@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.},
}

@article {pmid41700320,
year = {2026},
author = {Smith, D and Weir, IR and Ramirez, S and Coelho, CH and Manne-Goehler, J and Aziz, M and Benson, CA and Wu, X and Hyer, R and Dhillon, PK and Faraji, F and Bloom, N and Myers, A and Ramezani-Rad, P and Lopez, PG and Parikh, UM and Heaps, AL and Javan, AC and Bender Ignacio, RA and Li, JZ and Greninger, AL and Daar, ES and Wohl, DA and Crotty, S and Sieg, SF and Chew, KW},
title = {Impact of COVID-19 Monoclonal Antibody Therapy on Subsequent Vaccine-elicited SARS-CoV-2 Immune Responses.},
journal = {The Journal of infectious diseases},
volume = {},
number = {},
pages = {},
doi = {10.1093/infdis/jiag091},
pmid = {41700320},
issn = {1537-6613},
abstract = {BACKGROUND: How anti-SARS-CoV-2 monoclonal antibodies (mAbs) change subsequent vaccine responses remains uncertain.

METHODS: We conducted a prospective, phase IV, open-label study of adults who received mRNA-1273 or BNT162b2. Cohort 1 included outpatients with acute COVID-19 previously randomized to mAbs (tixagevimab/cilgavimab or amubarvimab/romlusevimab), camostat, or placebo in ACTIV-2/A5401. Cohort 2 included unvaccinated adults without reported prior COVID-19 and was analyzed as naïve or non-naïve by baseline neutralizing antibodies (nAbs). We measured binding IgG, nAbs, spike-specific memory B cells, and CD4+/CD8+ T cells at baseline and days 28, 56, and 140.

RESULTS: Forty-three participants were analyzed. At day 140, nAb titers were lower among prior mAb recipients and COVID-19-naïve participants than among placebo/camostat recipients and those with evidence of prior infection (overall p=0.018). RBD-specific, but not spike-specific, memory B cells were reduced after prior mAb therapy at days 56 and 140. Frequency of spike-specific CD4+ and CD8+ T-cell responses did not differ by prior mAb exposure. Adverse events were mostly grade 1-2 and consistent with vaccine trials.

CONCLUSIONS: Prior anti-SARS-CoV-2 mAb treatment limits endogenous RBD-focused B-cell responses to later mRNA vaccination without measurably affecting T-cell immunity. Timing of vaccination after mAb therapy may matter and warrants study.

TRIAL REGISTRATION: NCT04952402.},
}

@article {pmid41698677,
year = {2026},
author = {de la Calle, CM and Baras, AS and Lotan, TL},
title = {Digital pathology-based artificial intelligence algorithms in prostate cancer: inside the 'black box'.},
journal = {BJU international},
volume = {},
number = {},
pages = {},
doi = {10.1111/bju.70164},
pmid = {41698677},
issn = {1464-410X},
abstract = {Artificial intelligence (AI) algorithms leveraging digital pathology slides are currently transforming the way urological cancers are diagnosed and graded, and they add additional prognostic, predictive and molecular subtyping information beyond traditional pathological risk stratification. This review explores recent advances in histopathology-based AI systems for prostate cancer. We examine how these algorithms perform relative to pathologists for tumour diagnosis and grading, and the ways in which they surpass pathologists with respect to reducing inter-observer variability and providing quantified tumour metrics. We particularly focus on prognostic algorithms that have been benchmarked against 'gold standard' patient outcomes such as metastasis or death, and we highlight the emerging role of digital pathology-enabled AI for predicting response to therapy or underlying tumour molecular alteration status. Finally, we touch on the advantages of, and barriers to, implementation of digital pathology and histopathology-based AI algorithms in clinical practice. Through this synthesis of current literature, we underscore the emerging potential of AI for standardising pathological assessment, guiding clinical management, and improving patient outcomes in prostate cancer.},
}

@article {pmid41659627,
year = {2026},
author = {Sackey, SA and Schrum, JE and Mangalanathan, UM and Fish, RS and Sola, E and Selehi, A and Pi, R and Zack, JA and Kim, JT and Lehman, DA and Davis, MM and Blish, CA},
title = {Modeling HIV infection, treatment, rebound, and intervention in human immune organoids.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {41659627},
issn = {2692-8205},
abstract = {Targeting the HIV-infected reservoir in lymphoid tissues (LT) will be critical to developing a cure for people living with HIV (PLWH). LT explants used to study HIV infection enable the evaluation of human-specific disease progression and treatment response; however, their short lifespan makes it challenging to assess long-term treatment interventions. We therefore established an immune organoid model of HIV infection using human tonsil or spleen cells, demonstrating productive HIV infection and viral integration into CD4[+] T cells. Treatment with a protease inhibitor fully suppressed ongoing viral production, with virologic rebound occurring within days of treatment interruption. The transfer of healthy allogeneic NK cells to target the reservoir upon treatment interruption reduced the number of infected cells, intact viral genomes, and production of de novo infectious viral particles. Adoption of this immune organoid platform will accelerate the evaluation of cure-based strategies to eliminate the HIV reservoir in tissues for PLWH.},
}

@article {pmid41698311,
year = {2026},
author = {Heng, F and Magaret, CA and Rouphael, NG and Branche, AR and Fong, Y and Carpp, LN and Yu, C and Chen, S and Zhang, B and Diemert, DJ and Falsey, AR and Graciaa, DS and Baden, LR and Frey, SE and Whitaker, JA and Little, SJ and Kamidani, S and Walter, EB and Novak, RM and Rupp, R and Jackson, LA and Babu, TM and Kottkamp, AC and Luetkemeyer, AF and Immergluck, LC and Presti, RM and Bäcker, M and Winokur, PL and Mahgoub, SM and Goepfert, PA and Fusco, DN and Atmar, RL and Posavad, CM and Mu, J and Makowski, M and Makhene, MK and Nayak, SU and Simon, V and van Bakel, H and Roberts, PC and Gilbert, PB and , },
title = {The neutralizing antibody titer correlate of COVID-19 risk in the COVID-19 variant immunologic landscape (COVAIL) trial was not modified by SARS-CoV-2 amino acid sequence distances.},
journal = {Vaccine},
volume = {76},
number = {},
pages = {128348},
doi = {10.1016/j.vaccine.2026.128348},
pmid = {41698311},
issn = {1873-2518},
abstract = {In the Coronavirus Variant Immunologic Landscape Trial (COVAIL) conducted in the United States in 2022-2023, 985 participants received a second COVID-19 booster with one of twelve monovalent or bivalent mRNA inserts. Pseudovirus serum inhibitory dilution 50% neutralizing antibody titer (nAb titer) measured two-weeks post booster significantly associated with lower COVID-19 incidence over six months follow-up in this trial. COVAIL investigators sequenced SARS-CoV-2 Spike amino acid sequences for all COVID-19 cases, with a sequence successfully obtained from 129 of 195 cases. For COVID-19 endpoint cases we calculated five distances of the case-causing sequence to a reference sequence, the first two physico-chemical weighted Hamming distances of Spike or receptor binding domain (RBD) to a participant's nearest Spike or RBD vaccine-insert sequence, and the other three estimated degrees of neutralizing antibody escape from the XBB.1.5 RBD strain calculated with deep mutational scanning. Hypothesizing that the nAb titer correlate of risk may have a stronger association with COVID-19 when focusing on COVID-19 infections more closely matched to the vaccine insert in Spike or RBD amino acid sequence or with lower RBD antibody escape score, we tested this hypothesis for the combined group receiving a monovalent Prototype (ancestral strain) booster (n = 143) and for the combined group receiving an Omicron-containing booster (n = 744). For both combined groups, the nAb titer correlate of risk did not significantly vary across any of the assessed sequence distances from the vaccine insert (all p-values >0.10), although RBD Hamming distance had point estimates consistent with a weakening correlate with distance, motivating further exploration in settings with greater antigenic heterogeneity. Indeed, statistical power was bounded by the limited antigenic variability of viruses infecting trial participants over the follow-up period (April 21, 2022 to May 25, 2023), which spanned only a 3.02-fold nAb titer range of differential sensitivity to sera from XBB.1.5-infected individuals. ClinicalTrials.gov Identifier: NCT05289037.},
}

@article {pmid41697998,
year = {2026},
author = {Huang, BZ and Chen, F and Bogumil, D and Han, S and Paik, A and Wan, P and Sheng, X and Siegmund, KD and Peters, U and VoPham, T and Wang, L and Alderete, T and Salhia, B and Lenz, HJ and Stram, DO and Wilkens, LR and Le Marchand, L and Conti, DV and Haiman, CA},
title = {Interaction of genetic and lifestyle risk scores on colorectal cancer risk across five racial and ethnic populations.},
journal = {Journal of the National Cancer Institute},
volume = {},
number = {},
pages = {},
doi = {10.1093/jnci/djag045},
pmid = {41697998},
issn = {1460-2105},
abstract = {BACKGROUND: Integrating genetic and lifestyle information has the potential to greatly improve the prediction of colorectal cancer (CRC) risk. However, racial and ethnic minorities are generally underrepresented in gene-environment studies of CRC risk.

METHODS: We investigated the interplay of genetics and lifestyle on CRC risk in a prospective analysis of 68,397 African American, Japanese American, Latino, Native Hawaiian, and White individuals from the Multiethnic Cohort Study. Genetic predisposition was assessed using a 205-variant polygenic risk score (PRS). Lifestyle was assessed using a lifestyle risk score based on smoking, alcohol consumption, body mass index, physical activity, and diet. The independent and joint associations of the PRS and lifestyle risk score on CRC risk were evaluated using Cox regression.

RESULTS: We identified 1,303 incident CRC cases (median 15.1-year follow-up). The highest quintile of the PRS was associated with a 2.4-fold increase in CRC risk compared to the lowest quintile (HRQ5vQ1 2.40, 95% CI 1.99-2.89). The highest quintile of the lifestyle risk score was associated with a 54% increased risk (HRQ5vQ1 1.54, 95% CI 1.26-1.88). This association was stronger among those with high genetic risk (PRS≥50%) (HRQ5vQ1 1.82, 95% CI 1.41-2.35) and non-significant among those with low genetic risk (PRS<50%) (HRQ5vQ1 1.20, 95% CI 0.88-1.64; p-interaction=0.01). Results were similar across race and ethnicity.

CONCLUSIONS: Our study suggests that lifestyle modification may offer greater risk reduction among those at higher genetic risk. Future research is warranted to enhance the integration of genetics and lifestyle in CRC risk stratification and screening approaches across populations.},
}

@article {pmid41697987,
year = {2026},
author = {Chhetri, R and Modi, ND and Menz, BD and Cornelisse, E and Postma, D and Kuderer, NM and Lyman, GH and Swain, SM and Li, LX and Abuhelwa, AY and McKinnon, RA and Vatandoust, S and Kichenadasse, G and Rowland, A and Sorich, MJ and Hopkins, AM},
title = {Sex-based prognosis in industry-sponsored advanced solid tumour trials: an individual participant data meta-analysis of survival and adverse events.},
journal = {Journal of the National Cancer Institute},
volume = {},
number = {},
pages = {},
doi = {10.1093/jnci/djag046},
pmid = {41697987},
issn = {1460-2105},
abstract = {BACKGROUND: Sex is a recognised modifier of physiology, immunity, and social exposures, yet its independent association with survival and adverse event (AE) prognosis in contemporary anticancer therapy remains poorly defined. The aim of the present study was to assess the association between patient sex and OS, PFS, and grade ≥3 AEs across a pooled individual participant data (IPD) meta-analysis.

METHODS: IPD supporting FDA approval of anticancer medicines for solid tumours between 2011 and 2021 were accessed via the Vivli and YODA data sharing platforms. A two-stage random-effects meta-analysis approach was employed, using Cox proportional hazards regression to estimate sex-based prognostic differences in overall survival (OS), progression-free survival (PFS), and grade ≥3 AEs. Analyses were adjusted for key baseline covariates.

RESULTS: In a pooled cohort of 20,806 participants from 39 phase II-III trials supporting US FDA approvals of anticancer medicines for advanced solid tumours, across 12 tumour types, female sex was associated with significantly improved OS (HR 0.79, 95% CI 0.73-0.85; P < 0.001) and PFS (HR 0.84, 95% CI 0.79-0.89; P < 0.001). Conversely, females experienced a higher risk of grade ≥3 AEs (HR 1.12, 95% CI 1.07-1.18; P < 0.001).

CONCLUSIONS: In the largest analysis of IPD from trials supporting FDA drug approvals, we found that females had a 21% lower risk of death and a 16% lower risk of progression, but a 12% higher risk of severe adverse events. These findings highlight the value of the IPD sharing and the importance of sex-stratified evidence for risk stratification, dose optimisation and patient counselling.},
}

@article {pmid41697970,
year = {2026},
author = {Pocobelli, G and Del Vecchio, NJ and Cushing-Haugen, K and Kamineni, A and Corley, DA and Rendle, KA and Halm, EA and Li, CI and Oshiro, CES and Carroll, NM and Silver, MI and Greenlee, RT and Neslund-Dudas, C and Breslau, ES and Chubak, J},
title = {Up-to-date prevalence at recommended ages for discontinuing routine colorectal, cervical and lung cancer screening.},
journal = {Journal of the National Cancer Institute},
volume = {},
number = {},
pages = {},
doi = {10.1093/jnci/djag044},
pmid = {41697970},
issn = {1460-2105},
abstract = {Cancer screening guidelines specify ages at which routine screening should be discontinued and, except for cervical cancer screening, do not require specific screening history criteria be met for discontinuation. We estimated the prevalence of being up to date with average-risk screening guidelines for colorectal, cervical, and lung cancer as of the recommended ages for discontinuation of routine screening. We conducted a descriptive study among several U.S. healthcare systems during 2010-2019. Up-to-date screening prevalence, based on U.S. Preventive Services Task Force guidelines, was ascertained prior to 76th, 66th, and 81st birthdays among persons eligible for colorectal (N = 316,756 persons), cervical (N = 20,282 persons), and lung cancer (N = 1,151 persons) screening, respectively. Up-to-date screening prevalence was 84.4% for colorectal, 58.9% for cervical, and 6.3% for lung cancer screening. Up-to-date screening prevalence at the ages recommended for discontinuing routine colorectal, cervical, and lung cancer screening varied appreciably, and was particularly low for lung cancer screening.},
}

@article {pmid41648419,
year = {2026},
author = {Mallett, DR and Jiang, M and Minnuto, GM and Biggins, S},
title = {Kinetochore clustering is mediated by Mps1 phosphorylation of conserved MELT motifs in Stu1.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {41648419},
issn = {2692-8205},
abstract = {Unattached kinetochores promote microtubule capture while preventing cell cycle progression during mitosis. The Mps1 kinase controls these events by mediating kinetochore assembly of the fibrous corona in animal cells and by triggering the spindle checkpoint. In budding yeast, which does not assemble a fibrous corona, the Stu1 and Slk19 spindle proteins promote microtubule capture by clustering unattached kinetochores, but the underlying mechanism is unclear. Here, we show that Mps1 controls this pathway. We identify two conserved MELT motifs in Stu1 that are directly phosphorylated by Mps1 to recruit Slk19 and mediate kinetochore clustering. Structural analysis of the Stu1:Slk19 complex reveals long, string-like filaments and offers mechanistic insight into how kinetochores might cluster. Our findings reveal parallels between the Mps1-Stu1-Slk19 pathway and the fibrous corona and suggest the regulation of kinetochore capture is a conserved Mps1 function across eukaryotes.},
}

@article {pmid41646741,
year = {2026},
author = {Carr, LL and Sankaranarayanan, A and Ha, K and Rawlani, M and Kazerouni, AS and Specht, J and Kennedy, LC and Reiter, D and Dintzis, S and Hippe, DS and Kilgore, MR and Symonds, L and Partridge, SC and Mittal, S},
title = {TILseg: Automated Whole Slide-Level Spatial Scoring of Tumor-Infiltrating Lymphocytes Reveals Prognostic Patterns in Triple Negative Breast Cancer.},
journal = {medRxiv : the preprint server for health sciences},
volume = {},
number = {},
pages = {},
pmid = {41646741},
abstract = {Stromal tumor-infiltrating lymphocytes (sTILs) are promising biomarkers for predicting therapeutic outcomes in triple-negative breast cancer (TNBC), with higher sTIL levels correlating with improved chemotherapy response and survival outcomes. Currently, sTILs are manually evaluated by pathologists, which is prone to inter-reader variability. In this study, we have developed an AI-driven TIL segmentation pipeline to process entire diagnostic hematoxylin-and-eosin-stained whole slide images for reproducible scoring (global TILseg scoring) and reliable prognostication. This pipeline was optimized and tested using two independent TNBC patient cohorts (n = 57 in the discovery cohort, n = 43 in the validation cohort) with clinical outcomes and follow-up data. The global scores generated by TILseg showed moderate to high concordance with expert scoring (Spearman R = 0.84-0.89) and improved patient stratification (p-value = 0.0191) as compared to manual scoring (p-value = 0.0663). Additionally, we investigate how the spatial localization of sTILs (spatial TILseg) impact survival outcomes by identifying TILs in selected stromal subsets (0.02-2 mm from the epithelial clusters). Our findings have shown that TILs up to 50 μm from epithelial regions prove to be most prognostic in predicting recurrence-free survival post-neoadjuvant chemotherapy with higher statistical significance than both manual and global TILseg scoring. Further, spatial TILseg scoring was more significantly associated with pathological complete response status in both patient cohorts. In summary, we present an AI-based digital tool for robust sTIL scoring and spatial mapping to enhance its potential as both a diagnostic and prognostic biomarker, particularly in TNBC patients.},
}

@article {pmid41697969,
year = {2026},
author = {Rutter, CM and Maerzluft, CE and Matrajt, L and Nascimento de Lima, P and Issaka, RB and Marsh, TL},
title = {CRC-SPIN version 3.0: an updated policy model for colorectal cancer screening that includes the serrated pathway.},
journal = {Journal of the National Cancer Institute},
volume = {},
number = {},
pages = {},
doi = {10.1093/jnci/djag037},
pmid = {41697969},
issn = {1460-2105},
abstract = {BACKGROUND: Microsimulation models use empirical evidence about cancer epidemiology and screening test performance to predict the long-term effectiveness of screening regimens and are essential for developing cancer screening guidelines. Colorectal cancer (CRC) provides a clear example. CRC arises through two pathways, the adenoma-carcinoma pathway and the serrated pathway. Sessile serrated lesions (SSLs) are the primary serrated precursor lesion. SSLs are more difficult to detect and remove than adenomas.

METHODS: We describe version 3.0 of the Colorectal Cancer Simulated Population model for Incidence and Natural history (CRC-SPIN), which adds new information about the serrated pathway and CRC risk in adults under 50, then estimate the effectiveness of decennial colonoscopy from 45 to 75 years old. The model was calibrated using a Bayesian approach to estimate 95% credible intervals (CIs) that reflect uncertainty in predictions.

RESULTS: The model validated well to studies of the effect of one-time screening and outcomes from surveillance colonoscopy. In the absence of screening, SSLs accounted for 10.6% (95% CI: 3.3-21.6) of CRC, increasing to 23.5% (95% CI: 7.7%-46.0%) with screening due to selective removal of adenomas. Screening was predicted to prevent 93.9% (95% CI: 92.0%-94.3%) of CRC and 95.3% (95% CI: 93.8%-96.5%) of CRC mortality.

CONCLUSIONS: Although SSLs are less common than adenomas, they likely make up a large fraction of CRC that arises in people who participate in screening. This points to the importance of improving the ability to detect SSLs, especially large SSLs, at colonoscopy.},
}

@article {pmid41695969,
year = {2026},
author = {Bazzell, AF and Madsen, LT and Bandini, L and Harrington, T and Siman, J and Stein, CE and Greenlee, H and Fleming, JB and Huffman, A},
title = {Integrative Oncology Models of Care: Practice Patterns From NCCN Member Institutions.},
journal = {Journal of the advanced practitioner in oncology},
volume = {},
number = {},
pages = {1-10},
pmid = {41695969},
issn = {2150-0878},
abstract = {BACKGROUND: Patients with cancer frequently desire to incorporate integrative oncology (IO) practices into their care. However, patients are often uncertain about how to best access safe and effective IO practices and providers. The National Comprehensive Cancer Network (NCCN) Best Practices Committee (BPC), in collaboration with a National Cancer Institute (NCI)-Designated Comprehensive Cancer Center, sought information regarding IO practices of NCCN Member Institutions.

METHODS: The BPC conducted a survey of NCCN Member Institution IO practices, which was distributed via a web-based survey tool to a representative at each center. Results were compiled using descriptive statistics.

RESULTS: Twenty-nine centers responded to the survey, with 100% of the responding institutions offering IO services. Services provided included nutritional/dietary services (97%), stress and anxiety management services (76%), mind-body practices (72%), physical therapy/occupational therapy (72%), acupressure/acupuncture (69%), and massage therapy (59%). While the mechanism for patient access varied, the most common was provider referral with some services available by self-scheduling. Twenty-one percent of centers used institutionally designed algorithms for referrals. Significant variation in funding for services existed between institutions, including combinations of self-pay, insurance-based, and philanthropically funded models.

CONCLUSIONS: There was substantial variation in how NCCN Member Institutions deliver IO services. These results provide guidance for health-care organizations seeking to develop IO services and an opportunity to align best practices. As data were compiled solely from sites providing comprehensive cancer services, non-academic community settings may find similar implementation challenging. However, this information provides cancer providers insight into IO services most often sought by patients with cancer.},
}

@article {pmid41695294,
year = {2026},
author = {Yorke, AA and Muramuzi, A and Lin, LL and Awusa, K and Kibudde, S and Twum, PT and Yorke, CK and Ford, EC},
title = {Quantifying cervical cancer radiotherapy care gap: Baseline assessment prior to implementation of a digital Health App.},
journal = {Technical innovations & patient support in radiation oncology},
volume = {37},
number = {},
pages = {100381},
pmid = {41695294},
issn = {2405-6324},
abstract = {PURPOSE: Sub-Saharan Africa accounts for over one-third of global cervical cancer deaths, despite representing only 14% of the world's female population. Radiotherapy (RT) services are essential in the treatment of cervical cancer, and the Uganda Cancer Institute (UCI) is the only oncology center with RT in a country of 50 million. Prior studies show most of the cervical cancer (CxCa) patients do not complete RT within the recommended timeframe of 6-8 weeks, and some miss their brachytherapy boost. This study analyzes care gaps to establish a baseline before implementing a digital health patient navigation app GLOCASSA.

METHODOLOGY: We quantified radiotherapy care gaps among 104 cervical cancer patients (FIGO IB-IIIC) treated at the UCI between 2023 and 2024, representing 13% of the annual patient volume ethical approval was obtained. A mixed-methods approach was employed, combining retrospective review of radiotherapy charts with a custom mathematical framework for care gap assessment. Patient timelines were reconstructed from consultation through CT simulation, treatment initiation, completion, and follow-up, across three external beam radiotherapy regimens (45 Gy/15 fractions; 50 Gy/25 fractions; 50.4 Gy/28 fractions). We developed a Radiotherapy Care Gap (RCG) model incorporating professional benchmarks (ASTRO, ACR, ARS) to quantify delays, weighted by their clinical importance. Scores were normalized to reflect adherence (<1 expedited/incomplete; =1 standard; >1 delayed). Geospatial analyses were performed using ArcGIS Pro to measure travel distance from patient residence to UCI.

RESULTS: Among 104 cervical cancer patients treated with three EBRT regimens followed by brachytherapy, biologically equivalent doses were comparable across schedules (EQD2 ≈ 85-86 Gy). However, treatment completion within the recommended 6-8 weeks was rare, with on-time completion rates of 11% or lower at 6 weeks and ≤ 17% at 8 weeks. The majority of patients had Radiotherapy Care Gap Scores (RCGS) > 1, indicating significant delays, while only a small fraction achieved timely care (RCGS < 1). Extreme delays were observed, with some patients requiring over 30 weeks to complete therapy. Most patients (58%) were treated with 2D/3D techniques, though delays persisted across all modalities. Geospatial analysis showed a median travel time of 4 h to the radiotherapy center, and more than half of patients (53%) missed the recommended 6-week follow-up visit, highlighting substantial geographic and continuity-of-care barriers.

CONCLUSION: Our findings suggest that patient navigation and follow-up support are major unmet needs. Digital health platforms that provide real-time reminders, enable remote symptom reporting, and facilitate coordination between patients and care teams offer promising solutions. Future directions include the implementation of the GLOCASSA-App as a targeted intervention to mitigate identified care gaps.},
}

@article {pmid41691096,
year = {2026},
author = {Bouley, C and Fang, M and Radich, J and Yeung, CC and Campbell, J and Kroeger, K and Beppu, L and Mielcarek, M and Storb, R and Ueda Oshima, M},
title = {Donor-derived del[20q] following allogeneic-hematopoietic cell transplantation: a case with 26-year follow-up and literature review.},
journal = {Bone marrow transplantation},
volume = {},
number = {},
pages = {},
pmid = {41691096},
issn = {1476-5365},
support = {CA015704//U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)/ ; CA175008, CA233338, CA233381//U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)/ ; PO1 78902//U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)/ ; },
abstract = {Donor-derived cytogenetic abnormalities are a rare finding following allogeneic hematopoietic cell transplantation. Deletion of the long arm of chromosome 20 [del(20q)] is one of the more frequently observed structural abnormalities, but its significance in the post-transplant setting remains unclear. We describe a unique case of donor-derived del(20q) with 26 years of post-transplant follow-up, the longest reported to date. The recipient remains well with normal blood counts despite persistent del(20q) in both myeloid and lymphoid lineages and the presence of coexisting somatic mutations in DNMT3A and TP53. Retrospective analysis of the donor's marrow confirmed del(20q) and low-level DNMT3A and TP53 mutations at the time of transplant; the donor later developed therapy-related MDS after radiation therapy for thyroid cancer. To contextualize this case, we reviewed 20 published reports of donor-derived del(20q) post-transplant. The median time to detection was 16 months post-transplant, and 35% of cases progressed to donor-derived malignancy. Among those who progressed, the median time to malignancy diagnosis was 22 months post-transplant. Clinical outcomes across cases ranged from asymptomatic persistence and cytopenias to donor-derived myeloid malignancies, highlighting the need for long-term follow-up and potential use of molecular profiling to better define the neoplastic potential of donor-derived del(20q) after transplantation.},
}

@article {pmid41691093,
year = {2026},
author = {Stephan, SB and Cummings, CL and Fitzgerald, K and Stephan, MT},
title = {Drinkable gene therapy foam for the treatment of constrictive esophageal carcinoma.},
journal = {Gene therapy},
volume = {},
number = {},
pages = {},
pmid = {41691093},
issn = {1476-5462},
abstract = {Patients diagnosed with esophageal cancer (EC) currently rely on treatments given at specialist care centers (surgery, chemotherapy, radiation), which despite their low cure rates are extremely life-disruptive, cause severe pain, and have strong side effects. In particular, dysphagia is one of the most distressing and debilitating symptoms in patients with cancer-related esophageal obstruction. There is clearly an urgent need for new effective and accessible therapies for EC patients that allow patients to continue normal activity as much as possible. Here, we describe a drinkable methylcellulose/xanthan gum-based gene therapy foam that coats the esophagus and accumulates an apoptosis-inducing gene therapy drug (mRNA lipid nanoparticles encoding Pseudomonas exotoxin A) at the tumorous esophageal stricture. In an in vitro EC tissue model, we show that gene therapy foam induces 110-fold higher tumor regression compared to suspension treatment. We also establish that gene therapy foam given prior to radiotherapy strongly enhances anti-tumor effects. Once implemented in the clinic, this treatment, which can be administered orally by a local family doctor or at home by the patient or caregiver, could maximize the time EC patients can live normal lives outside of the hospital and allow them to maintain their ability to swallow and eat.},
}

@article {pmid41690558,
year = {2026},
author = {Meyer, J and Zoberi, JE and Kim, H and Tran, A and Lowenstein, JR and Al-Hallaq, HA},
title = {A National Survey of Medical Physicists: Part 1 - Practice Patterns for High-Dose Rate Brachytherapy.},
journal = {International journal of radiation oncology, biology, physics},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.ijrobp.2026.01.044},
pmid = {41690558},
issn = {1879-355X},
abstract = {PURPOSE: High dose rate Brachytherapy (HDR BT) is an effective but resource-intensive treatment modality, demanding a highly skilled workforce, team coordination, and logistics. This study presents findings from a comprehensive national survey conducted in 2023, targeting all XXX sites in the United States.

METHODS: The primary objective was to analyze national brachytherapy (BT) practice patterns and workload dynamics among medical physicists involved in HDR BT treatments. A secondary aim, explored in a companion publication (part 2), examines work effort, job satisfaction, and challenges faced by medical physicists in this field.

RESULTS: The survey received 365 complete responses, revealing an experienced workforce, with 71% reporting over 10 years of BT service and 75% performing complex gynecological treatments involving more than three channels. Two-thirds of respondents were employed at non-academic institutions and 53% indicated that medical physics full-time equivalent was <1 at their clinic. The most frequently performed procedure was gynecological BT (96%), followed by skin (34%), prostate (33%), and breast (23%). Adoption of advanced planning tools was variable, with 66% using inverse planning and 34% employing automatic catheter reconstruction. Additionally, 32% of all respondents performed magnetic resonance imaging (MRI) based planning, with 14% reporting frequent use. Of the subgroup performing complex gynecologic (gyne) treatments, 38% reported the utilization of MRIs. Uptake of MRI-based planning appears to have only slightly increased over the past decade.

CONCLUSION: The survey demonstrated that medical physicists are involved in and responsible for nearly every technical aspect of the HDR BT process. This study presents one of the largest national surveys on medical physics practice patterns to date. The findings highlight ongoing challenges in allocating resources, varying procedure complexity, and logistical demands. Future initiatives should focus on developing improved resource allocation metrics to optimize staffing based on procedure complexity and caseload.},
}

@article {pmid41689800,
year = {2026},
author = {La, C and Detavernier, A and Papadopoulou, M and Sanchez Sanchez, G and Martens, V and Thomas, S and Nguyen, M and Acolty, V and Melchior, M and Venturoli, D and de Toeuf, B and Azouz, A and Rezwani, M and Tafesse, Y and Verdebout, I and Rongvaux, A and Boehme, L and Taghon, T and Venken, K and Elewaut, D and Goriely, S and Vermijlen, D},
title = {In vivo modeling of human γδ T cell ontogeny reveals terminal deoxynucleotidyl transferase as a key regulator of type 3 Vδ2 T cell development.},
journal = {Cell reports},
volume = {45},
number = {2},
pages = {116977},
doi = {10.1016/j.celrep.2026.116977},
pmid = {41689800},
issn = {2211-1247},
abstract = {Profound differences in T cell receptor (TCR) repertoire and functional profiles between human and murine γδ T cells pose significant challenges for translational γδ T cell research. Therefore, we generated humanized immune system (HIS) NBSGW (NOD,B6.Prkdc[scid]Il2rγ[-/-]Kit[W41/W41]) mice reconstituted with human fetal liver CD34[+] hematopoietic stem and progenitor cells (HSPCs) enabling evaluation of human γδ T cells in vivo. The HIS mice accurately recapitulate the TCR-associated thymic programming of human γδ T cells-alongside αβ T cell development-and their peripheral effector functions, including the generation of phosphoantigen-reactive Vγ9Vδ2 T cells uniquely found in humans. Moreover, terminal deoxynucleotidyl transferase (TdT) is identified as a key regulator of type 3 Vδ2 T cell development. These findings demonstrate that HIS mice are a powerful model to screen human γδ T cell-targeting immunotherapies and to obtain mechanistic insights into human γδ T cell biology.},
}

@article {pmid41688657,
year = {2026},
author = {Tjader, NP and Ramroop, J and Gandhi, T and Dauch, C and Meadows, O and Stevens, P and Pearlman, R and Hampel, H and Aglago, EK and Berndt, SI and Bloomer, A and Brenner, H and Buchanan, DD and Campbell, PT and Cao, Y and Chan, AT and Cheng, I and Dimou, N and Drew, DA and French, AJ and Georgeson, P and Giannakis, M and Giles, GG and Gomez, M and Gruber, SB and Hoffmeister, M and Huang, WY and Hullar, MAJ and Huyghe, JR and Loroña, N and Moreno, V and Newton, CC and Nowak, JA and Obón-Santacana, M and Ogino, S and Pellatt, A and Peoples, AR and Permuth, JB and Schmit, SL and Schoen, RE and Siegel, EM and Steinfelder, RS and Sun, W and Teer, JK and Thomas, CE and Trinh, QM and Tsilidis, K and Ugai, T and Um, CY and Van Guelpen, B and Zaidi, SH and Figueiredo, J and Peters, U and Phipps, AI and McElroy, JP and Toland, AE},
title = {Association of germline variants with KRAS-mutation status in colorectal cancer.},
journal = {Scientific reports},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41598-026-39644-8},
pmid = {41688657},
issn = {2045-2322},
support = {Pelotonia Graduate Research Fellowship//Pelotonia/ ; Pelotonia Postdoctoral Fellowship//Pelotonia/ ; Undergraduate Research Fellowship//Pelotonia/ ; R01 CA81488/NH/NIH HHS/United States ; R01 CA248857/NH/NIH HHS/United States ; R50 CA274122/NH/NIH HHS/United States ; R01 CA155101/NH/NIH HHS/United States ; CRP-24-1185864-01-PROF//American Cancer Society/ ; Faculty Career Development Award//Brigham and Women's Hospital/ ; Investigator Initiated Grant//American Institute for Cancer Research/ ; R01 CA215151/CA/NCI NIH HHS/United States ; },
abstract = {Somatic mutations in KRAS are a common driver of colorectal cancer (CRC) and present at different frequencies by race, sex, tumor site, ethnicity, and genetic similarity. Inherited germline variants may influence tumor somatic mutation frequency by altering mutation or DNA repair processes or altering cellular, immunological and/or microenvironmental responses after a mutation. We hypothesized that the germline genetic background modifies somatic KRAS mutation frequency in CRC. To test this, we performed a genome-wide association study (GWAS) in 7071 individuals with CRC, using KRAS mutation status as the phenotype. Single-nucleotide variants were chosen for validation analyses based on P values from the discovery GWAS, predicted in silico functional effects, and proximity to genes with potential cancer relevance. A validation analysis of 101 SNVs of interest was performed in 2482 individuals. No SNVs were significantly associated with KRAS-mutant CRC (P value < 0.0005). One variant rs73067863-T showed a non-significant exploratory association with fewer KRAS-mutant tumors in the combined sample (P value = 9.7 × 10[-7], OR = 0.75). Follow-up studies are needed to determine if these or other germline variants impact population differences in KRAS mutations in CRC.},
}

@article {pmid41688063,
year = {2026},
author = {Neher, RA and Huddleston, J and Bedford, T and Lewis, NS and Harvey, R and Galiano, M and Byrne, AMP and James, S and Smith, D and Łuksza, M and Ruchnewitz, D and Laessig, M and Fujisaki, S and Watanabe, S and Hasegawa, H and Hassell, N and Wentworth, DE and Kondor, R and Deng, YM and Dapat, C and Subbarao, K and Barr, I},
title = {Nomenclature for Tracking of Genetic Variation of Seasonal Influenza Viruses.},
journal = {Influenza and other respiratory viruses},
volume = {20},
number = {2},
pages = {e70230},
pmid = {41688063},
issn = {1750-2659},
support = {/CRUK_/Cancer Research UK/United Kingdom ; //UK Medical Research Council/ ; /WT_/Wellcome Trust/United Kingdom ; },
mesh = {*Genetic Variation ; Humans ; *Influenza, Human/virology/epidemiology ; Phylogeny ; *Terminology as Topic ; *Influenza A Virus, H3N2 Subtype/genetics/classification ; *Influenza A Virus, H1N1 Subtype/genetics/classification ; *Influenza B virus/genetics/classification ; Seasons ; Genome, Viral ; Neuraminidase/genetics ; Hemagglutinin Glycoproteins, Influenza Virus/genetics ; },
abstract = {BACKGROUND: Genomic surveillance of human seasonal influenza viruses is an essential component of the Global Influenza Surveillance and Response system (GISRS) and informs the recommendations for the seasonal influenza vaccine composition. Phylogenetic analysis of viral genome sequences is used to identify groups of viruses sharing potential antigenic change, and computational models are used to predict which viral variants are likely to circulate at high levels in upcoming seasons. To facilitate discussion and reporting of genetic diversity, as well as to communicate antigen recommendations, up-to-date and sufficiently granular definitions of genetic clades are important.

METHODS: We implemented a nomenclature system for Segments 4 (haemagglutinin) and 6 (neuraminidase) of human Influenza A(H3N2), A(H1N1)pdm09, and Influenza B that dynamically adapts to the diversity of circulating viruses. New subclades were proposed by a clade suggestion algorithm based on criteria including (i) the number of sequences in the group, (ii) the distance from the direct parent clade, and (iii) the weighted number of amino acid substitutions on the branch leading to the common ancestor of the subclade.

RESULTS: Algorithmic clade proposals were reviewed and assigned a systematic hierarchical label consisting of a leading letter, followed by numbers (e.g., G.1.3). Names are kept short by aliasing that is collapsing prefixes into unique letters. Subclade definitions are shared openly to promote adoption and tool development. Nextclade is supporting this new nomenclature, and it is being used routinely by the GISRS network.

CONCLUSIONS: With increasing genomic surveillance, the need for up-to-date classification schemes is growing and we hope that the current dynamic proposal will adapt to growing data volumes and aid in simplifying the interpretation of these data.},
}

*Genetic Variation
Humans
*Influenza, Human/virology/epidemiology
Phylogeny
*Terminology as Topic
*Influenza A Virus, H3N2 Subtype/genetics/classification
*Influenza A Virus, H1N1 Subtype/genetics/classification
*Influenza B virus/genetics/classification
Seasons
Genome, Viral
Neuraminidase/genetics
Hemagglutinin Glycoproteins, Influenza Virus/genetics

@article {pmid41687672,
year = {2026},
author = {Mhlanga, FG and Szydlo, DW and Mayo, AJ and Bunge, K and Fairlie, L and Nakabiito, C and Musara, P and Mgodi, NM and Dadabhai, S and Scheckter, R and Anderson, PL and Marzinke, MA and Chappell, C and Gadama, LA and Richardson, BA and Piper, JM and Hillier, SL and , },
title = {Safety, acceptability, and adherence to dapivirine vaginal ring and oral pre-exposure prophylaxis for HIV prevention in the second trimester of pregnancy: a multicountry, open-label, phase 3b randomised trial.},
journal = {The lancet. HIV},
volume = {},
number = {},
pages = {},
doi = {10.1016/S2352-3018(25)00307-8},
pmid = {41687672},
issn = {2352-3018},
abstract = {BACKGROUND: Pregnant women are at a four times higher risk of HIV per coital act than non-pregnant women. MTN-042/DELIVER was a phase 3b randomised study of dapivirine vaginal ring (DVR) and oral pre-exposure prophylaxis (PrEP) with tenofovir disoproxil fumarate-emtricitabine to assess safety, adherence, and acceptability when used during pregnancy. Our hypothesis was that both DVR and oral PrEP would be safe and well tolerated when started early in the second trimester and continued until delivery.

METHODS: In MTN-042/DELIVER, an open-label, phase 3b randomised trial, healthy pregnant women without HIV and aged 18-40 years from Malawi, South Africa, Uganda, and Zimbabwe were enrolled and randomly allocated (4:1) to open-label monthly DVR PrEP or daily oral PrEP. Women were enrolled between 12 weeks' and 29 weeks' gestation. Product use continued until delivery or 42 weeks' gestation. The primary outcomes for safety following exposure to study product were a composite of all serious adverse events, including maternal deaths, all grade 3 or higher adverse events, and pregnancy outcomes stratified as term (≥37[+0] weeks), preterm (<37[+0] weeks), and pregnancy loss before 20 weeks' gestation. Pregnancy complications and adverse events were summarised with descriptive statistics. This study is registered with ClinicalTrials.gov, NCT03965923.

FINDINGS: Between July 12, 2022, and Jan 12, 2023, 251 mothers were enrolled, with 202 randomly allocated to receive DVR PrEP and 49 to receive oral PrEP. The median age was 24·0 years (IQR 22·0-29·0) and the median gestational age was 23·7 weeks (19·9-26·3). 28 mothers (11%) had safety events under the composite study primary outcome (all serious adverse events plus all grade 3 or higher adverse events), none of which was related to product use. No maternal deaths or HIV seroconversions occurred. There were 247 pregnancy outcomes of which 233 (94%) were at term (≥37[+0] weeks). Pregnancy complications were uncommon, and none was infectious.

INTERPRETATION: Adverse pregnancy outcomes related to DVR and oral PrEP use were uncommon among women starting PrEP in the second trimester. These findings support the use of these preventive approaches during pregnancy.

FUNDING: US National Institutes of Health.},
}

@article {pmid41686902,
year = {2026},
author = {Rawat, P and Shapiro, MR and Peters, LD and Widrich, M and Mayer-Blackwell, K and Motwani, K and Pavlović, M and Al Hajj, G and Posgai, AL and Kanduri, C and Isacchini, G and Chernigovskaya, M and Scheffer, L and Motwani, K and Balzano-Nogueira, LO and Pettenger-Willey, CM and Valkiers, S and Jacobsen, LM and Haller, MJ and Schatz, DA and Wasserfall, CH and Emerson, RO and Fiore-Gartland, AJ and Atkinson, MA and Klambauer, G and Sandve, GK and Greiff, V and Brusko, TM},
title = {Identification of a type 1 diabetes-associated T cell receptor repertoire signature from the human peripheral blood.},
journal = {Science advances},
volume = {12},
number = {7},
pages = {eadx7448},
pmid = {41686902},
issn = {2375-2548},
mesh = {Humans ; *Diabetes Mellitus, Type 1/immunology/genetics/blood ; *Receptors, Antigen, T-Cell/genetics ; Male ; Female ; HLA Antigens/genetics/immunology ; Alleles ; *Receptors, Antigen, T-Cell, alpha-beta/genetics ; Adult ; Cross-Sectional Studies ; },
abstract = {Type 1 diabetes (T1D) is a T cell-mediated disease with a strong immunogenetic human leukocyte antigen (HLA) dependence. HLA allelic influence on the T cell receptor (TCR) repertoire shapes thymic selection and controls activation of diabetogenic clones yet remains largely unresolved in T1D. We sequenced the circulating TCRβ chain repertoire from 2250 HLA-typed participants across three cross-sectional cohorts, including individuals with T1D and healthy related and unrelated controls. We found that HLA risk alleles show higher restriction of TCR repertoires in individuals with T1D. We leveraged deep learning to identify T1D-associated TCR subsequence motifs that were also observed in independent TCR cohorts residing in pancreas-draining lymph nodes of individuals with T1D. Collectively, our data demonstrate T1D-related TCR motif enrichment based on genetic risk, offering a potential metric for autoreactivity and groundwork for TCR-based diagnostics and therapeutics.},
}

Humans
*Diabetes Mellitus, Type 1/immunology/genetics/blood
*Receptors, Antigen, T-Cell/genetics
Male
Female
HLA Antigens/genetics/immunology
Alleles
*Receptors, Antigen, T-Cell, alpha-beta/genetics
Adult
Cross-Sectional Studies

@article {pmid41686530,
year = {2026},
author = {Grimm, LJ and Dodelzon, K and Bhole, S and Edmonds, CE and Mullen, LA and Parikh, JR and Daly, CP and Epling, JA and Christensen, S and Dontchos, BN},
title = {Patients Are Generally Supportive of Artificial Intelligence in Breast Imaging: A Multisite Survey of Breast Imaging Patients.},
journal = {Journal of breast imaging},
volume = {},
number = {},
pages = {},
doi = {10.1093/jbi/wbaf066},
pmid = {41686530},
issn = {2631-6129},
support = {//Duke Health Scholars Award/ ; //Principal Investigator Lars Grimm/ ; },
abstract = {OBJECTIVE: To understand the perspective of patients undergoing breast imaging on the use of artificial intelligence (AI) in breast cancer screening.

METHODS: A 36-item survey was administered to breast imaging patients at 6 academic and 2 private practice groups in the United States. The survey included questions regarding demographics, breast imaging history, and electronic health literacy. Respondents were asked Likert scale questions on the role of AI in breast cancer screening, the role of AI as an independent or complementary reader, and concerns regarding AI in breast imaging.

RESULTS: The survey yielded 3532 responses, a response rate of 69.9% (3532/5053). The median age was 55.9 years (SD, 12.3 years), and most respondents were White (73.0%, 2679/3532). Respondents indicated support for the role of AI to identify suspicious findings (70.6%, 2492/3532), triage findings for review (69.5%, 2382/3532), calculate breast density (73.2%, 2588/3532), and estimate breast cancer risk (61.9%, 2186/3532). Significantly higher support was noted among patients who were White, had more education, and had greater health literacy (all P <.05). There was strong agreement that it was necessary for radiologists to also review each examination (67.3%, 376/3532). Respondents were uncertain about whether AI (41.2%, 1456/3532) or radiologists (31.8%, 1124/3532) were responsible for errors. There was concern that AI will limit communication between patients and radiologists (75.7%, 2673/3532).

CONCLUSION: Breast imaging patients have an overall favorable view of AI in breast cancer screening, with variable support by demographics. Education and outreach efforts should target perceived challenges to AI adoption to improve patient acceptance.},
}

@article {pmid41686454,
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 = {41686454},
issn = {2473-9537},
}

@article {pmid41646762,
year = {2026},
author = {Ravindra, N and Lack, J and Dalgard, CL and vanCollenburg, E and Corner, A and Beppu, L and Erba, H and Othus, M and Radich, JP and Dillon, LW and Hourigan, CS},
title = {Whole Genome Sequencing Informed Patient Personalized Measurable Residual Disease Assays for Acute Myeloid Leukemia.},
journal = {medRxiv : the preprint server for health sciences},
volume = {},
number = {},
pages = {},
pmid = {41646762},
abstract = {Post-treatment measurable residual disease (MRD) in acute myeloid leukemia (AML) patients is associated with adverse clinical outcomes. Validated molecular methods for AML MRD are preferable to flow cytometry assays but are not available for all patients. The limit of detection (LOD) of next-generation sequencing (NGS) assays for single nucleotide variants is restricted by technical error rates. Structural alterations are common genetic features of AML, but MRD approaches for detecting this class of variants have primarily relied on RNA. However, RNA has suboptimal stability, not all structural alterations are expressed as transcripts, and the impact of anti-leukemic therapy on transcription may make leukemic disease burden quantification inaccurate. In this study, we demonstrate a whole genome sequencing (WGS)-based approach to identify genomic DNA breakpoints of chromosomal rearrangements that allowed design of highly sensitive patient-personalized digital droplet PCR (ddPCR) MRD assays. Acute myeloid leukemia (AML) is an aggressive malignancy of the hematopoietic precursor cells that predominantly affects older individuals. Oncogenic transformation occurring through the acquisition of structural chromosomal aberrations is noted in 35% of AML cases, and can result in the formation of fusion proteins that confer proliferation and survival advantages (1). When compared to classical cytogenetics for the identification of structural variants at diagnosis, newer techniques such as optical genome mapping can identify clinically pertinent aberrations that may be cryptic or smaller than the resolution of conventional karyotyping and FISH (2). Similarly, short-read whole genome sequencing (WGS) has been shown to increase diagnostic yield and better refine risk stratification when compared to traditional cytogenetic testing in myeloid malignancies (3). Additionally, WGS can be utilized to identify genomic breakpoints of chromosomal rearrangements at a basepair (bp) resolution.},
}

@article {pmid41686437,
year = {2026},
author = {LaMonte, MJ and Hyde, ET and Nguyen, S and Castro, E and Seguin-Fowler, RA and Eaton, CB and Miller, CR and Di, C and Stefanick, ML and LaCroix, AZ},
title = {Muscular Strength and Mortality in Women Aged 63 to 99 Years.},
journal = {JAMA network open},
volume = {9},
number = {2},
pages = {e2559367},
pmid = {41686437},
issn = {2574-3805},
mesh = {Humans ; Female ; Aged ; Aged, 80 and over ; Middle Aged ; Prospective Studies ; *Hand Strength/physiology ; *Muscle Strength/physiology ; *Mortality/trends ; Exercise/physiology ; Accelerometry ; Sedentary Behavior ; },
abstract = {IMPORTANCE: Muscular strength is an important resilience marker relevant to maintaining functional independence and longevity.

OBJECTIVE: To examine associations between muscular strength and mortality in women aged 63 to 99 years accounting for accelerometer-measured physical activity and sedentary behavior, systemic inflammation, and other markers of aging.

The Objective Physical Activity and Cardiovascular Health study was a prospective cohort study from baseline (March 2012 to April 2014) through February 19, 2023. Participants were ambulatory women aged 63 to 99 years who completed physical performance testing and 7 days of accelerometer wear.

EXPOSURES: Dominant hand grip strength,measured in kg by quartile (1: <14, 2: 14-19, 3: 19-24, and 4: >24) and time in seconds to complete 5 unassisted chair stands by quartile (standard criteria: 1: >16.7, 2: 16.6-13.7, 3: 13.6-11.2, and 4: ≤11.1).

MAIN OUTCOME AND MEASURE: All-cause mortality.

RESULTS: The present study included 5472 women (mean [SD] age, 78.7 [6.7] years; 1851 [33.8%] Black; 915 [16.7%] Hispanic/Latina; 2706 [49.5%] White) followed up for a mean (SD) of 8.4 (2.4) years. There were 1964 deaths during the study period. Controlling for age and sociodemographic, lifestyle, and clinical factors, significant inverse trends in mortality were evident across quartiles 2 through 4 of grip strength (quartile 2: hazard ratio [HR], 0.94; 95% CI, 0.85-1.06; quartile 3: HR, 0.85; 95% CI, 0.75-0.97; quartile 4: HR, 0.67; 95% CI, 0.58-0.78; P for trend < .001) and chair stand time (quartile 2: HR, 0.79; 95% CI, 0.69-0.88; quartile 3: HR, 0.76; 95% CI, 0.67-0.87; quartile 4: HR, 0.63; 95% CI, 0.54-0.73; P for trend < .001). Further controlling simultaneously for sedentary time and moderate to vigorous physical activity attenuated associations (grip strength: quartile 2: HR, 0.95; 95% CI, 0.86-1.07; quartile 3: HR, 0.87; 95% CI, 0.76-0.99; quartile 4: HR, 0.70; 95% CI, 0.61-0.82; P for trend < .001; chair stands: quartile 2: HR, 0.82; 95% CI, 0.73-0.92; quartile 3: HR, 0.82; 95% CI, 0.71-0.93; quartile 4: HR, 0.69; 95% CI, 0.59-0.79; P for trend < .001). Similar inverse associations were observed when controlling for walking speed and the inflammatory marker C-reactive protein. Magnitudes of association did not differ across subgroups defined by age, race and ethnicity, body mass index, moderate-to-vigorous physical activity, sedentary time, or timed walk.

CONCLUSIONS AND RELEVANCE: In this study of ambulatory older women, greater muscular strength was associated with lower mortality even when controlling for accelerometer-measured PA and sedentary time, walking speed, and systemic inflammation. These findings suggest that assessing strength and promoting its maintenance are instrumental for optimal aging.},
}

Humans
Female
Aged
Aged, 80 and over
Middle Aged
Prospective Studies
*Hand Strength/physiology
*Muscle Strength/physiology
*Mortality/trends
Exercise/physiology
Accelerometry
Sedentary Behavior

@article {pmid41686056,
year = {2026},
author = {Tam, CS and Shadman, M and Ong, SY and Wu, K and Salmi, T and Korde, R and Barnes, G and Brown, JR and Zhou, K and Qiu, L},
title = {Zanubrutinib versus ibrutinib in patients with relapsed/refractory chronic lymphocytic leukemia and small lymphocytic lymphoma: health-related quality of life in a subgroup of Chinese patients in the ALPINE trial.},
journal = {Current medical research and opinion},
volume = {},
number = {},
pages = {1-8},
doi = {10.1080/03007995.2026.2623629},
pmid = {41686056},
issn = {1473-4877},
abstract = {OBJECTIVES: Zanubrutinib demonstrated superiority to ibrutinib in the ALPINE (NCT03734016) phase 3 trial for relapsed/refractory chronic lymphocytic leukemia and small lymphocytic lymphoma (R/R CLL/SLL). This post hoc analysis examined patient-reported outcomes (PROs) in the Chinese subgroup.

METHODS: Adults with R/R CLL/SLL and ≥1 prior therapy were randomized 1:1 to zanubrutinib or ibrutinib. PROs, a secondary endpoint, were measured using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core-30. Differences between treatment arms from baseline to Cycles 7 and 13 for key PRO endpoints were assessed using a mixed model for repeated measures. Changes from baseline on the EQ visual analog scale (EQ-VAS) were examined descriptively.

RESULTS: As of February 28, 2024, 90 Chinese patients were randomized to zanubrutinib (n = 47) or ibrutinib (n = 43). Global health status/quality of life improved in both arms. Fatigue was reduced in both arms, with greater improvement in the zanubrutinib versus ibrutinib arm at Cycles 7 and 13. Nausea/vomiting scores generally remained unchanged, and all other symptoms showed similar improvement in both arms. Greater improvement in health status, measured by VAS score, was observed for the zanubrutinib arm at Cycle 13 (Cycle 7, 4.8 vs 4.1; Cycle 13, 5.7 vs 1.7).

CONCLUSIONS: In ALPINE, Chinese patients with R/R CLL/SLL treated with zanubrutinib showed better and faster PRO outcomes versus those treated with ibrutinib, particularly in fatigue. These results corroborate PRO findings in the intent-to-treat population and support the benefit of zanubrutinib as a valuable treatment option for Chinese patients with R/R CLL/SLL.

TRIAL REGISTRATION: NCT03734016. Registered 01 November, 2018 https://clinicaltrials.gov/study/NCT03734016.},
}

@article {pmid41685810,
year = {2026},
author = {Stankiewicz Karita, HC and Magaret, AS and Doody, DR and Schouten, JT and Mao, C and Huh, WK and Grieco, VS and Seymour, MA and Varon, D and Shrader, KH and Xi, LF and Galloway, DA and Wald, A and Madeleine, MM},
title = {Nonavalent HPV vaccine to prevent recurrent anal or vulvar high-grade squamous intraepithelial lesions (VIVA trial): A randomized, double-blind, placebo-controlled trial.},
journal = {International journal of cancer},
volume = {},
number = {},
pages = {},
doi = {10.1002/ijc.70366},
pmid = {41685810},
issn = {1097-0215},
support = {6R01CA213130-06/CA/NCI NIH HHS/United States ; },
abstract = {The nonavalent human papillomavirus (9vHPV) vaccine protects against HPV infection and high-grade squamous intraepithelial lesions (HSIL) when administered prior to exposure, but evidence supporting its potential therapeutic benefit has been inconsistent. This randomized, double-blind, placebo-controlled trial evaluated whether the 9vHPV vaccine reduces recurrence of HSIL or HPV persistence in 27-69-year-old persons previously treated for anal or vulvar HSIL. Participants were HSIL-free at enrollment and received 9vHPV or placebo at months 0, 2, and 6. High-resolution anoscopy or vulvoscopy was performed at months 18 and 36, and anal or vulvar swabs were collected at months 0, 18, 24, and 36 for HPV DNA detection. The primary endpoints were HSIL recurrence and HPV persistence (≥2 consecutive positive swabs for the same 9vHPV-type). Of 185 participants included in the intent-to-treat analysis, 91 received vaccine and 94 received placebo. The DSMB recommended early termination for futility. The 9vHPV vaccine was not more effective than placebo in preventing recurrent HSIL, with 16 HSIL among 9vHPV recipients versus 21 HSIL in placebo recipients (incidence 8.1 vs. 10.1/100 person-years; p = .54). HPV persistence was 21% in vaccine versus 31% in placebo recipients (p = .20). The 9vHPV vaccine delivered after treatment of anal or vulvar HSIL did not reduce HSIL recurrence or HPV detection. Our study underlines the importance of HPV vaccine administration prior to HPV exposure and the need for novel treatments for HSIL with high recurrence potential.},
}

@article {pmid41681979,
year = {2026},
author = {Chiorean, EG and Damle, SR and Zhen, DB and Whittle, M and George, B and Hochster, H and Coveler, AL and Hendifar, A and Dragovich, T and Safyan, RA and King, GT and Harris, WP and Dion, B and Stoll D'Astice, A and Lee, A and Thorsen, S and Kugel, S and Rosenthal, A and Hingorani, S},
title = {Phase II Study of Pegvorhyaluronidase Alfa (PEGPH20) and Pembrolizumab for Patients with Hyaluronan-High, Pretreated Metastatic Pancreatic Ductal Adenocarcinoma: PCRT16-001.},
journal = {Cancers},
volume = {18},
number = {3},
pages = {},
pmid = {41681979},
issn = {2072-6694},
support = {MISP 53041//Merck Pharmaceuticals/ ; 5P30CA015704-39//Fred Hutchinson Cancer Center Support Grant/ ; HALO 109-9902//Halozyme Therapeutics (United States)/ ; },
abstract = {Background: Stromal hyaluronic acid (HA) poses a physical barrier and protects tumor cells from immune surveillance. Stroma targeting with pegylated human recombinant PH20 hyaluronidase (PEGPH20) demonstrated improved infiltration of cytotoxic T-lymphocytes and delivery of chemotherapy and PD1/PD-L1 antibodies in tumor models. This multicenter phase II study of PEGPH20 plus pembrolizumab evaluated the efficacy, safety and immune and stromal biomarkers in patients with HA-high refractory metastatic pancreatic ductal adenocarcinoma (mPDA). Patients and Methods: Patients were treated with PEGPH20 3 µg/kg IV weekly and pembrolizumab 200 mg IV in 3-week cycles. Tumor and blood samples were collected at baseline and on-study for biomarker analyses. Results: Between May and November 2019, 38 patients were screened and 8 treated, with median age 68 years (range 60-73) and median two (range 1-4) prior therapies. The study was closed to accrual early by pharmaceutical sponsor. Treatment was well tolerated, with expected grade 1/2 musculoskeletal toxicities. Best response was stable disease in 2 of 7 evaluable patients (29%). Median overall and progression-free survival were 7.2 months (95% CI 1.2-11.8) and 1.5 months (95% CI 0.9-4.4), respectively. Prolonged survival (range 10.2-27.6 months) occurred in patients treated with subsequent chemotherapy. Higher baseline tumor T cell receptor (TCR) clonality correlated with longer survival. Conclusions: Pembrolizumab with PEGPH20 was safe but did not have significant efficacy in refractory HA-high metastatic PDA.},
}

@article {pmid41680482,
year = {2026},
author = {Talla, A and Azevedo, JLLC and Latif, MB and Enriquez, AB and Sanchez, GP and Pelletier, AN and Bal, SK and Kumari, S and Schuch, V and Ghneim, K and Rhodes, A and Maldarelli, F and Yarchoan, R and Lurain, K and Ramaswami, R and Sharon, E and Hess, BW and D'Amico, L and Martinez-Picado, J and Chomont, N and Lewin, SR and Deeks, SG and Fling, SP and Cheever, MA and Uldrick, TS and Sharma, AA and Sekaly, RP},
title = {Innate antiviral and immune functions associated with the HIV reservoir decay after anti-PD-1 therapy.},
journal = {Nature medicine},
volume = {},
number = {},
pages = {},
pmid = {41680482},
issn = {1546-170X},
support = {UM1AI164561//U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (NIAID)/ ; P01AI178376//U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (NIAID)/ ; UM1AI164561//U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (NIAID)/ ; P01AI178376//U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (NIAID)/ ; },
abstract = {Antiretroviral therapy (ART) suppresses HIV but does not eliminate the latent viral reservoir, which persists in programmed cell death protein 1 (PD-1)-expressing CD4[+] T cells. Anti-PD-1 therapies have reduced the HIV reservoir in people living with HIV (PLWH) and cancer; however, the individuals who benefit and the mechanisms driving reservoir reduction remain unclear. We performed a prespecified exploratory, longitudinal multiomic profiling of 30 PLWH (29 males and one female) with cancer in the phase 1 CITN-12 clinical trial, in which pembrolizumab was evaluated for safety and preliminary antitumor activity. The therapy was generally well tolerated, with most adverse events graded 1-2 and objective antitumor response observed in five participants (one complete response and four partial responses). Within 24 hours of treatment, we observed an expansion of proliferating HIV-specific effector CD8[+] T cells and a decline in plasma TGFβ. Furthermore, among the 14 participants tracked to the end of treatment (ranging from 44 to 315 days after therapy initiation), nine display early induction and sustained expression of interferon-stimulated genes (ISGs), antiviral restriction factors and Toll-like receptor (TLR) signaling and a reduction in the HIV reservoir. Mapping these transcriptomic signatures across more than 1,000 public single-cell RNA sequencing datasets reveals that anti-PD-1-induced programs are present in subsets of across subsets of disease states, indicating that some people already display a heightened antiviral state. Together, these findings define immune pathways that help identify PLWH most likely to experience reservoir decay with anti-PD-1 therapy and suggest that sustained ISG activation may contribute to reservoir reduction and prevention of viral rebound upon ART interruption. ClinicalTrials.gov registration: NCT02595866 .},
}

@article {pmid41680141,
year = {2026},
author = {Harris, ED and McGovern, M and Pernikoff, S and Ikeda, R and Kipnis, L and Hannon, W and Sobolik, EB and Gray, M and Greninger, AL and He, S and Chin, CN and Fu, TM and Pancera, M and Boonyaratanakornkit, J},
title = {Development of a potent monoclonal antibody for treatment of human metapneumovirus infections.},
journal = {Nature communications},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41467-026-69328-w},
pmid = {41680141},
issn = {2041-1723},
support = {Vaccine and Infectious Disease Division Faculty Initiative//Fred Hutchinson Cancer Research Center (Hutchinson Center)/ ; Evergreen Beyond Pilot Award//Fred Hutchinson Cancer Research Center (Hutchinson Center)/ ; R01-AI171186//U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (NIAID)/ ; P30 CA015704/CA/NCI NIH HHS/United States ; },
abstract = {Human metapneumovirus (HMPV) is a major cause of respiratory infections, particularly among vulnerable populations, yet effective therapeutics remain unavailable. Monoclonal antibodies (mAbs) offer a promising approach for treatment and prevention. We describe the discovery and characterization of 4F11, a highly potent neutralizing mAb with in vitro and in vivo efficacy against HMPV. Using cryo-electron microscopy, we define a unique mechanism of binding employed by 4F11. 4F11 targets an epitope located at the apex of the prefusion F protein (site Ø) with a 1:1 stoichiometry of Fab to trimer, distinct from the 3:1 stoichiometry observed with other HMPV site Ø antibodies. Unlike other site Ø antibodies which penetrate the glycan shield between Asn57 and Asn172, 4F11 binds vertically and directly interacts with the Asn172 glycan. In vitro, 4F11 displays high neutralization potency across diverse HMPV strains. It also shows low propensity for resistance development, with only a single escape mutation (K179E) identified, a mutation not found in any published HMPV sequence to date. Viruses rescued with the K179E escape mutation have significantly decreased fitness in vitro. In male hamsters, 4F11 significantly reduces viral loads in the lungs and nasal turbinates. These findings highlight 4F11 as a promising candidate for therapeutic development.},
}

@article {pmid41679770,
year = {2026},
author = {Hanna, M and Sun, Q and Bell-Brown, A and Issaka, RB},
title = {Colorectal Cancer Test Completion Among Adults Aged 45-75 in an Integrated Healthcare System: A Retrospective Analysis.},
journal = {Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology},
volume = {},
number = {},
pages = {},
doi = {10.1158/1055-9965.EPI-25-1512},
pmid = {41679770},
issn = {1538-7755},
abstract = {BACKGROUND: In 2021, the U.S. Preventive Services Task Force (USPSTF) lowered the recommended age for colorectal cancer (CRC) screening from 50 to 45. This study examined CRC test completion and test modalities used among adults aged 45-49 compared to those 50 and older.

METHODS: We conducted a retrospective cohort study using electronic health records from an integrated academic-community health system that implemented organized screening. Adults aged 45-75 eligible for CRC screening between 2021 and 2024 were included. Outcomes were CRC test completion and test modality: colonoscopy, fecal immunochemical test (FIT), FIT-DNA, CT colonography, or flexible sigmoidoscopy.

RESULTS: Approximately 80,000 adults were eligible for screening annually. CRC test completion rose from 61.8% (2021) to 70.8% (2024), with the largest increase in the 45-49 age group (25.6% to 51.7%). Colonoscopy and FIT were the most used modalities; among 45-49-year-olds, FIT increased by 12.2% and colonoscopy by 14.2%. FIT-DNA use rose slightly, while flexible sigmoidoscopy use declined. Racial and ethnic disparities in CRC test completion decreased across groups.

CONCLUSIONS: Following the 2021 USPSTF recommendation, CRC test completion improved across all age groups, especially adults 45-49. Colonoscopy and FIT use predominated. Ongoing efforts are needed to improve screening among younger adults to reach the 80% national screening goal.

IMPACT: This study demonstrated that expanding CRC testing to 45-49-year-olds led to increased uptake of colonoscopy and FIT. It highlights how organized outreach and providing options in screening modalities can improve CRC test completion across several patient populations.},
}

@article {pmid41678147,
year = {2026},
author = {Huang, SH and Cotler, J and Palis, B and Seethala, RR and Hosni, A and O'Sullivan, B and Vander Poorten, V and Bishop, JA and Glastonbury, CM and Beadle, B and Ha, P and Kakarala, K and Rodriguez, CP and Su, J and Xu, W and Alfaraj, F and Souied, O and Marta, GN and Kowalski, LP and Mierzwa, ML and Ho, AS and Eagan, A and Madera, M and Lydiatt, W and Patel, SG and Ganly, I},
title = {Proposed Version Nine of the AJCC and UICC TNM Classification for Salivary Gland Carcinoma.},
journal = {JAMA otolaryngology-- head & neck surgery},
volume = {},
number = {},
pages = {},
pmid = {41678147},
issn = {2168-619X},
abstract = {IMPORTANCE: A unified salivary gland carcinoma (SGC)-specific tumor-node-metastasis (TNM) classification can enhance prognostic accuracy, support clinical decision-making, and improve the quality of patient care.

OBJECTIVE: To derive and validate an SGC-specific pTNM classification with improved prognostic accuracy and optimized stage distribution for version nine of the American Joint Committee on Cancer/Union for International Cancer Control staging protocol.

This retrospective prognostic cohort study derived a novel pTNM classification using data from the National Cancer Database (NCDB) of patients with surgically treated major SGC (2012-2017) and validated it in an international major SGC cohort (2008-2021) and a single-institution minor SGC cohort (Memorial Sloan Kettering Cancer Center; 1985-2016). Data were analyzed from June to November 2024.

EXPOSURES: Surgery with or without postoperative radiotherapy or chemoradiotherapy.

MAIN OUTCOMES AND MEASURES: The primary end point was overall survival (OS). Cox proportional hazards multivariable analysis was used to confirm the prognostic importance of pathologically positive lymph node (LN) number and extranodal extension (pENE) and derive an optimal pTNM classification.

RESULTS: The NCDB dataset included 8409 patients with SGC: 7659 with M0 disease (5748 with pN0 disease and 1911 with pN+ disease) and 750 with M1 disease. Among the 7659 patients with M0 disease, the median (IQR) age was 60 (48-71) years, and 3861 (50.4%) were male. The median (IQR) follow-up was 88.4 (72.3-108.5) months. The 5-year OS was 87.2% (95% CI, 86.3-88.0) for N0 disease, 68.2% (95% CI, 63.9-72.8) for 1 positive LN without pENE, 60.2% (95% CI, 53.5-67.5) for 2 positive LNs without pENE, 68.4% (95% CI, 58.0-76.6) for 3 positive LNs without pENE, 47.5% (95% CI, 41.6-52.8) for more than 3 positive LNs without pENE, and 41.4% (38.1-44.8) for pENE-positive LNs. Multivariable analysis confirmed the independent prognostication of LN count compared with pN0 disease (1 positive LN: adjusted hazard ratio [aHR], 1.70; 95% CI, 1.44-2.01; 2 positive LNs: aHR, 1.61; 95% CI, 1.31-1.98; 3 positive LNs: aHR, 2.10; 95% CI, 1.65-2.68; 4 positive LNs : aHR, 2.46; 95% CI, 1.87-3.24; more than 4 positive LNs: aHR, 2.07; 95% CI, 2.08-2.91) and pENE-positive LNs compared with pENE-negative LNs (aHR, 1.27; 95% CI, 1.10-1.48). The proposed pN classification were pN1 for 1 to 3 positive LNs and pENE negativity and pN2 for more than 3 positive LNs or pENE positivity. Model fit improved with the proposed pN classification vs the current pN classification (Akaike Information Criterion, 26 442 vs 26 483). Based on the aHR model, the following stage groups were proposed: stage I: T1N0 (1 [reference]); stage II: T2N0 (aHR, 1.34; 95% CI, 1.11-1.61); stage IIIA: T1-2N1 or T3-4N0 (aHR, 2.36; 95% CI, 1.99-2.80); stage IIIB: T1-2N2 or T3-4N1-2 (aHR, 5.15; 95% CI, 4.38-6.06); and stage IV: M1 disease (aHR, 13.61; 95% CI, 11.37-16.29). The C index values were similar (proposed classification: 0.792; current classification: 0.790), while the AIC improved slightly (proposed classification: 26 441; current classification: 26 482). Stage-specific OS differences were evident in both the international major SGC cohort (n = 1015) and Memorial Sloan Kettering Cancer Center minor SGC cohort (n = 444).

CONCLUSIONS AND RELEVANCE: This unified, SGC-specific staging system improved prognostic accuracy and sample size balance and was applicable to both major and minor SGCs.},
}

@article {pmid41648631,
year = {2026},
author = {Pan, T and Shiau, CK and Lu, L and Wang, C and Wang, M and He, Y and Bhimaraj, A and Brat, D and Huse, J and Jessica Li, J and Gao, R},
title = {Hypatia: Comparative Isoform Profiling Across Cell Populations from Long-Read Single-Cell Transcriptomes.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {41648631},
issn = {2692-8205},
support = {P50 CA221747/CA/NCI NIH HHS/United States ; R35 GM142539/GM/NIGMS NIH HHS/United States ; },
abstract = {High-throughput long-read single-cell RNA-sequencing enables isoform-level study across single cells, yet methods for systematically assessing cell-to-cell variations remain limited. Here, we develop Hypatia, a comprehensive platform for dissecting isoform complexities across cell populations, devising Tsallis entropy and Cramer's V to facilitate robust comparative profiling. Hypatia revealed prominent isoform species variations and usage shifts across cell-types in glioblastoma, renal cell carcinoma, and heart, highlighting clinically relevant applications for studying isoform-derived, cell-specific functions.},
}