract = {OBJECTIVE: To parameterize and validate two existing algorithms for identifying out-of-bed time using 24 h hip-worn accelerometer data from older women.

APPROACH: Overall, 628 women (80  ±  6 years old) wore ActiGraph GT3X+  accelerometers 24 h d[-1] for up to 7 d and concurrently completed sleep-logs. Trained staff used a validated visual analysis protocol to measure in-bed periods on accelerometer tracings (criterion). The Tracy and McVeigh algorithms were adapted for optimal use in older adults. A training set of 314 women was used to choose two key thresholds by maximizing the sum of sensitivity and specificity for each algorithm and data (vertical axis, VA, and vector magnitude [VM]) combination. Data from the remaining 314 women were then used to test agreement in waking wear time (i.e. out-of-bed time while wearing the accelerometer) by computing sensitivity, specificity, and kappa comparing the algorithm output with the criterion. Waking wear time-adjusted means of sedentary time, light-intensity physical activity (light PA) and moderate-to-vigorous-intensity physical activity (MVPA) were then estimated and compared.

MAIN RESULTS: Waking wear time agreement with the criterion was high for Tracy_VA, Tracy_VM, McVeigh_VA, and highest for McVeigh_VM. Compared to the criterion, McVeigh_VM had mean sensitivity  =  0.92, specificity  =  0.87, kappa  =  0.80, and overall mean difference (±SD) of  -0.04  ±  2.5 h d[-1]. Minutes of sedentary time, light PA, and MVPA adjusted for waking wear time using the criterion measure and McVeigh_VM were not statistically different (p   >  0.43|all).

SIGNIFICANCE: The McVeigh algorithm with optimal parameters using VM performed best compared to criterion sleep-log assisted visual analysis and is suitable for automated identification of waking wear time in older women when visual analysis is not feasible.},
}

Accelerometry/*instrumentation
Activities of Daily Living
Aged
Aged, 80 and over
*Algorithms
*Beds
Female
*Hip
Humans
Monitoring, Physiologic/*instrumentation
Signal Processing, Computer-Assisted
Sleep/physiology

@article {pmid41740148,
year = {2026},
author = {Lau, N and Zhou, C and Hong, SJ and Aalfs, H and Higgins, S and Badillo, I and McCauley, E and Ketterl, T and Chow, EJ and Fann, JR and Heathcote, LC and Palermo, TM},
title = {Digital Attention Bias in Cancer Survivors Intervention for Adolescent and Young Adult Cancer Survivors: Protocol for a Pilot Randomized Controlled Trial.},
journal = {JMIR research protocols},
volume = {15},
number = {},
pages = {e82665},
doi = {10.2196/82665},
pmid = {41740148},
issn = {1929-0748},
abstract = {BACKGROUND: Adolescent and young adult cancer survivors face a high burden of psychological late effects, with cancer-related anxiety being a prevalent mental health concern. Despite the significant need for care, more than half of adolescent and young adult cancer survivors, who require psychosocial services, remain untreated. Digital health interventions offer a promising solution to bridge this care gap. Attention bias modification (ABM) is an evidence-based digital intervention for anxiety disorders. This intervention targets automatic and unconscious negative attention biases and retrains attention away from threat and toward neutral or positive stimuli. Recent research has successfully adapted ABM interventions for cancer survivors. However, ABM has not yet been adapted or tested for adolescent and young adult cancer survivors.

OBJECTIVE: This protocol describes a pilot randomized controlled trial designed to evaluate a novel digital anxiety intervention, the Attention Bias in Cancer survivors (ABCs) intervention, for adolescent and young adult cancer survivors.

METHODS: This is a single-site, 2-arm, pilot randomized controlled trial enrolling 60 cancer survivors aged 15 to 29 years. Participants will be randomized 1:1 to the ABCs intervention or a sham control condition. The ABCs intervention combines an ABM mobile intervention with daily gratitude and savoring SMS text messages (positive psychology prompts to savor positive emotions) over a 4-week period. The sham condition consists of sham ABM (showing the same cancer-related word stimuli as the active intervention condition but without attention retraining) and daily mood monitoring SMS text messages (prompts to report on current mood and stress levels). The primary objectives are to evaluate intervention feasibility (defined as ≥50% enrollment and ≥70% retention) and acceptability (defined by cutoff scores on the Client Satisfaction Questionnaire and System Usability Scale). Secondary exploratory outcomes include patient-reported measures of attention bias, anxiety, fear of recurrence, pain, resilience, and other psychosocial outcomes.

RESULTS: This study was funded in August 2023, and study recruitment began in November 2024. We have completed data collection as of February 2026. We anticipate that data analyses will be completed by September 2026. Manuscript preparation and submission are anticipated for December 2026.

CONCLUSIONS: This pilot trial examines the feasibility and acceptability of a digital positive psychological intervention targeting anxiety in adolescent and young adult cancer survivors. Exploratory outcomes will inform sample size calculations for a future-powered multisite clinical trial. The ABCs intervention may provide scalable and accessible evidence-based psychosocial care and improve health outcomes.

TRIAL REGISTRATION: ClinicalTrials.gov NCT06682039; https://clinicaltrials.gov/study/NCT06682039.

DERR1-10.2196/82665.},
}

@article {pmid41740062,
year = {2026},
author = {Hurwitz, LM and O'Brien, KM and Townsend, MK and Reid, BM and Fridley, BL and Fan, W and Schabath, MB and Bodelon, C and Chan, AT and Fortner, RT and Håkansson, N and Harris, HR and Lacey, JV and Liao, LM and Merritt, MA and Patel, AV and Poynter, JN and Robien, K and Sandler, DP and Wentzensen, N and Wolk, A and Zheng, W and Tworoger, SS and Trabert, B},
title = {Longer-term aspirin use and subsequent ovarian cancer risk in the Ovarian Cancer Cohort Consortium.},
journal = {International journal of epidemiology},
volume = {55},
number = {2},
pages = {},
doi = {10.1093/ije/dyag019},
pmid = {41740062},
issn = {1464-3685},
support = {W81XWH-19-1-0346//US Department of Defense Ovarian Cancer Research/ ; W81XWH-12-1-0561//US Department of Defense Ovarian Cancer Research Program/ ; //Intramural Research Program of the National Cancer Institute at the National Institutes of Health/ ; //Biostatistics and Bioinformatics Shared Resource/ ; //H. Lee Moffitt Cancer Center & Research Institute/ ; P30-CA076292//NCI-designated Comprehensive Cancer Center/ ; //American Cancer Society/ ; U01 CA199277/CA/NCI NIH HHS/United States ; P30 CA033572/CA/NCI NIH HHS/United States ; P30 CA023100/CA/NCI NIH HHS/United States ; UM1 CA164917/CA/NCI NIH HHS/United States ; R01 CA077398/CA/NCI NIH HHS/United States ; 103885//California Health and Safety Code Section/ ; 5NU58DP006344//Centers for Disease Control and Prevention's National Program of Cancer Registries/ ; //National Cancer Institute's Surveillance/ ; HHSN261201800032I/CA/NCI NIH HHS/United States ; HHSN261201800015I/CA/NCI NIH HHS/United States ; HHSN261201800009I/CA/NCI NIH HHS/United States ; R01 CA39742//National Cancer Institute at the National Institutes of Health/ ; UM1 CA186107/CA/NCI NIH HHS/United States ; P01 CA87969//National Cancer Institute at the National Institutes of Health/ ; U01 CA176726/CA/NCI NIH HHS/United States ; //NIH-AARP Diet and Health Study was funded by the Intramural Research Program of the National Cancer Institute at the National Institutes of Health/ ; //Division of Cancer Prevention at the National Cancer Institute/ ; /NH/NIH HHS/United States ; U01CA202979//National Cancer Institute Intramural Research Program. The Southern Community Cohort Study was supported by National Cancer Institute at the National Institutes of Health/ ; },
abstract = {BACKGROUND: Observational studies have reported lower ovarian cancer risk among individuals taking aspirin frequently (i.e. daily/near daily). However, most studies relied on a single assessment of aspirin use, which may have led to misclassification and precluded the examination of patterns of use over time. We examined the association between aspirin use, assessed at multiple time points, and ovarian cancer risk.

METHODS: Data were pooled from 10 prospective cohort studies from the Ovarian Cancer Cohort Consortium (n = 675 901 participants; 5528 cases; median follow-up = 13 years). Frequent aspirin use was self-reported via repeat questionnaires. We examined multiple time-updated, lagged aspirin-exposure metrics and risk of ovarian cancer by using pooled logistic regression adjusted for time-updated confounders.

RESULTS: While ever frequent aspirin use was not associated with ovarian cancer [odds ratio (OR) 0.97; 95% confidence interval (CI): 0.91-1.03], individuals who reported long-term use experienced a 14% reduction in ovarian cancer risk (>6 years; OR 0.86; 95% CI: 0.77-0.97). This risk reduction was evident among individuals with at least three ovarian cancer risk factors (OR 0.65; 95% CI: 0.50-0.85) but not among individuals with fewer than three ovarian cancer risk factors (OR 0.94; 95% CI: 0.82-1.08), P-interaction = .02). Reduced ovarian cancer risks were also observed for low-dose aspirin use (OR 0.90; 95% CI: 0.80-1.01 for ever low-dose use; OR 0.75; 95% CI: 0.56-0.99 for long-term low-dose use) but not ever regular-dose use (OR 1.09; 95% CI: 0.94-1.27).

CONCLUSION: Long-term use of aspirin, and particularly low-dose aspirin, is associated with lower ovarian cancer risk, especially among individuals with other established risk factors for ovarian cancer. Research should continue to explore the potential role of long-term, low-dose aspirin use for ovarian cancer primary prevention.},
}

@article {pmid41740031,
year = {2026},
author = {Dumbrava, EE and Shapiro, GI and Parikh, AR and Johnson, ML and Tolcher, AW and Thompson, JA and El-Khoueiry, AB and Vandross, AL and Kummar, S and Shepard, DR and LeDuke, K and Sheehan, L and Alland, L and Haque, A and Jalota, D and Fellous, M and Schram, AM},
title = {Phase 1 Study of Rezatapopt, a p53 Reactivator, in TP53 Y220C-Mutated Tumors.},
journal = {The New England journal of medicine},
volume = {394},
number = {9},
pages = {872-883},
doi = {10.1056/NEJMoa2508820},
pmid = {41740031},
issn = {1533-4406},
abstract = {BACKGROUND: Rezatapopt is an investigational, first-in-class, oral, selective p53 reactivator that specifically binds to Y220C-mutated p53, which stabilizes p53 in its wild-type conformation and restores its functionality.

METHODS: In this phase 1, single-group, dose-escalation and dose-optimization study, we assigned heavily pretreated patients with locally advanced or metastatic solid tumors harboring a TP53 Y220C mutation to receive rezatapopt during continuous 21-day treatment cycles. The primary objectives were to determine the maximum tolerated dose and recommended phase 2 dose. Primary end points included dose-limiting toxic effects and adverse events. Secondary end points included preliminary efficacy and pharmacokinetic features.

RESULTS: A total of 77 patients received rezatapopt at one of eight escalating doses: 150 mg, 300 mg, 600 mg, 1150 mg, 1500 mg, 2000 mg, or 2500 mg once daily or 1500 mg twice daily. The maximum tolerated dose was 1500 mg twice daily. On the basis of safety, efficacy, and pharmacokinetic data, 2000 mg once daily with food was selected as the recommended phase 2 dose. During the treatment period, 76 patients (99%) had at least one adverse event and 29 (38%) had an adverse event of grade 1 or 2. The most common adverse events were nausea (in 58% of patients), vomiting (in 44%), an increased blood creatinine level (in 39%), fatigue (in 39%), and anemia (in 36%). Treatment-related adverse events occurred in 67 patients (87%) and those of grade 1 or 2 in 48 (62%); 2 patients (3%) discontinued rezatapopt because of a treatment-related adverse event. Most gastrointestinal adverse events resolved with the treatment of symptoms and were less frequent when rezatapopt was given with food. Anemia was the most common adverse event of grade 3 or higher during the treatment period, occurring in 16% of patients. The overall response (complete or partial response) was 20% among all patients and 30% among those who had a KRAS wild-type tumor and received a dose of at least 1150 mg once daily. Confirmed responses were seen across multiple tumor types, including ovarian and breast cancers. All patients with a response had a solid tumor that harbored TP53 Y220C and wild-type KRAS.

CONCLUSIONS: In this phase 1 study involving heavily pretreated patients, the most common adverse events associated with rezatapopt were nausea and vomiting. Antitumor activity occurred across multiple tumor types, providing proof of concept for p53 reactivation. (Funded by PMV Pharmaceuticals; PYNNACLE ClinicalTrials.gov number, NCT04585750.).},
}

@article {pmid41739906,
year = {2026},
author = {Lima, NS and McCormick, L and Li, S and Wake, CG and Subramanian, R and Spangler, A and Pinto, Y and Catalano, W and Henry, AR and Laboune, F and Teng, IT and Lyke, KE and Atmar, RL and Deming, ME and Jackson, LA and Branche, AR and Rostad, CA and Martin, JM and Johnston, CM and Rupp, RE and Kottkamp, AC and Brady, RC and Backer, M and Edupuganti, S and , and Posavad, CM and Roberts, PC and Kwong, PD and Andrews, S and Schramm, CA and Douek, DC and , },
title = {The vaccine platform used for COVID-19 primary immunization shapes the quality of the human B cell response to a vaccine boost.},
journal = {Science translational medicine},
volume = {18},
number = {838},
pages = {eaeb9837},
doi = {10.1126/scitranslmed.aeb9837},
pmid = {41739906},
issn = {1946-6242},
abstract = {Improving long-term protective immunity elicited by prime-boost vaccinations requires a deeper understanding of the immunologic outcomes of different vaccine platforms. Given the variety of platforms used to develop vaccines against SARS-CoV-2, we reasoned that SARS-CoV-2 offered an opportunity to compare vaccine platforms in humans. We used flow cytometry and single-cell transcriptomics to explore the B cell response to different homologous and heterologous vaccine regimens. We found that an adenovirus vector prime followed by a messenger RNA (mRNA) vaccine boost showed the greatest short-term B cell expansion and preferentially elicited an activated atypical B cell subset that was associated with antibody binding titers against spike protein. In contrast, an mRNA primary series followed by homologous boost induced a different activated B cell subset with more proliferative potential and high frequencies of a long-lived resting memory subset. Moreover, immunoglobulin A (IgA)-expressing memory B cells had more somatic hypermutations than the predominant IgG-expressing B cell population. This heterogeneity in vaccine-elicited B cell responses underscores the potential of tailoring vaccine regimens that combine different platforms to achieve potent and durable protection against infectious diseases.},
}

@article {pmid41739467,
year = {2026},
author = {Childers, CP and Tracy, BM and Senkowski, CK},
title = {Beyond Modifier 22-A Path to Recognizing Surgical Complexity.},
journal = {JAMA surgery},
volume = {},
number = {},
pages = {},
doi = {10.1001/jamasurg.2025.6831},
pmid = {41739467},
issn = {2168-6262},
}

@article {pmid41738780,
year = {2026},
author = {Lilly, M and Ruiz, F and Foreman, WB and Chohan, V and Guenthoer, J and Depierreux, D and Baharani, VA and Ralph, D and Harteloo, A and Chu, HY and Bieniasz, PD and Starr, TN and Overbaugh, J},
title = {Re-infection with SARS-CoV-2 is associated with increased antibody breadth and potency against diverse sarbecovirus strains.},
journal = {mBio},
volume = {},
number = {},
pages = {e0361225},
doi = {10.1128/mbio.03612-25},
pmid = {41738780},
issn = {2150-7511},
abstract = {The ease with which emerging SARS-CoV-2 variants escape neutralizing antibodies limits the protection afforded by a prior exposure, be it infection or vaccination. While rare, broadly neutralizing antibodies with activity toward diverse sarbecoviruses have been detected in convalescent serum. Motivated by findings that plasma responses show increased neutralization breadth and potency with continued antigen exposure, we isolated monoclonal antibodies (mAbs) after a SARS-CoV-2 re-infection and compared them to those isolated 1 year prior, after the first breakthrough infection. Among clonal lineage members identified at both time points, mAbs from the later time point showed improved neutralization potency and breadth. One mAb isolated after re-infection, C68.490, targets a conserved region in the receptor binding domain and shows remarkable activity not only against SARS-CoV-2 variants, but also diverse sarbecoviruses from more distant clades present in animal reservoirs. These findings suggest that a focus on individuals with diverse and repeated antigen exposure could lead to the identification of antibodies with therapeutic utility not just toward current and future SARS-CoV-2 variants, but also distant sarbecoviruses in the event of a future spillover.IMPORTANCESpillover of SARS-related viruses (sarbecoviruses) from animal reservoirs into humans has occurred multiple times in the past few decades. The most recent spillover due to SARS-CoV-2 continues to cause significant disease burden, and treatment options are few, in part because of selection for new variants due to immune escape. Thus, discovering antibodies that can block infection with sarbecoviruses, including SARS-CoV-2 variants, remains critical for both the current pandemic as well as those to come. Our study shows that an individual who was vaccinated and then had repeated breakthrough infections with distinct SARS-CoV-2 variants generated more potent antibodies after the second infection compared to the first infection. Notably, we discovered an antibody in this individual that not only neutralized the dominant SARS-CoV-2 variants but also a range of diverse sarbecoviruses present in animal reservoirs. This antibody thus holds promise as a therapeutic for both the current pandemic and future spillover events.},
}

@article {pmid41736871,
year = {2026},
author = {Begnel, ER and Maqsood, R and Holland, LA and Ojee, E and Owiti, P and Adhiambo, J and Mabele, E and Gantt, S and Chohan, BH and Kinuthia, J and Wamalwa, D and Lim, ES and Lehman, DA and Slyker, J},
title = {Comparison of gut virome in Kenyan infants born to women with and without HIV.},
journal = {iScience},
volume = {29},
number = {3},
pages = {114900},
pmid = {41736871},
issn = {2589-0042},
abstract = {The gut virome develops in infancy, seeded from numerous sources including the maternal virome. Altered infant virome development from exposure to maternal HIV infection could contribute to the higher observed morbidity among children who are HIV-exposed, uninfected (CHEU) versus HIV-unexposed (CHUU). To assess whether infant HIV exposure affects gut virome development, we sequenced the DNA virome in stool samples collected between birth-2 years from 37 CHUU and 32 CHEU whose mothers received optimized antiretroviral therapy (ART). Richness and Shannon diversity increased with age and introduction of foods other than breastmilk, and Bray-Curtis distances varied by age. Virome richness was lower among CHEU than CHUU, but Shannon diversity and Bray-Curtis distances did not differ by HIV exposure. These findings suggest that HIV exposure is not a major determinant of the infant virome when mothers receive optimized ART.},
}

@article {pmid41735628,
year = {2026},
author = {Ogunjimi, B and Warren-Gash, C and Ouwendijk, WJD and Breuer, J and Mogensen, TH and Koelle, DM},
title = {Varicella zoster virus and the central nervous system.},
journal = {Nature reviews. Microbiology},
volume = {},
number = {},
pages = {},
pmid = {41735628},
issn = {1740-1534},
abstract = {Varicella zoster virus (VZV) causes varicella, also known as chickenpox, after which VZV remains latent in neural ganglia. VZV reactivation can result in herpes zoster, also known as shingles. In addition to its well-known effects on the peripheral nervous system, reports increasingly suggest that VZV can have potentially devastating effects on the central nervous system (CNS). Several epidemiological studies indicate that VZV reactivation is associated with stroke and interest is growing in potential associations of VZV with dementia. In the past 5-6 years, vaccination against herpes zoster has been reported to reduce the risk of developing cardiovascular events (including stroke) and dementia in observational studies, although interpretation of their findings is hindered by complex methodological challenges. This Review considers the relationship between VZV and the CNS from a multidisciplinary perspective that focuses on VZV physiology and immunity. The strengths and weaknesses of published studies are discussed, and areas for future investigation that remain to be addressed before the links between VZV and CNS conditions can be considered definitive and medically actionable are highlighted. Finally, these insights are integrated into an overarching conclusion that addresses potential consequences of the connection between VZV and the CNS for both public health and healthy ageing.},
}

@article {pmid41735346,
year = {2026},
author = {Kong, X and Wang, B and Wu, X and Cho, H and Fu, W and Li, Q and Zhang, R and Nasri, U and Zheng, M and Wu, A and Qin, H and Li, JH and Pillai, R and O'Sullivan, TE and Nakamura, R and Martin, PJ and Chen, Y and Zeng, D},
title = {Stem-like memory-T maintenance and differentiation into tissue-resident T cells sustain chronic graft-versus-host disease in mice.},
journal = {Nature communications},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41467-026-69975-z},
pmid = {41735346},
issn = {2041-1723},
support = {R01HL170099//U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)/ ; R01HL162847//U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)/ ; },
abstract = {Pathogenic CD4[+] memory T cells (Tm) sustain chronic inflammation, but mechanisms remain undefined. Here, we identify four donor-type CD4[+] Tm subsets in the target tissues of autoimmune-like chronic graft-versus-host disease in mice: Ly108[+]CD69[-] stem-like memory T cells (Tsm), Ly108[+]CD69[+] resident memory progenitor T cells (Trmp), Ly108[-]CD69[+] terminally differentiated tissue-resident T cells (Trm), and Ly108[-]CD69[-] intermediate T cells (Tint). Trm are terminally differentiated but not exhausted and show highly biased clonotypes with high proinflammatory cytokine expression. Tsm cells require TCR-MHCII interactions for their maintenance and expansion and show greater capacity than Trmp cells in self-renewal/expansion, generation of Trm, and pathogenicity in adoptive recipients. The transcription factors TCF1/BCL6 and BHLHE40 differentially regulate the stemness and differentiation of Tsm into Trm, respectively, and their selective targeting reduces the number of Trm in tissues and ameliorates inflammation. Thus, our findings indicate that targeting the Tsm subset, involved in the maintenance of the pathogenic Tm pool, offers an attractive approach to treat T cell-mediated chronic inflammation.},
}

@article {pmid41734386,
year = {2026},
author = {Sekeres, MA and DeZern, AE and Otterstatter, M and Padron, E and Al Baghdadi, T and Foran, JM and Komrokji, RS and Abel, GA and Saber, W and Gore, SD and Lee, C and Bejar, R and Liu, JJ and Deeg, HJ and Sherman, S and Lindsley, RC and Walter, MJ and Gillis, N},
title = {Exposure to Agent Orange and Association with Myelodysplastic Syndromes.},
journal = {Blood advances},
volume = {},
number = {},
pages = {},
doi = {10.1182/bloodadvances.2025019262},
pmid = {41734386},
issn = {2473-9537},
}

@article {pmid41734378,
year = {2026},
author = {Tan, CR and Usmani, SZ and Derkach, A and De Menezes Silva Corraes, A and Parrondo, RD and Ailawadhi, S and Asoori, S and Dave, M and Popat, R and Morjaria, O and Hajek, R and Mihalyova, J and Htut, M and Janakiram, M and Visram, A and Kastritis, E and Dimopoulos, MA and Martínez-López, J and Nagarajan, C and Bal, S and Costa, LJ and Einsele, H and Steinbrunn, T and Waldschmidt, JM and Riedhammer, C and Banerjee, R and Chng, WJ and Tso, AC and Lin, Y and Martin, TG and Mian, H},
title = {Early Mortality with Bispecific Antibody Therapy in RRMM: An IMWG Immunotherapy Database Real-World Analysis.},
journal = {Blood advances},
volume = {},
number = {},
pages = {},
doi = {10.1182/bloodadvances.2025019231},
pmid = {41734378},
issn = {2473-9537},
abstract = {Recent therapeutic advances, including bispecific antibody therapies (bsAbs) have improved outcomes for patients with relapsed/refractory multiple myeloma (RRMM). However, early mortality (EM) remains a significant challenge, even in the era of novel immunotherapies. We conducted a multicenter, retrospective analysis of real-world patients with RRMM treated with commercial bsAbs to evaluate the incidence and causes of EM. Between May 2022 and June 2025, 441 patients were treated across seven countries. EM, defined as death within 12 months of therapy initiation, occurred in 148 patients (34%) with median time from bsAb initiation to death of 2.87 months (IQR 1.38-6.85). The leading cause of EM was progressive disease (72%), followed by infection (13%); regardless of cause of death 82% had active disease at the time of death. Our findings highlight that despite encouraging efficacy, EM remains high among real-world bsAb recipients, emphasizing the need for improved disease control strategies and supportive care interventions.},
}

@article {pmid41734346,
year = {2026},
author = {Maynard, L and Starke, CE and Poole, NH and Rust, BJ and Zhu, H and Stensland, L and Huang, ML and Pérez-Osorio, AC and Atherley, JI and Einhaus, TK and Murray, JD and Pampena, MB and Betts, MR and Jerome, KR and Riley, JL and Kiem, HP and Peterson, CW},
title = {Antigen-boosted CD4 CAR-T cells fail to expand or control viremia in multiple nonhuman primate models of HIV.},
journal = {Blood},
volume = {},
number = {},
pages = {},
doi = {10.1182/blood.2025032142},
pmid = {41734346},
issn = {1528-0020},
abstract = {Chimeric antigen receptor T (CAR-T) cell therapy has demonstrated curative potential in B cell malignancies, yet translating this success to chronic infections like human immunodeficiency virus (HIV) remains a major challenge. In people living with HIV (PLWH) on suppressive antiretroviral therapy (ART), low antigen levels limit CAR-T cell expansion and persistence. We previously reported data from a pilot study which suggested that HIV-targeted CD4CAR-T cells could overcome this barrier through exogenous antigen supplementation, leading to robust in vivo expansion. Here, we sought to comprehensively confirm and expand on those findings. We tested a broad array of strategies to enhance CD4CAR-T cell efficacy, including CRISPR-Cas9-mediated gene editing of immune checkpoint and HIV-associated genes, single and pooled competitive infusions of engineered CAR-T cells, distinct CAR constructs incorporating either CD28 or 4-1BB costimulatory domains, and exogenous antigen boosting. We also developed highly sensitive droplet digital PCR (ddPCR) assays both to quantify CAR-T cell frequency and corroborate flow cytometry-based quantification of CD4CAR T-cell expansion. We evaluated these new approaches across multiple NHP models of HIV, including both simian immunodeficiency virus (SIV)- and simian-human immunodeficiency virus (SHIV)-infected, ART-suppressed NHPs. Although CD4CAR-T cell products exhibited antigen-specific proliferation and cytotoxicity ex vivo, they failed to expand, persist, or control viremia in vivo. We were also unable to confirm previously observed CD4CAR T cell expansions from our earlier studies, which will be retracted. Together these data highlight the need for alternative strategies to potentiate anti-HIV CD4CAR-T cells in the immunocompetent setting.},
}

@article {pmid41734278,
year = {2026},
author = {Piliper, E and Goya, S and Greninger, AL},
title = {RUMINA: high-throughput UMI deduplication for amplicon and whole-genome sequencing with enhanced error correction.},
journal = {Bioinformatics (Oxford, England)},
volume = {},
number = {},
pages = {},
doi = {10.1093/bioinformatics/btag097},
pmid = {41734278},
issn = {1367-4811},
abstract = {MOTIVATION: Unique molecular identifiers (UMIs) are widely used in next-generation sequencing to enable accurate molecular counting and error correction. However, challenges remain in accurately collapsing UMI clusters, especially when read counts are low or sparse read clusters arise from barcode sequencing errors.

RESULTS: We present RUMINA, a Rust-based pipeline for UMI-aware deduplication and error correction, optimized for both amplicon and shotgun sequencing. RUMINA supports multiple UMI cluster strategies, alongside majority-rule read selection independent of mapping quality, as well as discrete handling of 1-2 read clusters, paired-end merging, and read-length stratification. Benchmarking using simulated HIV population sequencing data and real-world iCLIP and TCR datasets showed that RUMINA improves ultra-low frequency SNV detection (0.01-1%), reduces false positives, enhances reproducibility, and processes sequencing data up to 10-fold faster than existing tools. By integrating UMI- and sequence-level correction in a high-performance framework, RUMINA offers a fast, scalable, and robust solution for UMI-enabled sequencing workflows.

AVAILABILITY: RUMINA is implemented in Rust and distributed as open-source code and precompiled binaries. Source code and installation instructions are available at https://github.com/greninger-lab/rumina. Documentation associated with this manuscript is available at https://github.com/greninger-lab/rumina_paper.

SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.},
}

@article {pmid41733980,
year = {2026},
author = {Biernacki, MA},
title = {The TCXpress lane to T-cell receptor-engineered T cells.},
journal = {Blood advances},
volume = {10},
number = {4},
pages = {1233-1235},
doi = {10.1182/bloodadvances.2025018859},
pmid = {41733980},
issn = {2473-9537},
}

@article {pmid41733968,
year = {2026},
author = {Murray, J and Einhaus, T and Radtke, S and Bar, KJ and Peterson, CW and Kiem, HP},
title = {Engraftment of gene-edited hematopoietic stem cells after antibody-drug conjugate conditioning in nonhuman primates.},
journal = {Blood advances},
volume = {10},
number = {4},
pages = {1094-1105},
doi = {10.1182/bloodadvances.2025017838},
pmid = {41733968},
issn = {2473-9537},
mesh = {Animals ; *Hematopoietic Stem Cell Transplantation/methods ; *Hematopoietic Stem Cells/metabolism/cytology/drug effects ; *Immunoconjugates/pharmacology ; *Transplantation Conditioning/methods ; Macaca mulatta ; *Gene Editing ; Receptors, CCR5/genetics ; Humans ; },
abstract = {Hematopoietic stem cell (HSC) gene therapies provide lifelong benefit in numerous hematological diseases and disorders, but safety and toxicity remain a critical barrier for routine application. In the setting of immunodeficiency syndromes and infectious diseases such as HIV infection, conditioning regimens may exacerbate immune dysfunction, blunting, or impairing overall efficacy. Here, we conduct a head-to-head comparison of 2 novel antibody-drug conjugates (ADCs) with a pyrrolobenzodiazepine payload for autologous transplant in rhesus macaques. These ADCs target either CD117 or CD45 and are benchmarked against the clinical standard busulfan. We quantified the extent of myeloablation and immunosuppression, time to hematopoietic recovery, long-term engraftment of CCR5 CRISPR-edited autologous HSCs, and resistance to infection when challenged with increasing concentrations of an HIV-like virus. Both ADCs enabled engraftment of CRISPR-edited HSCs, although with lower levels of long-term editing compared with busulfan. We observed myeloablation with similar times to hematopoietic recovery and preserved lymphocyte counts with all 3 conditioning regimens, but neither ADC conditioning nor busulfan enabled sufficient CCR5 editing for viral immunity. Although these results only apply to the specific ADC-conditioning protocols tested here, they are a step toward developing targeted strategies to engraft cells with therapeutic edits and highlight the need for further refinement of antibody-based selection.},
}

Animals
*Hematopoietic Stem Cell Transplantation/methods
*Hematopoietic Stem Cells/metabolism/cytology/drug effects
*Immunoconjugates/pharmacology
*Transplantation Conditioning/methods
Macaca mulatta
*Gene Editing
Receptors, CCR5/genetics
Humans

@article {pmid41733939,
year = {2026},
author = {Farhadfar, N and El Jurdi, N and Baker, KK and Ghosh, S and Bat-Erdene, M and Chen, H and Sahu, R and Weiss, R and Mi, J and Desatnik, G and Williams, LR and Tkaczyk, ER and Lee, SJ},
title = {Reproducibility and repeatability of the Myoton to quantify sclerotic chronic graft-versus-host disease.},
journal = {Blood advances},
volume = {10},
number = {4},
pages = {1145-1152},
doi = {10.1182/bloodadvances.2025016648},
pmid = {41733939},
issn = {2473-9537},
mesh = {Humans ; *Graft vs Host Disease/diagnosis/etiology/pathology ; Adult ; Male ; Female ; Reproducibility of Results ; Middle Aged ; Chronic Disease ; Sclerosis ; Observer Variation ; Aged ; Skin/pathology ; Hematopoietic Stem Cell Transplantation/adverse effects ; },
abstract = {There is an urgent need for validated tools to measure sclerotic cutaneous chronic graft-versus-host disease (scGVHD). We examined the interobserver reproducibility within a session and intraobserver repeatability between sessions of the Myoton device for quantifying skin sclerosis in 36 adults with scGVHD. The Myoton was used to measure oscillation frequency and relaxation time of soft tissues at 7 bilateral sites (14 anatomic sites) by 2 study personnel at 2 study sessions. Agreement was measured using mean pairwise absolute difference (MPD), and reliability was measured using intraclass correlation coefficient (ICC). For each of the 2 Myoton parameters, the overall interobserver MPD was <5% of the average overall values and the interobserver ICC was >0.90 between the 2 observers, indicating excellent agreement and reliability within a measurement session. The median time between sessions 1 and 2 was 47.5 days. The overall normalized intraobserver MPD was <7% of the average overall values for each of the 2 Myoton parameters, reflecting good agreement between sessions. The intraobserver ICC for frequency and relaxation time parameters were 0.85 and 0.84, respectively, indicating good reliability between sessions. The reproducibility and repeatability of a bonus site selected at each study visit were similar to the standard 14 anatomic sites. However, no individual site was nearly as reproducible or repeatable as the overall Myoton measurements averaged across the patient. Our findings emphasize the utility of the Myoton for assessing skin properties in scGVHD with patient-level measurements.},
}

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

@article {pmid41733389,
year = {2026},
author = {DeMeules, MM and Proll, SC and Hua, X and Srinivasan, S and Loeffelholz, T and Liu, C and Wu, MC and Fiedler, TL and Hoffman, NG and Bourassa, LA and Pergam, SA and Fredricks, DN},
title = {Gut Microbiota and Intestinal Monodomination as a Predictor for Bacteremia in Allogeneic Hematopoietic Cell Transplant Recipients.},
journal = {The Journal of infectious diseases},
volume = {},
number = {},
pages = {},
doi = {10.1093/infdis/jiag005},
pmid = {41733389},
issn = {1537-6613},
support = {R01 AI134808/NH/NIH HHS/United States ; //National Institute of Allergy and Infectious Diseases/ ; P30CA015704//Fred Hutch Cancer Center/ ; },
abstract = {BACKGROUND: Bacteremia is a frequent complication in patients undergoing allogeneic hematopoietic cell transplantation (HCT). Alterations to the gut microbiota after HCT have been associated with adverse outcomes including bacteremia and reduced overall survival. Previous studies suggest that loss of gut bacterial diversity and domination by a single species may predict bloodstream infections, but the degree of domination leading to the optimal positive predictive value (PPV) has not been defined.

METHODS: Stool samples were collected weekly from allogeneic HCT recipients and were analyzed by 16S rRNA gene PCR with sequencing to determine gut microbiota composition and document domination events. Bacteremia events were captured by review of medical records. The PPV for bacteremia of any detection of that species in stool and for domination events at 10%, 30%, and 50% abundance were calculated.

RESULTS: Of 277 HCT recipients, 95 experienced bacteremia, with 130 bacteremia events. Intestinal domination was associated with but not highly predictive for bacteremia, reflected by low PPV. Presence of coagulase-negative Staphylococcus in the gut at >30% relative abundance was associated with increased risk of coagulase-negative Staphylococcus bloodstream infections with PPV of 38%.

CONCLUSIONS: Hematopoietic cell transplantation is associated with significant disruption to the gut microbiota, particularly in patients who subsequently develop bacteremia. Intestinal domination may not be as useful as previously thought given its low PPV for most species implicated in bloodstream infections. The association between gut colonization with Staphylococcus and bacteremia events suggests that the gut may be an under-recognized portal of entry for these organisms in patients after HCT.},
}

@article {pmid41733330,
year = {2026},
author = {Su, M and Khan, AM and Cowan, AJ and Anderson, LD and Kaur, G and Banerjee, R},
title = {Resumption of bone-modifying agents in relapsed multiple myeloma does not improve outcomes: A real-world analysis.},
journal = {British journal of haematology},
volume = {},
number = {},
pages = {},
doi = {10.1111/bjh.70395},
pmid = {41733330},
issn = {1365-2141},
abstract = {While bone-modifying agents (BMAs) are well-established components of frontline therapy in multiple myeloma, there are no data in the modern era to support their use in the relapsed setting. We conducted a retrospective analysis of US patients with relapsed/refractory multiple myeloma (RRMM) diagnosed between 2014 and 2023. Progression-free survival (PFS) and overall survival (OS) were analysed using Cox proportional hazards models adjusting for covariates including BMA receipt (BMA-received) versus not (BMA-deferred) at relapse. Of 1112 RRMM patients, 633 (56.9%) patients received BMAs following relapse. Compared to BMA-received patients, BMA-deferred patients had slightly worsened renal function and were less likely to have received BMAs during frontline therapy. There were no differences in PFS between groups: median PFS 10.1 months (95% confidence interval [CI] 8.9-11.8 months) for BMA-deferred patients versus 9.2 months (95% CI 7.7-11.3 months; p = 0.08) for BMA-received patients. There were no differences in OS: median OS 39.6 months (95% CI 33.9-58.1 months) for BMA-deferred patients versus 51.5 months (95% CI 41.8-60.1 months; p = 0.10) for BMA-received patients. Given the lack of clear benefit to BMA in the modern era, our data support future investigations to better personalize decision-making around BMA resumption in RRMM.},
}

@article {pmid41674613,
year = {2026},
author = {Stefanovic, F and Robertson, I and Moloney, K and Edelson, J and Nguyen, S and Shinkawa, V and Uchimura, K and Lin, A and Le, L and Tokihiro, JC and Takezawa, MG and Phan, D and Schiffer, JT and Boeckh, M and Adams, KN and Waghmare, A and Errett, NA and Berthier, E and Lim, FY and Theberge, AB},
title = {Research In Your Mailbox: Remote Blood Self-sampling Enables Participation of Underserved Populations in Longitudinal Studies.},
journal = {medRxiv : the preprint server for health sciences},
volume = {},
number = {},
pages = {},
pmid = {41674613},
abstract = {IMPORTANCE: Remote sampling technologies are invaluable for protecting both participants and researchers when studying highly infectious diseases. When leveraged for longitudinal studies, remote sampling with transcriptomic readouts is a powerful tool for studying the host immune response. Additionally, remote study flexibility circumvents common barriers to research participation including length of commute, transportation, and scheduling, thereby expanding access to clinical research.

OBJECTIVE: In this work, we investigate the effectiveness of a remote study model for reaching women from underrepresented, underserved, and underreported (U3) populations. We sought to recruit individuals who qualify as underrepresented in clinical research, who are located in rural areas, or who come from disadvantaged backgrounds per the NIH definition.

DESIGN: In this longitudinal study, U3 women positive for COVID-19 were enrolled and followed over the course of 6 months. In the first month of the infection, participants (n = 40) self-collected a set of 5 nasal swabs, 5 homeRNA-stabilized blood samples, and 2 additional unstabilized blood samples at first and last sampling. Sampling time points were spaced 5 days apart, so that the total of the 5 time points was completed within 25 days. homeRNA is a platform for remote self-collection of blood samples with subsequent RNA stabilization. A subset of participants likely to develop post-acute sequelae of COVID-19 (PASC) and their age-matched controls were selected to self-collect an additional set of 5 nasal swabs and 5 homeRNA-stabilized blood samples during month 3 of study participation, with the same sampling frequency. All participants were resurveyed at months 4, 5, and 6 about their symptoms. Participants also completed surveys at each sampling and a more comprehensive survey about study experience after each set of 5 time points.

SETTING: This was a fully remote study with all sampling supplies and instructions shipped to the participants. Participants self-collected blood and nasal swabs at home and shipped these back to our lab for further processing. Surveys were administered electronically using REDCap.

PARTICIPANTS: For this study, we enrolled women who were 18 or older, met the NIH criteria for U3, and who had tested positive for SARS-CoV-2 within a week of enrollment. Further, we excluded protected populations including individuals who were pregnant and/or incarcerated. Of the 334 individuals who completed the screening process, 65 were invited into the study based on the eligibility criteria and balancing age, race/ethnicity, and state of residence to closely correspond to the demographics of the United States. Of the 65 invited individuals, 40 were fully enrolled in the study and 39 completed all study components.

MAIN OUTCOMES AND MEASURES: Prior to the study, we proposed that the increased flexibility of a remote study design would allow for participation of populations underrepresented in clinical research. The primary measurements planned for this study consisted of usability data and general experience in a longitudinal study. These data were collected by self report using electronically administered surveys. The Consolidated Framework for Implementation Research (CFIR), a well-established implementation science framework, was used to guide the development of questions about usability and study experience.

RESULTS: 40 women were recruited from 19 states, with diverse racial backgrounds (62% White, 15% Black or African American, 10% Asian, 5% American Indian or Alaska Native, 5% Other, 3% More than one race), a mostly even age distribution (26% ages 20 - 29, 15% ages 30 - 39, 31% ages 40 - 49, 28% ages 50+), and most of whom (80%) are categorized as having a disadvantaged background per the NIH. Survey responses show high satisfaction with the study, where all participants who completed the study (100%, n = 39/39) indicating that they would be willing to participate in a similar study again, with most (n = 32/39) indicating a willingness to participate for up to 4 years with around 15 samples collected per year. We note that 4 years was the longest time period that participants were able to select in their surveys, suggesting that participants may be willing to participate for even longer periods. Most (>90%) either agreed or strongly agreed that all components of the kit were easy to use.

CONCLUSIONS AND RELEVANCE: The high retention (98%, n = 39/40) and satisfaction of participants in this study indicates the utility of a remote study design for longitudinal research. We also find that study topic, flexibility of study, and positive interactions with the study team are important factors for participant recruitment and retention. This work suggests that the increased flexibility of a fully remote design enables engagement of individuals who may otherwise be excluded from clinical research.},
}

@article {pmid41737546,
year = {2024},
author = {Shao, Y and Gao, F},
title = {Likelihood-based inferences for active-arm trial with counterfactual incidence based on recency assay.},
journal = {Statistical communications in infectious diseases},
volume = {16},
number = {1},
pages = {},
pmid = {41737546},
issn = {2194-6310},
support = {R01 AI029168/AI/NIAID NIH HHS/United States ; R01 AI177078/AI/NIAID NIH HHS/United States ; },
abstract = {OBJECTIVES: The approach of using HIV recency assay to estimate the counterfactual incidence rate is being used as the primary efficacy method in a few ongoing large-scale HIV pre-exposure prophylaxis (PrEP) trials, and the current available approach for the inference is based on the Wald method that leverages the asymptotic distribution of the estimators. One issue with the Wald test is that it does not work well when the number of HIV infections are small in the active arm, and it fails to work when there are zero HIV infections. As future long-acting PrEP products are becoming more efficacious, it is very likely that a small or zero number of infections will be observed in HIV prevention trials, especially for subgroup analyses or interim analyses, hence there is a pressing need to develop inference methods that work under such scenarios.

METHODS: It is well known that when the sample size is small to moderate, likelihood ratio tests are more reliable than Wald tests in terms of actual error probabilities coming close to matching nominal levels. In this manuscript we derive the likelihood ratio test and the likelihood-based confidence intervals for HIV prevention trials based on recency assays.

RESULTS: Compared with the Wald test, the proposed method works when there are zero infections. Additionally, unlike the Wald test, the p-value from the likelihood ratio test is an increasing function with respect to the number of infections, which is a desirable property as otherwise it will cause confusions.

CONCLUSIONS: For HIV PrEP trials based on recency assay, the likelihood-based p-value and confidence interval can be preferable to the Wald based inference methods when the number of HIV infections is expected to be small.},
}

@article {pmid41732008,
year = {2026},
author = {Yu, EY and Gratzke, C and Burotto, M and Zhang, AY and Lévesque, E and Ortega, F and Peer, A and Vile, D and Chen, ZH and Song, Y and Schloss, C and Todoric, J and Garratt, C and Poehlein, C and Antonarakis, ES and Fizazi, K},
title = {Steroidogenesis inhibitor opevesostat (MK-5684) for metastatic castration-resistant prostate cancer: OMAHA-003 and OMAHA-004 trial designs.},
journal = {Future oncology (London, England)},
volume = {},
number = {},
pages = {1-8},
doi = {10.1080/14796694.2025.2595914},
pmid = {41732008},
issn = {1744-8301},
abstract = {Treatment options for metastatic castration-resistant prostate cancer (mCRPC) include androgen receptor pathway inhibitors (ARPIs), taxanes, radium-223, Lu-PSMA, poly (ADP-ribose) polymerase inhibitors, and immunotherapy in select patients. Resistance to ARPIs and hormone-based therapies has been associated with AR-ligand-binding domain mutations that can lead to promiscuous stimulation by other steroid hormones. There is a need to explore alternative targets and develop next-generation ARPIs or combination therapies that overcome this resistance. We describe the rationale and design of the randomized phase III trials OMAHA-003 (NCT06136624) and OMAHA-004 (NCT06136650), which will evaluate the efficacy and safety of opevesostat, a steroidogenesis inhibitor, versus ARPI switch in previously treated mCRPC. Results may support opevesostat as a potential new treatment option for mCRPC.Clinical trial registration: www.clinicaltrials.gov identifiers are NCT06136624 and NCT06136650.},
}

@article {pmid41730823,
year = {2026},
author = {Hudson, A and Borgetti, S and Rick, AM and Laurens, MB and Robinson, ST and Gay, CL and Baden, LR and Goepfert, PA and Rouphael, N and El Sahly, HM and Gray, GE and Grinsztejn, B and Sobieszczyk, ME and Falsey, AR and Huang, Y and Janes, H and Follmann, D and Koup, RA and Priddy, F and Hendriks, J and Shoemaker, K and Dunkle, LM and de Bruyn, G and Devlin, L and Neuzil, KM and Kublin, JG and Corey, L and Walsh, SR and Kotloff, KL and Gilbert, PB},
title = {Impact of prior SARS-CoV-2 acquisition on binding and neutralizing antibody responses following COVID-19 vaccination: A cross-protocol analysis of individual-level data from six phase 3 clinical trials.},
journal = {Vaccine},
volume = {77},
number = {},
pages = {128380},
doi = {10.1016/j.vaccine.2026.128380},
pmid = {41730823},
issn = {1873-2518},
abstract = {BACKGROUND: The COVID-19 Prevention Network (CoVPN) co-conducted six COVID-19 phase 3 vaccine efficacy (VE) trials that featured harmonized immunogenicity analyses using validated antibody assays. These trials enabled a uniquely comprehensive characterization of immunogenicity produced by different vaccine platforms and regimens in individuals with and without prior SARS-CoV-2 acquisition.

METHODS: Comparisons of serum binding antibody concentration and serum neutralization antibody ID50 titers were performed across three strata: vaccine immunity (vaccination in SARS-CoV-2-naïve individuals), natural immunity (placebo with prior SARS-CoV-2 acquisition), and hybrid immunity (vaccination after prior SARS-CoV-2 acquisition). We compared immunogenicity across immunity strata for each trial and each dose, adjusting for age, sex assigned at birth, and body mass index. Antibody levels were also examined in relation to VE.

RESULTS: Antibody levels in response to a single vaccine dose varied across trials and generally increased most substantially after a second dose in naïve participants. Fold rise in antibody levels after a single dose were more pronounced in participants with hybrid immunity: a single dose of any of the tested vaccine yielded responses comparable to or exceeding the post-dose-two (peak) response of any two-dose vaccine in naïve participants. Population-level antibody levels demonstrated high concordance with VE across trials and immunity strata.

CONCLUSIONS: In SARS-CoV-2-naïve individuals, a two-dose vaccine regimen is needed to provide antibody levels correlated with protection against disease caused by the cognate virus strain. In contrast, in individuals with prior SARS-CoV-2 acquisition, a single dose of any of the tested vaccines/platforms (mRNA/protein/vector) provides comparably high antibody levels.},
}

@article {pmid41730389,
year = {2026},
author = {Chari, ST and Feng, Z},
title = {Reply to Zhu and Yang, to Scherübl, to Wan and Liu, and to Zhang.},
journal = {Gastroenterology},
volume = {},
number = {},
pages = {},
doi = {10.1053/j.gastro.2026.02.019},
pmid = {41730389},
issn = {1528-0012},
}

@article {pmid41730232,
year = {2026},
author = {Singal, AG and Jin, Q and Marrero, J and Parikh, ND and Lok, AS and Lopez, C and Page-Lester, S and Roberts, LR and Reddy, R and Luster, M and Khaderi, S and Asrani, SK and El-Serag, HB and Kanwal, F and Feng, Z and Tayob, N},
title = {Validation of longitudinal biomarker screening algorithms for HCC detection in patients with cirrhosis.},
journal = {Hepatology communications},
volume = {10},
number = {3},
pages = {},
pmid = {41730232},
issn = {2471-254X},
mesh = {Humans ; *Carcinoma, Hepatocellular/diagnosis/blood/etiology ; *Liver Neoplasms/diagnosis/blood/etiology ; Male ; Female ; Middle Aged ; *Liver Cirrhosis/complications/blood ; *Algorithms ; *Early Detection of Cancer/methods ; Aged ; *Biomarkers, Tumor/blood ; Longitudinal Studies ; Sensitivity and Specificity ; },
abstract = {BACKGROUND: Blood-based biomarker panels, including GALAD, have been proposed as an alternative to abdominal ultrasound for hepatocellular carcinoma (HCC) surveillance. Studies suggest longitudinal evaluation of biomarkers can improve test performance; however, no large studies have validated these findings.

METHODS: We leveraged the HCC Early Detection Strategy (HEDS) study (n=1019 patients with cirrhosis; 99 incident HCC) and Texas HCC Consortium (THCCC) (n=2345 patients with cirrhosis; 126 incident HCC) to compare the performance of fixed-threshold GALAD (cutoff of -1.36), and 4 longitudinal algorithms: longitudinal GALAD, PALAD, mFB-ALAD, and mPEB-ALAD. The HEDS cohort was used to derive longitudinal algorithms, and external validation was performed in THCCC. Patient-level sensitivity and test-level false-positive rate (FPR) were examined overall and across subgroups by age, sex, and cirrhosis etiology.

RESULTS: In THCCC, fixed-threshold GALAD had higher sensitivity in the 6 months before HCC diagnosis (71.4%, 95% CI: 62.9%-81.7%) than longitudinal GALAD (55.1%, 95% CI: 49.3-66.4), PALAD (55.1%, 95% CI: 50.0%-70.5%), mPEB-ALAD (53.1%, 95% CI: 43.6%-62.0%), and mFB-ALAD (42.9%, 95% CI: 32.3-48.5). However, fixed-threshold GALAD had a higher FPR (25.4%, 95% CI: 23.7%-26.9%) compared with longitudinal GALAD (15.0%, 95% CI: 12.8%-15.8%), PALAD (13.0%, 95% CI: 10.2%-14.6%), and mFB-ALAD (11.2%, 95% CI: 9.6%-12.1%) but comparable to mPEB-ALAD (22.9%, 95% CI: 21.2%-23.8%). In subgroup analyses, fixed-threshold GALAD had the highest FPR in males (35.6%) and those aged ≥65 (43.5%); longitudinal algorithms had significantly lower FPRs in subgroups but with lower sensitivity for HCC.

CONCLUSIONS: Improvements in FPRs with longitudinal GALAD algorithms, as compared with fixed-threshold GALAD, are offset by significantly decreased sensitivity for HCC detection.},
}

Humans
*Carcinoma, Hepatocellular/diagnosis/blood/etiology
*Liver Neoplasms/diagnosis/blood/etiology
Male
Female
Middle Aged
*Liver Cirrhosis/complications/blood
*Algorithms
*Early Detection of Cancer/methods
Aged
*Biomarkers, Tumor/blood
Longitudinal Studies
Sensitivity and Specificity

@article {pmid41730188,
year = {2026},
author = {Hong, SJH and Patton, M and Barton, KS and Palermo, TM and Mulholland, K and Chow, EJ and Lau, N},
title = {Facilitators and Barriers to Implementing Mobile Mental Health Interventions: Qualitative Study of the Consolidated Framework for Implementation Research in Pediatric Oncology Providers.},
journal = {Journal of medical Internet research},
volume = {28},
number = {},
pages = {e87533},
doi = {10.2196/87533},
pmid = {41730188},
issn = {1438-8871},
mesh = {Humans ; *Telemedicine ; Female ; Qualitative Research ; Adult ; Male ; Adolescent ; *Mobile Applications ; *Medical Oncology ; *Neoplasms/psychology/therapy ; *Mental Health ; Young Adult ; *Health Personnel ; Pediatrics ; Middle Aged ; },
abstract = {BACKGROUND: Adolescent and young adult (AYA) cancer survivors experience unique psychosocial needs during and after treatment. Mobile health (mHealth) interventions are an emerging area of research to help address unmet psychosocial needs. However, few studies have examined provider perspectives on the design-to-implementation pipeline.

OBJECTIVE: Guided by the Consolidated Framework for Implementation Research (CFIR), our study aimed to examine provider perspectives on facilitators and barriers to implementing mHealth apps in routine clinical care.

METHODS: AYA oncology providers participated in a semistructured 1:1 interview on facilitators and barriers to incorporating mHealth apps as psychosocial standard of care. We conducted a directed content analysis of the interviews using a standardized CFIR codebook and construct definitions, with codebook adaptations for mHealth innovations and the population of AYAs with cancer.

RESULTS: A total of 20 providers (mean 39, SD 7.0 years; 80% female and 70% non-Hispanic White) representing various medical and psychosocial roles participated in the interviews. The data were analyzed with 16 CFIR constructs. We identified the following facilitators to mHealth implementation across four CFIR domains: (1) Innovation: alignment with patient needs, patient-centered co-design, strong research evidence, and user-friendly design; (2) Outer Setting: shared commitment to addressing mental health needs and openness to mHealth use; (3) Inner Setting: openness to training on mHealth use; and (4) Individuals: engaging key implementation partners such as bedside nurses and social workers and strong clinical team buy-in. We identified the following barriers to mHealth implementation across three CFIR domains: (1) Innovation: associated costs, (2) Outer Setting: heavy clinical workloads, and (3) Inner Setting: lack of cross-team collaboration and communication and clinical workflow integration.

CONCLUSIONS: Our findings highlight key considerations for mHealth co-design, the adoption of mHealth apps into routine care, implementation strategies, and provider training opportunities in the context of AYA cancer care. Partnering with AYA cancer survivors, families, and providers will be crucial for developing and implementing mHealth apps with the ultimate goal of advancing universally accessible evidence-based digital health care.},
}

Humans
*Telemedicine
Female
Qualitative Research
Adult
Male
Adolescent
*Mobile Applications
*Medical Oncology
*Neoplasms/psychology/therapy
*Mental Health
Young Adult
*Health Personnel
Pediatrics
Middle Aged

@article {pmid41728684,
year = {2026},
author = {Chiusolo, P and Bacigalupo, A and Salit, R and Schroeder, T and Finazzi, MC and Gurnari, C and Pagliuca, S and Metzdorf, J and Rautenberg, C and Robin, M and Rubio, MT and Maciejewski, J and Popat, U and Rambaldi, A and Reinhardt, HC and Scott, B and Kröger, N and Gagelmann, N},
title = {PTCy or ATG for Matched Transplantation in Myelofibrosis.},
journal = {American journal of hematology},
volume = {},
number = {},
pages = {},
doi = {10.1002/ajh.70244},
pmid = {41728684},
issn = {1096-8652},
}

@article {pmid41728343,
year = {2026},
author = {Burugupally, G and Nakamura, M and Aarrestad, C and Parkhurst, SM},
title = {The LDL pathway regulates actomyosin ring dynamics necessary for optimal cell wound repair.},
journal = {microPublication biology},
volume = {2026},
number = {},
pages = {},
pmid = {41728343},
issn = {2578-9430},
abstract = {Individual cells must rapidly repair any cortical damage from environmental or physiological stresses, to survive and to contribute to maintaining the proper function of tissues and organs. The formation of an actomyosin ring around the wound periphery is an important step in physically closing the cell wound. Here, we find that the Low-Density Lipoprotein (LDL) pathway, which is usually associated with plasma membrane homeostasis, is needed for optimal cell wound repair. In this context, the LDL pathway is required for robust actomyosin ring formation, revealing an unexpected role in regulating actin dynamics during cell wound repair.},
}

@article {pmid41674614,
year = {2026},
author = {Kung, E and Deo, R and Choudhary, MC and Chew, KW and Evering, TH and Ignacio, RB and Jagannathan, P and Flynn, JP and Regan, J and Moser, C and Giganti, MJ and Hughes, MD and Ritz, J and Javan, AC and Greninger, AL and Singh, U and Fischer, W and Daar, ES and Wohl, DA and Eron, JJ and Currier, JS and Coombs, RW and Smith, DM and Li, JZ},
title = {Viral shedding and symptom severity across populations during acute COVID in the ACTIV-2 study.},
journal = {medRxiv : the preprint server for health sciences},
volume = {},
number = {},
pages = {},
pmid = {41674614},
abstract = {To evaluate the impact of sex on acute SARS-CoV-2 infection, 668 participants from the ACTIV-2/A5401 study were followed over a 28-day period. A primary analysis was performed on the 469 participants who had quantifiable viral loads at baseline. Male and female participants had comparable nasal SARS-CoV-2 RNA levels at study entry and throughout follow-up. However, sex-specific differences in viral shedding emerged when stratified by duration of symptoms. In the first three days from symptom onset, female participants exhibited higher nasal SARS-CoV-2 RNA levels than males, but lower viral RNA levels thereafter. The higher viral RNA levels in females during the earliest phase of acute COVID-19 was seen even after adjusting for age, race and region of enrollment. Female participants also tended to have higher symptom scores across days since symptom onset but no significant correlation was observed between nasal SARS-CoV-2 RNA levels and symptom score regardless of sex. These findings highlight the impact of sex on both viral shedding and symptom dynamics and underscore the importance of considering time since symptom onset when evaluating respiratory virus antiviral therapies in clinical trials.},
}

@article {pmid41726464,
year = {2024},
author = {Yaseen, F and , and Hippe, DS and Soni, PV and Wang, S and Duan, C and Gennari, JH and Bowen, SR},
title = {Variogram Modeling of Spatially Variant Early Response to Therapy in Advanced Non-Small Cell Lung Cancer.},
journal = {AMIA ... Annual Symposium proceedings. AMIA Symposium},
volume = {2024},
number = {},
pages = {1454-1463},
pmid = {41726464},
issn = {1942-597X},
mesh = {*Carcinoma, Non-Small-Cell Lung/therapy/pathology/diagnostic imaging ; Humans ; *Lung Neoplasms/therapy/pathology/diagnostic imaging ; },
abstract = {Predicting heterogeneity in treatment response for non-small cell lung cancer (NSCLC) at multiple scales, both between patients and spatially within each patient, can support clinical decisions that personalize oncologic management. In this study, we evaluated different variogram models of voxel-level spatial correlation in tumor response in locally advanced NSCLC and metastatic NSCLC from two different clinical trials. The Stable model achieved the lowest root mean squared error (RMSE) on average (mean: 5.2-5.5%), followed by the Matérn model (mean: 5.8-7.4%), both of which performed better than most other models. In contrast, the Exponential model had the highest RMSE (mean: 9.4-15.6%). These results remained consistent across two different cohorts of NSCLC. Given the robust performance of the Stable model, it may generalize for modeling spatial response in other clinical settings beyond NSCLC and should be further studied.},
}

*Carcinoma, Non-Small-Cell Lung/therapy/pathology/diagnostic imaging
Humans
*Lung Neoplasms/therapy/pathology/diagnostic imaging

@article {pmid41725518,
year = {2026},
author = {Kikawa, C and Loes, AN and Huddleston, J and Figgins, MD and Steinberg, P and Griffiths, T and Drapeau, EM and Peck, H and Barr, I and Englund, JA and Hensley, SE and Bedford, T and Bloom, JD},
title = {High-throughput neutralization measurements correlate strongly with evolutionary success of human influenza strains.},
journal = {eLife},
volume = {14},
number = {},
pages = {},
pmid = {41725518},
issn = {2050-084X},
support = {R01AI165821//National Institute of Allergy and Infectious Diseases/ ; 75N93021C00015/AI/NIAID NIH HHS/United States ; T32AI083203//National Institute of Allergy and Infectious Diseases/ ; },
mesh = {Humans ; *Influenza, Human/virology/immunology ; *Influenza A Virus, H3N2 Subtype/immunology/genetics/growth & development ; *Neutralization Tests/methods ; *Antibodies, Neutralizing/blood/immunology ; *Antibodies, Viral/blood/immunology ; Child ; Hemagglutinin Glycoproteins, Influenza Virus/genetics/immunology ; Adult ; *Evolution, Molecular ; Child, Preschool ; Adolescent ; Young Adult ; High-Throughput Screening Assays ; },
abstract = {Human influenza viruses rapidly acquire mutations in their hemagglutinin (HA) protein that erode neutralization by antibodies from prior exposures. Here, we use a sequencing-based assay to measure neutralization titers for 78 recent H3N2 HA strains against a large set of children and adult sera, measuring ~10,000 total titers. There is substantial person-to-person heterogeneity in the titers against different viral strains, both within and across age cohorts. The growth rates of H3N2 strains in the human population in 2023 are highly correlated with the fraction of sera with low titers against each strain. Notably, strain growth rates are less correlated with neutralization titers against pools of human sera, demonstrating the importance of population heterogeneity in shaping viral evolution. Overall, these results suggest that high-throughput neutralization measurements of human sera against many different viral strains can help explain the evolution of human influenza.},
}

Humans
*Influenza, Human/virology/immunology
*Influenza A Virus, H3N2 Subtype/immunology/genetics/growth & development
*Neutralization Tests/methods
*Antibodies, Neutralizing/blood/immunology
*Antibodies, Viral/blood/immunology
Child
Hemagglutinin Glycoproteins, Influenza Virus/genetics/immunology
Adult
*Evolution, Molecular
Child, Preschool
Adolescent
Young Adult
High-Throughput Screening Assays

@article {pmid41724648,
year = {2026},
author = {Gupta, S and Li, R and Hensley, PJ and Daneshmand, S and Faltas, BM and Grivas, P and Lobo, N and Mir, MC and Meeks, JJ and Mouw, KW and Moschini, M and Necchi, A and Oualla, K and Pohar, KS and Rosenberg, JE and Schmidt, B and Siefker-Radtke, AO and Steinberg, GD and Stenzl, A and Buckley, RJ and Kamat, AM},
title = {Optimal Management of Muscle-invasive Bladder Cancer: Recommendations from the International Bladder Cancer Group.},
journal = {European urology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.eururo.2026.01.029},
pmid = {41724648},
issn = {1873-7560},
abstract = {BACKGROUND AND OBJECTIVE: The management of muscle-invasive bladder cancer (MIBC) is evolving rapidly with the emergence of new perioperative treatments and approaches for bladder preservation. We provide guidance on clinical staging and optimal therapeutic sequencing for patients with MIBC in clinical practice and within the context of clinical trial design.

METHODS: The International Bladder Cancer Group (IBCG) convened global experts in bladder cancer to develop recommendations for the management of MIBC and to guide clinical trial design. Working groups reviewed the literature and developed draft recommendations. This was followed by voting by the IBCG members during a live meeting in August 2024 using a modified Delphi process. Recommendations achieving ≥75% agreement during the meeting were further refined and presented.

KEY FINDINGS AND LIMITATIONS: The IBCG recommends thorough clinical staging and multidisciplinary care for patients with MIBC. Contemporary retrospective comparisons suggest that radical cystectomy (RC) and trimodal therapy have similar oncologic efficacy. Patients with pure squamous-cell carcinoma or adenocarcinoma are best managed with upfront RC, while cisplatin-based neoadjuvant therapy before RC is recommended for other histologic subtypes. Risk-stratified adjuvant therapy approaches should be used after RC. There are no currently validated predictive biomarkers to guide clinical decision-making in MIBC outside the context of a clinical trial. The IBCG recommends the use of time-to-event endpoints for perioperative therapy trials, and bladder-intact event-free survival for bladder preservation trials, with an emphasis on incorporating patient-reported quality-of-life endpoints.

The IBCG consensus recommendations provide practical guidance on optimal treatment sequencing strategies in the management of MIBC.},
}

@article {pmid41724531,
year = {2026},
author = {Brück, CC and Mwangi, LW and van Wifferen, F and Hsu, L and Thomas, M and Peters, U},
title = {Risk-based screening for early detection of colorectal cancer: an overview.},
journal = {Best practice & research. Clinical gastroenterology},
volume = {80},
number = {},
pages = {102014},
doi = {10.1016/j.bpg.2025.102014},
pmid = {41724531},
issn = {1532-1916},
mesh = {Humans ; *Colorectal Neoplasms/diagnosis/epidemiology/genetics ; *Early Detection of Cancer/methods/economics ; Risk Assessment ; Risk Factors ; Cost-Benefit Analysis ; *Mass Screening/methods/economics ; },
abstract = {Screening programs for colorectal cancer (CRC) reduce CRC incidence and mortality, while balancing benefits and harms of the population. However, benefits vary widely among individuals. Low-risk individuals may face unnecessary burdens, while high-risk individuals could benefit from more intensive screening. Risk-based screening addresses these issues by tailoring screening strategies using risk factors such as age, sex, race, ethnicity, lifestyle factors, genetic predisposition, and previous screening results. Potential benefits of risk-based screening include improved cost-effectiveness, efficient resource use and reduced unnecessary procedures. Challenges include a lack of validated risk stratification tools, data availability, healthcare capacity, and ethical considerations. Several countries started to evaluate risk-based screening programs with optimistic results. While promising, further research is necessary to address the remaining challenges. Nevertheless, risk-based screening has the potential to enhance patient experiences, optimize the balance of individual-level benefits and harms, and positively impact the overall burden and costs associated with CRC screening.},
}

Humans
*Colorectal Neoplasms/diagnosis/epidemiology/genetics
*Early Detection of Cancer/methods/economics
Risk Assessment
Risk Factors
Cost-Benefit Analysis
*Mass Screening/methods/economics

@article {pmid41722572,
year = {2026},
author = {Abadie, FMC and Suiter, CC and Smith, NT and Daza, RM and Rominger, MC and Parrish, P and McDiarmid, TA and Lalanne, JB and Martin, B and Calderon, D and Ellison, A and Berger, AH and Shendure, J and Starita, LM},
title = {A multiplex, prime editing framework for identifying drug resistance variants at scale.},
journal = {Cell genomics},
volume = {},
number = {},
pages = {101167},
doi = {10.1016/j.xgen.2026.101167},
pmid = {41722572},
issn = {2666-979X},
abstract = {CRISPR-based genome editing has revolutionized functional genomics, enabling thousands of perturbations to be concurrently assayed in single experiments. However, for methods such as saturation genome editing (SGE), which aims to generate and assay libraries of point mutations, a challenge is that only one region (e.g., one exon) is studied per experiment. Here, we describe prime-SGE, a prime editing-based framework in which libraries of specific point mutations are installed into genes throughout the genome and then functionally assessed by sequencing of prime editing guide RNAs (pegRNAs) rather than the mutations themselves. We apply prime-SGE in two cell lines to assay thousands of point mutations in eight oncogenes for their ability to confer drug resistance to four tyrosine kinase inhibitors. Our prime-SGE strategy, combined with ongoing improvements in prime editing efficiency, opens the door to efficient positive selection screens of large numbers of point mutations at locations throughout the genome.},
}

@article {pmid41721421,
year = {2026},
author = {Kenny, A and Voldal, EC and Xia, F and Chan, KCG and Heagerty, PJ and Hughes, JP},
title = {Factors affecting power in stepped wedge trials when the treatment effect varies with time.},
journal = {Trials},
volume = {},
number = {},
pages = {},
doi = {10.1186/s13063-026-09558-x},
pmid = {41721421},
issn = {1745-6215},
support = {R37AI029168//National Institute of Allergy and Infectious Diseases/ ; },
abstract = {BACKGROUND: Stepped wedge cluster randomized trials (SW-CRTs) have historically been analyzed using immediate treatment (IT) models, which assume the effect of the treatment is immediate after treatment initiation and subsequently remains constant over time. However, recent research has shown that this assumption can lead to severely misleading results if treatment effects vary with exposure time, i.e., time since the intervention started. Models that account for time-varying treatment effects, such as the exposure time indicator (ETI) model, allow researchers to target estimands such as the time-averaged treatment effect (TATE) over an interval of exposure time, or the point treatment effect (PTE) representing a treatment contrast at one time point. However, this increased flexibility results in reduced power.

METHODS: In this paper, we use public power calculation software and simulation to characterize factors affecting SW-CRT power. Key elements include choice of estimand, study design considerations, and analysis model selection.

RESULTS: For common SW-CRT designs, the sample size (clusters per sequence or individuals per cluster-period) must be increased substantially, commonly by a factor of 1.5 to 3, but often by much more, to maintain 90% power when switching from an IT model to an ETI model (targeting the TATE over the study). However, the inflation factor is lower for TATE estimands over shorter periods that exclude longer exposure times. In general, SW-CRT designs (including the "staircase" variant) have much greater power for estimating "short-term effects" relative to "long-term effects." For an ETI model targeting a TATE estimand, substantial power can be gained by adding time points to the start of the study or increasing baseline sample size, but surprisingly, little power is gained from adding time points to the end of the study. More restrictive choices for modeling the exposure time or calendar time trends (e.g., splines or linear terms) have little effect on power for TATE estimands but increases power for PTE estimands. If the effect curve is constant after a washout period, a "delayed constant treatment" model that uses exposure time indicators during the washout period but assumes a constant effect thereafter can slightly increase power relative to an IT model that discards washout period data.},
}

@article {pmid41720947,
year = {2026},
author = {Hart, SFM and Alcala, N and Feder, AF and Harris, K},
title = {A signature-agnostic test for differences between tumor mutation spectra reveals carcinogen and ancestry effects.},
journal = {Communications biology},
volume = {},
number = {},
pages = {},
doi = {10.1038/s42003-026-09652-5},
pmid = {41720947},
issn = {2399-3642},
support = {2R35GM133428//U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS)/ ; T32-HG000035//U.S. Department of Health & Human Services | NIH | National Human Genome Research Institute (NHGRI)/ ; 24-0106/AICR_/Worldwide Cancer Research/United Kingdom ; 1DP2CA280623//U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)/ ; },
abstract = {Despite dozens of tools to identify mutational signatures in cancer samples, there is not an established metric for quantifying whether signature exposures differ significantly between two heterogeneous groups of samples. We demonstrate that a signature-agnostic metric - the aggregate mutation spectrum distance permutation method (AMSD) - can rigorously determine whether mutational exposures differ between groups, a hypothesis that is not directly addressed by signature analysis. First, we reanalyze a study of carcinogen exposure in mice, determining that eleven of twenty tested carcinogens produce significant mutation spectrum shifts. Only three of these carcinogens were previously reported to induce distinct mutational signatures, suggesting that many carcinogens perturb mutagenesis by altering the composition of endogenous signatures. Next, we interrogate whether patient ancestry has a measurable impact on human tumor mutation spectra, finding significant ancestry-associated differences across ten cancer types. Some have been previously reported, such as elevated SBS4 in African lung adenocarcinomas, while some have not to our knowledge been reported, such as elevated SBS17a/b in European esophageal carcinomas. These examples suggest that AMSD is a robust tool for detecting differences among groups of tumors or other mutated samples, complementing descriptive signature deconvolution and enabling the discovery of environmental and genetic influences on mutagenesis.},
}

@article {pmid41720775,
year = {2026},
author = {Scheck, R and Melzer, M and Gladkov, G and Leyre, L and Ward, AR and Reeves, DB and Perkins, N and Huynh, TT and McMahon, DK and Bosch, RJ and Macatangay, BJ and Cyktor, JC and Eron, JJ and Mellors, JW and Gandhi, RT and Buchauer, L and Jones, RB and Gaebler, C},
title = {Q4ddPCR: a flexible, 4-target assay for high-resolution HIV reservoir profiling.},
journal = {Nature communications},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41467-026-69413-0},
pmid = {41720775},
issn = {2041-1723},
support = {101162138//EC | EU Framework Programme for Research and Innovation H2020 | H2020 Excellent Science (H2020 Priority Excellent Science)/ ; Walter-Benjamin Stipendium, 549131684//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; R01 AI186721-01//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; UM1 AI068634, UM1 AI068636, UM1 AI106701//U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (NIAID)/ ; UM1 AI068634, UM1 AI068636, UM1 AI106701//U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (NIAID)/ ; UM1 AI068634, UM1 AI068636, UM1 AI106701//U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (NIAID)/ ; UM1 AI068634, UM1 AI068636, UM1 AI106701//U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (NIAID)/ ; UM1 AI068634, UM1 AI068636, UM1 AI106701//U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (NIAID)/ ; UM1 AI068634, UM1 AI068636, UM1 AI106701//U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (NIAID)/ ; UM1 AI068634, UM1 AI068636, UM1 AI106701//U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (NIAID)/ ; },
abstract = {Precise and scalable quantification of the intact HIV reservoir is critical for advancing curative strategies. Current reservoir assays, such as the intact proviral DNA assay (IPDA), are limited by quantification failures or misclassification of defective proviruses due to HIV sequence heterogeneity. Q4ddPCR is a modular, droplet digital PCR simultaneously targeting four conserved regions in the HIV genome to improve specificity, reduce quantification gaps, and provide multi-layered readouts. It comprises two configurations: one fully based on Q4PCR primer/probes and one combining IPDA with gag and pol primer/probes from Q4PCR. We benchmark Q4ddPCR against 3650 near full-length proviral sequences from 13 virally suppressed people with HIV (PWH) generated by Q4PCR. Q4ddPCR closely matches sequence-confirmed reservoir measurements, and multi-probe readouts reveal clonal reservoir dynamics not detectable by IPDA. Q4ddPCR enables intact reservoir quantification in 95% of samples across four independent cohorts and in 16 PWH, strongly correlates with viral outgrowth. In longitudinal samples from 42 participants over the first 4.5 years on antiretroviral therapy (ART), Q4ddPCR reports lower proviral frequencies and a steeper decline in intact proviral DNA compared to IPDA. Collectively, our findings confirm key predictions from mathematical modeling, demonstrating that multi-target assays improve specificity and more accurately capture intact reservoir dynamics.},
}

@article {pmid41720768,
year = {2026},
author = {Singh, R and Venkadakrishnan, VB and Imada, E and Yamada, Y and Brady, NJ and Dunmore, KE and Garner, R and Booker, MA and Hanratty, B and Haffner, MC and Tolstorukov, MY and Marchionni, L and Robinson, BD and Rickman, DS and Beltran, H},
title = {Crosstalk between EZH2 and DNA methylation mediates neuroendocrine prostate cancer lineage plasticity.},
journal = {Nature communications},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41467-026-69308-0},
pmid = {41720768},
issn = {2041-1723},
support = {R37CA241486-01A1//U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)/ ; W81XWH2210197//U.S. Department of Defense (United States Department of Defense)/ ; 23YOUNG15//Prostate Cancer Foundation (PCF)/ ; },
abstract = {Prostate cancer lineage plasticity is associated with changes in DNA methylation and enhancer of zeste homolog 2 (EZH2) activity. How these epigenetic programs functionally interact to modulate transcriptional reprogramming in neuroendocrine prostate cancer (NEPC) is not well understood. In this study, we demonstrate that hypomethylated regions of DNA preferentially accumulate the repressive mark, H3K27me3. We established an NEPC mouse model with deletion of Ezh2 in the background of Pten and Rb1 loss plus human MYCN overexpression. Deletion or pharmacological inhibition of EZH2 in NEPC murine or patient-derived models leads to a genome-wide rewiring of DNA methylation, characterized by hypomethylation and upregulation of neuroendocrine-lineage genes along with hypermethylation and repression of polycomb repressive complex 2 (PRC2) targets. On the other hand, deletion of DNA methyltransferase 1 (DNMT1) results in significant changes in H3K27me3 distribution, particularly affecting bivalent promoters bearing both H3K27me3 and active H3K4me3 marks. In NEPC models, neuroendocrine-lineage genes are repressed upon DNMT1 deletion associated with increased H3K27me3. Conversely, in prostate adenocarcinoma models, DNMT1 deletion leads to de-repression of neuroendocrine lineage genes with a loss of H3K27me3 marks. Our findings reveal a functional interplay between two repressive epigenetic machineries that mediates lineage plasticity in prostate cancer.},
}

@article {pmid41720427,
year = {2026},
author = {Motzer, RJ and Albiges, L and Aguirre, SAT and Kanesvaran, R and Centkowski, P and Reimers, MA and Sade, JP and Pouessel, D and Biscaldi, E and Esteban, E and Arranz Arija, JÁ and Tykodi, SS and van Kooten Losio, M and Dighe, A and Ma, H and Valmeekam, V and Simmons, A and Scheffold, C and Andrianova, S and Braun, DA and Powles, T and Choueiri, TK},
title = {Cabozantinib plus nivolumab and ipilimumab in previously untreated, advanced renal cell carcinoma: final results and biomarker analyses from the phase III COSMIC-313 study.},
journal = {Annals of oncology : official journal of the European Society for Medical Oncology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.annonc.2026.02.011},
pmid = {41720427},
issn = {1569-8041},
abstract = {BACKGROUND: Primary results from COSMIC-313 demonstrated significantly longer progression-free survival (PFS) with first-line cabozantinib plus nivolumab and ipilimumab versus placebo plus nivolumab and ipilimumab in patients with advanced renal-cell carcinoma (RCC). Final efficacy and safety results, as well as data from exploratory biomarker analyses, are reported here.

PATIENTS AND METHODS: The design, participants, and primary-endpoint PFS outcomes have been reported previously for this phase III, double-blind, randomized (1:1) study of cabozantinib or placebo plus nivolumab and ipilimumab in adults with previously untreated, advanced clear cell RCC. The secondary endpoint was overall survival (OS) in the intention-to-treat population. Exploratory biomarker analyses investigated the potential association between immune cell types and gene signatures with clinical outcomes.

RESULTS: After a median follow-up of 45.0 months, the updated median PFS in the cabozantinib (triplet) arm was longer than in the placebo (doublet) arm (16.6 versus 11.2 months; hazard ratio [HR] 0.82, 95% confidence interval [CI] 0.69-0.98]). There was no significant difference in median OS (HR 1.02, 95% CI 0.85-1.23, P = 0.84), and the safety profile was consistent with the earlier analysis (grade 3/4 treatment-related adverse events occurred in 75% and 43% of patients in the triplet and doublet arms, respectively). In patients with higher levels of M2-like macrophages, the triplet regimen was associated with significantly improved PFS and OS compared with the doublet regimen. Responders in the triplet arm exhibited elevated angiogenic signatures and reduced immune-related pathways, while responders in the doublet arm had robust immune activation.

CONCLUSIONS: Long-term results from COSMIC-313 continue to demonstrate a PFS benefit with the addition of cabozantinib to nivolumab and ipilimumab. There was no OS benefit and no new safety signals were observed. Exploratory biomarker analyses suggest adding cabozantinib to nivolumab and ipilimumab improves survival in patients with high levels of M2-like macrophages.},
}

@article {pmid41720346,
year = {2026},
author = {Xiao, J and Guo, D and Xing, X and Jiang, L and Qi, S and Wang, J and Bai, W and Yu, S and Shen, F and Guo, X and Wang, X and Zhou, W and Li, H and Zhao, F and Feng, L and Zhang, J and Xu, Y and Yang, D and Liu, H and Sun, D},
title = {Phloretin targeting the 3CLpro Cys144 exhibits broad-spectrum antiviral activity against swine enteric coronavirus.},
journal = {Virologica Sinica},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.virs.2026.02.011},
pmid = {41720346},
issn = {1995-820X},
abstract = {Swine enteric coronavirus (SECoVs) infections cause severe watery diarrhea and high mortality in piglets, resulting in significant economic losses to the global pig industry. However, frequent mutations in SECoVs significantly compromise vaccine-induced immunity while limiting cross-protection against emerging variants. Therefore, there is an urgent need to develop new broad-spectrum antiviral drugs to be the last line of defense to supplement vaccine immunity. In this study, we utilized molecular docking and molecular dynamics simulation to identify phloretin as a broad-spectrum SECoVs inhibitor. Phloretin has demonstrated prophylactic and therapeutic efficacy in vitro and in vivo, improving the survival of SECoV-infected piglets. It was further found that phloretin exerts a broad-spectrum antiviral effect by acting on the conserved 3CLpro Cys144 site of three SECoVs. It's worth noting that derivative A12, designed on the basis of the SAR between phloretin and 3CLpro, showed a 15.7-fold, 2.6-fold, and 8.4-fold increase in antiviral effect against porcine epidemic diarrhea virus (PEDV), transmissible gastroenteritis virus (TGEV), and porcine delta-coronavirus (PDCoV), respectively. This study reveals a 3CLpro Cys144 broad-spectrum targeting strategy for use against SECoVs, providing a candidate drug to bridge the vaccine immunity gap.},
}

@article {pmid41719110,
year = {2026},
author = {Beyrer, C and Ratevosian, J and Carpino, T and Rosenberg, NE and Gelderblom, HC and Sullivan, PS and Deeks, SG and Gray, G},
title = {The HIV/AIDS response as we knew it is over: Where do we go from here?.},
journal = {Journal of the International AIDS Society},
volume = {29},
number = {2},
pages = {e70077},
pmid = {41719110},
issn = {1758-2652},
mesh = {Humans ; *HIV Infections/prevention & control/drug therapy/epidemiology ; Global Health ; Pre-Exposure Prophylaxis ; *Acquired Immunodeficiency Syndrome/prevention & control/epidemiology/drug therapy ; Public Health ; },
abstract = {INTRODUCTION: The global HIV response, once a model of progress and innovation, faces a profound moment. Despite four decades of pivotal scientific and programmatic advances-most notably in antiretroviral therapy (ART) and pre-exposure prophylaxis (PrEP)-the world remains off track to meet the 2025 and 2030 targets for ending AIDS as a public health threat. New acquisitions and AIDS-related deaths remain unacceptably high, particularly among key populations and in low- and middle-income countries. The abrupt U.S. funding reversals in 2025 have severely disrupted support for HIV efforts. Cuts to U.S. and international institutions have compromised HIV prevention, treatment and surveillance systems worldwide, and may already have begun reversing two decades of progress.

DISCUSSION: To avert this crisis, the HIV and public health community, together with governments and global funders, must urgently invest in scaling long-acting treatment and prevention tools, rebuild disaggregated data systems and strengthen implementation science rooted in community-led approaches. Digital health technologies offer promise to enhance service delivery, surveillance, monitoring and evaluation, especially in resource-constrained settings, but demand ethical governance and infrastructure investment. The global research ecosystem must become more evenly distributed and inclusive, with a shift towards country-led partnerships, national data sovereignty and regional co-operation.

CONCLUSIONS: Looking to 2030 and beyond, the strategy to end HIV should include expanded access to long-acting ART and PrEP, sustained investments in HIV vaccine and cure research, and robust monitoring and evaluation systems. Achieving epidemic control-and ultimately ending the HIV pandemic-will require not only biomedical tools but also political will, community leadership and equitable financing. The lessons of the past underscore that sustained progress is possible, but only if we meet this moment with urgency, imagination and solidarity.},
}

Humans
*HIV Infections/prevention & control/drug therapy/epidemiology
Global Health
Pre-Exposure Prophylaxis
*Acquired Immunodeficiency Syndrome/prevention & control/epidemiology/drug therapy
Public Health

@article {pmid41718400,
year = {2026},
author = {Kuhlmann, AS and Peters, T and Hamlin, DK and Li, Y and Wang, X and Stackhouse, M and Cole, FM and Martinez-Reyes, J and Sandmaier, BM and Kiem, HP and Wilbur, DS and Harrington, RD and Pincus, SH},
title = {Comparative In Vitro Evaluation of Anti-HIV Immunotoxin, Antibody-Drug Conjugate, and Radioimmunoconjugate Targeted by the Same Antibody.},
journal = {Antibodies (Basel, Switzerland)},
volume = {15},
number = {1},
pages = {},
pmid = {41718400},
issn = {2073-4468},
support = {R01AI136758//National Institute of Allergy and Infectious Diseases/ ; P30 CA015704/CA/NCI NIH HHS/United States ; },
abstract = {BACKGROUND: We are developing cytotoxic immunoconjugates (CICs) to eliminate HIV-infected cells. We investigated the efficacy and kinetics of killing by different forms of CICs targeted by the same monoclonal antibody (mAb), an immunotoxin (IT), antibody-drug conjugate (ADC), and radioimmunoconjugate (RIC).

METHODS: We compared in vitro effects of CICs made by conjugating anti-gp41 mAb 7B2 to deglycosylated ricin A chain (7B2-dgA), the anthracycline derivative PNU-159682 (7B2-PNU), or the α-emitting isotope actinium-225 (7B2-[225]Ac). Kinetic analyses of cell growth were performed measuring electrical impedance every 15 min over a 7-day period using cells stably expressing the HIV envelope and Env-negative parent cells.

RESULTS: 7B2-dgA and 7B2-[225]Ac were more potent and acted more rapidly to kill cells than 7B2-PNU. Both the 7B2-PNU and 7B2-[225]Ac induced bystander-cell killing, whereas the IT did not and consequently allowed the outgrowth of Env-negative cells. Low dose or brief exposure to 7B2-PNU resulted in an increased rate of cell growth.

CONCLUSIONS: An IT, ADC, and RIC showed substantial differences in the degree of specific toxicity, kinetics, and mechanisms of killing. The results of this side-by-side comparison have implications for the development of CICs to treat HIV, as well as other conditions.},
}

@article {pmid41716520,
year = {2025},
author = {Friedman, EM and Wang, J and Weden, MM and Slaughter, ME and Shih, RA and Rutter, CM},
title = {Projected Demographic Trends in the Likelihood of Having or Becoming a Dementia Family Caregiver in the U.S. Through 2060.},
journal = {Populations},
volume = {1},
number = {2},
pages = {},
pmid = {41716520},
issn = {3042-4372},
support = {R21 AG055815/AG/NIA NIH HHS/United States ; },
abstract = {This study predicts how sociodemographic trends-smaller family sizes, increased longevity, and marital patterns-could affect family care for people with dementia through 2060. By coupling dementia information from the Health and Retirement Study with a well-established kinship microsimulation model, we analyze the impact of demographic changes on the future care landscape, focusing on changes in race and gender differences in two key areas: (1) the availability of family caregivers for people with dementia, and (2) the likelihood of having a family member with dementia, among those without dementia. Our model projections suggest that future dementia cohorts will be more likely to have a living spouse than the current ones, with diminishing gender disparities due to increased male longevity. However, racial disparities will persist, particularly for Black women. The likelihood of older adults lacking spouses, children, and siblings will increase, but remain low. For potential caregivers, we predict an increased likelihood and longer duration of exposure to family members with dementia in future birth cohorts, particularly for Black individuals, potentially placing more people at risk of the adverse health and well-being outcomes associated with caregiving.},
}

@article {pmid41716469,
year = {2026},
author = {Rankin, AW and Keating, AK and Abu-Arja, RF and Thakar, MS and Rangarajan, HG},
title = {Current and emerging maintenance strategies after stem cell transplantation in children and adolescents with acute leukemias.},
journal = {Molecular therapy. Oncology},
volume = {34},
number = {1},
pages = {201141},
pmid = {41716469},
issn = {2950-3299},
abstract = {Hematopoietic stem cell transplantation (HSCT) can promote durable long-term remissions for children and adolescents with high-risk acute leukemias. While many patients with acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) can achieve a cure, post-HSCT relapse remains a possibility for many. Recent therapeutic advances, particularly in the realm of targeted therapeutics, have revolutionized both first-line and relapsed/refractory management strategies, opening the door to more personalized and potentially less toxic approaches to treatment. Many of these agents have also either been proposed or have been actively investigated as having a role in the post-HSCT setting. Post-HSCT relapse often carries a dismal prognosis, and early prophylactic intervention has in many cases been shown to improve outcomes. Herein, we comprehensively review maintenance strategies for prevention of post-HSCT relapse of ALL and AML, with a specific focus on pediatric and adolescent populations. While drawing on experience in adult patients, we highlight data specific to pediatrics where available and draw attention to areas where further research in children and adolescents is needed. Future efforts aimed at determining who will benefit from, when to initiate and discontinue, and what agent(s) to employ as maintenance will be crucial to optimizing post-HSCT outcomes.},
}

@article {pmid41714624,
year = {2026},
author = {Paila, YD and Pajon, R and Banbury, B and Fields, P and Maglinao, M and De Rosa, SC and Morris, D and McElrath, MJ and Siangphoe, U and Cohen, KW and Paris, R},
title = {Potent and dose-sparing next-generation SARS-CoV-2 vaccine, mRNA-1283, induces polyfunctional and durable T cell immunity.},
journal = {NPJ vaccines},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41541-026-01402-2},
pmid = {41714624},
issn = {2059-0105},
support = {N/A//Moderna, Inc./ ; N/A//Moderna, Inc./ ; N/A//Moderna, Inc./ ; N/A//Moderna, Inc./ ; N/A//Moderna, Inc./ ; N/A//Moderna, Inc./ ; N/A//Moderna, Inc./ ; N/A//Moderna, Inc./ ; N/A//Moderna, Inc./ ; N/A//Moderna, Inc./ ; N/A//Moderna, Inc./ ; },
abstract = {Cell-mediated immunity contributes to durable protection against severe COVID-19, particularly as antibody responses wane or viral variants partially evade neutralization. Here, we characterize SARS-CoV-2-specific T cell responses elicited by a next-generation COVID-19 vaccine, mRNA-1283, which encodes the receptor-binding and N-terminal domains of the spike protein, in a phase 1 randomized clinical trial (NCT04813796). COVID-19-naïve, healthy adults (18-55 years) received two doses of mRNA-1283 (10 µg, 30 µg, or 100 µg), two doses of mRNA-1273 (100 µg; full-length spike comparator), or a single-dose regimen of mRNA-1283. Using intracellular cytokine staining, we show that two-dose regimens of mRNA-1283 or mRNA-1273 induce Th1-biased, polyfunctional spike-specific CD4+ and CD8+ T cell responses that were maintained through Day 209. TCRβ sequencing demonstrated significant increases in the breadth and frequency of SARS-CoV-2-associated TCRs, which correlated with functional spike-specific T cell responses. Therefore, the low-dose (10 µg) regimen of the next-generation COVID-19 vaccine, mRNA-1283, induces polyfunctional and durable CD4+ and CD8+ T cell immunity comparable to the standard 100 µg mRNA-1273 vaccine, supporting a dose-sparing strategy without compromising long-term cellular protection against severe COVID-19.},
}

@article {pmid41713639,
year = {2026},
author = {Jenkins, MT and Dubin, R and Dickerson, KM and Nguyen, P and Wang, J and Lee, SC and Lu, R and Welner, RS and Ferrell, PB},
title = {TET2 loss enhances early response to inflammation in primitive and committed myeloid cells.},
journal = {Experimental hematology},
volume = {},
number = {},
pages = {105383},
doi = {10.1016/j.exphem.2026.105383},
pmid = {41713639},
issn = {1873-2399},
abstract = {In vivo IL-1β exposure elicits enhanced hematopoietic stem cell (HSC) self-renewal and myeloid priming in Tet2[KO] mice, but information on how Tet2[KO] affects the early transcriptional response to IL-1β is lacking. To address this, we used an inducible, in vitro model of myeloid differentiation coupled with RNA-sequencing (RNAseq) to study the effects of Tet2[KO] on short-term IL-1β stimulation. In both Tet2[KO] progenitor and differentiated states, we identified baseline increases in expression of several cytokine signaling receptors, including Il1r1, as well as increases in inflammasome components. Interaction effect modeling revealed that loss of TET2 and IL-1β stimulation collaborate, leading to significant increases in both inflammatory cytokine expression and regulators of proliferation and differentiation in the progenitor state, and elevated cytokine production in differentiated cells. We then show that IKK-complex inhibition prevents both the IL-1β-induced proliferation of Tet2[KO] progenitors and TNFα production in differentiated myeloid cells, highlighting a potential therapeutic target in TET2-deficient cells. Teaser Abstract: TET2 loss and IL-1β stimulation collaborate to induce cytokine expression as well as proliferation and differentiation related transcription factors in myeloid progenitors, while differentiated myeloid cells lacking TET2 produce a much larger, more diverse repertoire of inflammatory cytokine transcripts. Both of these cell-state specific effects of TET2 loss were countered with IKK-complex inhibition, highlighting a potential therapeutic avenue for clonal blood disorders.},
}

@article {pmid41713588,
year = {2026},
author = {Akaike, T and Thakuria, M and Silk, AW and Hippe, DS and Ch'en, PY and Guja, KE and Youn Park, S and Tsai, K and Yom, SS and Yu, SS and Choi, J and Chandra, S and Nghiem, PT and Zaba, LC},
title = {Response to Gao and Chen, "Comments on Akaike et al.'s 'Circulating tumor DNA level is associated with time to clinical recurrence in Merkel cell carcinoma: Implications for patient management'".},
journal = {Journal of the American Academy of Dermatology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jaad.2026.01.094},
pmid = {41713588},
issn = {1097-6787},
}

@article {pmid41709952,
year = {2026},
author = {Eyrich, NW and Huang, Y and Zheng, Y and Wei, J and Sokoll, L and Chan, DW and Patil, D and Chinnaiyan, A and Tomlins, SA and Lotan, Y and Lin, D and Scherr, D and Wang, Y and Kibel, A and Taneja, SS and Bidair, M and Thompson, IM and Sanda, MG and Narayan, VM},
title = {Combining Serum Prostate Health Index With Urinary PCA3 and TMPRSS2:ERG RNA Testing Improves Detection of Clinically Significant Prostate Cancer.},
journal = {JU open plus},
volume = {4},
number = {2},
pages = {e00019},
pmid = {41709952},
issn = {2771-554X},
abstract = {PURPOSE: We sought to determine whether combining prostate health index (Phi) with urinary prostate cancer antigen 3 (PCA3) and TMPRSS2:ERG (T2:ERG) could improve selection of men for prostate biopsy. These biomarkers have been validated in prostate cancer (PCa) detection separately, but their combination has not previously been developed.

MATERIALS AND METHODS: Prebiopsy blood and post-digital rectal examination urine specimens were assayed to predict subsequent biopsy outcomes from training and validation cohorts (1073 participants across 11 academic centers). Clinical algorithms for combining Phi and PCA3-T2:ERG to predict Grade Group ≥ 2 (GG ≥ 2) PCa were formulated using the training cohort (N = 512). Prediction rules and hypotheses were locked before validation using biopsy-naïve men from the NCI Early Detection Research Network urinary PCA3 trial (N = 561). Rules were compared in weighted sum of specificity and sensitivity with weights specified a priori, and P values were obtained through bootstrap in the validation study.

RESULTS: Primary validation analysis showed that Phi combined with urinary PCA3 outperformed Phi alone (P = .002). Furthermore, serum Phi combined with urinary PCA3-T2:ERG outperformed urinary PCA3-T2:ERG in each of the 3 algorithms reflecting different potential clinical workflows: (1) serum Phi and urine PCA3-T2:ERG tested simultaneously, either exceeding its own threshold (P = .04); (2) urine PCA3-T2:ERG first and those in the grey zone resolved by subsequent serum Phi (P = .03); and (3) serum Phi first and those in the grey zone resolved by subsequent urine PCA3-T2:ERG (P = .002).

CONCLUSIONS: Combining serum Phi with urinary PCA3 RNA alone or together with urinary T2:ERG RNA, simultaneously or sequentially, improves selection of men for initial prostate biopsy and represents an avenue to improve early detection of aggressive PCa.},
}

@article {pmid41708595,
year = {2026},
author = {Moses, AB and Yeh, AC},
title = {The gut microbiome in graft-versus-host disease: mechanisms of immune modulation and therapeutic approaches.},
journal = {Gut microbes},
volume = {18},
number = {1},
pages = {2631224},
doi = {10.1080/19490976.2026.2631224},
pmid = {41708595},
issn = {1949-0984},
mesh = {*Graft vs Host Disease/immunology/therapy/microbiology ; Humans ; *Gastrointestinal Microbiome/immunology ; Animals ; Hematopoietic Stem Cell Transplantation/adverse effects ; Immunity, Innate ; T-Lymphocytes/immunology ; Gastrointestinal Tract/microbiology/immunology ; Adaptive Immunity ; Probiotics/administration & dosage ; },
abstract = {Graft-versus-host disease (GvHD) remains a major complication of allogeneic hematopoietic stem cell transplantation and occurs when T cells from the donor graft target recipient-derived antigen on host tissue. The involvement of the gastrointestinal (GI) tract drives morbidity and mortality-not coincidentally, the GI tract also harbors the most complex and abundant human microbial reservoir. In this review, we first revisit how the microbiota initiates, propagates, and protects against GvHD in the context of both innate and adaptive immunity. Historically, the impact of the microbiota on GvHD has been ascribed primarily to the activation of innate immunity, setting the stage for donor alloreactivity. Although established models of GvHD focus on donor-host genetic disparity as the principal driver of donor T-cell activation, commensal microbes in the GI tract, whose collective gene content exceeds that of the human genome by more than two orders of magnitude, constitutes an immense and poorly understood source of potential T-cell antigens. We next discuss the evolution of therapeutic approaches aimed at modifying the microbiota to improve GvHD outcomes, incorporating over 40 clinical studies spanning the last 40 years, from broad decontamination strategies to pre/probiotic approaches and targeted ecosystem replacement, including fecal microbiota transplantation.},
}

*Graft vs Host Disease/immunology/therapy/microbiology
Humans
*Gastrointestinal Microbiome/immunology
Animals
Hematopoietic Stem Cell Transplantation/adverse effects
Immunity, Innate
T-Lymphocytes/immunology
Gastrointestinal Tract/microbiology/immunology
Adaptive Immunity
Probiotics/administration & dosage

@article {pmid41707657,
year = {2026},
author = {Chhan, CB and Lang, K and Davis, AR and Wan, YH and Aldridge, NT and Kher, G and Scharffenberger, SC and Hardy, SR and Iureniev, R and Giltiay, NV and Edwards, KR and Radtke, S and Kiem, HP and Pancera, M and McGuire, AT},
title = {Transgenic mouse-derived human monoclonal antibodies targeting EBV gp350 and gp42 provide basis for therapeutic development.},
journal = {Cell reports. Medicine},
volume = {7},
number = {2},
pages = {102618},
pmid = {41707657},
issn = {2666-3791},
mesh = {Animals ; Mice, Transgenic ; Humans ; *Herpesvirus 4, Human/immunology ; *Antibodies, Monoclonal/immunology ; Mice ; Epstein-Barr Virus Infections/immunology ; Antibodies, Neutralizing/immunology ; B-Lymphocytes/immunology ; *Antibodies, Viral/immunology ; },
abstract = {Epstein-Barr virus (EBV) causes infectious mononucleosis and contributes to neurodegenerative disorders and malignancies, particularly in immune-compromised hosts. Transplant patients face high risk of post-transplant lymphoproliferative disease, a life-threatening EBV-driven lymphoma. There are no EBV-specific vaccines or treatments; however, neutralizing antibodies against EBV glycoproteins may offer utility as therapeutic agents. EBV entry into B cells involves gp350, which binds complement receptors, and gp42, which engages HLA class II to trigger fusion. Most existing monoclonal antibodies (mAbs) against these antigens are non-human, limiting clinical use. Using a transgenic mouse model, we generate two gp350 and eight gp42 genetically human neutralizing mAbs that block receptor binding. Structural analyses reveal extended sites of vulnerability relevant to vaccine development. Delivery of a gp42 mAb protects humanized mice from EBV challenge, while a gp350 mAb provides partial protection. These mAbs highlight the utility of transgenic mice to produce therapeutic mAbs for preventing EBV-driven disease.},
}

Animals
Mice, Transgenic
Humans
*Herpesvirus 4, Human/immunology
*Antibodies, Monoclonal/immunology
Mice
Epstein-Barr Virus Infections/immunology
Antibodies, Neutralizing/immunology
B-Lymphocytes/immunology
*Antibodies, Viral/immunology

@article {pmid41659606,
year = {2026},
author = {Barnett, EE and Castillo, A and Du Plessis, IA and Kistler, K and Carrillo, L and Leon, AS and Liu, T and Rutherford, MG and Ploug, J and McCrone, JT and Ávila-Arcos, MC and Blanco-Melo, D},
title = {Recovery of an 18[th] Century Rhinovirus Genome through Ancient RNA Isolation of Human Lungs.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {41659606},
issn = {2692-8205},
support = {DP2 AI177896/AI/NIAID NIH HHS/United States ; },
abstract = {RNA viruses cause substantial global morbidity, yet their impact prior to the twentieth century remains obscured. While ancient DNA studies have transformed our understanding of past pathogens, ancient RNA (aRNA) isolation is largely restricted to exceptionally preserved samples. Here, we simultaneously recover aDNA and aRNA from non-formalin-fixed human lung specimens and reconstructed an 18th-century Human Rhinovirus (HRV) A genome-the oldest human RNA virus identified to date. The RNA is highly fragmented, with distinctive terminal misincorporations and coverage patterns consistent with double-stranded RNA. Phylogenetic analyses indicate that this historical HRV genome is an extinct lineage related to contemporary genotypes, providing a unique perspective on rhinovirus evolution. These findings demonstrate that centuries-old medical specimens can retain informative aRNA, expanding the temporal scope of paleovirology.},
}

@article {pmid41659500,
year = {2026},
author = {Lieberman, NAP and Garcia, LN and Mohamed Bakhash, SAK and Furlong, J and Nunley, BE and Rabinovich, A and Pardal, PF and Leiro, V and Xie, H and Aghakhanian, F and Passos, MRL and Campos Arze, WN and Andrade, HB and Vargas, SK and Konda, KA and Diaz, MR and Caceres, C and Klausner, JD and Parr, JB and Seña, A and Manathunge, A and Giacani, L and Altcheh, J and Greninger, AL},
title = {Lineage-specific tprK diversification and Treponema pallidum transmission dynamics in Buenos Aires, Argentina.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {41659500},
issn = {2692-8205},
support = {INV-036560/GATES/Gates Foundation/United States ; R01 AI139265/AI/NIAID NIH HHS/United States ; },
abstract = {BACKGROUND: Syphilis rates are rising globally, with increases in congenital syphilis in South America particularly concerning. The characterization of contemporary South American Treponema pallidum (Tp) strains is crucial to syphilis vaccine development, yet few genomic epidemiology studies have focused on this region. Here, we performed whole genome sequencing of Tp from Buenos Aires, Argentina, as well as deep sequencing of the hypervariable tprK locus, which is critical to Tp immune evasion.

METHODS: People with primary, secondary, or congenital syphilis were enrolled at two clinics in Buenos Aires between October 2018 and January 2023, including individuals associated with intra-household transmission. Tp DNA from swabs was quantified by tp0574 qPCR, and whole-genome sequencing was performed on samples with sufficient treponemal burden. Tp reads were assembled to the SS14 strain reference genome, recombinant regions masked, and a core genome phylogeny was generated. Full-length tprK was sequenced using PacBio reads.

FINDINGS: Tp genomes were recovered from 96 samples from 70 individuals in Buenos Aires and primarily belonged to globally dominant SS14 sublineage-1 and Nichols sublineage-8, as did Tp recovered from contemporary samples from Brazil (n=8). Peruvian samples (n=3) all belonged to sublineage-1. Two individuals from Buenos Aires had co-infections with Nichols- and SS14-lineage strains. Macrolide resistance via A2058G mutation occurred in 27/70 (39%) samples. Across 56 samples, tprK allelic diversity was significantly increased in secondary syphilis, oral lesions, and SS14-lineage strains compared to primary syphilis, anogenital lesions, and Nichols-lineage strains, respectively. Increased tprK diversity in SS14-lineage strains is driven by an enhanced repertoire of V7-specific donor sequences. Using multiple approaches, tprK sequences from intra-household transmission events were more similar than unrelated samples with identical core genomes.

INTERPRETATION: Tp circulating in South America is closely related to dominant global sublineages. Increased tprK diversity in the SS14 lineage may influence Tp's ability to escape host adaptive immunity. We confirmed that tprK profiling is a promising tool to elucidate syphilis transmission networks. This study underscores the utility of genomics to yield insights into Tp pathogenesis.},
}

@article {pmid41659404,
year = {2026},
author = {Zhang, Y and Zhao, X and Wang, H and Hu, YM and Sun, XX and Zhao, F and Du, S and Dai, RS and Andeen, NK and Sears, RC and Corey, E and Brody, JR and Alumkal, JJ and Mills, GB and Nelson, PS and Dai, MS and Xia, Z},
title = {Global mRNA 3'UTR lengthening in small-cell neuroendocrine carcinoma.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {41659404},
issn = {2692-8205},
support = {R01 CA251245/CA/NCI NIH HHS/United States ; R01 GM147365/GM/NIGMS NIH HHS/United States ; P01 CA298991/CA/NCI NIH HHS/United States ; S10 OD034224/OD/NIH HHS/United States ; R01 CA282005/CA/NCI NIH HHS/United States ; R01 CA262104/CA/NCI NIH HHS/United States ; P01 CA163227/CA/NCI NIH HHS/United States ; R01 CA266452/CA/NCI NIH HHS/United States ; P50 CA097186/CA/NCI NIH HHS/United States ; R01 CA280056/CA/NCI NIH HHS/United States ; },
abstract = {Small-cell neuroendocrine carcinoma (SCNC) is a rare but highly malignant tumor subtype that primarily arises in the lung, also rarely in other organs, and as a consequence of treatment induced lineage transdifferentiation of prostate adenocarcinomas. The molecular convergence of SCNC across diverse tissues enables its identification through conserved SCNC-specific molecular markers, facilitating tumor subtype classification. As a critical post-transcriptional regulatory mechanism, alternative polyadenylation (APA) modulates 3'UTR length and significantly impacts tumor progression. However, its role in SCNC remains largely unclear. Here, we report a global 3'UTR lengthening pattern driven by APA in SCNC. We identified a set of conserved 3'UTR lengthening events across SCNCs of different tissue origins, which are strongly associated with neural development and related signaling pathways. Furthermore, we developed a neural network-based prediction model to classify SCNC by leveraging these specific APA signatures. Our study provides new insights into the post-transcriptional landscape of SCNCs and highlights APA signatures as promising biomarkers for SCNC identification.},
}

@article {pmid41706623,
year = {2026},
author = {Dontchos, BN and Narayan, AK and Grimm, LJ and Edmonds, CE and Lam, DL and Lawson, MB and Miles, RC},
title = {The Advantages and Disadvantages of Same-Day Breast Imaging Services: Clinical Review, Implications, and Future Directions.},
journal = {Journal of breast imaging},
volume = {},
number = {},
pages = {},
doi = {10.1093/jbi/wbaf061},
pmid = {41706623},
issn = {2631-6129},
abstract = {Combining patient services into fewer clinical visits has been increasingly explored across medical specialties as more attention is given to patient-centered care, patient access, and care delivery efficiency from health enterprises. The typical breast imaging care model requires multiple clinical visits to achieve a final diagnosis and, therefore, might be optimized to perform 2 or more steps in the process in 1 patient clinical visit. Recent studies suggest that this model can mitigate patient disparities in timeliness of care, improve patient satisfaction, and even improve patient adherence. Despite the potential benefits, there is variability in the use of same-day services across breast imaging facilities because of various local/institutional level barriers, staffing limitations, and concerns about interpreting examinations in real time. In this review, we describe the various same-day models that have been reported in the breast imaging literature, discuss their impact, and present evidence that may support further adoption of these care models. We also explore the barriers and limitations to this model and future directions of same-day services.},
}

@article {pmid41707096,
year = {2026},
author = {Mulenga, H and Mendelsohn, SC and Fiore-Gartland, A and Penn-Nicholson, A and Musvosvi, M and Tameris, M and Walzl, G and Naidoo, K and Churchyard, G and Scriba, TJ and Hatherill, M},
title = {Risk factors for immunological sensitization to Mycobacterium tuberculosis and progression to incident TB disease among HIV-uninfected adults in a high burden setting.},
journal = {The Journal of infectious diseases},
volume = {},
number = {},
pages = {},
doi = {10.1093/infdis/jiag100},
pmid = {41707096},
issn = {1537-6613},
abstract = {BACKGROUND: Identifying risk factors for Mtb sensitization (defined as IGRA-positive) and progression to TB disease is critical to guide targeted prevention strategies.

METHODS: We analyzed data from a prospective cohort of adults (18-60 years) without HIV, enrolled at five high-incidence South African sites. Participants underwent testing for Mtb sensitization and microbiologically-confirmed TB at baseline, and during 15 months follow-up. Multivariable logistic and Cox regression models were used to assess factors associated with Mtb sensitization and TB progression. Sampling weights were applied to reflect the screened population.

RESULTS: Among 2,912 participants with valid IGRA results, 63.4% (n=1895) were Mtb-sensitized. Prevalent TB was detected in 1.81% (62/1895) of Mtb-sensitized versus 0.62% (12/1017) of Mtb-unsensitized individuals (p=0.01). During follow-up of participants without prevalent TB, 2.01% (48/1833) Mtb-sensitized and 0.53% (8/1005) Mtb-unsensitized individuals developed TB (p=0.01). Factors associated with Mtb sensitization included increasing age (adjusted-odds-ratio; aOR=1.02 , 95%CI 1.01-1.03), male sex (aOR=1.34, 95%CI 1.08-1.67), smoking (aOR=1.31, 95%CI 1.05-1.64), prior TB (aOR=2.20, 95%CI 1.40-3.47), and TB contact history (aOR=1.40, 95%CI 1.08-1.83). Risk factors for progression to TB were Mtb sensitization (adjusted-hazard-ratio; aHR=3.05, 95%CI 1.14-8.18), smoking history (aHR=2.34, 95%CI 1.03-5.31), and lower body-mass index (aHR=0.89, 95%CI 0.82-0.97).

CONCLUSION: Mtb-sensitized individuals had a three-fold higher risk of prevalent TB and progressing to TB compared to Mtb-unsensitized individuals. In high-prevalence settings, identifying individuals at greatest risk-such as those recently infected, with a history of smoking, or low BMI-could help refine TB prevention efforts and reduce community-level transmission.},
}

@article {pmid41706088,
year = {2026},
author = {Pidala, J and Onstad, L and Carpenter, P and Hamilton, BK and Kitko, CL and Juckett, M and Cutler, C and Lee, SJ},
title = {Longitudinal Study of Late Acute and Chronic Graft-Versus-Host Disease after Allogeneic Hematopoietic Cell Transplantation: A Long-Term Follow-up Study from the Chronic Graft-Versus-Host Disease Consortium.},
journal = {Transplantation and cellular therapy},
volume = {32},
number = {2},
pages = {205.e1-205.e12},
pmid = {41706088},
issn = {2666-6367},
support = {R01 CA118953/CA/NCI NIH HHS/United States ; U54 CA163438/CA/NCI NIH HHS/United States ; },
mesh = {Humans ; *Graft vs Host Disease/etiology/mortality/pathology ; *Hematopoietic Stem Cell Transplantation/adverse effects ; Female ; Male ; Middle Aged ; Adult ; Longitudinal Studies ; Chronic Disease ; Follow-Up Studies ; Transplantation, Homologous ; Acute Disease ; Adolescent ; Young Adult ; Aged ; Bronchiolitis Obliterans/etiology ; Child ; },
abstract = {Late acute and chronic graft-versus-host disease (GVHD) contribute to morbidity and death after allogeneic hematopoietic cell transplantation (HCT). A prior national Chronic GVHD Consortium longitudinal study enrolled patients pre- or early post-HCT and identified the incidence of late acute GVHD, chronic GVHD, and chronic GVHD subtypes of bronchiolitis obliterans syndrome (BOS) and cutaneous sclerosis. We now report 10-yr follow-up from that study in a long-term follow-up analysis (N = 911 subjects). Late acute GVHD occurred in 11% at a median of 5.5 mo. Chronic GVHD in total occurred in 54% with median onset of 7.4 mo. BOS (4% of subjects, median onset 12.6 mo) and cutaneous sclerosis (10% of subjects, median onset of 17.2 mo) were less frequent and had later-onset. The long-term analysis demonstrated additional GVHD events occurring beyond 1 to 2 yr post-HCT. Inter-conversion between GVHD types was common, and notably included new development of BOS and cutaneous sclerosis after initial chronic GVHD presentation without these manifestations. GVHD-free, relapse-free survival (GVHD-DFS, survival without relapse or development of late acute or chronic GVHD) was 22% at 2 yr, 18% at 5 yr, and 15% at 10 yr post-HCT. Non-relapse mortality continued to increase beyond 2 yr, with 10-yr estimates up to 35% (late acute), 31% (chronic GVHD), 62% (BOS), and 36% (cutaneous sclerosis). Durable complete discontinuation of immune suppression was uncommon for all GVHD types. These data suggest that extended surveillance for late acute and chronic GVHD is needed post-HCT due to late occurrences, and that associated mortality is high through 10 yr post-GVHD onset.},
}

Humans
*Graft vs Host Disease/etiology/mortality/pathology
*Hematopoietic Stem Cell Transplantation/adverse effects
Female
Male
Middle Aged
Adult
Longitudinal Studies
Chronic Disease
Follow-Up Studies
Transplantation, Homologous
Acute Disease
Adolescent
Young Adult
Aged
Bronchiolitis Obliterans/etiology
Child

@article {pmid41705757,
year = {2026},
author = {Onerup, A and Liu, Q and Izumi, S and Martínez-Martínez, JM and Dixon, SB and Chow, EJ and Hudson, MM and Snyder, C and Nathan, PC and Armstrong, GT and Ness, KK and Yasui, Y},
title = {Potential of Exercise for Prevention of Cardiovascular Disease in Survivors of Childhood Hodgkin Lymphoma.},
journal = {JACC. CardioOncology},
volume = {8},
number = {1},
pages = {87-89},
doi = {10.1016/j.jaccao.2025.11.002},
pmid = {41705757},
issn = {2666-0873},
}

@article {pmid41705755,
year = {2026},
author = {Fiorica, PN and Zimbalist, A and Sheng, H and Laurent, CA and Roh, JM and Lee, VS and Ergas, IJ and Delmerico, J and Zhu, Q and Cheng, RK and Rillamas-Sun, E and Iribarren, C and Rana, JS and Nguyen-Huynh, M and Hershman, DL and Ambrosone, CB and Kushi, LH and Greenlee, H and Kwan, ML and Yao, S},
title = {Polygenic Risk for Cardiometabolic and Cardiovascular Disease in a Multiethnic Cohort of Breast Cancer Survivors.},
journal = {JACC. CardioOncology},
volume = {8},
number = {1},
pages = {65-76},
doi = {10.1016/j.jaccao.2025.10.004},
pmid = {41705755},
issn = {2666-0873},
abstract = {BACKGROUND: Because of cancer treatment-related cardiotoxicities, women with histories of breast cancer are at increased risk for cardiovascular disease (CVD). Many polygenic scores (PGS) have been developed for predicting risk for CVD-related conditions in the general population, but their performance in breast cancer patients remains largely unexplored.

OBJECTIVES: The aim of this study was to examine the performance of PGS for CVD-related traits to predict incident cardiometabolic disorder (CMD) and CVD in women with histories of breast cancer.

METHODS: In a prospective multiethnic cohort of 3,620 breast cancer survivors, 27 PGS for CVD-related traits were we computed, and their associations with 12 incident CMD and CVD events were examined. The performance of these PGS was compared relative to clinical covariates-only models and by cardiotoxic cancer treatment.

RESULTS: Twenty-three significant associations were identified after Bonferroni correction between PGS and CMD or CVD events in breast cancer patients. Although the model performance of PGS and multi-PGS added to or combined with clinical models for CMD and CVD risk prediction was numerically greater, these were not statistically significant. For some outcomes, PGS performed worse among patients who received cardiotoxic cancer treatments.

CONCLUSIONS: Although there may be potential value of PGS in predicting the risk for CMD and CVD events in women with histories of breast cancer, current PGS performance is limited. This work highlights the need to develop de novo PGS in breast cancer patients and to include ancestrally diverse patient populations.},
}

@article {pmid41705193,
year = {2026},
author = {Boppana, S and Blosser, CD and Webber, AB and Gupta, G and Singh, N and Master, S and Parasuraman, R and Campagnaro, EL and Java, A and Sprangers, B and Bhasin-Chhabra, B and Lum, EL and Khirfan, D and Alexander, M and Leung, N and Landau, H and Murakami, N},
title = {Clinical practice pattern of management of plasma cell dyscrasia for kidney transplant candidates and recipients in the United States.},
journal = {Journal of onco-nephrology},
volume = {},
number = {},
pages = {},
pmid = {41705193},
issn = {2399-3707},
support = {K08 DK120868/DK/NIDDK NIH HHS/United States ; },
abstract = {BACKGROUND: Plasma cell dyscrasia (PCD) is a rare but important cause of end stage kidney disease (ESKD). Kidney transplant is the treatment of choice in patients with ESKD. However, the complexity of PCD care and risk of disease recurrence poses challenges to kidney transplant candidacy and outcomes. We examined the current clinical practice patterns of clinicians who care for patients with PCD and identified barriers to kidney transplantation for patients with PCD.

METHODS: A web-based survey was developed and distributed from January to July 2024 to kidney transplant clinicians (American Society of Transplant (AST) members), hematologists (PCD experts), and onco-nephrologists.

RESULTS: Seventy clinicians (50 transplant nephrologists, 18 hematologists, and two surgeons) from 42 transplant centers in the US participated in the survey. Clinical practice patterns pre and post kidney transplant for patients with PCD are highly variable among institutions, and only 36% reported having a protocol for pre- and post-transplant management for patients with PCD. Particularly, the requirement for pre-transplant hematologic remission criteria, induction and maintenance immunosuppression regimens and protocols for prophylaxis and screening for opportunistic infection are areas of future study. Clinicians listed lack of data and practice guidance as well as communication challenges among multiple specialties especially hematology and kidney transplant clinicians as notable barriers.

CONCLUSIONS: Our study identified the highly variable current practice patterns when evaluating and managing patients with PCD for kidney transplant. Our findings emphasize the need for collecting and sharing clinical data to support standardized practices and serve as a basis for the upcoming multi-societal management recommendation for kidney transplant for patients with PCD.},
}

@article {pmid41703731,
year = {2026},
author = {Pitcher, TJ and Long, KJ and Kammer, MN and Schuldheisz, S and Bajantri, B and Gleeson, T and Zanchi, D and Bansal, S and Yuhico, L and Peek, LJ and Jett, JR and Nair, VS and Silvestri, GA},
title = {Validation of a blood-based autoantibody test to assess lung cancer risk in 4-30 mm pulmonary nodules: a retrospective pooled analysis of four cohort studies.},
journal = {Future oncology (London, England)},
volume = {},
number = {},
pages = {1-12},
doi = {10.1080/14796694.2026.2626339},
pmid = {41703731},
issn = {1744-8301},
abstract = {AIM: To validate a blood-based autoantibody test (AAT) as a high specificity, rule-in biomarker for 4-30 mm indeterminate pulmonary nodules (IPN) across malignancy risk.

METHODS: Retrospective pooled analysis of four cohorts including adults with a 4-30 mm IPN, AAT result, and benign or malignant diagnosis. AAT results were classified as Moderate Level (all patients with elevated autoantibodies), High Level (stricter subset within Moderate Level), or No Significant Level of Autoantibodies Detected (NSLAD). Post-test probability of cancer (pCA) was calculated by applying AAT likelihood ratios to pretest pCA. Performance was assessed overall, by nodule size, and risk strata.

RESULTS: Among 1164 patients (35% cancer prevalence), Moderate Level results showed sensitivity 16%, specificity 91%, and PPV 50%. A stricter subset of positives at the High Level, specificity 96%, and PPV 57%, with sensitivity 9%. When post-test pCA exceeded 65%, specificity was 97% and PPV 69%, while sensitivity was 12%. Performance was consistent across cohorts, nodule sizes, and risk strata, indicating size- and risk-independent discrimination. ~10% of intermediate-risk cancers (pretest 5-65%) were reclassified above the 65% threshold, creating a group with enriched malignancy risk.

CONCLUSIONS: AAT provides size- and risk-independent, high-specificity rule-in performance, identifying subsets of patients whose malignancy risk may justify expedited evaluation.},
}

@article {pmid41703241,
year = {2026},
author = {Topalidou, I and Lehrbach, N},
title = {Coordinated control of proteasome subunit gene expression promotes stress resistance, proteostasis, and longevity.},
journal = {GeroScience},
volume = {},
number = {},
pages = {},
pmid = {41703241},
issn = {2509-2723},
support = {R35GM142728/GM/NIGMS NIH HHS/United States ; P30AG013280/AG/NIA NIH HHS/United States ; },
abstract = {The proteasome is essential for cellular protein homeostasis through selective destruction of damaged and misfolded proteins. Failure of proteasome-dependent turnover accompanied by accumulation and aggregation of aberrant proteins is a hallmark of aging and late-onset neurodegenerative diseases. SKN-1A/Nrf1, a member of the NFE2L/Nrf family of transcription factors, is a master regulator of proteasome biogenesis. Through transcriptional control of proteasome subunit gene expression, SKN-1A/Nrf1 controls homoeostatic and stress-responsive upregulation of proteasome levels in adaptation to proteasome dysfunction or protein misfolding. SKN-1A/Nrf1 acts in concert with another Nrf family transcription factor, SKN-1C/Nrf2, to regulate many aspects of physiology including stress responses, redox balance, immunity, and metabolism. Here, we demonstrate that a small deletion in the promoter of the pbs-5 gene, which encodes an essential proteasome subunit, uncouples its expression from transcriptional regulation by SKN-1A/Nrf1. This disruption leads to compensatory SKN-1A/Nrf1-dependent upregulation of other proteasome subunit genes, resulting in a homeostatic imbalance in proteasomal gene expression. This pbs-5 regulatory mutation phenocopies some, but not all, aspects of SKN-1A/Nrf1 inactivation, providing evidence that coordinated regulation of proteasomal subunit gene expression underlies a subset of SKN-1A/Nrf1's physiological roles. In comparing the effects of the pbs-5 promoter deletion with isoform-specific inactivation of SKN-1A or SKN-1C, we show that the pbs-5 promoter mutation completely abrogates multiple lifespan extension paradigms. These results reveal that coordinated homeostatic regulation of proteasome subunit gene expression is critical for longevity and healthy aging.},
}

@article {pmid41701631,
year = {2026},
author = {Osmancevic, A and Daka, B and Larson, JC and Allison, M and Burney, RO and Shadyab, AH and Cauley, JA and Crandall, CJ},
title = {Endogenous sex hormones, sex hormone-binding globulin, and muscle health: insights into sarcopenia and sarcopenic obesity from the Women's Health Initiative.},
journal = {Menopause (New York, N.Y.)},
volume = {},
number = {},
pages = {},
pmid = {41701631},
issn = {1530-0374},
support = {ALFGBG-966255//ALF-agreement/ ; },
abstract = {OBJECTIVE: The relationship between sex hormones and lean body mass in postmenopausal women is unclear. To address this, we conducted a longitudinal observational study using data from the Women's Health Initiative study.

METHODS: We analyzed endogenous serum sex hormones and sex hormone-binding globulin (SHBG) at baseline in 1,565 postmenopausal women not using hormone therapy, who underwent 3 lean body mass measurements over 6 years. Sex hormone concentrations were assessed at baseline using radioimmunoassay. Lean body mass was assessed by dual-energy x-ray absorptiometry at baseline, year 3 and 6. Free estradiol and free testosterone concentrations were calculated. Each sex hormone was analyzed independently of the other hormones. Associations between sex hormones or SHBG were examined using repeated-measures linear regression for lean mass and repeated-measures logistic regression for sarcopenia/sarcopenic obesity. Regression models were adjusted for age, race/ethnicity, lifestyle, and metabolic confounders.

RESULTS: Concentration of free testosterone in the highest quartile was associated with a 55% lower odds for sarcopenia compared with the lowest quartile (OR: 0.45; 95% CI: 0.25-0.81). Similarly, individuals with the highest concentration of free estradiol had a 54% reduced odds of sarcopenia (OR: 0.46, 95% CI: 0.28-0.76). Conversely, a higher concentration of SHBG at baseline was significantly associated with reduced total lean mass and a higher odds of sarcopenia.

CONCLUSION: Among postmenopausal women, higher SHBG concentrations at baseline were associated with lower lean body mass and a higher odds of sarcopenia, while higher free estradiol and free testosterone concentrations were associated with a lower odds of sarcopenia.},
}

@article {pmid41701629,
year = {2026},
author = {Emamekhoo, H and Riaz, IB and Martin, DB and Gabriel, PE and Shah, NJ and Bruckner, L and Arafat, W and Fu, P and Freimuth, RR and Liebovitz, DM and Stillman, RC and Stapp, RT and Perkins, RM and Sugalski, J and Heinrichs, T and Tevaarwerk, AJ},
title = {Deriving wisdom from data: The value and continued rationale for structured data in the era of artificial intelligence-driven oncology care.},
journal = {Cancer},
volume = {132},
number = {4},
pages = {e70307},
doi = {10.1002/cncr.70307},
pmid = {41701629},
issn = {1097-0142},
mesh = {Humans ; *Artificial Intelligence ; *Electronic Health Records ; *Medical Oncology/methods ; *Neoplasms/therapy ; Decision Support Systems, Clinical ; },
abstract = {The adoption of electronic health records (EHRs) has transformed health care, improving efficiency and chart accessibility. However, the widespread reliance on unstructured data entry and the lack of standardized documentation frameworks have resulted in significant data fragmentation across health care systems. The prevalence of unstructured data in EHRs limits their potential for clinical decision support, trial matching, real-world evidence (RWE) generation, and quality measurement. Data fragmentation in health care triggers a cascade of challenges that ultimately compromise patient care. Clinicians face an excessive documentation burden and struggle to locate critical information buried in unstructured notes. Researchers encounter difficulties in extracting reliable clinical data. EHR vendors grapple with standardizing unstructured information for interoperability, and payers are unable to process unstructured clinical data efficiently to support value-based care models. These challenges are particularly acute in oncology, where complex clinical elements like cancer staging, disease status, and treatment changes require precise, structured documentation. Emerging artificial intelligence (AI) technologies, such as large language models (LLMs) and ambient listening, offer a path to automate structured data generation while reducing the workload on providers. Here, the authors propose LLM-based workflows that balance automation with clinician verification, streamlining data entry without compromising accuracy. Realizing these benefits requires coordinated efforts among clinicians, researchers, EHR vendors, payers, and policymakers to align regulatory frameworks with AI-driven innovations. This article outlines a strategy to enhance structured data capture within EHRs, ultimately improving patient care, research, and health care efficiency.},
}

Humans
*Artificial Intelligence
*Electronic Health Records
*Medical Oncology/methods
*Neoplasms/therapy
Decision Support Systems, Clinical

@article {pmid41701126,
year = {2026},
author = {Carter, JA and Dickerson, LK and Stephanou, A and Damle, SR and Goodsell, KE and Daniel, SK and Sullivan, KM and Shui, B and Jiang, X and Kenerson, HL and van den Bijgaart, RJE and Farghli, AR and Liu, Y and Beirne, E and Labadie, KP and Cernak, J and Chauhan, SSB and Bello Pineda, JM and Long, AN and Elz, AE and Newell, EW and Kim, TS and Riehle, KJ and Yeung, RS and Akilesh, S and Crispe, IN and Barry, KC and Sethupathy, P and Pillarisetty, VG},
title = {Overcoming CXCR4-Mediated T-Cell Exclusion Potentiates Antitumor Cytotoxicity in Fibrolamellar Carcinoma.},
journal = {Gastroenterology},
volume = {},
number = {},
pages = {},
doi = {10.1053/j.gastro.2025.10.006},
pmid = {41701126},
issn = {1528-0012},
abstract = {BACKGROUND & AIMS: Fibrolamellar carcinoma (FLC) is a rare liver cancer affecting young adults without underlying cirrhosis. Although almost all FLC patients share an immunogenic DNAJB1-PRKACA fusion oncogene, endogenous antitumor immunity and clinical response to immunotherapy are limited. We hypothesized that the lack of response to immunotherapy is mediated by both T-cell exclusion and intratumoral immunosuppression.

METHODS: We used high-throughput single-nucleus RNA sequencing to explore the tumor immune microenvironment (TIME) of FLC. We then used multiplex immunohistochemistry, live imaging, single-cell sequencing, and spatial proteomics in a human tumor slice culture (TSC) system to dissect and experimentally modulate the FLC TIME.

RESULTS: We identified significant dysregulation of stromal-immune signaling pathways within the FLC TIME relative to adjacent nontumor liver, notably including interactions between CXCL12[+] myofibroblasts and CXCR4[+] lymphocytes. CXCR4 inhibition was sufficient to mobilize stromal T cells into the carcinoma compartment, with the addition of PD-1 blockade independently activating T-cell antitumor effector function. Combination CXCR4 and PD-1 blockade resulted in a significant increase in tumor cell death relative to either treatment alone in a human TSC model.

CONCLUSIONS: Our findings demonstrate that immune resistance in FLC is mediated by both local T-cell exclusion and exhaustion, with combination CXCR4 and PD-1 blockade acting cooperatively to overcome these independent mechanisms. These results highlight the versatility of the human TSC system to aid in the study of rare cancer types and provide important preclinical evidence for the rational design of combination immunotherapy in FLC, which currently lacks any effective systemic therapy.},
}