@article {pmid41858873,
year = {2026},
author = {Sanchez-Cespedes, M and Lockwood, WW and Suda, K and Gardner, EE and Mitsudomi, T and Politi, K and Rolfo, C and Sen, T and Sos, ML and Tammela, T and Wynes, MW and Tsao, MS and Berger, AH},
title = {Tolerance and Resistance to Targeted Therapy in NSCLC: Emerging Concepts and Strategies.},
journal = {JTO clinical and research reports},
volume = {7},
number = {4},
pages = {100944},
pmid = {41858873},
issn = {2666-3643},
abstract = {The discovery of EGFR mutations two decades ago launched an era of rapid development and clinical application of targeted therapies in NSCLC. Today, increasing numbers of targeted therapies against somatic aberrations involving nine different genes have become available for treating patients with lung cancer and have improved their outcomes. However, acquired resistance and tumor tolerance to these therapies remains one of the biggest challenges in lung cancer treatment today. Most, if not all, targeted therapies have limited durability, which we now recognize is due to both genetic and non-genetic mechanisms of resistance. The state of our current understanding of resistance and new approaches to prevent or overcome resistance were recently presented at the International Association for the Study of Lung Cancer Hot Topics Meeting. Here, we summarize and discuss the emerging concepts and new strategies for combating drug tolerance and resistance in targeted therapies, including our understanding of the role of genetics, drug-tolerant persister cells, tumor plasticity and lineage transformation, spatial and temporal heterogeneity, microenvironmental influence, and novel therapeutic approaches.},
}

@article {pmid41859811,
year = {2026},
author = {Coronado, GD and Rutter, C and Nascimento De Lima, P},
title = {Response to Piscitello et al.},
journal = {Journal of the National Cancer Institute},
volume = {},
number = {},
pages = {},
doi = {10.1093/jnci/djag075},
pmid = {41859811},
issn = {1460-2105},
}

@article {pmid41860387,
year = {2026},
author = {Blew, RM and Ziller, SG and Odegaard, AO and Caan, BJ and Chen, Z and Roe, DJ and Manson, JE and Rohan, TE and Felix, AS and Harris, HR and Luo, J and Lane, DS and Bea, JW},
title = {DXA-Derived Abdominal Adiposity and Obesity-Related Cancer Risk Among Postmenopausal Women in the Women's Health Initiative.},
journal = {Obesity (Silver Spring, Md.)},
volume = {},
number = {},
pages = {},
doi = {10.1002/oby.70168},
pmid = {41860387},
issn = {1930-739X},
support = {R01CA253302//National Cancer Institute at the National Institutes of Health/ ; R01CA253302-02S1//National Cancer Institute at the National Institutes of Health/ ; R25CA217725//National Cancer Institute at the National Institutes of Health/ ; P30CA023074//National Cancer Institute at the National Institutes of Health/ ; 75N92021D00001/HL/NHLBI NIH HHS/United States ; 75N92021D00002/HL/NHLBI NIH HHS/United States ; 75N92021D00003/WH/WHI NIH HHS/United States ; 75N92021D00004/WH/WHI NIH HHS/United States ; 75N92021D00005/WH/WHI NIH HHS/United States ; R01AG055018//National Institute on Aging of the National Institutes of Health/ ; },
abstract = {OBJECTIVE: Obesity is associated with the risk of several cancers, yet conventional anthropometric measures do not distinguish the contributions of different compartments of abdominal adipose tissue. This study examined the relationship between visceral (VAT) and subcutaneous (SAT) abdominal adiposity and the incidence of 13 obesity-related cancers (ObRCs) in postmenopausal women.

METHODS: Data from 9950 postmenopausal participants in the Women's Health Initiative (WHI) dual-energy X-ray absorptiometry (DXA) cohort were analyzed. Abdominal VAT and SAT were quantified from DXA scans using validated imaging software. Fine and Gray competing-risks models estimated associations with ObRC incidence over 177,295 person-years of follow-up.

RESULTS: Higher abdominal VAT was significantly associated with higher ObRC risk, independently of BMI, waist circumference (WC), and other confounders. Each 100-cm[2] increase in VAT corresponded to a 32% higher risk, with a nearly twofold increase for women in the highest VAT quartile. SAT and the VAT/SAT ratio were also significantly associated with risk, though more modestly. Findings were consistent across BMI, WC, age, and race/ethnicity strata and in time-varying models.

CONCLUSIONS: Visceral adiposity has a strong, independent association with ObRC risk in postmenopausal women. Incorporating imaging-based body composition measures may improve cancer risk stratification and guide targeted prevention strategies.

TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00000611 https://clinicaltrials.gov/study/NCT00000611.},
}

@article {pmid41860999,
year = {2026},
author = {Henikoff, S and Henikoff, JG},
title = {Superabundant microRNAs are transcribed from human rDNA spacer promoters insulated by CTCF.},
journal = {Science advances},
volume = {12},
number = {12},
pages = {eaec1451},
pmid = {41860999},
issn = {2375-2548},
mesh = {Humans ; *MicroRNAs/genetics ; *Promoter Regions, Genetic ; *CCCTC-Binding Factor/metabolism/genetics ; *Transcription, Genetic ; RNA Polymerase II/metabolism/genetics ; *DNA, Ribosomal/genetics ; *DNA, Ribosomal Spacer/genetics ; },
abstract = {microRNAs are ~22-nucleotide RNAs processed from primary transcripts and exported from the nucleus to repress gene expression by base-pairing to mRNAs. Unexpectedly, we find that the highest levels of RNA polymerase II (Pol II) at human microRNA genes are within the ribosomal gene repeat arrays (rDNAs). Alignment of public nascent transcript data to the hs1 human genome assembly reveals a 50-nucleotide transcript for both miR-1275 and miR-6724, which exits from the nucleus with exceptional rapidity. We show that the miR-1275/miR-6724 transcription unit is closely flanked by CCCTC-binding factor (CTCF) within a <400-bp span of the rDNA spacer promoter. miR-1275/miR-6724 and microRNA precursors expressed from the 5' external transcribed spacer (5'ETS) are exported independently of known RNA processing activities and are detected in exosomes and as circulating cancer biomarkers. We propose that the rDNA spacer promoter and 5'ETS microRNA genes have evolved for general regulatory functions in recipient cells.},
}

Humans
*MicroRNAs/genetics
*Promoter Regions, Genetic
*CCCTC-Binding Factor/metabolism/genetics
*Transcription, Genetic
RNA Polymerase II/metabolism/genetics
*DNA, Ribosomal/genetics
*DNA, Ribosomal Spacer/genetics

@article {pmid41861692,
year = {2026},
author = {Lam, AC and Li, Y and Brown, MC and Deng, Y and Hueniken, K and Leighl, NB and Shepherd, FA and Murison, K and Wang, Z and Kothari, J and Wenzlaff, AS and Liu, H and Kohno, T and Pesatori, AC and Harris, C and Ma, H and Dai, J and Barnett, MJ and Diver, R and Leal, LF and Fernandez-Tardon, G and Pérez-Ríos, M and Davies, MP and Holleczek, B and Brennan, P and Zaridze, D and Holcatova, I and Lissowska, J and Świątkowska, B and Mates, D and Savic, M and Brenner, H and Andrew, AS and Taylor, F and Field, JK and Ruano-Ravina, A and Shete, SS and Tardon, A and Wang, Y and Marchand, LL and Reis, RM and Schabath, MB and Neuhouser, ML and Shen, H and Landi, MT and Shiraishi, K and Zhang, J and Schwartz, AG and Tsao, MS and Christiani, DC and Yang, P and Hung, RJ and Xu, W and Liu, G},
title = {Evaluating eight smoking metrics for modelling survival in non-small cell lung cancer.},
journal = {Cancer epidemiology},
volume = {102},
number = {},
pages = {103052},
doi = {10.1016/j.canep.2026.103052},
pmid = {41861692},
issn = {1877-783X},
abstract = {INTRODUCTION: Smoking is a strong modifiable prognostic factor for lung cancer survival. We compared eight smoking metrics to determine which metric best models the relationship between smoking exposure with overall survival (OS) and lung cancer-specific survival (LCSS). These metrics included cigarettes-per-day, smoking duration, pack-years, square-root pack-years, logcig-years, the comprehensive smoking index, age-of-initiation, and years-since-quit.

MATERIALS/METHODS: This retrospective, pooled analysis included 25 International Lung Cancer Consortium studies between June 1, 1983-December 31, 2019. The performance of smoking metrics for modelling OS was compared based on 1) strength and significance in adjusted Cox-proportional hazard models and 2) linearity based on the goodness-of-fit assuming the log-hazard varies linearly with each smoking metric (i.e. the hazard ratio is constant across different values of the smoking metric) compared to models using non-linear splines. This process was repeated across clinicodemographic subgroups and for LCSS.

RESULTS: In total, 28,702 lung cancer patients were included (median age 64 [IQR: 57-71]; 53% male). Logcig-years (log(cigarettes/day+1)·years-smoked) had the highest adjusted hazard ratio per standard deviation (aHR 1.11; 95% CI: 1.09-1.13) and best goodness-of-fit when modelled linearly. Square-root pack-years had a similar effect size (aHR 1.11; 95% CI: 1.09-1.13) and had a strong linear relationship on visual assessment of spline curves. In subgroup analyses, logcig-years had a large effect size and maintained a linear relationship regardless of age, sex, stage, and histology. For lung cancer-specific survival (LCSS), logcig-years again had the highest aHR (1.09; 95% CI: 1.05-1.12) and the best linear goodness-of-fit, while square-root pack-years demonstrated the most linear relationship on visual assessment.

DISCUSSION: Logcig-years best modelled the relationship between smoking exposure and OS as well as LCSS, and had consistent associations across clinicodemographic subgroups. Logcig-years should be considered in clinical and research applications for quantifying smoking exposure in lung cancer.},
}

@article {pmid41862775,
year = {2026},
author = {Rees, MJ and Cassano, RC and Tan, M and Zolotov, E and Sidana, S and Dima, D and Kort, J and Afrough, A and Gaballa, M and Pasvolsky, O and Mikkilineni, L and Khouri, J and Raza, S and Zanwar, SS and Ferreri, CJ and Kumar, S and Khan, AM and Atrash, S and Portuguese, AJ and Rana, MS and Banerjee, R and Freeman, C and Blue, B and Patel, KK and Anderson, LD and Puglianini, OC and Shune, LO and Biran, N and Hansen, DK and Lin, Y},
title = {The Safety and Efficacy of Commercial BCMA-Directed CAR T-Cell Therapy in Systemic AL Amyloidosis With Concurrent Myeloma.},
journal = {American journal of hematology},
volume = {},
number = {},
pages = {},
doi = {10.1002/ajh.70294},
pmid = {41862775},
issn = {1096-8652},
}

@article {pmid41855500,
year = {2026},
author = {Baek, G and Varma, G and Yamshon, S and van Besien, HJ and Bartlett, NL and Watkins, MP and Shah, HR and Baron, K and Merryman, RW and Falade, AS and Svoboda, J and Prischak, S and D'Angelo, CR and Lukowski, JD and Advani, RH and Yeung, AH and Rosenberg, MC and Voutsinas, JM and Di, M and Lynch, RC and Poh, C and Raghunathan, V and Shadman, M and Smith, SD and Till, BG and Ujjani, CS and Diefenbach, C and Gopal, AK},
title = {Real-World Evidence for Pembrolizumab Gemcitabine Vinorelbine and Liposomal Doxorubicin in Classical Hodgkin Lymphoma.},
journal = {Blood advances},
volume = {},
number = {},
pages = {},
doi = {10.1182/bloodadvances.2025018267},
pmid = {41855500},
issn = {2473-9537},
}

@article {pmid41856415,
year = {2026},
author = {Liu, L and Sathees, S and Sobel, A and Pepper, G and Greninger, AL and Jerome, KR and Fong, Y and Roychoudhury, P},
title = {BlotDx: A deep learning tool for Western blot-based diagnostics.},
journal = {Journal of virological methods},
volume = {343},
number = {},
pages = {115385},
doi = {10.1016/j.jviromet.2026.115385},
pmid = {41856415},
issn = {1879-0984},
abstract = {BACKGROUND: Western blot (WB) is the gold standard for herpes simplex virus (HSV-1/HSV-2) serology but requires manual interpretation by trained laboratory personnel, which is time-consuming and variable. This study presents BlotDx, a deep learning tool to assist in HSV WB interpretation to improve efficiency and diagnostic consistency.

METHODS: BlotDx uses a two-stage approach: (1) instance segmentation or object detection to identify blots from input images, and (2) classification models to determine positive or negative serostatus for HSV-1 and HSV-2, excluding indeterminate results. We developed three classifiers that differ in how information flows between stages. The primary dataset consisted of 926 blot pairs derived from samples collected between 2016 and 2017 and photographed in 2018; and a second institutional validation dataset containing 185 blot pairs from samples collected between 2019 and 2024 and photographed in a different laboratory space in 2025.

RESULTS: Evaluated against the ground truth of expert human review by three independent technicians, BlotDx demonstrated high diagnostic accuracy by 5-fold cross validation in both the primary dataset (98.8% for HSV-1, 95% confidence interval (CI): 97.9%-99.3%; and 98.9% for HSV-2, 95% CI: 98.0%-99.4%), and in the institutional validation dataset (97.3% for HSV-1, 95% CI: 93.8%-98.8%; and 96.2% for HSV-2, 95% CI: 92.4%-98.1%).

CONCLUSIONS: This study highlights the utility of AI as a diagnostic assistant for image-based assays like HSV Western blots, with potential applications in other diseases. The proposed two-stage approach, combined with modern deep learning techniques is scalable and offers a step towards transforming traditional diagnostic workflows by reducing costs and increasing efficiency.},
}

@article {pmid41856486,
year = {2026},
author = {Barachini, S and Cassano Cassano, R and Ronca, F and Petrini, I and Galimberti, S and Buda, G},
title = {The Role of Microenvironment in Bispecific Antibodies Treatment in Multiple Myeloma.},
journal = {European journal of haematology},
volume = {},
number = {},
pages = {},
doi = {10.1111/ejh.70168},
pmid = {41856486},
issn = {1600-0609},
abstract = {Multiple myeloma (MM) is a clonal plasma cell malignancy that remains largely incurable despite major therapeutic advances. T-cell-redirecting bispecific antibodies (BsAbs) and chimeric antigen receptor T (CAR-T) cells have recently emerged as highly effective therapies in relapsed/refractory MM, inducing deep responses even in heavily pretreated patients. However, disease relapse, limited durability of response, and treatment-related toxicities remain frequent, underscoring the need to better understand mechanisms of resistance. Accumulating evidence indicates that the tumor microenvironment (TME) plays a central role in shaping BsAb efficacy in MM. Immunosuppressive cellular components, including regulatory T-cells, myeloid-derived suppressor cells, and dysfunctional antigen-presenting cells, as well as inhibitory cytokines, hypoxia, and metabolic constraints within the TME, profoundly impair T-cell activation, expansion, and persistence following BsAb engagement. In addition, chronic CD3 stimulation within the TME may promote T-cell exhaustion, contributing to suboptimal responses and disease progression. This review focuses on the dynamic interplay between BsAbs and the MM TME, highlighting how microenvironment-driven immune suppression, antigen escape, and impaired T-cell fitness influence clinical outcomes. We further discuss emerging strategies designed to overcome these barriers, including rational combination approaches, immunomodulatory agents, and next-generation trispecific antibodies that enhance co-stimulation or dual-antigen targeting. Understanding and therapeutically modulating the TME represents a critical step toward improving the depth, durability, and safety of BsAb-based therapies in MM.},
}

@article {pmid41856667,
year = {2026},
author = {Gogebakan, KC and Kunst, N and Ghodsi, A and Owens, L and Iravani, A and Etzioni, R},
title = {Cost-Effectiveness Analysis of [177]Lu-PSMA-617 Versus Cabazitaxel in Metastatic Castration-Resistant Prostate Cancer from a U.S. Health Care Perspective.},
journal = {Journal of nuclear medicine : official publication, Society of Nuclear Medicine},
volume = {},
number = {},
pages = {},
doi = {10.2967/jnumed.125.271825},
pmid = {41856667},
issn = {1535-5667},
abstract = {The TheraP trial demonstrated that [177]Lu-PSMA-617 improved progression-free survival (PFS) compared with cabazitaxel, with no significant difference in overall survival (OS). However, [177]Lu-PSMA-617 was associated with fewer severe adverse events, better patient-reported outcomes, and lower health care utilization rates. In this study, we evaluated the impact of these benefits on the cost-effectiveness of [177]Lu-PSMA-617 versus cabazitaxel from a U.S. health care perspective. Methods: A partitioned survival model was developed to estimate lifetime costs and health outcomes associated with [177]Lu-PSMA-617 versus cabazitaxel over a 60-mo horizon. OS and PFS associated with[177]Lu-PSMA-617 were derived from a retrospective cohort, and relative treatment effects (hazard ratios [HRs]) from the TheraP trial were applied to generate outcomes for patients treated with cabazitaxel. Health state utilities, adverse-event disutilities, and costs were obtained from published sources. Outcomes included total costs, quality-adjusted life-years (QALYs), incremental cost-effectiveness ratio, and net monetary benefit at willingness-to-pay (WTP) thresholds up to $200,000/QALY. Results: In the base case analysis, [177]Lu-PSMA-617 was not cost-effective compared with cabazitaxel (incremental cost-effectiveness ratio, $358,990/QALY). Cost-effectiveness results were most sensitive to the OS HR, the per-cycle cost of [177]Lu-PSMA-617, and the per-cycle cost of cabazitaxel. [177]Lu-PSMA-617 would become cost-effective if the per-cycle treatment cost was $27,656 or if the OS HR improved to 0.76 at a WTP threshold of $200,000/QALY. Probabilistic analyses found that [177]Lu-PSMA-617 was cost-effective in 19.7% of iterations at a WTP threshold of $200,000/QALY, 4.7% at $100,000/QALY, and 2.2% at $50,000/QALY. Conclusion: Although [177]Lu-PSMA-617 was not cost-effective compared with cabazitaxel in the base case analysis, it may achieve cost-effectiveness under more favorable assumptions of survival benefit or reduced cost per cycle. Probabilistic analyses further highlighted substantial uncertainty, with a low likelihood of cost-effectiveness.},
}

@article {pmid41856883,
year = {2026},
author = {Wang, Y and Ouyang, WO and Wang, C and Nourmohammad, A and Liu, G and Wu, NC},
title = {Experimental immunologists in the era of artificial intelligence.},
journal = {Trends in immunology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.it.2026.01.003},
pmid = {41856883},
issn = {1471-4981},
abstract = {While artificial intelligence (AI) is transforming biological science, its full potential in immunology has yet to be realized due to limited data and the need for extensive experimental validation. This review provides a practical guide for experimental immunologists to actively contribute to AI development, with a focus on applications for B- and T-cell receptors. It not only gives an overview of common AI techniques in immunology but also highlights the important role of high-throughput experimental methodologies. Overall, we believe that the synergy between AI and experimental innovation will be a crucial catalyst for advancing the field of immunology.},
}

@article {pmid41851041,
year = {2026},
author = {Kundu, P and Zhu, C and Huentelman, M and Deoni, SCL and Naymik, M and Taguinod, F and De Both, M and Lewis, CR and Müller, HG},
title = {Brain volume trajectories in young children are associated with polygenic scores for late-onset Alzheimer's disease risk.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {22},
number = {3},
pages = {e71279},
doi = {10.1002/alz.71279},
pmid = {41851041},
issn = {1552-5279},
support = {DMS-2014626//National Science Foundation/ ; DMS-2310450//National Science Foundation/ ; },
mesh = {Humans ; *Alzheimer Disease/genetics/pathology/diagnostic imaging ; Magnetic Resonance Imaging ; Male ; Female ; *Brain/pathology/diagnostic imaging/growth & development ; Child, Preschool ; *Multifactorial Inheritance/genetics ; *Genetic Predisposition to Disease/genetics ; Longitudinal Studies ; Organ Size ; Gray Matter/diagnostic imaging/pathology ; Child ; Genome-Wide Association Study ; White Matter/pathology/diagnostic imaging ; Cohort Studies ; },
abstract = {INTRODUCTION: Polygenic risk scores (PRSs) for Alzheimer's disease (AD) capture an individual's genetic susceptibility to AD. Although thoroughly studied in older populations, there exists a notable gap in comprehensively exploring the association of AD PRS with early brain development.

METHODS: We examined longitudinal brain magnetic resonance imaging (MRI) data from 348 typically developing children in the RESONANCE cohort. Proportional cerebrospinal fluid (pCSF), white matter (pWM), and gray matter (pGM) volumes were analyzed using functional concurrent regression and Riemannian functional principal component analysis. AD-PRS scores (AD25 and AD54) were computed using genome-wide data.

RESULTS: Higher AD PRS was significantly associated with reduced pCSF during early childhood (ages 2.5 to 5.5 years for AD54). Energy and distance-based tests revealed overall significant differences in brain volume trajectories between moderate and low AD54 risk groups.

DISCUSSION: These findings suggest that genetic risk for late-onset AD is linked to early neurodevelopmental patterns, indicating that AD vulnerability may originate during critical windows of early brain maturation.},
}

Humans
*Alzheimer Disease/genetics/pathology/diagnostic imaging
Magnetic Resonance Imaging
Male
Female
*Brain/pathology/diagnostic imaging/growth & development
Child, Preschool
*Multifactorial Inheritance/genetics
*Genetic Predisposition to Disease/genetics
Longitudinal Studies
Organ Size
Gray Matter/diagnostic imaging/pathology
Child
Genome-Wide Association Study
White Matter/pathology/diagnostic imaging
Cohort Studies

@article {pmid41855168,
year = {2026},
author = {Templin, T and Song, S and Fort, S and Sinnott-Armstrong, N},
title = {Participatory-informed preference optimization (PiPrO): A reinforcement learning simulation study.},
journal = {PLOS digital health},
volume = {5},
number = {3},
pages = {e0001294},
pmid = {41855168},
issn = {2767-3170},
abstract = {Artificial intelligence (AI) has transformative potential in public health, but its impact is limited by models that implicitly prioritize a single stakeholder perspective and do not make explicit and tunable trade-offs between community and clinician endorsement. To address this gap, we introduce Participatory-informed Preference Optimization (PiPrO), a large language model embedding-based calibration framework that generates a single clinical outcome prediction while explicitly accounting for differences between community and physician interpretations of the same scenario. PiPrO takes as input two embeddings derived from a large language model representing a community-facing context and a physician-facing context. It then applies a shared lightweight feedforward predictor to produce per-stakeholder scores which are then mixed using a single global mixing weight (alpha). Alpha controls how strongly the final prediction reflects the community versus physician responses and is learned using a policy-gradient update driven by an abundant but noisy community text and a sparse and biased physician text. PiPrO reliably learned stable alpha values and a consistent reward signal. Alpha shifts systematically toward physician weighting as community feedback becomes noisier and shifts toward community weighting as physician feedback becomes more biased. Our results suggest PiPrO's potential to produce more transparent, and context-sensitive AI-driven healthcare recommendations. Future research should validate this approach using real-world community inputs to ensure generalizability and practical impact.},
}

@article {pmid41822160,
year = {2026},
author = {Lu, SZ and Vermani, A and Sanno, K and Lu, J and Matsen, FA and Jagota, M and Song, YS},
title = {Conditionally Site-Independent Neural Evolution of Antibody Sequences.},
journal = {ArXiv},
volume = {},
number = {},
pages = {},
pmid = {41822160},
issn = {2331-8422},
abstract = {Common deep learning approaches for antibody engineering focus on modeling the marginal distribution of sequences. By treating sequences as independent samples, however, these methods overlook affinity maturation as a rich and largely untapped source of information about the evolutionary process by which antibodies explore the underlying fitness landscape. In contrast, classical phylogenetic models explicitly represent evolutionary dynamics but lack the expressivity to capture complex epistatic interactions. We bridge this gap with CoSiNE, a continuous-time Markov chain parameterized by a deep neural network. Mathematically, we prove that CoSiNE provides a first-order approximation to the intractable sequential point mutation process, capturing epistatic effects with an error bound that is quadratic in branch length. Empirically, CoSiNE outperforms state-of-the-art language models in zero-shot variant effect prediction by explicitly disentangling selection from context-dependent somatic hypermutation. Finally, we introduce Guided Gillespie, a classifier-guided sampling scheme that steers CoSiNE at inference time, enabling efficient optimization of antibody binding affinity toward specific antigens.},
}

@article {pmid41848013,
year = {2026},
author = {Janakiram, M and Fan, L and Ghosh, S and Alegria, V and Perciavalle, M and Emond, B and Maitland, J and Bixby, T and Nagar, SP and Qureshi, ZP and Dima, D},
title = {Real-world healthcare resource utilization and clinical outcomes among patients with relapsed/refractory multiple myeloma receiving ciltacabtagene autoleucel after four or more prior lines of therapy in inpatient versus outpatient settings.},
journal = {Journal of medical economics},
volume = {29},
number = {1},
pages = {871-884},
doi = {10.1080/13696998.2026.2640811},
pmid = {41848013},
issn = {1941-837X},
mesh = {Humans ; Male ; *Multiple Myeloma/drug therapy/therapy ; Female ; Middle Aged ; Aged ; *Patient Acceptance of Health Care/statistics & numerical data ; Adult ; Retrospective Studies ; *Immunotherapy, Adoptive/methods ; *Health Resources/statistics & numerical data/economics ; },
abstract = {BACKGROUND: Ciltacabtagene autoleucel (cilta-cel) has demonstrated remarkable efficacy in relapsed or refractory multiple myeloma (RRMM). Outpatient (OP) administration of cilta-cel is increasingly used to improve access and reduce healthcare resource utilization (HCRU) compared to inpatient (IP) administration. We compared all-cause HCRU and clinical outcomes of IP versus OP administration of cilta-cel in patients with RRMM after ≥4 prior lines of therapy (LOT) in clinical practice.

METHODS: We identified adults receiving cilta-cel between 02/28/2022 and 06/30/2024 after ≥4 prior LOT using Komodo Research Database claims data and classified patients into cohorts by setting of administration (IP/OP). All-cause HCRU, treatment-free interval (TFI), overall survival (OS), and clinical events (e.g. cytokine release syndrome [CRS], immune effector cell-associated neurotoxicity syndrome [ICANS]) were assessed. Outcomes were compared using multivariate regression and reported as incidence rate ratios (IRR) with 95% confidence intervals (CI).

RESULTS: Among 242 patients, 148 (61.2%) received cilta-cel in IP and 94 (38.8%) in OP. Baseline characteristics were comparable between cohorts. Of patients in the OP cohort, 31.9% did not require an IP admission within 3 months post-infusion. During this period, the OP cohort had significantly fewer IP days per-patient-per-month (2.4 vs. 6.6; IRR [95% CI]: 0.37 [0.28; 0.48], p < 0.001) and more OP days (8.5 vs 5.4; IRR [95% CI]: 1.43 [1.26; 1.63], p < 0.001) than the IP cohort. From the fourth month post-infusion, no significant differences in HCRU were observed. Rates of CRS and ICANS, and long-term outcomes including 6 and 12 month TFI and OS were similar.

CONCLUSION: OP administration of cilta-cel yielded similar effectiveness and safety outcomes relative to IP administration, while significantly reducing IP resource use. These findings support the feasibility of OP administration of cilta-cel in treating RRMM patients and its potential to reduce the burden on the healthcare system.},
}

Humans
Male
*Multiple Myeloma/drug therapy/therapy
Female
Middle Aged
Aged
*Patient Acceptance of Health Care/statistics & numerical data
Adult
Retrospective Studies
*Immunotherapy, Adoptive/methods
*Health Resources/statistics & numerical data/economics

@article {pmid41848929,
year = {2026},
author = {Richman, DH and Zhang, C and Matsen, FA},
title = {Vector Encoding of Phylogenetic Trees by Ordered Leaf Attachment.},
journal = {Bulletin of mathematical biology},
volume = {88},
number = {4},
pages = {},
pmid = {41848929},
issn = {1522-9602},
support = {AI162611/NH/NIH HHS/United States ; S10OD028685//Office of Research Infrastructure Programs, National Institutes of Health/ ; },
mesh = {*Phylogeny ; Mathematical Concepts ; *Models, Genetic ; Computational Biology ; Machine Learning ; Algorithms ; },
abstract = {As part of work to connect phylogenetics with machine learning, there has been considerable recent interest in vector encodings of phylogenetic trees. We present a simple new "ordered leaf attachment" (OLA) method for uniquely encoding a binary, rooted phylogenetic tree topology as an integer vector. OLA encoding and decoding take linear time in the number of leaf nodes, and the set of vectors corresponding to trees is a simply-described subset of integer sequences. The OLA encoding is unique compared to other existing encodings in having these properties. The integer vector encoding induces a distance on the set of trees, and we investigate this distance in relation to the NNI and SPR distances.},
}

*Phylogeny
Mathematical Concepts
*Models, Genetic
Computational Biology
Machine Learning
Algorithms

@article {pmid41849087,
year = {2026},
author = {Ogata, S and Manson, JE and Rist, PM and Hamaya, R and Aragaki, AK and Allison, M and Haring, B and Martin, LW and Nishimura, K and Clar, A and Sesso, HD and , },
title = {Cocoa flavanol supplementation and prevention of cardiovascular disease: a novel analysis of the COSMOS randomized trial using "win ratio".},
journal = {European journal of epidemiology},
volume = {},
number = {},
pages = {},
pmid = {41849087},
issn = {1573-7284},
support = {AG050657//National Institutes of Health, Bethesda/ ; AG071611//National Institutes of Health, Bethesda/ ; EY025623//National Institutes of Health, Bethesda/ ; HL157665//National Institutes of Health, Bethesda/ ; 75N92021D00001/HL/NHLBI NIH HHS/United States ; 75N92021D00002/HL/NHLBI NIH HHS/United States ; 75N92021D00003/WH/WHI NIH HHS/United States ; 75N92021D00004/WH/WHI NIH HHS/United States ; 75N92021D00005/WH/WHI NIH HHS/United States ; JP22K17821//JSPS KAKENHI/ ; 25K02863//JSPS KAKENHI/ ; },
abstract = {Cocoa flavanols may reduce cardiovascular disease (CVD) risk, yet large randomized trials remain inconclusive. The COcoa Supplement and Multivitamin Outcomes Study (COSMOS) suggested a modest, nonsignificant benefit using Cox models, which do not account for event severity in composite outcomes. To address this, we applied generalized pairwise comparison (GPC), or "win ratio" (WR), to assess cocoa flavanols versus placebo on hierarchical CVD outcomes among healthy older US adults. This secondary analysis of COSMOS, a randomized, placebo-controlled, 2 × 2 factorial trial of cocoa extract and multivitamins for preventing CVD and cancer, included 21,442 adults (women ≥ 65, men ≥ 60 years) followed for a median of 3.6 years. The primary outcome was a hierarchical composite of total CVD, prioritizing: fatal CVD, non-fatal myocardial infarction (MI), non-fatal stroke, coronary revascularization, carotid surgery, peripheral artery surgery, and hospitalized unstable angina. Analyses followed the intention-to-treat principle. GPC estimated WRs and net treatment benefits (NTBs) for cocoa flavanols versus placebo. GPC analyses showed cocoa flavanol wins of 3.41% and placebo wins of 2.87%, yielding a reciprocal WR of 0.84 (95% CI 0.72-0.99) and negative NTBs of - 0.54% (- 1.04 to - 0.03), p = 0.037. Sensitivity analyses prioritizing stroke over MI produced similar findings. By contrast, Cox regression of the same composite yielded a nonsignificant hazard ratio of 0.90 (95% CI 0.79-1.03), suggesting standard time-to-first-event models underestimated benefit. GPC "WR" analyses showed cocoa flavanols significantly reduced CVD events by accounting for event severity in the composite CVD outcome, whereas Cox regression marginally missed these effects.},
}

@article {pmid41849329,
year = {2026},
author = {Jisuvei, CS and Kinuthia, J and Richardson, BA and Srinivasan, S and Lokken, EM and Mandaliya, K and Jaoko, W and Munch, M and Fiedler, TL and Fredricks, DN and McClelland, RS},
title = {Association between vaginal washing and group B Streptococcus colonization from periconception through the first trimester of pregnancy in a cohort of Kenyan women.},
journal = {PloS one},
volume = {21},
number = {3},
pages = {e0344736},
pmid = {41849329},
issn = {1932-6203},
mesh = {Humans ; Female ; Pregnancy ; Adult ; Kenya/epidemiology ; *Streptococcus agalactiae/isolation & purification/genetics ; Pregnancy Trimester, First ; *Streptococcal Infections/epidemiology/microbiology ; *Vagina/microbiology ; Young Adult ; *Vaginal Douching/adverse effects ; *Pregnancy Complications, Infectious/epidemiology/microbiology ; Prevalence ; Cohort Studies ; RNA, Ribosomal, 16S/genetics ; },
abstract = {INTRODUCTION: Vaginal washing has been associated with adverse reproductive health outcomes including pelvic inflammatory disease, reduced fecundability, and HIV acquisition. This analysis tested the hypothesis that vaginal washing is associated with increased risk of group B streptococcus (GBS) colonization.

METHOD: Women planning pregnancies contributed monthly visits during which vaginal fluid specimens were collected and urine pregnancy testing was performed. In women who became pregnant, additional samples were collected at 9-12 weeks gestation. Broad-range 16S rRNA gene PCR with next generation sequencing (NGS) was performed to identify vaginal bacterial species. Generalized estimating equations with a log link, Poisson family, independent correlation structure and robust errors were used to generate prevalence ratios comparing the prevalence of GBS detection at vaginal washing visits versus non-vaginal washing visits.

RESULTS: The 189 women who became pregnant contributed 506 samples used in this analysis. Samples were collected at periconception 196 (38.9%), early first trimester 151 (29.8%), and late first trimester visits 159 (31.4%). The prevalence of GBS during the three time periods was 20/196 (10.2%), 11/151 (7.3%) and 2/159 (1.3%) respectively. Vaginal washing was practiced by 51/196 (26.0%), 27/151 (17.9%) and 32/159 (20.1%) participants during the three time periods. Compared to visits with no vaginal washing, there was no increased prevalence of GBS detection at visits where vaginal washing with water was reported (prevalence ratio [PR] 0.51, 95% confidence interval [CI] 0.16-1.62). However, the prevalence of GBS detection was nearly five-fold higher at visits when vaginal washing using water and soap was reported (PR 4.66, 95% CI 1.51, 14.33).

CONCLUSION: Vaginal washing with soap and water was associated with a nearly five-fold increase in GBS prevalence. Future studies should evaluate this association in later pregnancy and peripartum. Cessation or modification of vaginal washing practices could be a useful strategy for decreasing GBS colonization.},
}

Humans
Female
Pregnancy
Adult
Kenya/epidemiology
*Streptococcus agalactiae/isolation & purification/genetics
Pregnancy Trimester, First
*Streptococcal Infections/epidemiology/microbiology
*Vagina/microbiology
Young Adult
*Vaginal Douching/adverse effects
*Pregnancy Complications, Infectious/epidemiology/microbiology
Prevalence
Cohort Studies
RNA, Ribosomal, 16S/genetics

@article {pmid41849750,
year = {2026},
author = {O'Neill, AF and Zeme, EL and Abou-Alfa, GK and Baretti, M and Bondoc, AJ and Church, A and Ferrone, CR and Fitzgerald, M and Geller, JI and Gill, AE and Harris, WP and Kim, HB and Lee, SS and Liu, KX and Ortiz, MV and Rangaswami, A and Riehle, KJ and Rosenberg, AR and Torbenson, MS and Yarchoan, M and Gordan, JD},
title = {Clinical guideline for the diagnosis and treatment of fibrolamellar carcinoma.},
journal = {Hepatology (Baltimore, Md.)},
volume = {},
number = {},
pages = {},
pmid = {41849750},
issn = {1527-3350},
}

@article {pmid41850278,
year = {2026},
author = {Dai, Y and Brouillard, J and Jaycox, JR and Yeon, SM and Huck, JD and Yandamuri, SS and Zhong, Z and O'Connor, KC and Burnina, I and Henkel, C and LeMay, AK and Lilov, A and McGurk, E and Morrill, M and Parker, L and Sackett, T and Sandberg, C and Sivasubramanian, A and Geoghegan, JC and Ring, AM},
title = {Off-target reactivity in clinical monoclonal antibodies.},
journal = {Structure (London, England : 1993)},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.str.2026.02.012},
pmid = {41850278},
issn = {1878-4186},
abstract = {Biologics, including monoclonal antibodies (mAbs), are widely used therapeutics due to their high specificity, yet off-target interactions remain an underappreciated risk for safety and efficacy. To systematically assess antibody specificity, we applied rapid extracellular antigen profiling (REAP) to evaluate 174 FDA-approved and clinical-stage antibodies against 6,172 human extracellular proteins. We found a substantial burden of off-target reactivity, with 28% of antibodies exhibiting at least one off-target hit. Structural and biophysical analyses revealed that off-target binding arises from antibody intrinsic properties and epitope mimicry, either within related protein families or across structurally unrelated proteins. We further identified new off-target interactions of tanezumab and engineered its variable domains to eliminate off-target binding while preserving target affinity and developability. These findings highlight the prevalence of specific off-target reactivity in therapeutic antibodies and underscore the importance of evaluating specificity early in biologic drug development.},
}

@article {pmid41844245,
year = {2026},
author = {Tran-Kiem, C and Perofsky, AC and Lessler, J and Bedford, T},
title = {Characterizing the informativeness of pathogen genome sequence datasets about transmission between population groups.},
journal = {Proceedings. Biological sciences},
volume = {293},
number = {2067},
pages = {},
doi = {10.1098/rspb.2025.2983},
pmid = {41844245},
issn = {1471-2954},
support = {/TW/FIC NIH HHS/United States ; //EPSRC/ ; /CC/CDC HHS/United States ; /GATES/Gates Foundation/United States ; /HHMI/Howard Hughes Medical Institute/United States ; //National Institute of General Medical Sciences (NIH)/ ; },
mesh = {Mutation ; Phylogeography ; },
abstract = {Pathogen genome analysis helps characterize transmission between population groups. The information carried by pathogen sequences comes from the accumulation of mutations within their genomes; thus, the pace at which mutations accumulate should determine the granularity of transmission processes that pathogen sequences can characterize. Here, we investigate how the complex interplay between mutation, transmission, population mixing and sampling impacts study power. First, we develop a conceptual probabilistic framework to quantify the ability of pairs of sequences in capturing between-group transmission history. This allows us to comprehensively explore the space of possible phylogeographic analyses by explicitly considering the pace at which mutations accumulate and the pace at which between-group transmission events occur. Using this framework, we identify a pathogen-intrinsic limit in the mixing scale at which their sequence data remain informative, with faster mutating pathogens enabling finer spatial characterization. Second, we perform a simulation study exploring a range of assumptions regarding sequencing intensity. The sample size further imposes a limit on the characterization of between-group transmission processes. This work highlights inherent horizons of resolvability for population mixing processes that depend on the interaction between evolution, transmission, mixing and sampling. Such considerations are important for the design of pathogen genomic studies.},
}

Mutation
Phylogeography

@article {pmid41844546,
year = {2026},
author = {Safyan, RA and White, RA and Gonda, TA and Lee, SM and Han, J and Kuriakose, N and Yamamoto, NK and Kugel, S and Jamison, JK and Manji, GA and Schwartz, GJ and Oberstein, PE and Bates, SE},
title = {Phase 2 Study of Azacitidine plus Pembrolizumab as Second-Line Treatment in Patients with Locally Advanced or Metastatic Pancreatic Ductal Adenocarcinoma.},
journal = {The oncologist},
volume = {},
number = {},
pages = {},
doi = {10.1093/oncolo/oyag091},
pmid = {41844546},
issn = {1549-490X},
abstract = {BACKGROUND: Epigenetic regulators represent a novel strategy to modulate the tumor immune microenvironment in pancreatic ductal adenocarcinoma (PDAC). In preclinical models, DNA hypomethylating agents enhance cytotoxic T-cell infiltration, synergize with PD-1 blockade, and improve survival when combined with immune checkpoint blockade. This single-institution, phase II study evaluated the safety, efficacy, and biomarkers of azacitidine plus pembrolizumab in patients with previously treated PDAC.

METHODS: Patients with locally advanced or metastatic PDAC after one prior regimen received 50 mg/m2 subcutaneous azacitidine on days 1-5 of a 28-day cycle, starting week 1, and pembrolizumab 200 mg intravenously every 3 weeks starting week 3. Baseline and on-treatment blood and tumor was collected for exploratory biomarker analysis.

RESULTS: Thirty-six patients enrolled between October 2017 and September 2021 (median age: 62.5 years); 34 were evaluable for safety; 31 for efficacy. Treatment was generally well-tolerated, with Grade 1-2 fatigue and diarrhea most common AEs. Three patients (9.7%) had a partial response, and the disease control rate was 35.5%. Median progression-free and overall survival was 1.51 and 4.83 months, respectively. Exploratory analysis suggested higher baseline CD8+ T cells and lower tumor Ki-67 was associated with response, whereas low baseline CD8+ T cell and Granzyme B infiltration correlated with higher exponential tumor growth rate. PD-L1 and CD68 expression were not predictive of benefit.

CONCLUSION: Azacitidine plus pembrolizumab demonstrated limited clinical activity in second line, locally advanced or metastatic PDAC. Biomarker analysis suggests higher baseline CD8+ T-cell infiltration and lower proliferative index may identify patients more likely to benefit. (NCT03264404).},
}

@article {pmid41845032,
year = {2026},
author = {Chanda, A and Song, Y and Nazir, J and Lin, C and Cheng, A and Sargent, J and Sikora, AE},
title = {Comparable immunogenicity from murine blood collection methods in intranasal gonococcal vaccination with ACP and MtrE supports refinement of preclinical vaccine studies.},
journal = {Scientific reports},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41598-026-44505-5},
pmid = {41845032},
issn = {2045-2322},
support = {R01-AI117235//National Institute of Allergy and Infectious Diseases/ ; },
}

@article {pmid41846317,
year = {2026},
author = {Choi, SH and Ramesh, S and Reed, S and Menyah, G and Ganschow, P and Henderson, V and Dunnenberger, HM},
title = {Breaking Barriers to Completing Genetic Testing for Inherited Breast Cancer among At-Risk Black Women Using a Community-Based Participatory Research Approach.},
journal = {HGG advances},
volume = {},
number = {},
pages = {100591},
doi = {10.1016/j.xhgg.2026.100591},
pmid = {41846317},
issn = {2666-2477},
abstract = {National guidelines from the U.S. Preventive Services Task Force and the National Comprehensive Cancer Network recommend the use of family-health-history (FHH)-based risk assessment tools to guide genetic testing (GT) among women with an increased risk of inherited cancer and inform personalized cancer risk management. Prior research has focused on attitudes towards and decisions about initial uptake of GT in Black patients but little is known about the factors that impact the subsequent completion of GT after they have already provided consent. Using a community-based participatory research (CBPR) approach, we aimed to identify barriers and actionable strategies to improve GT completion offered through the Breast Health Assessment (BHA), an FHH screening tool administered at routine mammography visits. We conducted semi-structured interviews with 12 Black women who screened high-risk for inherited breast cancer and consented to GT through the BHA, but did not complete saliva sample collection. Thematic analysis revealed that lack of dedicated support throughout the BHA workflow emerged as a key obstacle to sample collection, whereas medical mistrust, shame, and limited knowledge were largely regarded as cultural barriers that had no impact on GT completion. Low utilization among participants reflected logistical challenges highlighting the need to evaluate multi-level implementation processes to better understand and address inequities in GT completion. Participants suggested implementing early educational outreach, culturally-relevant messaging, and interpersonal touchpoints to promote GT uptake. By applying a CBPR approach, we translated these findings into actionable, equity-focused strategies to improve GT completion within a population genetic screening program.},
}

@article {pmid41841734,
year = {2026},
author = {Banerjee, R and Dong, S and McCaughan, G and Mehra, N and Wang, B and Sperling, AS and Cowan, AJ and Anderson, LD and Rajkumar, SV and Kaur, G},
title = {Preferred standard-of-care carfilzomib dosing in multiple myeloma: An international survey of haematologists/oncologists.},
journal = {British journal of haematology},
volume = {},
number = {},
pages = {},
doi = {10.1111/bjh.70435},
pmid = {41841734},
issn = {1365-2141},
support = {UL1 TR002319/NH/NIH HHS/United States ; },
}

@article {pmid41834265,
year = {2026},
author = {Bradley, R and A Staab, C and E Jamieson, P and O Langley, B and O Metz, T and F Stevens, J},
title = {Safety and Tolerability of Xanthohumol in Adults With Crohn's Disease: Results of a Triple-Masked, Randomized, Placebo-Controlled Phase 2 Trial.},
journal = {Molecular nutrition & food research},
volume = {70},
number = {6},
pages = {e70438},
pmid = {41834265},
issn = {1613-4133},
support = {R01HL146549/HL/NHLBI NIH HHS/United States ; R01AT010271/AT/NCCIH NIH HHS/United States ; K24AT011568/AT/NCCIH NIH HHS/United States ; },
mesh = {Humans ; *Propiophenones/adverse effects/therapeutic use ; *Crohn Disease/drug therapy ; Adult ; Male ; Female ; *Flavonoids/adverse effects/therapeutic use ; Middle Aged ; Double-Blind Method ; Young Adult ; gamma-Glutamyltransferase/blood ; Body Mass Index ; Humulus/chemistry ; },
abstract = {Xanthohumol (XN), a flavonoid from hops (Humulus lupulus), exhibits mucosal anti-inflammatory, antioxidant, and microbiome-modulating effects, making it a candidate therapeutic for inflammatory bowel disease. We assessed the safety and tolerability of XN in adults with Crohn's disease (CD) over 8 weeks. In this randomized, triple-masked, placebo-controlled phase 2 trial, 20 adults with unremitted CD received either 24 mg/day XN or placebo for 8 weeks. Primary outcomes included clinical laboratory toxicology parameters, vital signs and adverse events (AEs). Disease activity was screened and assessed using the Crohn's Disease Activity Index (CDAI). XN was well tolerated, with adherence exceeding 95%. Neither halting nor stopping criteria were met, and all laboratory elevations were minor and transient in both groups. There were no attributable serious AEs in either group, and all moderate AEs were short-term and self-resolving. Between-group comparisons demonstrated differences for changes in BMI and gamma-glutamyltransferase (GGT), favoring XN: BMI: -0.67 (0.0, 1.3), p = 0.04 and GGT: -4.8 U/L, 95% CI 0.8-8.8, p = 0.02, which may reflect beneficial effects on hepatic and metabolic health in CD. XN at 24 mg/day was safe and well tolerated in adults with active CD, supporting further research in inflammatory bowel disease.},
}

Humans
*Propiophenones/adverse effects/therapeutic use
*Crohn Disease/drug therapy
Adult
Male
Female
*Flavonoids/adverse effects/therapeutic use
Middle Aged
Double-Blind Method
Young Adult
gamma-Glutamyltransferase/blood
Body Mass Index
Humulus/chemistry

@article {pmid41837286,
year = {2026},
author = {Pache, L and Bui, JK and Klouser, LM and Fennessey, CM and Noyola, AC and Einhaus, T and Zhu, H and Stensland, L and Leguizamo, I and Koroma, AA and Teriete, P and Chang, WLW and Hyrien, O and Duggan, NN and Heimann, D and Pérez-Osorio, AC and Bar, KJ and Cosford, ND and Keele, BF and Hartigan-O'Connor, DJ and Farzan, M and Gardner, MR and Jerome, KR and Chanda, SK and Kiem, HP and Peterson, CW},
title = {Smac mimetic combined with eCD4-Ig reverses latency without reducing SHIV reservoirs in rhesus macaques.},
journal = {The Journal of clinical investigation},
volume = {136},
number = {6},
pages = {},
pmid = {41837286},
issn = {1558-8238},
mesh = {Animals ; Macaca mulatta ; *Simian Immunodeficiency Virus/physiology/drug effects/genetics ; *Simian Acquired Immunodeficiency Syndrome/drug therapy/virology/genetics ; *Virus Latency/drug effects ; Dependovirus/genetics ; Apoptosis Regulatory Proteins ; Viremia ; *Mitochondrial Proteins ; Humans ; },
abstract = {Despite the success of antiretroviral therapy in controlling HIV replication, latent viral reservoirs persist, presenting a major barrier to a cure. Current treatment approaches that aim to reactivate latent virus and eliminate infected cells, termed "shock and kill," hold promise but have yet to demonstrate meaningful reservoir reduction in vivo. In this study, we explored combining ciapavir, a Smac mimetic latency-reversing agent, with adeno-associated virus-delivered (AAV-delivered) eCD4-Ig to treat antiretroviral therapy-suppressed, SHIV-infected rhesus macaques. We could demonstrate that a Smac mimetic can induce modest reactivation of the latent SHIV reservoir, as evidenced by transient increases in plasma viremia. However, while AAV-expressed eCD4-Ig conferred partial protection against intrarectal SHIV challenge in uninfected animals, neither eCD4-Ig nor ciapavir reduced the viral reservoir in SHIV-infected rhesus macaques, as determined by total SHIV DNA and a 5-target intact provirus detection assay. Animals treated with the combination showed no significant differences in viral rebound kinetics post-analytical treatment interruption compared with controls. Additionally, repeated ciapavir dosing resulted in adverse effects in some animals, suggesting potential toxicity with repeat administration. These findings highlight the challenges in reducing viral reservoirs using this shock-and-kill approach, particularly in SHIV-infected models, and suggest that further optimization of both latency-reversing agent and immune-mediated clearance strategies is required.},
}

Animals
Macaca mulatta
*Simian Immunodeficiency Virus/physiology/drug effects/genetics
*Simian Acquired Immunodeficiency Syndrome/drug therapy/virology/genetics
*Virus Latency/drug effects
Dependovirus/genetics
Apoptosis Regulatory Proteins
Viremia
*Mitochondrial Proteins
Humans

@article {pmid41838964,
year = {2026},
author = {Filigrana, P and Moon, JY and Gallo, LC and González, HM and Lipton, RB and Tarraf, W and Kaplan, RC and Daviglus, ML and Testai, FD and Marquine, MJ and Cai, J and Perreira, KM and Stickel, AM and DeCarli, C and Isasi, CR},
title = {Contribution of Life-Course Socioeconomic Position to Later-Life Brain Volumes in US Hispanic/Latino Adults.},
journal = {Neurology},
volume = {106},
number = {7},
pages = {e214716},
pmid = {41838964},
issn = {1526-632X},
support = {N01 HC065236/HL/NHLBI NIH HHS/United States ; N01 HC065235/HL/NHLBI NIH HHS/United States ; RF1 AG054548/AG/NIA NIH HHS/United States ; N01 HC065234/HL/NHLBI NIH HHS/United States ; N01 HC065237/HL/NHLBI NIH HHS/United States ; R01 AG077639/AG/NIA NIH HHS/United States ; N01 HC065233/HL/NHLBI NIH HHS/United States ; },
mesh = {Humans ; Male ; Female ; *Brain/diagnostic imaging/anatomy & histology ; Middle Aged ; Magnetic Resonance Imaging ; *Hispanic or Latino ; Aged ; Longitudinal Studies ; United States ; Organ Size ; *Social Class ; Aged, 80 and over ; Adult ; White ; },
abstract = {BACKGROUND AND OBJECTIVES: Low life-course socioeconomic position (SEP) has been associated with worse cognitive function in older age. However, its association with brain structure remains unclear. We assessed whether SEP at 3 periods of the life-course and socioeconomic mobility are associated with later-life MRI-derived brain volumes.

METHODS: We used longitudinal data from the Hispanic Community Health Study/Study of Latinos and its Investigations of Neurocognitive Aging-MRI ancillary study. We determined childhood SEP using participant self-reports of their parent's educational attainment (
RESULTS: We included 2,400 adults aged 50-85 years. Higher childhood SEP (TGMV 0.13; 95% CI 0.02-0.24) and higher height residuals (TGMV 0.17; 95% CI 0.09-0.24) were associated with larger brain volumes. Similarly, higher adult SEP at visit 1 (TGMV 0.18; 95% CI 0.05-0.31) and visit 2 (TGMV 0.16; 95% CI 0.04-0.29), upward socioeconomic mobility, and stable high SEP were associated with larger brain volumes. Higher adult SEP at visit 2 (log-WMHV -0.16; 95% CI -0.29 to -0.02) and upward mobility were also associated with smaller log-WMHV.

DISCUSSION: This study highlights the contribution of higher life-course SEP to greater brain health as indexed by larger brain volumes in later life. Our results suggest that the effect of early-life socioeconomic disadvantages persists beyond socioeconomic conditions in adulthood.},
}

Humans
Male
Female
*Brain/diagnostic imaging/anatomy & histology
Middle Aged
Magnetic Resonance Imaging
*Hispanic or Latino
Aged
Longitudinal Studies
United States
Organ Size
*Social Class
Aged, 80 and over
Adult
White

@article {pmid41839859,
year = {2026},
author = {Gupta, A and Morella, N and Sutormin, D and Li, N and Gaisser, K and Robertson, A and Ispolatov, Y and Seelig, G and Dey, N and Kuchina, A},
title = {Dynamics of phage-host interactions in Bacteroides fragilis resolved by single-cell transcriptomics.},
journal = {Nature communications},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41467-026-70381-8},
pmid = {41839859},
issn = {2041-1723},
support = {R35GM150994//U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS)/ ; DE-SC0023091//DOE | SC | Biological and Environmental Research (BER)/ ; DE-SC0023091//DOE | SC | Biological and Environmental Research (BER)/ ; Postdoctoral Fellowship//Washington Research Foundation (WRF)/ ; U54 CA274374/CA/NCI NIH HHS/United States ; P30 CA015704/CA/NCI NIH HHS/United States ; },
abstract = {The interactions between lytic phages and their hosts are typically studied in bulk culture, which obscures cell-cell differences in infection susceptibility or expression of protective factors. Here, we use bacterial single-cell RNA sequencing to profile the transcriptomes of ~50,000 cells from cultures of a human pathobiont, Bacteroides fragilis, infected with a lytic bacteriophage. From a single sampling, we quantified the asynchronous progression of phage infection in individual bacterial cells and reconstructed the infection timeline, characterizing both host and phage transcriptomic changes as infection unfolded. Further, we discovered phenotypic subpopulations of bacteria that remained uninfected. Each cell's vulnerability to phage infection was influenced by expression of multiple genetic loci, most prominently phase-variable capsular polysaccharide (CPS) biosynthesis pathways and an operon predicted to encode fimbrial genes. These findings uncovered genome-wide phase variation and stochasticity that enable bacterial survival and re-growth without acquiring additional mutations. Overall, we establish bacterial single-cell RNA sequencing as a powerful platform for investigating the dynamics of host-phage interactions and revealing the roles of phase variation and stochasticity in bacterial defenses.},
}

@article {pmid41840226,
year = {2026},
author = {Turcsanyi, L and Zhang, XS and Kudelka, M and Kubikova, K and Radvansky, M and Yang, S and Kriegova, E and Juranova, J and Mayer, J and Klamova, H and Belohlavkova, P and Karas, M and Stejskal, L and Cmunt, E and Othus, M and Gale, RP and Jiang, Q and Faber, E},
title = {Chronic myeloid leukaemia: have basophils gone the way of the Dodo bird?.},
journal = {Leukemia},
volume = {},
number = {},
pages = {},
pmid = {41840226},
issn = {1476-5551},
support = {IGA_LF_2025_014//Univerzita Palackého v Olomouci (Palacký University Olomouc)/ ; IGA_LF_2025_14//Univerzita Palackého v Olomouci (Palacký University Olomouc)/ ; IGA_LF_2025_05//Univerzita Palackého v Olomouci (Palacký University Olomouc)/ ; IGA_LF_2025_014//Univerzita Palackého v Olomouci (Palacký University Olomouc)/ ; MH CZ - DRO (FNOL, 00098892)//Ministerstvo Zdravotnictví Ceské Republiky (Ministry of Health of the Czech Republic)/ ; MH CZ - DRO (FNOL, 00098892)//Ministerstvo Zdravotnictví Ceské Republiky (Ministry of Health of the Czech Republic)/ ; MH CZ-DRO (FNOL 00098892)//Ministerstvo Zdravotnictví Ceské Republiky (Ministry of Health of the Czech Republic)/ ; MH CZ (FNOL, 00098892)//Ministerstvo Zdravotnictví Ceské Republiky (Ministry of Health of the Czech Republic)/ ; },
}

@article {pmid41827907,
year = {2026},
author = {Chesney, KM and Whiteaker, JR and Hood, B and Zhou, M and Zhang, H and Rivero-Hinojosa, S and Paulovich, AG and Conrads, TP and Rood, BR},
title = {Longitudinal Detection of Tumor-Specific Peptides in Cerebrospinal Fluid for Pediatric Brain Tumor Surveillance.},
journal = {Cells},
volume = {15},
number = {5},
pages = {},
pmid = {41827907},
issn = {2073-4409},
support = {R50 CA211499/CA/NCI NIH HHS/United States ; U01 CA271407/CA/NCI NIH HHS/United States ; 44844//Lilabean/ ; 44568//Jeff Gordon/ ; },
mesh = {Humans ; *Brain Neoplasms/cerebrospinal fluid/diagnosis ; Child ; Male ; *Peptides/cerebrospinal fluid ; Female ; *Biomarkers, Tumor/cerebrospinal fluid ; Child, Preschool ; Medulloblastoma/cerebrospinal fluid ; Proteomics/methods ; Longitudinal Studies ; Adolescent ; Infant ; },
abstract = {Pediatric brain tumor survivors remain at high risk of recurrence, yet current surveillance strategies relying on neuroimaging and cerebrospinal fluid (CSF) cytology have limited sensitivity for early or minimal disease. Tumor-specific peptides (TSPs) derived from individual tumors represent a promising class of highly specific biomarkers for longitudinal disease monitoring through CSF-based proteomic analysis. In this study, tumor tissue and serial CSF samples from six pediatric brain tumor patients (five medulloblastomas and one atypical teratoid/rhabdoid tumor (ATRT)) were analyzed using an integrated proteogenomic workflow combining discovery and targeted mass spectrometry. TSPs were identified from resected tumor tissue and matched against shotgun CSF proteomic datasets to nominate candidate biomarkers. High-confidence peptides were synthesized as isotopically labeled standards and quantified longitudinally using targeted multiple reaction monitoring. Two TSP biomarkers derived from individualized pediatric brain tumors (one medulloblastoma and one ATRT) demonstrated robust detection in serial CSF samples and exhibited temporal concordance with radiographic disease course, declining with treatment response and increasing during disease progression. These findings establish the feasibility of detecting and longitudinally quantifying TSPs in CSF and support further investigation of individualized proteomic biomarkers for treatment response monitoring and disease surveillance in pediatric brain tumors.},
}

Humans
*Brain Neoplasms/cerebrospinal fluid/diagnosis
Child
Male
*Peptides/cerebrospinal fluid
Female
*Biomarkers, Tumor/cerebrospinal fluid
Child, Preschool
Medulloblastoma/cerebrospinal fluid
Proteomics/methods
Longitudinal Studies
Adolescent
Infant

@article {pmid41827933,
year = {2026},
author = {McHenry, PR and Fakhruddin, N and Homer, K and Gil da Costa, RM and True, LD and Morrissey, C},
title = {Characterization and Evaluation of CD24 and NPY as Biomarkers for Metastatic Castration-Resistant Prostate Cancer.},
journal = {Diagnostics (Basel, Switzerland)},
volume = {16},
number = {5},
pages = {},
pmid = {41827933},
issn = {2075-4418},
support = {PO1CA163227/GF/NIH HHS/United States ; },
abstract = {Background/Objectives: Prostate cancer is the most diagnosed and third most deadly cancer among men in Europe. Metastatic castration-resistant prostate cancer (mCRPC) is incurable and resistant to standard androgen ablation therapy. More biomarkers are needed to select patients for novel personalized treatments. Previous whole-genome RNA sequencing results indicated a possible role for cluster of differentiation 24 (CD24) and neuropeptide Y (NPY) as diagnostic or prognostic biomarkers in androgen receptor-positive (AR[+]) mCRPC. Methods: We analyzed tissue microarrays representing 127 primary prostate cancers (with matched adjacent benign prostatic glands) and 124 metastases (from 34 patients) using immunohistochemistry to detect CD24 or NPY. Results: CD24 was more highly expressed in primary prostate cancer than in adjacent benign tissue for nuclear (p: <0.001), cytoplasmic (p: <0.001), and membranous staining (p: <0.001), while NPY showed no difference. Average NPY scores were lower in prostate cancers that later recurred (geometric mean 17.6, 95% CI: 9.5-32.5) compared to those that did not (38.7, CI: 23.2-64.4; p: 0.044, d: 0.773). In mCRPC, CD24 was detectable in 76% of cores at the cell membrane and in 58% in the nucleus. NPY was detectable in the cytoplasm of 17%. Scores for NPY and nuclear (but not membranous) CD24 were higher in AR[+] mCRPC. In the RNA sequencing results, CD24 did not correlate with AR or kallikrein-related peptidase 3 (KLK3), while NPY positively correlated with AR (rs: 0.313; p: <0.004) and KLK3 (rs: 0.400; p: <0.004). NPY and CD24 scores did not correlate with neuroendocrine mCRPC markers. Nuclear and membranous CD24 showed differential expression by metastatic site. Conclusions: We did not find strong evidence to support the use of CD24 or NPY alone as clinical biomarkers. Membranous and nuclear CD24 were expressed in the majority of mCRPC specimens, while NPY expression was more limited. NPY and nuclear CD24 were more highly expressed in AR[+] mCRPC than AR[-] neuroendocrine disease, and nuclear CD24 displayed site-specific expression, suggesting a potential role for nuclear CD24 in promoting AR[+] mCRPC.},
}

@article {pmid41830051,
year = {2026},
author = {Ong, SC and Kosmach-Park, B and Alomar, O and Woodside, K and Blosser, CD and Twombley, K and Basu, A and Herrera, N and Jittirat, A and Merzkani, M and George, R and Alhamad, T},
title = {Perspectives and Practices in Pediatric to Adult Healthcare Transition in Kidney Transplantation: An American Society of Transplantation (AST) Member Survey.},
journal = {Pediatric transplantation},
volume = {30},
number = {3},
pages = {e70286},
doi = {10.1111/petr.70286},
pmid = {41830051},
issn = {1399-3046},
mesh = {Humans ; *Kidney Transplantation ; *Transition to Adult Care ; Adolescent ; Adult ; United States ; Young Adult ; Male ; Surveys and Questionnaires ; Female ; Child ; Societies, Medical ; *Attitude of Health Personnel ; Middle Aged ; },
abstract = {BACKGROUND: Adolescent and young adult (AYA) kidney transplant recipients (KTR) are susceptible to risk-taking behaviors that peak during transfer from pediatric to adult healthcare, resulting in poorer outcomes. Professional guidelines support healthcare transition (HCT) practices to mitigate this risk; however, HCT perspectives and practices among providers, especially adult providers caring for KTR in the US, have not been widely studied.

METHODS: An online survey of American Society of Transplantation (AST) members was conducted targeting both adult providers (AP) and pediatric providers (PP).

RESULTS: The survey was completed by 135 respondents (predominantly US), including 61 PP and 74 AP. US respondents who disclosed their center ID represented 30% of all programs. Providers agreed that HCT was important (PP 97%, AP 94%) and a shared responsibility (PP 91% and AP 84%). Respondents to our survey frequently worked within transition programs (PP 70% vs. AP 48%), but the majority did not have a formal HCT policy to guide them (PP 43%, AP 21%). Multidisciplinary transition clinics were rare (PP 27%, AP 23%). Only 64% of PP included targeted HCT education either as part of a routine visit or a HCT session. Perceived barriers to providing HCT interventions were similar in both groups, including a lack of provider resources, outcomes tracking, provider communication, and patient/caregiver feedback.

CONCLUSION: Providers recognize the importance of HCT and the joint responsibility of PP and AP but have difficulty following best practices. A multipronged approach will be necessary to address barriers. Our survey reminds us of the gap that persists in providing AYAs with a seamless transfer from pediatric to adult care.},
}

Humans
*Kidney Transplantation
*Transition to Adult Care
Adolescent
Adult
United States
Young Adult
Male
Surveys and Questionnaires
Female
Child
Societies, Medical
*Attitude of Health Personnel
Middle Aged

@article {pmid41831609,
year = {2026},
author = {Keenan, BP and Fan, Z and Le, BK and Harris, Q and Chen, J and Clark, M and Lea, A and Zhang, L and Cheung, A and Lara, F and Gordan, JD and Bracci, P and Behr, SC and Fong, L and Venook, AP and Kim, EJ and Kelley, RK},
title = {Phase II trial with nivolumab and sorafenib in HCC identified enrichment of immunosuppressive monocytes in patients with Child-Pugh B liver dysfunction.},
journal = {JHEP reports : innovation in hepatology},
volume = {},
number = {},
pages = {101817},
doi = {10.1016/j.jhepr.2026.101817},
pmid = {41831609},
issn = {2589-5559},
abstract = {BACKGROUND AND AIMS: Immune checkpoint inhibition (ICI) and anti-angiogenic therapies are active in hepatocellular carcinoma (HCC), although patients with impaired hepatic function have worse outcomes.

METHODS: We conducted an open-label phase II clinical trial to assess the safety and efficacy of the multikinase inhibitor, sorafenib, combined with nivolumab, in patients with advanced HCC and varying liver function. In a Part 1 safety lead-in, we investigated the maximum-tolerated dose (MTD) of the combination in patients with Child-Pugh A or B7. In Part 2, we enrolled patients with Child-Pugh B7-9 HCC with the primary endpoint of grade >/=3 treatment-related adverse events (TRAE) incidence. Exploratory endpoints included immunologic biomarkers.

RESULTS: Overall, 25 patients were consented and 16 eligible patients enrolled. In Part 1, dose-limiting toxicity occurred in 1 of 6 patients in Dose Level -1, and 2 of 5 patients in Dose Level 1; Dose Level -1 was determined to be the MTD. In total, 69% of patients experienced a Grade >/=3 TRAE, with similar distribution for patients with Child-Pugh A and B (70%, 95% CI: 0.35, 0.93 vs 66.7%, 95% CI: 0.22, 0.96). The objective response rate was 6%; median overall survival was 12.99 months (Child-Pugh A: 15.26 and Child-Pugh B: 10.41). We found that patients with Child-Pugh B liver disease harbored more circulating suppressive CD14[+] monocytes at baseline.

CONCLUSIONS: While combination sorafenib and nivolumab demonstrated acceptable safety at the MTD in both Child-Pugh subgroups, the objective response rate was below the pre-specified threshold to be declared worthy of further exploration. A distinct immune cell profile in Child-Pugh B patients may define mechanisms of resistance and potential therapeutic targets in this population with unmet clinical need.

IMPACT AND IMPLICATIONS: This study addresses the critical need for effective therapies for patients with advanced hepatocellular carcinoma (HCC) and compromised liver function, a population historically excluded from many clinical trials. The findings suggest that while the combination of sorafenib and nivolumab demonstrated acceptable safety across different liver function subgroups, there was a low response rate overall. Importantly, the discovery of distinct immune profiles, particularly an increase in suppressive immune cells in patients with worse liver function, provides insights into potential mechanisms of resistance to immunotherapy. These results are crucial for understanding how we can improve the treatment of advanced HCC, especially in patients with impaired liver function.

GOV IDENTIFIER: NCT03439891.},
}

@article {pmid41832336,
year = {2026},
author = {Kimura, A and Peck, A and Bell-Brown, A and Todd, K and Akinsoto, NO and Fang, V and Wood, J and Issaka, RB},
title = {Navigation activities in an organized colorectal cancer screening program improve follow-up colonoscopy completion.},
journal = {Scientific reports},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41598-026-44477-6},
pmid = {41832336},
issn = {2045-2322},
support = {K08CA241296/CA/NCI NIH HHS/United States ; },
}

@article {pmid41832601,
year = {2026},
author = {Anderson, AK and Georgakopoulou, A and Kuhlmann, AS and Wang, H and Riker, A and Karuppusamy, KV and Radtke, S and Bui, JK and Kiem, HP and Lieber, A and Li, C},
title = {In vitro and in vivo base editing of CCR5 in hematopoietic stem cells confers HIV-1 resistance.},
journal = {Molecular therapy : the journal of the American Society of Gene Therapy},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.ymthe.2026.03.018},
pmid = {41832601},
issn = {1525-0024},
abstract = {Here we present an HIV gene therapy strategy by in vivo precision gene editing in hematopoietic stem cells (HSC). We successfully generated a panel of helper-dependent adenoviral vectors expressing all-in-one base editors (HDAd-BEs) targeting the CCR5 gene. In a HIV-permissive cell line, transduction with the HDAd-BE vector led to near complete target site editing, CCR5 knockout, and inhibition of HIV infection. In HSC-enriched human CD34[+] cells from mobilized donors or cord blood, we measured efficient precision base editing after HDAd-BE transduction and selection. Following in vitro T cell differentiation and HIV infection, we demonstrated that HIV genome titers were significantly lower with precision CCR5 base editing. Importantly, in a humanized mouse model, in vivo transduction with the HDAd-BE vector followed by selection resulted in ∼50% base editing at the CCR5 target site in bone marrow mononuclear cells, which conferred ∼12-fold lower HIV plasma titers than control animals after HIV challenge. No significant off-target editing and adverse effects associated with the treatment were observed. By targeting HSCs to precisely engineer HIV-resistant cells in vivo, our strategy represents an efficient, durable, and affordable approach to achieve a functional cure for HIV infection.},
}

@article {pmid41817876,
year = {2026},
author = {Donzella, SM and Newton, CC and VoPham, T and Peoples, AR and Bodelon, C and Shams-White, MM and Patel, AV and Zhong, C and Phipps, AI},
title = {Change in sleep duration following a cancer diagnosis.},
journal = {Cancer causes & control : CCC},
volume = {37},
number = {4},
pages = {},
pmid = {41817876},
issn = {1573-7225},
mesh = {Humans ; Female ; Middle Aged ; Male ; *Neoplasms/diagnosis/epidemiology ; Adult ; Aged ; *Sleep/physiology ; Prospective Studies ; Follow-Up Studies ; United States/epidemiology ; Time Factors ; Incidence ; Registries ; Sleep Duration ; },
abstract = {INTRODUCTION: The objective of this study was to investigate how the experience of a cancer diagnosis impacts sleep duration among Cancer Prevention Study-3 (CPS-3) participants.

METHODS: CPS-3 is a prospective cohort of US adults aged 30-65 years. At baseline (2006-2013), 2015, and 2018, participants reported their average sleep duration during the prior year. Cancer incidence was determined via linkage to state registries. Participants who experienced a cancer diagnosis during study follow-up with complete sleep data prior to (pre-reference) and after cancer diagnosis (post-reference) were included. We matched individuals with a cancer diagnosis to participants without a cancer diagnosis during follow-up (1:4 ratio) based on age, sex, cohort entry year, and timepoint of sleep duration measures. Change in sleep duration was calculated as the difference between average sleep duration measurements at two survey timepoints (pre- and post-reference) (decrease, no change [ref], increase). We used multivariable multinomial logistic regression to estimate odds ratios (OR) and 95% confidence intervals (CI) for the association between receiving a cancer diagnosis (exposure) and change in sleep duration (outcome) adjusted for demographic, lifestyle, and health factors.

RESULTS: Among the 20,210 included CPS-3 participants (4,042 cancer survivors), participants who received a cancer diagnosis had higher odds of increasing sleep duration (OR = 1.16, 95% CI 1.07, 1.27) compared to participants who did not receive a cancer diagnosis. Restricting to female participants with a diagnosis of any cancer and breast cancer only showed similar results.

CONCLUSION: The experience of a cancer diagnosis may contribute to increased sleep duration beyond expected age-related changes.},
}

Humans
Female
Middle Aged
Male
*Neoplasms/diagnosis/epidemiology
Adult
Aged
*Sleep/physiology
Prospective Studies
Follow-Up Studies
United States/epidemiology
Time Factors
Incidence
Registries
Sleep Duration

@article {pmid41818265,
year = {2026},
author = {Depierreux, DM and Ruiz, F and Lilly, M and Guenthoer, J and Chohan, V and Overbaugh, J},
title = {Determinants of natural killer cell-mediated antibody dependent cellular cytotoxicity in SARS-CoV-2 antibodies.},
journal = {PLoS pathogens},
volume = {22},
number = {3},
pages = {e1014026},
doi = {10.1371/journal.ppat.1014026},
pmid = {41818265},
issn = {1553-7374},
abstract = {A growing body of evidence underscores the role of antibody-dependent cellular cytotoxicity (ADCC) in antiviral immunity. Yet, the mechanisms underlying the ability of certain antibodies (Abs) to mediate potent ADCC activity remain poorly characterized - in particular the contribution of features within the antigen-binding Fab region remains largely unexplored. In this study, we leveraged a collection of 142 SARS-CoV-2 monoclonal Abs to systematically dissect the determinants of ADCC activity. We analyzed their epitope domain target, binding characteristics, neutralization potency, somatic hypermutation (SHM) and CDR3 length to determine the contribution of these features to ADCC activity. We found that ADCC activity is primarily shaped by epitope target - particularly targeting of the S2 domain of the Spike glycoprotein. ADCC potency was not associated with the degree of SHM or neutralization. Notably, ADCC activity was not correlated with binding activity and moderate binding to antigen was sufficient for ADCC activity. By integrating these analyses, we provide a comprehensive framework for understanding the molecular and functional determinants of ADCC. Together, these findings offer novel insights into the mechanisms that underpin ADCC functions, with implications for vaccine design and therapeutic Abs development.},
}

@article {pmid41819545,
year = {2026},
author = {Chae, YK and Othus, M and Lyu, J and Lee, S and Paik, S and Dietrich, E and Jung, CM and Chung, LI and Patel, S and Kurzrock, R},
title = {Evaluation of mixed response in tumor size and survival in patients with rare cancers treated with dual checkpoint inhibitor therapy (DART SWOG S1609).},
journal = {Journal for immunotherapy of cancer},
volume = {14},
number = {3},
pages = {},
pmid = {41819545},
issn = {2051-1426},
mesh = {Humans ; *Immune Checkpoint Inhibitors/therapeutic use/pharmacology ; Male ; Female ; *Neoplasms/drug therapy/mortality/pathology ; Middle Aged ; Retrospective Studies ; Aged ; Nivolumab/therapeutic use/pharmacology ; Adult ; *Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Ipilimumab/therapeutic use/pharmacology ; Response Evaluation Criteria in Solid Tumors ; *Rare Diseases/drug therapy/mortality ; Tumor Burden ; },
abstract = {BACKGROUND: Mixed response, where different lesions within the same patient show discordant responses to treatment, remains poorly understood. To better understand the complex effects of mixed response on patient survival, we devised three different definitions of mixed response. This retrospective analysis provides the first evaluation of the association between mixed response and survival outcomes in patients with rare cancers treated with dual checkpoint blockade using ipilimumab plus nivolumab, based on data from 52 baskets in the DART SWOG S1609 trial.

METHODS: We included 438 patients with Response Evaluation Criteria in Solid Tumors (RECIST) V.1.1-measurable disease and at least two target lesions, after exclusions for ineligibility, early death, or missing data. Overall survival (OS) and progression-free survival (PFS) were compared using log-rank tests and Cox regression, stratified by basket and using a day 65 landmark. A mixed response was evaluated using three definitions: Method 1-RECIST discordance across lesions; Method 2-presence of ≥1 lesion with >5 mm increase or ≥1 with >5 mm decrease; and Method 3-same as Method 2 but with a 1 mm cut-off.

RESULTS: Mixed response was significantly associated with worse OS and PFS using both Method 1 (OS: HR 1.80; PFS: HR 1.58) and Method 2 (OS: HR 1.55; PFS: HR 1.57) compared with "all SD/stable per lesion". Among patients classified as "SD by RECIST", those who exhibited a mixed per lesion response according to Method 1 had significantly worse OS (median 9.9 months (8.8-12.4)) than those with a non-mixed per lesion response (median 22.7 months (19.2-32.0)). Further stratification showed that any lesion increasing >5 mm was linked to worse outcomes (OS: HR >2.37, p<0.05).

CONCLUSIONS: Mixed response was significantly associated with worse survival outcomes in patients treated with dual immune checkpoint inhibitors, even among those with RECIST-defined stable disease. Our findings suggest that the "worst"-responding lesion drives prognosis, underscoring the limitations of RECIST in capturing clinically relevant heterogeneity. This study highlights the need to incorporate lesion-level assessment into immunotherapy decision-making and provides a foundation for guiding earlier transition to the next line therapies or other therapeutic options. Future studies integrating molecular biomarkers are warranted to refine response evaluation criteria and optimize immune checkpoint inhibitor-based strategies.},
}

Humans
*Immune Checkpoint Inhibitors/therapeutic use/pharmacology
Male
Female
*Neoplasms/drug therapy/mortality/pathology
Middle Aged
Retrospective Studies
Aged
Nivolumab/therapeutic use/pharmacology
Adult
*Antineoplastic Combined Chemotherapy Protocols/therapeutic use
Ipilimumab/therapeutic use/pharmacology
Response Evaluation Criteria in Solid Tumors
*Rare Diseases/drug therapy/mortality
Tumor Burden

@article {pmid41819830,
year = {2026},
author = {Ghodsi, A and Demirci, RA and Gulati, R and Nelson, PS and Raychaudhuri, R and Cheng, HH and Sunkara, R and Khan, H and Rios, RN and Hsieh, A and Grivas, P and Montgomery, B and Yezefski, TA and Yu, EY and Schweizer, MT and Chen, DL and Iravani, A},
title = {Prognostic Value of Cycle 1 SPECT SUVmean in Patients with Metastatic Castration-Resistant Prostate Cancer Treated with [177]Lu-PSMA-617.},
journal = {Journal of nuclear medicine : official publication, Society of Nuclear Medicine},
volume = {},
number = {},
pages = {},
doi = {10.2967/jnumed.125.271593},
pmid = {41819830},
issn = {1535-5667},
abstract = {This study aimed to determine whether SPECT SUVmean measured after the first cycle of [177]Lu-PSMA-617 is associated with oncologic outcomes in patients with metastatic castration-resistant prostate cancer (mCRPC). Methods: This retrospective study included 192 consecutive patients with mCRPC treated with [177]Lu-PSMA-617 who underwent SPECT 24 h after cycle 1. Associations of total tumor SPECT SUVmean with a decline of 50% or more from baseline in prostate-specific antigen (PSA) levels (PSA50), PSA progression-free survival (PSA-PFS), and overall survival (OS) were evaluated using logistic and Cox regression adjusted for prostate-specific membrane antigen PET SUVmean and scan interval. Results: Higher SPECT SUVmean quartiles were independently associated with greater odds of PSA50 response (odds ratios of 4.45, 10.2, and 17.1 for quartiles 2 (Q2), 3 (Q3), and 4 (Q4), respectively (P < 0.05 for all), longer PSA-PFS (hazard ratios of 0.52, 0.29, and 0.17 for Q2-Q4, respectively; P < 0.05 for all), and longer OS (hazard ratios of 1.03, 0.82, and 0.42 for Q2-Q4, respectively; P < 0.05 for Q4 only). Conclusion: SPECT SUVmean measured after the first cycle of [177]Lu-PSMA-617 in patients with mCRPC was prognostic for PSA50 and PSA-PFS, independent of the prostate-specific membrane antigen PET SUVmean, whereas its association with OS was limited and observed only in the highest quartile.},
}

@article {pmid41820080,
year = {2026},
author = {Henikoff, S and Hahn, S},
title = {RNA polymerase II: the elephant in the room.},
journal = {Trends in genetics : TIG},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.tig.2026.01.008},
pmid = {41820080},
issn = {0168-9525},
abstract = {How genes respond to external signals is poorly understood, with transcription factors and histones proposed as mediators of signals to RNA polymerase II (Pol II). However, recent work shows that Pol II is the direct target of more than 100 protein kinases, a previously underappreciated mechanism for generating epigenetic complexity.},
}

@article {pmid41821238,
year = {2026},
author = {Williams, DM and Reilly, S and Lord, T and Ayers, K and Kissiah-Grove, S and Robinson, M and Fong, L and Angel, J},
title = {"Give me the sense that I matter:" Queer women's recommendations for an ideal cervical cancer screening exam and pathways to screening equity.},
journal = {Women's health (London, England)},
volume = {22},
number = {},
pages = {17455057261428108},
pmid = {41821238},
issn = {1745-5065},
mesh = {Humans ; Female ; Young Adult ; Adult ; Middle Aged ; *Uterine Cervical Neoplasms/diagnosis/prevention & control ; *Early Detection of Cancer/psychology ; *Sexual and Gender Minorities/psychology ; *Healthcare Disparities ; *Patient Acceptance of Health Care/psychology ; Qualitative Research ; Interviews as Topic ; Professional-Patient Relations ; },
abstract = {BACKGROUND: Cervical cancer screening is a powerful tool in the prevention, early detection, and diagnosis of precancers and cancer. There is mounting evidence, however, demonstrating that Queer cisgender women experience disparities in cervical cancer screening access and uptake compared to their heterosexual counterparts. To close gaps in screening, Queer women's voices and visions must foreground recommendations aimed at remedying screening inequities.

OBJECTIVES: This study aims to explore perceptions on an ideal cervical cancer screening exam among a racially and ethnically diverse group of Queer women.

DESIGN: This qualitative interview study is led in partnership with a multidisciplinary community steering committee. Our work is grounded in the Reproductive Justice Framework.

METHODS: We held in-depth interviews with 19 Queer women to understand their recommendations for improving cervical cancer screening experiences for their community. Data from these interviews were analyzed through thematic analysis.

RESULTS: We identified five themes around creating an ideal cervical cancer screening experience among Queer women: (1) community outreach and education, (2) cues of affirmation and safety, (3) Queer patient navigation and advocacy, (4) Queer-affirming and knowledgeable providers, and (5) trauma-informed care.

CONCLUSION: Engaging Queer women in developing solutions to address screening disparities is a missing link in cervical cancer prevention and the advancement of reproductive health equity. We share actionable strategies at the healthcare professional, community, and organizational levels to support healthcare systems in translating Queer women's visions into practice. Our findings also inform medical organizations, expert panels, and health authorities on patient-defined strategies and pathways to remedying screening inequity.},
}

Humans
Female
Young Adult
Adult
Middle Aged
*Uterine Cervical Neoplasms/diagnosis/prevention & control
*Early Detection of Cancer/psychology
*Sexual and Gender Minorities/psychology
*Healthcare Disparities
*Patient Acceptance of Health Care/psychology
Qualitative Research
Interviews as Topic
Professional-Patient Relations

@article {pmid41821313,
year = {2026},
author = {Bridge, J and Johnson, MJ and Kar, B and Kim, J and Wenthe, S and Krueger, J and Wick, B and Kluesner, MG and Crane, AT and Bell, J and von Dissen, L and Stelljes, E and Skeate, JG and Moriarity, BS and Webber, BR},
title = {Efficient multiplex non-viral engineering and expansion of polyclonal γδ CAR-T cells for immunotherapy.},
journal = {Molecular therapy : the journal of the American Society of Gene Therapy},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.ymthe.2026.03.007},
pmid = {41821313},
issn = {1525-0024},
abstract = {Gamma delta (γδ) T cells are defined by their unique ability to recognize a limited repertoire of non-peptide, non-MHC-associated antigens on transformed and pathogen-infected cells. In addition to their inability to mediate GvHD, γδ T cells exhibit properties distinct from other lymphocyte subsets, prompting significant interest in their development as an off-the-shelf cellular immunotherapeutic. However, their low abundance in circulation, heterogeneity, limited methods for ex vivo expansion, and under-developed methodologies for genetic modification have hindered basic study and clinical application of γδ T cells. Here, we implement a feeder-free, scalable approach for ex vivo manufacture of polyclonal, non-virally modified, gene edited chimeric antigen receptor (CAR)-γδ T cells for therapeutic application. Engineered CAR-γδ T cells demonstrate robust functionality in vitro and in vivo. Longitudinal in vivo pharmacokinetic profiling of adoptively transferred polyclonal CAR-γδ T cells uncover subset-specific responses to IL-15 cytokine armoring and multiplex base editing. Our results present a robust platform for genetic modification of polyclonal CAR-γδ T cells and present unique opportunities to further define synergy and the contribution of discrete, engineered CAR-γδ T cell subsets to therapeutic efficacy in vivo.},
}

@article {pmid41822483,
year = {2026},
author = {Brackett, C and Zhang, L and Do, BTN and Baral, S and Fisher, LH and Hahn, WO and Carnacchi, AJ and Hilliard, S and Li, SS and Premkumar, L and Greninger, AL and Hyrien, O and Seaton, KE and Tomaras, GD},
title = {Early rise in nasal secretory IgA associated with shorter duration of SARS-CoV-2 virus shedding in an acute infection cohort.},
journal = {Frontiers in immunology},
volume = {17},
number = {},
pages = {1722585},
pmid = {41822483},
issn = {1664-3224},
mesh = {Humans ; *Virus Shedding/immunology ; *COVID-19/immunology/virology ; *SARS-CoV-2/immunology/physiology ; *Immunoglobulin A, Secretory/immunology/blood ; Male ; Female ; *Antibodies, Viral/immunology/blood ; Adult ; Middle Aged ; Immunity, Mucosal ; Cohort Studies ; Spike Glycoprotein, Coronavirus/immunology ; *Nasal Mucosa/immunology ; Nasal Lavage Fluid/immunology ; },
abstract = {INTRODUCTION: Understanding the role of mucosal immune responses in preventing coronavirus replication is essential for the development of broad-spectrum therapeutics and vaccines capable of interrupting transmission. Investigating the relationship between mucosal antibodies and viral shedding may provide critical insights into protective mechanisms against SARS-CoV-2 and inform strategies for enhancing mucosal immunity.

METHODS: In a subset of the larger CoVPN 5001 cohort, 143 participants from the US, Mexico, and South America were characterized as either short (<7 days), intermediate (7-21 days), or prolonged (>21 days) virus shedders based on RT-qPCR measurements over the first month of acute SARS-CoV-2 infection. We measured systemic circulating serum IgA and secretory IgA (SIgA) in serially collected nasal lavage fluids to 15 SARS-CoV-2 antigens, including spike variants, receptor binding domain (RBD), and N-terminal Domain (NTD) and evaluated the relationship between antibody titers and duration of viral shedding using multivariate and binary logistic regression modeling. We also assessed antibody responses to RBD proteins of endemic alpha and beta coronaviruses to compare variations in antibody kinetics throughout the course of infection.

RESULTS: We found that increased serum IgA and mucosal secretory IgA antibody titers during the earliest phase of acute infection were associated with decreased viral shedding duration, with nasal IgA responses to the spike NTD being the strongest factor associated with viral shedding (adjusted p<0.1). In contrast, antibody titers against endemic human coronaviruses remained stable throughout the course of infection, consistent with a specific role for newly elicited SARS-CoV-2 antibodies in virus control.

DISCUSSION: These findings demonstrate that early rises in serum and mucosal IgA titers are associated with reduced duration of viral shedding. Notably, nasal secretory IgA responses targeting the spike N-terminal domain were most strongly associated with shorter shedding, suggesting a potentially protective role for SARS-CoV-2-specific nasal IgA during acute SARS-CoV-2 infection. These results highlight the importance of mucosal immunity for limiting viral transmission and shedding, offering future insights for pan-coronavirus therapeutics and vaccine development aimed for enhancing SARS-COV-2 mucosal antibody responses.},
}

Humans
*Virus Shedding/immunology
*COVID-19/immunology/virology
*SARS-CoV-2/immunology/physiology
*Immunoglobulin A, Secretory/immunology/blood
Male
Female
*Antibodies, Viral/immunology/blood
Adult
Middle Aged
Immunity, Mucosal
Cohort Studies
Spike Glycoprotein, Coronavirus/immunology
*Nasal Mucosa/immunology
Nasal Lavage Fluid/immunology

@article {pmid41826235,
year = {2026},
author = {Yorke, AA and Ignatius, K and Schreiner, JL and Kron, T},
title = {Estimating the Carbon Footprint of External Beam Radiotherapy: Should This Be a Concern for LMICs?.},
journal = {Journal of medical imaging and radiation oncology},
volume = {},
number = {},
pages = {},
doi = {10.1111/1754-9485.70083},
pmid = {41826235},
issn = {1754-9485},
abstract = {PURPOSE: This study aims to estimate the carbon footprint associated with external beam radiotherapy in a low- and middle-income country (LMIC) context, specifically at the Uganda Cancer Institute (UCI), and to evaluate whether sustainability should be a priority alongside treatment access in such radiation therapy settings.

METHODOLOGY: A carbon footprint analysis was conducted for patients treated for locally advanced cervical cancer at UCI between 2023 and 2024. The assessment included emissions from three key components: (1) patient travel to and from the facility, (2) pre-treatment imaging using CT and 2D simulation and (3) energy consumption by three Varian TrueBeam linear accelerators during treatment and idle times. Emission estimates were calculated using activity data and standard global warming potential (GWP) conversion factors.

RESULTS: Patient travel emerged as a major contributor to carbon emissions due to the centralisation of services in Kampala and the lack of regional treatment centres. Energy use from LINACs and imaging contributed less significantly, owing in part to Uganda's low-carbon electricity grid powered largely by hydropower. CT scans generated approximately 0.105 kg CO2 per scan, and LINAC operations added modest emissions depending on usage patterns and machine idle time.

CONCLUSION: While radiotherapy-related emissions in LMICs like Uganda are relatively modest compared to high-income countries, they are non-negligible and expected to rise with growing access to cancer care. Incorporating sustainability considerations into the future planning of radiotherapy infrastructure and service expansion is both feasible and necessary. Carbon-conscious planning should be integrated into decisions around siting and radiotherapy expansion to promote environmentally responsible cancer care in LMICs.},
}

@article {pmid41826733,
year = {2026},
author = {Kousa, AI and Jahn, L and Zhao, K and Flores, AE and Acenas, D and Lederer, E and Argyropoulos, KV and Lemarquis, AL and Granadier, D and Cooper, K and D'Andrea, M and Sheridan, JM and Tsai, J and Sikkema, L and Lazrak, A and Nichols, K and Lee, N and Ghale, R and Malard, F and Andrlova, H and Velardi, E and Youssef, S and Burgos da Silva, M and Docampo, M and Sharma, R and Mazutis, L and Wimmer, VC and Rogers, KL and DeWolf, S and Gipson, B and Gomes, ALC and Setty, M and Pe'er, D and Hale, L and Manley, NR and Gray, DHD and van den Brink, MRM and Dudakov, JA},
title = {Author Correction: Age-related epithelial defects limit thymic function and regeneration.},
journal = {Nature immunology},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41590-026-02489-4},
pmid = {41826733},
issn = {1529-2916},
}

@article {pmid41722658,
year = {2026},
author = {Al-Hallaq, HA and Zoberi, JE and Tran, A and Kim, H and Lowenstein, JR and Meyer, J},
title = {A National Survey of Medical Physicists: Part 2-Assessing Work Effort and Perceived Challenges and Satisfaction in HDR Brachytherapy.},
journal = {International journal of radiation oncology, biology, physics},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.ijrobp.2026.02.229},
pmid = {41722658},
issn = {1879-355X},
abstract = {PURPOSE: To collect national data from medical physicists on work effort, challenges, and job satisfaction in high-dose rate (HDR) brachytherapy (BT) as a function of procedure complexity.

METHODS AND MATERIALS: A survey was administered in cooperation with IROC-Houston. Question topics included demographics, practice patterns, caseload, procedure complexity, relative time and effort required for simple and complex cases, and challenges/satisfaction associated with HDR BT.

RESULTS: Of 429 completed responses, 365 performed HDR BT. The most commonly treated anatomic sites were gynecologic, prostate, and skin, with 56% of respondents' clinics performing interstitial procedures. Respondents indicated that the median time and intensity ratios of a single-channel HDR BT, relative to a weekly chart check (CPT77336), were 5 and 3, respectively, implying a work ratio of 15. When comparing the most complex procedure with a single-channel treatment, the median time and intensity ratios reported were both 5, implying a work ratio of 25. The time and intensity ratios scaled with increasing complexity for gyne procedures (ie, 1, 2-3, and ≥4 channels). Most respondents reported that it was more stressful to cover HDR BT versus external beam radiation therapy (EBRT) (82%) and to switch between services (73%). Job satisfaction was impacted most positively by direct patient contact and the experience level of authorized users, but most negatively by increased stress compared with other services and maintaining skill levels due to infrequent cases. Only the subset of respondents at clinics treating complex gyne with a high caseload (≥25 patients/y) indicated that staff allocation was inadequate or that a colleague had left their position due to HDR BT.

CONCLUSIONS: The results show a relationship between work effort and procedure complexity, which is currently not addressed in national staffing recommendations. To sustain a workforce capable of supporting HDR brachytherapy into the future, professional societies/leaders must recognize the stress and intensity of complex cases and adjust staffing recommendations accordingly.},
}

@article {pmid41816837,
year = {2026},
author = {Oehler, VG and Berman, E and Huang, IJ},
title = {Management of chronic myeloid leukemia with tyrosine kinase inhibitors: adverse events, toxicities and therapy dosing.},
journal = {Haematologica},
volume = {},
number = {},
pages = {},
doi = {10.3324/haematol.2025.288334},
pmid = {41816837},
issn = {1592-8721},
abstract = {Targeted therapies have made near normal life span an attainable goal for many patients with chronic phase (CP) chronic myeloid leukemia (CML). Most patients require years of therapy and not everyone may be able to discontinue treatment permanently without CML recurrence. BCR::ABL1 targeted tyrosine kinase inhibitors (TKIs) including ATP binding site and allosteric inhibitors that bind to the myristoyl pocket are associated with treatment-emergent adverse events (TEAEs) that may compromise quality of life and well-being. Although alternative treatment options exist, side effects may persist, or new ones occur after a therapy switch. Using a case-based approach, this review examines the incidence of non-hematologic and hematologic TEAEs with specific therapies, provides guidance on AE management, and describes the impact of therapy dose reduction on efficacy and tolerability.},
}

@article {pmid41816965,
year = {2026},
author = {Cheung, C and Anita, NZ and Filigrana, P and Fornage, M and Gonzalez, KA and Gallo, LC and Isasi, CR and Kaplan, RC and Li, X and Márquez, F and Parada, H and Perreira, KM and Ramos, AR and Rundek, T and Tarraf, W and Testai, FD and DeCarli, C and González, HM and Sofer, T},
title = {APOE and plasma AD biomarkers: The role of genetic ancestry in Hispanics/Latinos.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {22},
number = {3},
pages = {e71213},
doi = {10.1002/alz.71213},
pmid = {41816965},
issn = {1552-5279},
support = {R01 AG048642/AG/NIA NIH HHS/United States ; R01 AG080598/AG/NIA NIH HHS/United States ; R01AG075758//National Institute on Aging (NIA)/ ; R01 AG075758/AG/NIA NIH HHS/United States ; R56AG048642//National Institute on Aging (NIA)/ ; R01AG048642//National Institute on Aging (NIA)/ ; },
mesh = {Humans ; *Hispanic or Latino/genetics ; Female ; Male ; *Alzheimer Disease/genetics/blood/ethnology ; Biomarkers/blood ; tau Proteins/blood ; Aged ; Amyloid beta-Peptides/blood ; *Apolipoproteins E/genetics ; Glial Fibrillary Acidic Protein/blood ; Neurofilament Proteins/blood ; Middle Aged ; Aged, 80 and over ; Apolipoprotein E4/genetics ; Peptide Fragments/blood ; White ; },
abstract = {BACKGROUND: Apolipoprotein E (APOE) alleles are well-established genetic risk factors for Alzheimer's disease (AD), but their effects on AD biomarkers (amyloid beta [Aβ]42/40, phosphorylated tau [p-tau]181, neurofilament light chain [NfL], and glial fibrillary acidic protein [GFAP]) may vary across populations due to ancestry-, age-, and sex-related differences. We hypothesized that these effects vary across Hispanic/Latino background groups with distinct ancestral admixture.

METHODS: We analyzed ε2 and ε4 allele associations with AD biomarkers using survey-weighted linear regression models, adjusting for demographic covariates. Secondary analyses examined genetic analysis group- and ancestry-specific effects.

RESULTS: ε4 was associated with lower Aβ42/40 and higher p-tau181and GFAP levels, but not with NfL, suggesting its role in Aβ and tau deposition and neuroinflammation. ε4 associations were stronger in those with higher European and lower African ancestry.

DISCUSSION: These findings expand on prior studies suggesting that genetic ancestry modifies APOE-associated AD risk in Hispanic/Latino populations and highlight the importance of capturing ancestry-based heterogeneity in AD biomarker research.},
}

Humans
*Hispanic or Latino/genetics
Female
Male
*Alzheimer Disease/genetics/blood/ethnology
Biomarkers/blood
tau Proteins/blood
Aged
Amyloid beta-Peptides/blood
*Apolipoproteins E/genetics
Glial Fibrillary Acidic Protein/blood
Neurofilament Proteins/blood
Middle Aged
Aged, 80 and over
Apolipoprotein E4/genetics
Peptide Fragments/blood
White

@article {pmid41817149,
year = {2026},
author = {Banerjee, R and Dhodapkar, MV},
title = {Reading the "T" Leaves: Predicting Outcomes with Bispecific Antibodies in Multiple Myeloma.},
journal = {Blood cancer discovery},
volume = {},
number = {},
pages = {OF1-OF3},
doi = {10.1158/2643-3230.BCD-26-0041},
pmid = {41817149},
issn = {2643-3249},
abstract = {In this issue of Blood Cancer Discovery, Frenking and colleagues demonstrate the prognostic potential of three risk score models to predict hematotoxicity, infections, response rates, and survival following bispecific T-cell engager (TCE) therapy in multiple myeloma. These risk score models, which the authors validated using retrospective real-world data from 278 patients, can easily be calculated using routine blood testing and offer the potential to improve the efficacy and safety of TCE therapy. See related article by Frenking et al., p. XX .},
}

@article {pmid41817312,
year = {2026},
author = {McKay, RR and Nazari, SS and Elliott, A and Smith, N and Barata, P and Kilari, D and Garje, R and Haffner, MC and Morrissey, C and Rupnow, BA and Basu, S and Drake, C and Rose, B and Bagrodia, A and Agarwal, N and Antonarakis, ES and Beltran, H},
title = {Molecular Characterization of KLK2 RNA Expression in Prostate Cancer.},
journal = {Clinical cancer research : an official journal of the American Association for Cancer Research},
volume = {},
number = {},
pages = {},
doi = {10.1158/1078-0432.CCR-25-4293},
pmid = {41817312},
issn = {1557-3265},
abstract = {PURPOSE: KLK2 is an androgen-regulated gene critical in prostate cancer biology with multiple KLK2-targeted therapies in clinical development. We investigated KLK2 RNA expression patterns and associations with molecular features to provide context for emerging KLK2-targeted treatments.

EXPERIMENTAL DESIGN: DNA/RNA next-generation sequencing was performed on 7,078 prostate cancer specimens. KLK2-high/low RNA expression was defined as ≥75th/<25th percentiles (transcripts per million, TPM). KLK2 expression was evaluated across histologic subtypes, disease states, and metastatic sites, with correlative analyses of genomic alterations, RNA signatures, and clinical outcomes.

RESULTS: KLK2 gene expression varied significantly by histology, with highest levels in adenocarcinoma (8.79 log2[TPM+1]) and minimal expression in histologic neuroendocrine prostate cancer (0.33 log2[TPM+1]). Expression was significantly higher in androgen deprivation therapy (ADT)/androgen receptor pathway inhibitor (ARPI)-sensitive versus ADT/ARPI-exposed tumors (8.97 vs. 8.38 log2[TPM+1], q<0.001). Localized tumors demonstrated higher expression than lymph node (8.93 vs. 8.76 log2[TPM+1]) or distant metastases (8.23 log2[TPM+1]), with visceral metastases showing the lowest levels. In the overall cohort, KLK2 expression correlated positively with androgen receptor signaling (r=0.25-0.47) and negatively with neuroendocrine signaling. High KLK2 expression was associated with significantly improved overall survival (93.9 vs. 74.4 months, hazard ratio 0.68, p<0.001) in the total cohort, with similar patterns in patients with ADT/ARPI-sensitive and ADT/ARPI-exposed disease.

CONCLUSIONS: This large-scale clinico-genomic analysis reveals distinct KLK2 expression patterns across prostate cancer histologies, tumor sites, and clinical states. These findings provide a molecular framework understanding KLK2 as a therapeutic target in prostate cancer.},
}

@article {pmid41808921,
year = {2026},
author = {Hudson, A and Carone, M and Shojaie, A},
title = {Inference on function-valued parameters using a restricted score test.},
journal = {Journal of the Royal Statistical Society. Series B, Statistical methodology},
volume = {},
number = {},
pages = {},
pmid = {41808921},
issn = {1467-9868},
support = {R01 GM114029/GM/NIGMS NIH HHS/United States ; R01 GM133848/GM/NIGMS NIH HHS/United States ; R01 HL137808/HL/NHLBI NIH HHS/United States ; RF1 AG090462/AG/NIA NIH HHS/United States ; },
abstract = {It is often of interest to make inference on an unknown function that is a local parameter of the data-generating mechanism, such as a density or regression function. Such estimands can typically only be estimated at a slower-than-parametric rate in nonparametric and semiparametric models, and performing calibrated inference can be challenging. In many cases, these estimands can be expressed as the minimizer of a population risk functional. Here, we propose a general framework that leverages such representation and provides a nonparametric extension of the score test for inference on an infinite-dimensional risk minimizer. We demonstrate that our framework is applicable in a wide variety of problems. As both analytic and computational examples, we describe how to use our general approach for inference on a mean regression function under (i) nonparametric and (ii) partially additive models, and evaluate the operating characteristics of the resulting procedures via simulations. Assessment of effect heterogeneity, inference on density functions, and conditional independence testing are discussed as additional examples.},
}

@article {pmid41812087,
year = {2026},
author = {Owens, CA and Ludmir, EB and Liu, Q and Qiu, W and Gupta, AC and Smith, SA and Rigaud, B and Brock, KK and Bates, JE and Meyers, TG and Paulino, AC and Peterson, CB and Kry, SF and Teepen, JC and Ronckers, CM and Neglia, JP and Leisenring, WM and Oeffinger, KC and Nathan, PC and Turcotte, LM and Hodgson, DC and Hudson, MM and Robison, LL and Moskowitz, CS and Armstrong, GT and Henderson, TO and Yasui, Y and Howell, RM},
title = {Reply to: Methodologic Considerations for Subsequent Colorectal Cancer in Survivors of Childhood Cancer.},
journal = {Journal of clinical oncology : official journal of the American Society of Clinical Oncology},
volume = {},
number = {},
pages = {JCO2600051},
doi = {10.1200/JCO-26-00051},
pmid = {41812087},
issn = {1527-7755},
}

@article {pmid41813924,
year = {2026},
author = {Feder, AF and DeWitt, WS},
title = {Context dependency is essential for predicting intrahost evolution.},
journal = {Nature ecology & evolution},
volume = {10},
number = {3},
pages = {389-391},
pmid = {41813924},
issn = {2397-334X},
}

@article {pmid41805422,
year = {2026},
author = {Hunter, NB and Parsons, HA and Cope, L and Canzoniero, JV and Navarro, FCP and El-Refai, S and Anampa, JD and Sparano, JA and Rimawi, M and Storniolo, AM and Mainor, C and Nanda, R and DeMichele, A and Gupta, GP and Stringer-Reasor, EJ and Lynce, F and Cobain, EF and Puhalla, S and Jankowitz, R and Rexer, B and Mayer, I and Hwang, ES and Blackwell, K and El Ayass, W and Lee, Y and Tweed, C and Wilkinson, M and Pennisi, A and Sun, B and Wright, P and Gralow, JR and Chen, R and Boyle, SM and Stearns, V and Wolff, AC and Park, BH},
title = {The Pathologic Response Evaluation and Detection in Circulating Tumor-DNA Study: Ultrasensitive Circulating Tumor-DNA Assessment of Breast Cancer Minimal Residual Disease.},
journal = {Journal of clinical oncology : official journal of the American Society of Clinical Oncology},
volume = {},
number = {},
pages = {JCO2502934},
doi = {10.1200/JCO-25-02934},
pmid = {41805422},
issn = {1527-7755},
abstract = {PURPOSE: Patients with stage II/III human epidermal growth factor receptor 2 (HER2)-positive or triple-negative breast cancer (TNBC) frequently receive neoadjuvant therapy (NAT). Although pathologic complete response (pCR) correlates with improved outcomes, many non-pCR patients have long-term survival. Circulating tumor-DNA (ctDNA) minimal residual disease (MRD) assessment may provide additional or superior risk stratification.

METHODS: Pathologic Response Evaluation and Detection in Circulating Tumor-DNA is a prospective, multicenter study evaluating ctDNA as a biomarker of treatment response using a tumor-informed, ultrasensitive (<100 parts per million) assay. The primary objective was to determine whether the negative predictive value (NPV) of post-NAT ctDNA for pCR was ≥90%. A prespecified secondary objective for the TNBC cohort was to assess associations between ctDNA and 5-year invasive disease-free survival (IDFS). ctDNA was evaluated at baseline, after NAT before surgery, and after surgery.

RESULTS: Of 227 enrolled patients, 220 were evaluable for pCR (48% HER2-positive; 52% TNBC) and 91 patients (41%) had pCR. The primary objective was not met. Although all patients with pCR were ctDNA-negative after NAT, 40% of non-pCR patients were also ctDNA-negative (NPV, 60% [95% CI, 0.50 to 0.69]). However, the prespecified secondary objective was met. Detectable ctDNA after NAT was prognostic for recurrence (hazard ratio [HR], 8.9 [95% CI, 2.4 to 33]; P = .001), independent of pCR. Additionally, detectable ctDNA after surgery identified patients at extremely high recurrence risk (HR, 128 [95% CI, 15 to 1,083]; P < .001), while ctDNA-negative patients after surgery had 94% 5-year IDFS.

CONCLUSION: In HER2-positive breast cancer and TNBC, ctDNA after NAT does not discriminate pCR from non-pCR. However, ctDNA provides markedly superior prognostic stratification, identifying patients with exceptional outcomes and those at extreme risk. These findings support ctDNA-guided therapeutic de-escalation and escalation strategies.},
}

@article {pmid41807764,
year = {2026},
author = {Hurlburt, NK and Lubow, J and Goo, L and Pancera, M},
title = {Structural basis for antibody cross-neutralization of Dengue and Zika viruses.},
journal = {Communications biology},
volume = {},
number = {},
pages = {},
doi = {10.1038/s42003-026-09805-6},
pmid = {41807764},
issn = {2399-3642},
abstract = {Safe and effective vaccines against co-circulating mosquito-borne orthoflaviviruses such as Zika virus (ZikV) and the four serotypes of Dengue virus (DenV1-4) must elicit broadly neutralizing antibodies (bnAbs) to prevent the risk of enhancement of infection by non-neutralizing antibodies. We recently discovered new orthoflavivirus-directed bnAbs, including F25.S02, which neutralizes DenV1-4 and ZikV with comparable or superior potency to the previously characterized E dimer epitope (EDE) bnAbs. Here, we used cryoEM and X-ray crystallography to understand the basis of cross-neutralization of F25.S02 at the molecular level. We obtained a ~ 4.2 Å cryoEM structure of F25.S02 Fab bound to a stabilized DenV3 soluble E protein dimer and a 2.3 Å crystal structure of F25.S02 Fab bound to ZikV soluble E protein dimer. Like previously described EDE1 bnAbs, the structural epitope of F25.S02 is at the E dimer interface, encompassing predominantly conserved regions in domain II, including the fusion loop. However, unlike EDE1 bnAbs, F25.S02 binding is almost entirely dependent on the heavy chain and is shifted slightly away from the dimer symmetry axis. Our findings emphasize the importance of this cross-neutralizing site of vulnerability for DenV and ZikV that can facilitate rational design of vaccines and therapeutics.},
}

@article {pmid41808348,
year = {2026},
author = {Frutoso, M and DeJong, CS and Shree, R and McCartney, SA and Prlic, M},
title = {Phenotypically similar but functionally distinct NK cell populations within the human maternal-fetal interface.},
journal = {ImmunoHorizons},
volume = {10},
number = {3},
pages = {},
pmid = {41808348},
issn = {2573-7732},
support = {1R01AI179712/NH/NIH HHS/United States ; R21AI144677/NH/NIH HHS/United States ; },
mesh = {Humans ; *Killer Cells, Natural/immunology/metabolism ; Female ; Pregnancy ; *Decidua/immunology/cytology ; *Placenta/immunology/cytology ; Cytokines/metabolism ; Interferon-gamma/metabolism ; Placentation/immunology ; Lymphocyte Activation ; Phenotype ; Flow Cytometry ; },
abstract = {Natural killer (NK) cell function within tissues extends beyond exerting cytotoxicity, encompassing a range of functions that are just starting to become fully elucidated. In the context of human placentation, NK cells play a key role in enabling initial placentation, which is associated with the acquisition of tolerance-like properties. If and to which extent NK cells maintain these tolerance-like properties over the course of human pregnancy is still poorly understood. We asked if NK cells isolated from the decidual-placental interface of full-term human pregnancies are able to exert effector function. We observed a significant and striking lack in the ability of NK cells isolated from the decidual-placental interface (DPI) to produce interferon-g (IFN-γ) in response to the activating cytokines interleukin (IL)-12, IL-15, and IL-18. In contrast, NK cells from the decidua retained their responsiveness to cytokine-mediated activation. Notably, CD103+CD69+ tissue-resident NK cells were present in both DPI and decidua, yet exhibited distinct effector function from one another. Using high-parameter flow cytometry and single-cell sequencing, we found that this functional discrepancy was not directly predictable based on their cell surface phenotype or cell transcript. Together, our findings reveal the presence of distinct functional resident NK cell populations in 2 anatomically adjacent tissues at healthy full-term pregnancies.},
}

Humans
*Killer Cells, Natural/immunology/metabolism
Female
Pregnancy
*Decidua/immunology/cytology
*Placenta/immunology/cytology
Cytokines/metabolism
Interferon-gamma/metabolism
Placentation/immunology
Lymphocyte Activation
Phenotype
Flow Cytometry

@article {pmid41804865,
year = {2026},
author = {Ma, J},
title = {Inference for microbe-metabolite association networks using a latent graph model.},
journal = {Biometrics},
volume = {82},
number = {1},
pages = {},
doi = {10.1093/biomtc/ujag042},
pmid = {41804865},
issn = {1541-0420},
support = {R01 GM145772/GF/NIH HHS/United States ; },
mesh = {Algorithms ; Computer Simulation ; Humans ; *Models, Statistical ; Female ; *Microbiota ; *Metabolic Networks and Pathways ; Stochastic Processes ; },
abstract = {Correlation networks are commonly used to infer associations between microbes and metabolites. The resulting $p$-values are then corrected for multiple comparisons using existing methods such as the Benjamini & Hochberg (BH) procedure to control the false discovery rate (FDR). However, most existing methods for FDR control assume the $p$-values are weakly dependent. Consequently, they can have low power in recovering microbe-metabolite association networks that exhibit important topological features, such as the presence of densely associated modules. We propose a novel inference procedure that is both powerful for detecting significant associations in the microbe-metabolite network and capable of controlling the FDR. Power enhancement is achieved by modeling latent structures in the form of a bipartite stochastic block model. We develop a variational expectation-maximization (EM) algorithm to estimate the model parameters and incorporate the learned graph in the testing procedure. In addition to FDR control, this procedure provides a clustering of microbes and metabolites into modules, which is useful for interpretation. We demonstrate the merit of the proposed method in simulations and an application to bacterial vaginosis.},
}

Algorithms
Computer Simulation
Humans
*Models, Statistical
Female
*Microbiota
*Metabolic Networks and Pathways
Stochastic Processes

@article {pmid41804750,
year = {2026},
author = {van Creij, NCH and Tymoszuk, P and Handle, F and Seeber, A and Sellemond, T and Martowicz, A and Comperat, E and Wafa, H and Ormanns, S and Günther, M and Parson, W and Noeparast, M and Santer, FR and Subiela, JD and Grivas, P and Li, R and Culig, Z and Pichler, R},
title = {Multi-omic profiling defines three distinct molecular subtypes of urothelial carcinoma with implications for precision therapy.},
journal = {Clinical and translational medicine},
volume = {16},
number = {3},
pages = {e70638},
pmid = {41804750},
issn = {2001-1326},
mesh = {Humans ; *Precision Medicine/methods ; *Urinary Bladder Neoplasms/genetics/classification ; Gene Expression Profiling/methods ; Cell Line, Tumor ; Transcriptome ; Multiomics ; },
abstract = {BACKGROUND: Urothelial carcinoma (UC) is a biologically heterogeneous disease, and current molecular classifications have limited integration into clinical decision-making. To further pursue precision oncology efforts in UC, we developed a molecular classification framework applicable to transcriptomic and proteomic data from non-muscle-invasive bladder cancer (NMIBC), muscle-invasive bladder cancer (MIBC) and urothelial cancer cell lines.

METHODS: Using a whole-transcriptome self-organised map and regularised semi-supervised clustering of 4439 bulk NMIBC and MIBC transcriptomes and proteomes, and 33 UC cell lines, we identified three molecular UC clusters. Making use of both in silico and in vitro approaches, we selected promising treatment approaches for each cluster.

RESULTS: The three developed clusters displayed distinct signatures of mRNA, proteins, biological processes, metabolism and essential driver genes. They also differed in prognosis and machine learning-predicted treatment vulnerabilities and resistance. High-risk, stroma-rich Cluster #1 cancers were predicted to respond to selected cytotoxic drugs, ferroptosis inducers and PARP inhibitors. For the aggressive, fast-proliferating, immune-infiltrated Cluster #2 tumours with basal/squamous differentiation, cytotoxic agents and EGFR/ERBB- and MEK/ERK-targeting therapies were proposed. Cluster #3 cancers of predominantly luminal papillary phenotype with scarce stroma and immune infiltration were enriched with NMIBC and low-risk malignancies. For patients with Cluster #3 tumours, selected epigenetic drugs or EGFR/FGFR inhibitors may represent attractive treatment options.

CONCLUSIONS: Our novel molecular taxonomy holds promise as a practical framework for patient risk stratification and clinical trials in UC. Our molecular classification scheme may facilitate personalised transcriptome- and proteome-based risk assessment and clinical trial design for the development of various therapeutics.

KEY POINTS: We developed three UC clusters, applicable for MIBC and NMIBC, which were validated using transcriptomic- and proteomic datasets. Publically available UC cell lines were assigned to the clusters, to have in vitro models representing each cluster. The clusters differ in molecular and biological signatures, with distinct prognostic and therapeutic characteristics.},
}

Humans
*Precision Medicine/methods
*Urinary Bladder Neoplasms/genetics/classification
Gene Expression Profiling/methods
Cell Line, Tumor
Transcriptome
Multiomics

@article {pmid41803327,
year = {2026},
author = {Zhang, W and Allen, EK and Li, S and Tarasova, I and Farrukee, R and Kedzierski, L and Gilbertson, B and McQuilten, HA and Habel, JR and Allen, LF and Rockman, S and Londrigan, SL and Kent, SJ and Wheatley, AK and Trubiano, JA and Kotsimbos, TC and Cheng, AC and Schroeder, J and Crawford, JC and Thomas, PG and Kedzierska, K and Nguyen, THO},
title = {IFN-gene signatures in B cells following influenza A and B virus infection and influenza vaccination.},
journal = {EMBO molecular medicine},
volume = {},
number = {},
pages = {},
pmid = {41803327},
issn = {1757-4684},
support = {2033783//DHAC | National Health and Medical Research Council (NHMRC)/ ; 1194036//DHAC | National Health and Medical Research Council (NHMRC)/ ; 2016491//DHAC | National Health and Medical Research Council (NHMRC)/ ; 2026762//DHAC | National Health and Medical Research Council (NHMRC)/ ; 2012463//DHAC | National Health and Medical Research Council (NHMRC)/ ; 2038242//DHAC | National Health and Medical Research Council (NHMRC)/ ; T11-712/19-N//Theme-based Research Scheme of the Research Grants Council of the Hong Kong Special Administrative Region (HKSAR), China/ ; 1U01AI144616-01//HHS | NIH | National Institute of Allergy and Infectious Diseases (NIAID)/ ; HHS-NIH-NIAID-BAA2018//HHS | National Institutes of Health (NIH)/ ; },
abstract = {Influenza viruses continue to cause a substantial global disease burden. Despite influenza vaccination, some individuals succumb to life-threatening influenza or death. Yet our understanding of immune features elicited by vaccination and influenza A and B virus (IAV, IBV) infection is limited. To define molecular signatures of influenza-specific B-cells, we performed scRNA-sequencing of influenza-specific B-cells in vaccinees and hospitalized IAV/IBV-infected patients using HA-probes. We observed increased interferon-stimulated gene signatures (IF44L, IFITM1 and XAF1), in total B-cells from IBV-patients, but not at 1-month following patients' recovery or in IAV-patients or vaccinees. Phenotypic differentiation and isotype class-switching of HA-specific B-cells were observed following vaccination, with clonal sharing between memory and atypical B-cell phenotypes. In-vitro influenza virus infection experiments showed IBVs having higher infectivity of human PBMCs, including B-cells, and reduced B-cell proliferation compared to IAV, potentially associated with antiproliferative effect of IFITM1. We provide key insights into B-cell immunity towards IBV and IAV infections and vaccination, which will inform rational vaccine design and therapeutic strategies aimed at eliciting robust HA-specific B-cell responses, while minimizing adverse effects caused by natural infection.},
}

@article {pmid41802602,
year = {2026},
author = {Treister, NS and Liang, L and Lee, SJ and Cutler, C and Gooley, TA and Hujoel, P and Gbujie, D and Oh, UY and Bennett-Johnson, L and Hagstrom, MK and Rothen, M and Lloid, M and Dean, D and Sroussi, H},
title = {Tooth loss and oral health-related quality of life in a sub-cohort within the Chronic Graft-versus-Host Disease Consortium.},
journal = {Transplantation and cellular therapy},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jtct.2026.03.004},
pmid = {41802602},
issn = {2666-6367},
abstract = {BACKGROUND: Chronic graft-versus-host-disease (cGVHD) is a major complication of allogeneic hematopoietic cell transplantation (alloHCT) that frequently affects the oral cavity with manifestations of oral mucosal inflammation, salivary gland hypofunction, and trismus. However, the long-term consequences of oral cGVHD on oral health outcomes are not defined.

OBJECTIVE: This report assesses long-term tooth loss and oral health-related quality of life (OHRQL) measures in patients who have received alloHCT.

STUDY DESIGN: Participants were evaluated at an initial post-transplant dental visit which consisted of dental and periodontal examination, oral mucosal examination, and panoramic radiographs. The National Institutes of Health (NIH) Modified Oral Mucosa Rating Scale (OMRS) and World Health Organization (WHO) Oral Health Assessment for Adults were used for diagnosis and grading of oral cGVHD and dental status. Pre-transplant dental records were available and utilized to calculate tooth loss data. Participants also completed the Oral Health Impact Profile-14 (OHIP-14) questionnaire, the NIH mouth sensitivity score, the Lee Symptom Scale (oral cavity items), and the shortened summated Xerostomia Inventory (XI).

RESULTS: This study enrolled 70 participants at a median of 8.8 years after alloHCT (range 6.7-11.8 years); 19 (27.1%) had no past oral cGVHD, 22 (31.4%) had past but no current oral cGVHD, and 29 (41.4%) had current oral cGVHD. Patients with current oral cGVHD had a mean tooth loss of 2.3, patients with past but no current oral cGVHD had a mean tooth loss of 1.0, and patients with no past oral cGVHD had a mean tooth loss of 2.1 (p=0.54, ANOVA). The mean overall OHIP-14 scores for the current, past but no current, and no past oral cGVHD groups were 13.6, 6.3, and 6.3, respectively (p=0.02, ANOVA). Oral cGVHD significantly impacted various aspects related to eating and meal choices.

CONCLUSIONS: The rate of tooth loss was not definitively different based on past/current oral cGVHD status. Further efforts at mitigating the adverse impacts of oral cGVHD on nutrition and oral-health-related quality of life has the potential to improve the lives of alloHCT recipients.},
}

@article {pmid41802242,
year = {2026},
author = {Hurvitz, SA and Layman, RM and Curigliano, G and André, F and Cristofanilli, M and Kim, SB and Martínez Rodríguez, JL and Nadal, JC and Kim, GM and Lo, L and Remolina-Bonilla, YA and Rosselli, G and Emile, G and Korbenfeld, E and Puig, JM and Wesolowski, R and Martin, M and Ring, A and Han, HS and Giordano, A and Mutka, SC and Moss, K and Suzuki, S and Sullivan, B and Gorbatchevsky, I and Pistilli, B and , },
title = {VIKTORIA-1 Trial of Gedatolisib Plus Fulvestrant With or Without Palbociclib in Hormone Receptor-Positive/HER2-/PIK3CA Wild-Type Advanced Breast Cancer.},
journal = {Journal of clinical oncology : official journal of the American Society of Clinical Oncology},
volume = {},
number = {},
pages = {JCO2502643},
doi = {10.1200/JCO-25-02643},
pmid = {41802242},
issn = {1527-7755},
abstract = {PURPOSE: Gedatolisib potently targets all four class I PI3K isoforms and mTORC1 and mTORC2 to comprehensively block the PI3K/AKT/mTOR pathway and has shown compelling activity in early clinical trials with palbociclib and fulvestrant.

METHODS: This phase III randomized trial (VIKTORIA-1; ClinicalTrials.gov identifier: NCT05501886) evaluated the efficacy of gedatolisib-based therapy, comparing gedatolisib, palbociclib, and fulvestrant (gedatolisib triplet) and gedatolisib plus fulvestrant (gedatolisib doublet) with fulvestrant monotherapy in patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative (HER2-), PIK3CA wild-type (WT) advanced breast cancer. Eligible patients had disease progression during or after CDK4/6 inhibitor and aromatase inhibitor treatment. Comparison of progression-free survival as assessed by blinded independent central review for gedatolisib triplet versus fulvestrant and gedatolisib doublet versus fulvestrant was the primary objective.

RESULTS: A total of 392 patients were randomly assigned 1:1:1. The median study follow-up was 10.1 months. The median progression-free survival was 9.3 months in the gedatolisib-triplet group, 2.0 months in the fulvestrant group (hazard ratio [HR] for progression or death, 0.24 [95% CI, 0.17 to 0.35]; P < .001), and 7.4 months in the gedatolisib-doublet group (HR, 0.33 [95% CI, 0.24 to 0.48]; P < .001 v fulvestrant). Grade ≥3 treatment-related adverse events (TRAEs) reported in the gedatolisib-triplet and gedatolisib-doublet groups, respectively, included neutropenia (62.3%, 0.8%), stomatitis (19.2%, 12.3%), rash (4.6%, 5.4%), hyperglycemia (2.3%, 2.3%), and diarrhea (1.5%, 0.8%). Study treatment discontinuation because of TRAEs was reported in 2.3% (triplet) and 3.1% (doublet) of patients.

CONCLUSION: The addition of gedatolisib to fulvestrant, with or without palbociclib, significantly reduced the risk of disease progression or death in patients with hormone receptor-positive/HER2-, PIK3CA WT advanced breast cancer.},
}

@article {pmid41802176,
year = {2026},
author = {Mukasa, D and Kinuthia, J and Meisner, A and Matemo, D and Schaafsma, T and Morton, J and Wandera, C and Budiawan, E and Kemuto, V and Irine, C and Odhiambo, S and Bii, M and Oduor, B and Achieng, E and Oyombra, T and Ukah, UV and Mugwanya, KK and , },
title = {Oral preexposure prophylaxis use and the risk of bacterial sexually transmitted infections and HIV among African women: A prospective observational cohort study.},
journal = {PLoS medicine},
volume = {23},
number = {3},
pages = {e1004962},
doi = {10.1371/journal.pmed.1004962},
pmid = {41802176},
issn = {1549-1676},
abstract = {BACKGROUND: Oral preexposure prophylaxis (PrEP) effectively reduces HIV incidence when used with sufficient adherence, but does not protect against bacterial sexually transmitted infections (STIs). Several studies have documented high rates of bacterial STIs among individuals initiating and using PrEP. We evaluated the association between PrEP use and the risk of STI among African women accessing family planning clinics.

METHODS AND FINDINGS: We conducted a prospective cohort study nested within a large pragmatic stepped-wedge cluster randomized trial of PrEP delivery in Kenyan family planning clinics, with participant enrollment from June 18, 2021, to May 18, 2023, and follow-up through February 02, 2024 (ClinicalTrials.gov: NCT04666792). The study population included sexually active HIV-negative women aged ≥15 years at elevated HIV risk per Kenyan PrEP guidelines. Participants were offered standard-of-care oral PrEP with the option to decline and followed quarterly for 12 months with assessments of HIV status, sexual behavior, and PrEP use. Urine samples were batch tested for Neissseria gonorrhoeae and Chlamydia trachomatis using the GeneXpert CT/NG real-time polymerase chain reaction nucleic acid amplification test assay. The primary exposure was self-reported PrEP initiation and PrEP use consistency through 6 months, categorized as never used PrEP, inconsistently on PrEP, or consistently on PrEP. Multivariable modified Poisson generalized estimating equation (GEE) models with robust standard errors were used to estimate associations between PrEP use and incident STI; clinic-level intracluster correlation coefficients were negligible. The secondary outcomes were incident HIV infection and sexual behaviors, which included condomless sex at last sex, sex with any new partners in the past 3 months, and multiple sex partners. HIV testing was performed at each scheduled visit, at enrollment, and 1, 3, 6, 9, and 12 months following the Kenya national HIV testing algorithm, using Determine HIV-1/2 and Fast Response test kits. All models for the primary outcome were adjusted for baseline covariates determined apriori as potential confounders, which included age, STI diagnosis at enrollment, any contraceptive use, number of sexual partners (categorized as any more than one sexual partner), education status, marital status, last partner HIV status, any transactional sex in 3 months pre-enrollment, and clinic site. Among 650 women enrolled, 60.0% (389) initiated PrEP at baseline and 14.6% (38/261) initiated post-enrollment. Median age was 26 years (IQR 23-30), 40% (262/650) were aged ≤24 years, and 67% (436/648) did not know their primary partner's HIV status. At baseline, 11% (74/650) had an STI, including 9.9% (23/232) of consistent PrEP users, 9.2% (13/141) of inconsistent users, and 14.0% (38/277) of women who declined PrEP. During follow-up, 19.1% (114/597) had at least one STI diagnosis, with similar risk among women who initiated PrEP at baseline compared with those who declined (19.2% [68/354] versus 18.9% [46/244]; aRR 1.11, 95% CI 0.76-1.61; p = 0.580). Compared with non-PrEP users (12.7% [25/195]), STI risk was 6.0% (12/200) among consistent PrEP users (aRR 0.56, 95% CI 0.27-1.19; p = 0.130) and 16.5% (17/103) among inconsistent users (aRR 1.43, 95% CI 0.73-2.77; p = 0.290). Chlamydia accounted for 87.7% (100/114) of STI diagnoses. STI risk was higher among women aged ≤24 years (aRR 1.47, 95% CI 1.04-2.07; p = 0.029) and those with a baseline STI (aRR 2.96, 95% CI 2.12-4.14; p < 0.001). Four HIV infections occurred over 594 person-years (incidence 0.67, 95% CI 0.18-1.72 per 100 person-years), including three among women who declined PrEP (incidence 1.25, 95% CI 0.26-3.66 per 100 person-years). The main study limitation was oral PrEP use was assessed based on client self-report and not objectively through drug levels testing.

CONCLUSIONS: In this prospective cohort study among African women at elevated risk for HIV, 60% initiated PrEP at baseline and 14.6% (38/261) post-enrollment. PrEP use was not associated with increased risk for STI diagnosis through one year of follow-up. HIV incidence was low overall, consistent with expanded PrEP availability in similar populations.},
}

@article {pmid41798119,
year = {2026},
author = {Ronsley, R and Choe, M and Wright, J and Seidel, K and Lee, A and Wendler, J and Annesley, C and Jensen, MC and Park, JR and Vitanza, NA and Gust, J},
title = {Tumor inflammation-associated neurotoxicity in children with diffuse intrinsic pontine glioma receiving B7-H3-targeting CAR T cells on BrainChild-03.},
journal = {Neuro-oncology practice},
volume = {13},
number = {1},
pages = {105-111},
pmid = {41798119},
issn = {2054-2577},
support = {R37 CA289981/CA/NCI NIH HHS/United States ; },
abstract = {BACKGROUND: Chimeric antigen receptor (CAR) T cell therapy is a promising treatment for central nervous system (CNS) tumors like diffuse intrinsic pontine glioma (DIPG) and diffuse midline glioma (DMG). Unlike systemic administration, locoregional CAR T therapy may result in tumor inflammation-associated neurotoxicity (TIAN), which was recently defined. This study retrospectively applies TIAN criteria to patients with DIPG/pontine DMG treated with intraventricular B7-H3 CAR T cells in the BrainChild-03 (BC-03) trial (NCT04185038).

METHODS: A retrospective analysis of DIPG/pontine DMG patients treated with locoregional B7-H3 CAR T cells in BC-03 was conducted. Neurological symptoms, headache, fever, hydrocephalus, and inflammatory markers were extracted from case reports and medical records. TIAN was classified as type 1 (mechanical damage) or type 2 (electrophysiologic dysfunction), and symptom patterns, resolution, imaging findings, and management were analyzed.

RESULTS: Among 21 patients (ages 2-22) receiving ≥1 infusion, 16 (76%) met TIAN criteria at least once. TIAN occurred in 49 of 152 infusions (32%), mostly grade 1 (n = 34) or grade 2 (n = 14), with one grade 3 event. Common symptoms included headache with fever (51%) and neurologic changes with headache (31%). In most patients, Type 1 vs Type 2 TIAN could not be defined; however, 1 patient required CSF diversion (type 1 TIAN), and 13 had worsening preexisting deficits (type 2). Median symptom resolution was <24 h (range: 0-33).

CONCLUSIONS: TIAN was common within this cohort but mostly low-grade and transient. Refining its classification and understanding its clinical impact will aid safety assessments and trial comparisons for CNS-directed CAR T therapies.},
}

@article {pmid41797392,
year = {2026},
author = {Vega, P and Bhattacharyya, P and Lieberman, JA and Kuczmarski, TM and Yoke, LH and So, LM and Smith, HZ and Lengermann, R and Cohen, S and Fredricks, DN and Pergam, SA},
title = {Fusariosis in Patients With Hematologic Malignancies in the Era of Antifungal Prophylaxis.},
journal = {Transplant infectious disease : an official journal of the Transplantation Society},
volume = {},
number = {},
pages = {e70203},
doi = {10.1111/tid.70203},
pmid = {41797392},
issn = {1399-3062},
support = {T32AI118690//National Institute of Allergy and Infectious Diseases of the National Institutes of Health/ ; P30-CA015704//National Cancer Institute Cancer Center/ ; },
abstract = {BACKGROUND: Invasive fusariosis (IF) is an uncommon but frequently fatal infection among patients with hematologic malignancies (HM). Despite widespread mould-active prophylaxis, breakthrough infections and treatment failures may occur. We aim to describe the clinical epidemiology, diagnostic approaches, antifungal management strategies, and outcomes of IF in the era of routine antifungal prophylaxis.

METHODS: We conducted a retrospective study of all cancer patients diagnosed with IF at a tertiary cancer center that met probable/proven criteria for IF from 2015 to 2024. We collected data on demographics, oncologic history, diagnostics, therapy, and outcomes.

RESULTS: Twenty-two patients met criteria for proven IF. Most had acute myeloid leukemia (73%), and many underwent prior hematopoietic cell transplant (36%); nearly all were neutropenic (96%, median:48 days). Skin was the most common clinical site of infection (68%), followed by sino-pulmonary involvement (41%); fungemia occurred in 32%. Fever (77%) and skin nodules (64%) were frequent, while serum galactomannan was uniformly negative. Most common species complex was Fusarium fujikuroi. In our cohort, 82% occurred during antifungal prophylaxis, most often posaconazole. Minimum inhibitory concentrations were high for azoles and lower for amphotericin B and terbinafine. Antifungal regimens ranged from monotherapy to triple therapy. Overall mortality was 68%, of which 45% of deaths were attributed to IF. Mortality did not differ by antifungal regimen, species complexes, or presence of fungemia.

CONCLUSIONS: IF remains a life-threatening infection in patients with HM, often presenting as disseminated disease, despite prophylaxis. High azole MICs and the observed diversity of antifungal regimens highlight the ongoing uncertainty regarding optimal treatment and the need for prospective studies to define the role of combination therapy.},
}

@article {pmid41796432,
year = {2026},
author = {Lam, BD and Ryu, J and Jafari, O and Kim, RB and Ma, S and Ranjan, M and Jiang, JY and Li, A},
title = {Epidemiology of Cancer-Associated Venous Thromboembolism Across the United States.},
journal = {American journal of hematology},
volume = {},
number = {},
pages = {},
doi = {10.1002/ajh.70271},
pmid = {41796432},
issn = {1096-8652},
abstract = {Prior epidemiological studies on cancer-associated venous thromboembolism (VTE) were limited by homogenous patient populations. We leverage Cosmos, a collaborative dataset of Epic electronic health record systems, to conduct an updated evaluation of cancer-associated VTE in the United States (US). Cosmos includes patients from all 50 states, and the dataset is representative of the US census in terms of age, race, ethnicity, and insurance coverage. We included patients in the US with a new cancer diagnosis between 2018 and 2023. We computed the cumulative incidence of VTE at 6 and 12 months after the diagnosis date and used Cox regression to identify risk factors and examine the association between VTE type within the first year and mortality. We identified 1 628 626 patients, with a cumulative incidence of VTE at 6 months of 2.7% and at 12 months of 3.7%. Major risk factors included prior VTE, cancer type, advanced stage, and chemotherapy-based treatment regimens. The occurrence of VTE within the first year of cancer diagnosis was independently associated with increased mortality.},
}

@article {pmid41796372,
year = {2026},
author = {Zhang, X and Pan, L and Zhao, Y and Ma, R and Zhang, L and Zhang, Y and Li, G and Zhai, W and Ma, Q and Pang, A and Yang, D and Feng, S and Zhang, P and He, Y and Qin, G and Jiang, E and Han, M},
title = {Efficacy and safety of ruxolitinib for graft-versus-host disease prophylaxis in patients with aplastic anemia undergoing PBSC-only allogeneic stem cell transplantation: a prospective phase II study.},
journal = {Experimental hematology & oncology},
volume = {15},
number = {1},
pages = {},
pmid = {41796372},
issn = {2162-3619},
support = {3332021055//Fundamental Research Funds for the Central Universities/ ; 82100225//National Natural Science Foundation of China/ ; 82070192//National Natural Science Foundation of China/ ; 2023ZD0502400//Noncommunicable Chronic Diseases-National Science and Technology Major Project/ ; 2023YFC2508900//National Key R&D Program of China/ ; 2023-I2M-2-007//CAMS Innovation Fund for Medical Sciences/ ; 23JCZXJC00220//Tianjin Natural Science Foundation/ ; },
abstract = {BACKGROUND: While peripheral blood hematopoietic stem cell transplantation (PB-HSCT) supports rapid engraftment and reduces graft failure risk in aplastic anemia (AA) patients, it compromised higher risk of acute graft-versus-host disease (aGVHD), highlighting the need for more effective prophylactic strategies. This phase II clinical trial was designed to assess the efficacy and safety of ruxolitinib, a JAK1/2 inhibitor, as part of GVHD prophylaxis regimen following PB-HSCT.

METHODS: This open-label, single-arm, Phase II clinical trial (ClinicalTrials.gov: NCT05914714) enrolled patients with AA between June 2023 and December 2024. Ruxolitinib was initiated at the start of conditioning and continued for 3 months post-transplant at a dose of 5 mg twice daily. A historical control cohort receiving standard GVHD prophylaxis between January 2019 and May 2023 was included for comparison. To address baseline imbalances, propensity score-based inverse probability of treatment weighting (IPTW) was applied. The primary objective was the incidence of aGVHD six months after HSCT. Secondary endpoints included one-year overall survival (OS) and GVHD-free, failure-free survival (GFFS). Immune reconstitution-including T cells, B cells, NK cells-and levels of pro-inflammatory cytokines were also evaluated to explore potential mechanisms.

RESULTS: A total of 82 patients were enrolled (ruxolitinib group n = 46, historical control cohort n = 36). Comparative analysis showed that ruxolitinib significantly reduced the cumulative incidence of grade II-IV aGVHD (HR 0.24; p = 0.004) and severe aGVHD (0% vs 15.8%; p = 0.008) compared with the control group. At a median follow-up of 417 days (range: 112-725), the ruxolitinib group demonstrated significantly superior 1-year GFFS (91.6% vs. 72.1%; HR 0.23, weighted log-rank p = 0.012). Notably, the ruxolitinib group not only exhibited more rapid recovery of CD4 + Tregs at 3 months post-HSCT. Notably, but also suppressed proinflammatory cytokine levels during engraftment.

CONCLUSIONS: The peri-transplantation addition of ruxolitinib to the standard GVHD prophylaxis regimen in PB-HSCT for AA patients has shown to be a safe and effective approach to reducing both the incidence of aGVHD, while improving patient outcomes. Our study suggests that ruxolitinib may offer a promising strategy for improving survival and immune recovery. Trial registration clinicaltrials.gov identifier: NCT05914714.},
}

@article {pmid41795834,
year = {2026},
author = {Kang, DW and Courneya, KS and Swartz, MC and Maleki Vareki, S and Gordon, NB and Cesar Rosa Neto, J and Simpson, RJ and Baker, KS and Schadler, KL and Lavoy, EC},
title = {Chronic exercise training intensity, immune cells, and cancer outcomes: a scoping review.},
journal = {JNCI cancer spectrum},
volume = {},
number = {},
pages = {},
doi = {10.1093/jncics/pkag021},
pmid = {41795834},
issn = {2515-5091},
abstract = {BACKGROUND: Exercise has emerged as a potent, non-pharmacological intervention to enhance immune function in patients with cancer. The effects of exercise are likely influenced by patients' oncologic characteristics, such as cancer treatment, and intervention variables, such as exercise intensity, which can lead to heterogeneous outcomes. This scoping review aims to identify patterns, trends, and gaps in the literature regarding the relationship between chronic exercise training intensity and immune cell parameters in the context of treatment status.

METHODS: Reports were retrieved from PubMed, MEDLINE, and CINAHL. Eligible reports were controlled clinical trials of an exercise training intervention with more than one exercise session, included an objectively defined exercise intensity, and reported cellular immune outcomes.

RESULTS: 21 articles (15 randomized controlled trials) were included. Results suggest a dose-response effect of intensity, where vigorous-intensity exercise (reported in 6 studies) elicited beneficial immunomodulation, such as enhanced natural killer cell cytotoxicity. Light-to-moderate and moderate-intensity exercise (reported in 8 studies) resulted in no significant immunological changes in 5 studies, particularly for patients undergoing active treatment. Comparisons across studies were difficult due to heterogeneity in patients' clinical characteristics, intervention details, and immune parameters. Few reported cancer clinical outcomes such as disease progression, and none directly examined the relationships between immune and clinical endpoints.

CONCLUSIONS: While direct comparisons of exercise intensities are lacking, these results suggest that vigorous exercise training may exert greater immune modulation than low-to-moderate intensity exercise training. Rigorously designed trials are needed to confirm these findings and establish the role of exercise in oncologic care.},
}

@article {pmid41794050,
year = {2027},
author = {Sabo, MC and Shah, JA and Lund, JM and McClelland, RS},
title = {Understanding the cervicovaginal immune response to Lactobacillus crispatus CTV-05.},
journal = {The Lancet. Microbe},
volume = {},
number = {},
pages = {101377},
doi = {10.1016/j.lanmic.2026.101377},
pmid = {41794050},
issn = {2666-5247},
}

@article {pmid41793956,
year = {2026},
author = {Wu, AH and Wu, J and Tseng, C and Darst, BF and Park, SY and Stram, DO and Larson, T and Fruin, S and Setiawan, VW and Yu, X and Wilkens, LR and Hu, H and Haiman, C and Ritz, B and Crimmins, EM and Lim, U and Cheng, I and Marchand, LL},
title = {Racial and ethnic differences in the impact of air pollution on the risk of Alzheimer's disease and related dementias in the Multiethnic Cohort Study.},
journal = {Environment international},
volume = {209},
number = {},
pages = {110169},
doi = {10.1016/j.envint.2026.110169},
pmid = {41793956},
issn = {1873-6750},
abstract = {BACKGROUND AND OBJECTIVES: Meta-analysis results, based largely among Whites, suggested that fine particulate matter (PM2.5) exposure increases the risk of clinical dementia. This study investigated the association of air pollution and incidence of Alzheimer's disease and related dementias (ADRD) by race and ethnicity.

METHODS: We investigated incidence of AD (n = 4,010) and other dementia (n = 4,971) among 44,954 California Multiethnic Cohort (MEC) participants (28% African American, 14% Japanese American, 44% Latino, 14% White adults) who were enrolled in the fee-for-service component of Medicare (2001-2016). We used Cox proportional hazards regression to examine associations between exposure to PM, airport-related ultrafine particles (aUFP) and gaseous pollutants and incidence of AD, other dementia, and ADRD in a minimally- and fully-adjusted model, considering 12 established ADRD risk factors. We conducted stratified analyses to examine associations by sex, and race/ethnicity.

RESULTS: ADRD incidence was associated with PM2.5 (per 2 µg/m[3]), airport-related UFP (aUFP, per 4400 particles/cm[3]) and nitrogen dioxide (NO2, per 10 µg/m[3]) with hazard ratios (HRs, 95%CI), respectively, of 1.04 (1.02-1.06), 1.03 (1.01-1.05) and 1.09 (1.06-1.12). The AD-associations with PM2.5 and NO2, were stronger than the corresponding associations with other dementia (Pheterogeneity ≤ 0.003). Similar patterns of results were observed by sex and across race and ethnicity. Statistically significant findings for ADRD with PM2.5, aUFP and NO2 were observed among African American (respective HRs 1.03, 1.04, 1.09), and Latino and White participants for NO2 (HR 1.10, 1.08). Results in all and African American participants remained statistically significant in fully-adjusted models. Although the effect of PM2.5 was diluted in a co-pollutant with NO2, both PM2.5 and aUFP were significantly associated with ADRD incidence in a co-pollutant model, and NO2 and aUFP (but not PM2.5) remained associated in a multipollutant model. We did not observe consistent modifying effects for any of the 12 established ADRD risk factors.

CONCLUSIONS: In this multiethnic population, incidence of ADRD increased with exposures to PM2.5, aUFP, and NO2 in all subjects and this pattern was most prominent among African American adults. These results emphasize that ADRD prevention should include not only individual-level factors but also population-wide policies and regulation to curb air pollution.},
}

@article {pmid41793312,
year = {2026},
author = {Arthur, KC and Wilson, KB and Berry, B and Binion, B and Becker, M and Derus, A and Diop, SL and Gachuiri, M and Green, BB and Koné, A and Licitra, J and Liou, C and McCracken, CE and Nisotel, LE and Owens, SE and Piccorelli, AV and Ramsey, S and Schwartz, LB and Senturia, K and Svoboda, J and Volney, J and Williamson, BD and Hsu, C},
title = {Codesigning COVID-19 booster promotion materials in online workshops with long-term care staff: a process evaluation.},
journal = {Health education research},
volume = {41},
number = {2},
pages = {},
doi = {10.1093/her/cyag004},
pmid = {41793312},
issn = {1465-3648},
support = {COVID-2021C2-13168/PCORI/Patient-Centered Outcomes Research Institute/United States ; },
mesh = {Humans ; *COVID-19/prevention & control ; Female ; Male ; SARS-CoV-2 ; *COVID-19 Vaccines/administration & dosage ; United States ; *Long-Term Care ; *Health Promotion/methods ; Middle Aged ; Adult ; *Health Personnel/education ; *Immunization, Secondary ; Focus Groups ; },
abstract = {When engaging communities in vaccine promotion efforts, it is critical to understand who has availability and interest in participating, and how participants experience the process. Guided by the Reach, Effectiveness, Adoption, Implementation, Maintenance framework, we evaluated an online codesign process with long-term care center staff to design coronavirus disease (COVID-19) booster promotion materials for their colleagues. Twenty-six staff joined codesign teams organized by self-identified race to culturally tailor materials during a cluster-randomized controlled trial with 40 centers in two US states. Data sources included surveys; interviews; screening, enrollment, and attendance data; fidelity assessment; codesigned materials; and focus groups. We report summary statistics and thematic analyses. We found that time constraints could impede enrollment. Most codesigners enjoyed collaborating and identified their individual contributions. Many linked having shared characteristics with their teammates (e.g. race, gender, age) to a feeling of connection. A few reported feeling motivated to engage in booster promotion. The process resulted in messages aligned with known psychological antecedents of vaccination. Considering recruitment challenges and limited participation of direct care staff, organizers should consider shorter codesign processes. Organizing teams based on shared characteristics could promote comfort. Community input should inform codesign structure and team composition to achieve optimum enrollment and engagement.},
}

Humans
*COVID-19/prevention & control
Female
Male
SARS-CoV-2
*COVID-19 Vaccines/administration & dosage
United States
*Long-Term Care
*Health Promotion/methods
Middle Aged
Adult
*Health Personnel/education
*Immunization, Secondary
Focus Groups

@article {pmid41792766,
year = {2026},
author = {Bouka, M and Nimptsch, K and Pham, TT and Bouras, E and Kanellopoulou, A and Phipps, AI and Van Guelpen, B and Brenner, H and Li, L and Le Marchand, L and Tsilidis, KK and Pischon, T},
title = {Associations of genetically predicted interleukin-6 and tumor necrosis factor signaling pathways with mortality among persons with colorectal cancer: a two-sample Mendelian randomization.},
journal = {BMC medicine},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12916-026-04736-9},
pmid = {41792766},
issn = {1741-7015},
abstract = {BACKGROUND: Despite significant progress in identifying risk factors for colorectal cancer (CRC), factors influencing survival in people with CRC remain less understood. Pro-inflammatory cytokines like interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) have been implicated in cancer progression and may influence CRC outcomes. We investigated associations between genetically predicted levels of IL-6 and TNF-α signaling pathways and mortality in people with CRC.

METHODS: We conducted a two-sample Mendelian randomization (MR) analysis using cis-acting single nucleotide polymorphisms (SNPs) associated with soluble IL-6 receptor alpha (sIL6-RA) and IL-6 signal transducer gp130 (IL6ST), representing IL-6 signaling, and with TNF-α, and its soluble receptors (sTNF-R1, sTNF-R2). SNPs were obtained separately from two large genome-wide association studies (GWAS): deCODE and UK Biobank (UKB). The outcome was CRC-specific mortality among 16,964 CRC cases (4010 deaths) in the Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO). Analyses were stratified by tumor site and stage. The inverse variance weighted (IVW) method, incorporating a correlation matrix for dependent SNPs, was used for primary analyses. Because literature links TNF-α to CRC incidence, we additionally performed a simulation study to evaluate the potential impact of collider bias resulting from restricting analyses to CRC cases.

RESULTS: Genetically predicted sIL6-RA was weakly positively associated with CRC-specific mortality (deCODE-SNPs (n = 13) HR per 1 SD increase: 1.06; 95% CI: 1.00-1.12; UKB-SNPs (n = 11) HR: 1.09; 95% CI: 1.02-1.17). Genetically proxied IL6ST levels showed no association with CRC-specific mortality in the overall sample (deCODE-SNPs (n = 19) HR: 1.04; 95% CI: 0.90-1.21; UKB-SNPs (n = 9) HR: 1.11; 95% CI: 0.87-2.42), while higher IL6ST levels were associated with increased mortality among patients with stage 2/3 disease (deCODE-SNPs (n = 19) HR: 1.45; 95% CI: 1.10-1.91; UKB-SNPs (n = 9) HR: 1.87; 95% CI: 1.22-2.89). No associations were observed for TNF-α, sTNF-R1, or sTNF-R2. Findings for all exposures were consistent across both GWAS datasets. Simulation analyses for TNF-α indicated collider bias was present but limited in magnitude.

CONCLUSIONS: Our findings suggest that IL-6 signaling may play a role in CRC progression although of limited magnitude, whereas TNF-related pathways appear less relevant for prognosis.},
}

@article {pmid41792585,
year = {2026},
author = {Lee, HH and Avery, CL and Graff, M and Kim, D and Arias, J and Van Horn, L and Kooperberg, C and North, KE},
title = {Impact of Genetic Predisposition to Obesity on Long-Term Maintenance of Modest Weight Loss in Postmenopausal Women.},
journal = {Obesity (Silver Spring, Md.)},
volume = {},
number = {},
pages = {},
doi = {10.1002/oby.70175},
pmid = {41792585},
issn = {1930-739X},
support = {75N92021D00001/HL/NHLBI NIH HHS/United States ; 75N92021D00002/HL/NHLBI NIH HHS/United States ; 75N92021D00003/WH/WHI NIH HHS/United States ; 75N92021D000//National Heart, Lung, and Blood Institute, National Institutes/ ; T32HL129982//National Heart, Lung, and Blood Institute, National Institutes/ ; /NH/NIH HHS/United States ; //U.S. Department of Health and Human Services/ ; /NH/NIH HHS/United States ; //U.S. Department of Health and Human Services/ ; //Intramural Research Program/ ; /CP/NCI NIH HHS/United States ; /CA/NCI NIH HHS/United States ; /NH/NIH HHS/United States ; },
abstract = {OBJECTIVE: Long-term weight regain limits the population-level benefits of obesity interventions. We tested whether the polygenic risk score of BMI (PRSBMI) modifies weight trajectories following modest weight loss.

METHODS: The analytic sample included 9897 postmenopausal women from the Women's Health Initiative Dietary Modification Trial (6132 European American; 3749 African American). PRSBMI was derived from a trans-ancestry GWAS of ~2 million participants. Longitudinal weight change (7 years) was modeled using weighted GEE.

RESULTS: In European Americans, the PRSBMI × randomization × time interactions approached significance at the 95th percentile (p = 0.052) and 85th percentile (p = 0.07). No interaction was observed in African Americans. In analyses restricted to European Americans who lost ≥ 5% of initial weight by year 1 (20%; n = 1273), women in the ≥ 95th percentile of PRSBMI regained nearly twice as much per year as those with average risk (0.94 vs. 0.48 kg/year, p = 0.0016).

CONCLUSIONS: A high PRSBMI was associated with faster weight regain following modest weight loss in European American women. While further validation is required in a diverse population, these results suggest the potential for genetics to inform targeted strategies for sustaining long-term weight management.

TRIAL REGISTRATION: ClinicalTrials.gov identifier: 75N92021D00001, 75N92021D00002, 75N92021D00003, 75N92021D00004, and 75N92021D00005.},
}

@article {pmid41792574,
year = {2026},
author = {Azhideh, A and Haseli, S and Park, C and Lee, H and Kim, HS and Mirghaderi, P and Chalian, M},
title = {Comparative analysis of RADS classification systems for solitary bone lesions: malignancy risk stratification performance and clinical utility.},
journal = {European radiology},
volume = {},
number = {},
pages = {},
pmid = {41792574},
issn = {1432-1084},
abstract = {OBJECTIVE: To compare the malignancy risk stratification performance and inter-reader reliability of four Reporting and Data System (RADS) algorithms for solitary bone lesions: CT Bone-RADS, MRI Bone-RADS, Osseous Tumor (OT)-RADS, and Bone Tumor Imaging (BTI)-RADS.

MATERIALS AND METHODS: This retrospective analysis included patients with solitary bone lesions who underwent both CT and MRI between March 2005 and September 2021. Three radiologists independently categorized each lesion using CT Bone-RADS (1-4), MRI Bone-RADS (1-4), OT-RADS (2-5), and BTI-RADS (1-4). Categories were dichotomized into high- versus low-risk for malignancy. Diagnostic performance metrics and area under the receiver operating characteristic curve (AUC) were calculated for each reader as well as for a consensus interpretation generated using a majority-vote method. The reference standard was either histopathologic confirmation or imaging surveillance. Inter-reader reliability was assessed using Gwet's AC1 statistic.

RESULTS: A total of 207 patients (mean age, 49 ± 18 years; 111 men and 96 women) were included. Consensus malignancy risk stratification performance (AUC; sensitivity/specificity/positive predictive value/negative predictive value/accuracy, %) was as follows: CT Bone-RADS (0.52; 95/9/43/73/44), MRI Bone-RADS (0.60; 98/12/44/88/47), OT-RADS (0.91; 93/71/69/94/80), and BTI-RADS (0.89; 98/39/53/96/63). Inter-reader reliability (AC1) was excellent for CT Bone-RADS (0.978), MRI Bone-RADS (0.931), and BTI-RADS (0.822), and moderate for OT-RADS (0.585).

CONCLUSION: Among the evaluated bone tumor-RADS, OT-RADS demonstrated the most balanced diagnostic performance with moderate inter-reader reliability. CT Bone-RADS, MRI Bone-RADS, and BTI-RADS showed excellent inter-reader reliability.

KEY POINTS: Question Evaluation of solitary bone lesions is important but often challenging. This study compared four bone tumor-RADS algorithms to determine which provides the best malignancy risk stratification. Findings Among the four RADS algorithms, OT-RADS demonstrated the most balanced overall diagnostic performance in consensus analysis, while CT Bone-RADS, MRI Bone-RADS, and BTI-RADS showed excellent inter-reader reliability. Clinical relevance Knowledge of each RADS system's performance characteristics helps clinicians apply these algorithms appropriately to optimize the assessment of solitary bone lesions.},
}

@article {pmid41791419,
year = {2026},
author = {Schiffer, JT and Esmaeili, S and Owens, K and Boeckh, M and Waghmare, A},
title = {Is it "time to eliminate" time to elimination of symptoms as a primary trial endpoint for respiratory virus targeting drugs?.},
journal = {The Journal of infectious diseases},
volume = {},
number = {},
pages = {},
doi = {10.1093/infdis/jiag148},
pmid = {41791419},
issn = {1537-6613},
}

@article {pmid41757210,
year = {2026},
author = {Liu, J and Gang, S and Kikawa, C and Rodriguez, AJ and Li, SH and Ye, N and Griffiths, T and Drapeau, EM and Atkinson, RK and Loes, AN and Collman, RG and Ferguson, JA and Han, J and Ward, AB and Bloom, JD and Hensley, SE},
title = {Mapping the specificity of H3N2 strain-specific and cross-reactive human neutralizing antibodies elicited by the 2025-2026 influenza vaccine.},
journal = {medRxiv : the preprint server for health sciences},
volume = {},
number = {},
pages = {},
pmid = {41757210},
abstract = {An H3N2 variant, named subclade K, continues to circulate widely during the 2025-2026 influenza season. This virus possesses a hemagglutinin (HA) protein that has eleven substitutions relative to the HA of the Northern Hemisphere 2025-2026 H3N2 vaccine strain. Many of these substitutions are in epitopes in well-characterized HA antigenic sites. Despite this, interim vaccine effectiveness studies indicate that the 2025-2026 influenza vaccine provides moderate protection against H3N2 subclade K infection. We previously reported that many individuals who received the 2025-2026 influenza vaccine produced antibodies that inhibit H3N2 subclade K virus cellular attachment. Here, we show these individuals also produced antibodies that neutralize H3N2 subclade K virus infection, and we observed a strong correlation between hemagglutination-inhibition titers and neutralizing antibody titers. We completed additional specificity studies using samples from individuals who did or did not have antibodies that cross-reacted to H3N2 subclade K viruses. Using high-throughput neutralization assays, we determined that antibodies that bound to the vaccine strain but not H3N2 subclade K viruses typically targeted antigenic site B of HA. Conversely, we found that cross-reactive neutralizing antibodies elicited by vaccination commonly targeted antigenic site A, D, and E of HA that are conserved between the vaccine strain and H3N2 subclade K viruses. Additional electron microscopy-based polyclonal epitope mapping studies confirmed that cross-reactive antibodies elicited by vaccination typically target epitopes on the side of HA. Together, our studies provide an immunological explanation of why the 2025-2026 influenza vaccine was partially effective against antigenically advance H3N2 subclade K viruses. Our data suggest that vaccine strains for subsequent seasons need to be carefully considered, since subclade K viruses have already started to acquire additional substitutions in HA antigenic sites targeted by cross-reactive antibodies.},
}

@article {pmid41791098,
year = {2026},
author = {Tsai, CS and Lee, H and Szewczyk, W and Palmer, JK and Putnam, S and Munson, SA and Heffner, JL and Vasbinder, A and Paullada, A and Yuwen, W and Reding, KW},
title = {Exploring Feature Priorities and User Needs in Developing Virtual Study Assistants.},
journal = {JMIR formative research},
volume = {10},
number = {},
pages = {e86945},
doi = {10.2196/86945},
pmid = {41791098},
issn = {2561-326X},
mesh = {Humans ; *Artificial Intelligence ; *User-Computer Interface ; *Virtual Reality ; },
abstract = {This formative research explored health science researchers' perspectives on the development of an artificial intelligence-based virtual study assistant and identified 8 potential features and their priorities.},
}

Humans
*Artificial Intelligence
*User-Computer Interface
*Virtual Reality

@article {pmid41790934,
year = {2026},
author = {Snyder, AJ and Garrison, SM and Kluesner, MG and Nutt, WS and Shasha, C and Ho, T and Marsh, SA and Linde, M and Wu, F and Meyer, L and Wilhelm, AR and Ortiz-Espinosa, S and Zepeda, V and Bingham, E and Malik, H and Mak, SR and Gad, E and Bhise, SS and Fan, E and Sarvothama, M and Wang, X and Potluri, S and Long, A and Elz, A and Ghajar, CM and Furlan, SN and Newell, EW and Srivastava, S},
title = {Modulating AP-1 enables CAR T cells to establish an intratumoral stemlike reservoir and overcomes resistance to PD-1 blockade.},
journal = {Science immunology},
volume = {11},
number = {117},
pages = {eadw7685},
doi = {10.1126/sciimmunol.adw7685},
pmid = {41790934},
issn = {2470-9468},
mesh = {Animals ; *Programmed Cell Death 1 Receptor/antagonists & inhibitors/immunology ; Mice ; *Immunotherapy, Adoptive/methods ; *Receptors, Chimeric Antigen/immunology ; *Transcription Factor AP-1/immunology/metabolism ; Humans ; Immune Checkpoint Inhibitors/pharmacology ; *Lung Neoplasms/immunology/therapy ; Drug Resistance, Neoplasm/immunology ; B7-H1 Antigen/immunology/antagonists & inhibitors ; Mice, Inbred C57BL ; Cell Line, Tumor ; },
abstract = {Chimeric antigen receptor T (CAR T) cell therapy has shown limited synergy with immune checkpoint inhibitors, but the mechanisms underlying resistance remain unclear. Stemlike T cells coexpressing programmed cell death protein 1 (PD-1) and T cell factor 1 (TCF1) mediate responses to PD-1-PD-L1 (programmed death ligand 1) blockade and are maintained by major histocompatibility complex (MHC)-dependent interactions with dendritic cells in lymphoid tissues. Because CAR T cells recognize intact antigen rather than peptide-MHC, their activation is restricted to tumors, potentially limiting maintenance of this critical subset. In murine models of lung cancer, CAR T cells down-regulated TCF1, became exhausted, and were not enhanced by PD-L1 blockade. Overexpression of the transcription factor c-Jun increased intratumoral PD-1[+]TCF1[+] CAR T cells but did not prevent exhaustion, given that PD-1 induced posttranscriptional c-Jun down-regulation. PD-L1 blockade restored c-Jun levels, markedly increased CAR T cells, and enabled near-complete tumor clearance, revealing a mechanism by which MHC-independent CAR T cells can be engineered to overcome resistance to PD-1-PD-L1 blockade.},
}

Animals
*Programmed Cell Death 1 Receptor/antagonists & inhibitors/immunology
Mice
*Immunotherapy, Adoptive/methods
*Receptors, Chimeric Antigen/immunology
*Transcription Factor AP-1/immunology/metabolism
Humans
Immune Checkpoint Inhibitors/pharmacology
*Lung Neoplasms/immunology/therapy
Drug Resistance, Neoplasm/immunology
B7-H1 Antigen/immunology/antagonists & inhibitors
Mice, Inbred C57BL
Cell Line, Tumor

@article {pmid41787068,
year = {2026},
author = {Setiawan, T and Muhammad, JA and Julianto, NM and Wirawan, LM and Jun, N and Sari, IN and Oehler, VG and Kim, DW and Kwon, HY},
title = {Correction: Regulation of metabolic adaptation and leukemia progression by MUSASHI2-DEPTOR-KIF11 axis.},
journal = {Leukemia},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41375-026-02909-2},
pmid = {41787068},
issn = {1476-5551},
}

@article {pmid41787039,
year = {2026},
author = {Huang, SH and Seethala, RR and Patel, SG and O'Sullivan, B and Lydiatt, W and Ho, AS and Hosni, A and Vander Poorten, V and Glastonbury, CM and Bishop, J and Beadle, B and Ha, P and Kakarala, K and Rodriguez, CP and Ganly, I},
title = {Key Updates on the Version 9 AJCC/UICC Staging System for Salivary Gland Carcinoma.},
journal = {Annals of surgical oncology},
volume = {},
number = {},
pages = {},
pmid = {41787039},
issn = {1534-4681},
abstract = {BACKGROUND: Multiple studies have identified limitations in the nodal (N) category definitions of the eighth-edition tumor-node-metastasis classifi cation (TNM8) for major salivary gland carcinoma (SGC). Minor SGCs have traditionally been staged according to site of origin despite distinct biology and patterns of spread, and the feasibility of a unified staging system for both major and minor SGCs had not been systematically evaluated. These shortcomings prompted a comprehensive reassessment of SGC staging.

METHOD: A multidisciplinary international expert panel, in collaboration with the American Joint Committee on Cancer (AJCC) Head and Neck Core Group, developed and validated a refined TNM classification for SGC. The proposed system was subsequently adopted by both the AJCC and the Union for International Cancer Control (UICC).

RESULTS: The ninth edition (TNM9) introduces the first unified SGC-specific staging system applicable to both major and minor SGCs. Key revisions include: (1) exclusion of extremely rare or non-salivary-origin histologies (e.g., squamous cell carcinoma, neuroendocrine carcinoma, and basosquamous carcinoma); (2) integration of major and minor SGCs into a single staging framework, with clarification of T3-T4 definitions to ensure applicability across both groups; (3) simplified N categorization based on lymph node count and extranodal extension (ENE): N0 (no nodal disease), N1 (1-3 nodes without ENE), and N2 (3 nodes or any ENE); and (4) restriction of stage IV exclusively to M1 disease, allowing future refinement of metastatic subcategories. Clinical TNM (cTNM) applies the same criteria as pathologic TNM (pTNM), incorporating radiologic assessment of abnormal lymph node count and imaging-detected ENE (iENE).

CONCLUSIONS: By establishing a unified, biologically relevant staging system with improved prognostic discrimination, TNM9 enhances clinical applicability and promotes more consistent management of both major and minor salivary gland carcinomas.},
}

@article {pmid41756883,
year = {2026},
author = {Wirbel, J and Saber, W and Martens, MJ and Peled, JU and Andermann, TM and Fei, T and Brooks, EF and Doyle, B and Pincus, NB and Jenq, RR and Bar, M and Bolaños-Meade, J and Bratrude, B and Chhabra, S and Choi, SW and Clark, W and Das, S and Elmariah, H and Gooptu, M and Holtan, SG and Jones, RJ and Levine, JE and Logan, BR and Al Malki, MM and Murthy, HS and Rashidi, A and Rezvani, AR and Riches, ML and Runaas, L and Sandhu, K and Spahn, A and Sung, AD and van den Brink, MRM and Horowitz, MM and Hamadani, M and Kean, LS and Perales, MA and Bhatt, AS},
title = {Differential effects of two common GVHD prophylaxis regimens on the gut microbiome: Results from the BMT CTN 1801 study.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {41756883},
issn = {2692-8205},
abstract = {Allogeneic hematopoietic cell transplantation (allo-HCT) is a potentially curative treatment for many hematological malignancies, but graft-versus-host disease (GVHD) is a common complication. Low gut microbiome diversity is associated with higher GVHD risk and shorter survival in multiple studies. Recently, the BMT CTN 1703 clinical trial demonstrated superiority of a GVHD-prophylaxis regimen including post-transplant cyclophosphamide (PTCy) compared to the standard prophylaxis (tacrolimus and methotrexate, Tac/MTX) in terms of GVHD-free, relapse-free survival at one year among reduced intensity conditioning allo-HCT recipients. However, the effect of PTCy on the gut microbiome and its association with clinical outcome have not been described. Here, we report on a companion randomized clinical controlled trial (BMT CTN 1801), which collected 2575 longitudinal stool samples from 304 study participants. Samples were obtained up to weekly up to day 84 post allo-HCT and at less frequent intervals thereafter, up to 2 years. Microbiome diversity and absolute microbial load were lower in the PTCy group compared to the Tac/MTX group on days 14-28 post-HCT. However, diversity at the timepoint closest to neutrophil engraftment was not significantly associated with non-relapse mortality after one year or other clinical outcomes, contrary to expectations from previous studies. Microbial domination events, when a single species exceeds 30% relative abundance, were comparable across treatment arms and reflected both pathogen blooms as well as less severe disruptions of the microbial community. Clostridium scindens and secondary bile acid metabolism pathways were less prevalent in the PTCy arm than in the Tac/MTX arm post-HCT, yet presence of secondary bile acid metabolism pathways was associated with a lower risk of chronic GVHD. Given that PTCy was associated with a greater disruption of the microbiome as measured by diversity, absolute microbial abundance, and bile acid metabolism capability, but better clinical outcomes overall, these data suggest that the importance of the microbiome in modulating the host immune systems after allo-HCT is specific to different types of GVHD prophylaxis.},
}

@article {pmid41756882,
year = {2026},
author = {Zambidis, AE and Siddaramaiah, LK and Konecny, AJ and Gray, M and Prlic, M},
title = {CaptureBody - an anti-CD45 × anti-IgG bispecific antibody enables accurate unmixing for spectral flow cytometry.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {41756882},
issn = {2692-8205},
abstract = {Accurate spectral unmixing is a critical step for flow cytometry data analysis and requires a single stain control for every fluorescent parameter used in an experiment. Currently, compensation particles are often used for making single stain controls when a target protein is of low abundance or a cell type is of low frequency. However, compensation particles introduce incongruencies in emission spectra compared to cells resulting in spectral unmixing or compensation errors. To enable the use of cells regardless of the abundance of target proteins or immune cell type, we generated a bispecific antibody that links a human anti-CD45 and mouse anti-IgG variable region. We refer to this new bispecific tool as CaptureBody (CB) and highlight the benefits of its final nanobody-based design. We provide all sequences and methods necessary for the in-house expression of a CaptureBody to disseminate their use for spectral flow cytometry experiments.},
}

@article {pmid41786253,
year = {2026},
author = {Engels, EA and Castenson, D and Luo, Q and Shiels, MS and Israni, A and Li, J and Madeleine, MM and Pawlish, K and Ramirez Aguilar, D and Zeng, Y and Pfieffer, RM},
title = {Population-level cancer trends among solid organ transplant recipients in the United States during 1995-2021.},
journal = {American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.ajt.2026.02.036},
pmid = {41786253},
issn = {1600-6143},
abstract = {Solid organ transplant recipients (SOTRs) experience elevated cancer risk from immunosuppression and underlying medical conditions. Medical management has improved over time, and SOTRs are living longer. We used registry data covering 693,718 SOTRs in the United States (US) to evaluate population-level cancer trends during 1995-2021. Compared with SOTRs in 1995-2003, those in 2013-2021 were living at older ages and were followed at a longer time since their transplant. Based on 65,081 cancers, cancer incidence in SOTRs was higher during 2013-2021 than 1995-2003 (unadjusted incidence rate ratio [IRR] 1.29, 95% confidence interval [95%CI] 1.26-1.32). However, cancer incidence was lower in 2013-2021 after adjustment for age (IRR 0.93, 95%CI 0.91-0.95) and multivariable adjustment (0.93, 0.90-0.96). Results for the six most common cancer types showed varying trends during 1995-2021. Overall cancer incidence was higher in SOTRs than in the US general population during 1995-2021 and, most recently, in 2013-2021 (standardized incidence ratio 1.66, 95%CI 1.64-1.67). In conclusion, after accounting for age, there was an encouraging decline in cancer incidence among US SOTRs during 1995-2021. However, incidence remained elevated compared with the general population in 2013-2021. Measures are needed to reduce the cancer burden as SOTRs live longer after transplantation and the population ages.},
}

@article {pmid41785903,
year = {2026},
author = {Kim, Y and Bates, JE and Yoon, HI and Grassberger, C},
title = {Cardiac radiosensitivity in the era of thoracic chemoradiotherapy and immunotherapy: a scoping review.},
journal = {The Lancet. Oncology},
volume = {27},
number = {3},
pages = {e130-e140},
doi = {10.1016/S1470-2045(25)00651-5},
pmid = {41785903},
issn = {1474-5488},
mesh = {Humans ; *Chemoradiotherapy/adverse effects ; *Immune Checkpoint Inhibitors/adverse effects ; *Cardiotoxicity/etiology ; *Immunotherapy/adverse effects ; *Lung Neoplasms/therapy/pathology ; *Carcinoma, Non-Small-Cell Lung/therapy/pathology ; *Radiation Tolerance/drug effects ; *Heart/radiation effects/drug effects ; *Thoracic Neoplasms/therapy ; Risk Factors ; },
abstract = {Concurrent chemoradiotherapy followed by immune checkpoint inhibitor (ICI) consolidation is now the standard of care for unresectable stage III non-small-cell lung cancer (NSCLC) and is increasingly applied to other thoracic malignancies. Although survival outcomes have improved, concerns about cardiac toxicity have emerged, as both chemoradiotherapy and ICIs are independently cardiotoxic and their combined effects remain unclear. This scoping review first examines chemoradiotherapy-associated and ICI-associated cardiac toxicity separately, and then evaluates their convergence in combined chemoradiotherapy and ICI therapy. For this examination and evaluation, we draw on ten clinical studies, two reviews, and five preclinical reports that together address six key questions: (1) does ICI add cardiac risks to chemoradiotherapy, (2) does previous radiotherapy increase cardiac risks with ICI, (3) does ICI alter the radiosensitivity of cardiac subregions, (4) how should cardiac endpoints be defined, (5) can molecular or pharmacological interventions mitigate toxicity, and (6) what are the major risk factors and management strategies? We also highlight four major gaps: extension beyond NSCLC, long-term survivorship, the potential of advanced radiotherapy techniques, and the interplay between lymphopenia and cardiotoxicity. The convergence of chemoradiotherapy and ICIs represents a new cardiac risk profile. Addressing these questions through larger, long-term studies is essential to balance oncological efficacy with cardiovascular safety.},
}

Humans
*Chemoradiotherapy/adverse effects
*Immune Checkpoint Inhibitors/adverse effects
*Cardiotoxicity/etiology
*Immunotherapy/adverse effects
*Lung Neoplasms/therapy/pathology
*Carcinoma, Non-Small-Cell Lung/therapy/pathology
*Radiation Tolerance/drug effects
*Heart/radiation effects/drug effects
*Thoracic Neoplasms/therapy
Risk Factors

@article {pmid41785446,
year = {2026},
author = {Khor, S and Yu, K and Fedorenko, CR and Ramsey, S and Rivers, Z and Kreizenbeck, K and Khan, HM and Li, L and Kestner, ST and Kwendakwema, CN and Shankaran, V},
title = {Financial Hardship Before Diagnosis: Influence on Late-Stage Cancer Presentation and the Role of Screening.},
journal = {Journal of clinical oncology : official journal of the American Society of Clinical Oncology},
volume = {},
number = {},
pages = {JCO2501360},
doi = {10.1200/JCO-25-01360},
pmid = {41785446},
issn = {1527-7755},
abstract = {PURPOSE: This study investigates the relationship between prediagnosis financial hardship (FH) and cancer stage, and the mediating role of cancer screening in breast cancer.

METHODS: This case-control study used linked, deidentified records from adult cancer patients diagnosed with stage I to IV solid tumors (2014-2017) from the Western Washington SEER registry, along with credit report data from TransUnion and health care claims, encompassing various cancers. FH was defined as at least one record of collections, charge-offs, delinquent mortgage payments, tax liens, foreclosures, repossessions, or bankruptcies within 2 years before diagnosis. We used multivariable log-binomial regression to assess the association between FH and late-stage diagnosis (stages III and IV) overall and by cancer screening category, and mediation analysis to evaluate the role of screening mammography in breast cancer.

RESULTS: Among 50,148 patients with cancer (mean age 64 years, 52% female, 85% non-Hispanic White), 30% experienced FH before diagnosis, which was associated with a 14% higher probability of late-stage diagnosis (adjusted risk ratio [aRR], 1.14 [95% CI, 1.11 to 1.17]). This association was stronger for cancers with organized screening (aRR, 1.25 [95% CI, 1.21 to 1.29]) and those detectable by physical examinations (aRR, 1.44 [95% CI, 1.31 to 1.59]), but not for cancers without these protocols (aRR, 1.00 [95% CI, 0.94 to 1.07]), with variations among individual sites. Among patients with breast cancer, 70% of the increased risk of late-stage diagnosis was attributable to the nonreceipt of screening.

CONCLUSION: FH significantly affects cancer stage at diagnosis, especially for cancers with organized screening and physical examinations. In breast cancer, this association is largely attributed to lack of screening. These findings underscore FH as an important social determinant of health and the need for targeted interventions to improve screening access.},
}

@article {pmid41785374,
year = {2026},
author = {Muffly, LS and Lee, CJ and Gandhi, A and Varma, A and Scott, BL and Patel, SS and Shiraz, P and Youn, M and Yanagiba, C and Arulprakasam, J and Le, A and Kwon, HS and Long-Boyle, JR and Shizuru, JA and Pang, W and Artz, AS},
title = {Nonmyeloablative Conditioning Combined with Anti-CD117 Antibody Briquilimab in Older Adults with High-Risk AML and MDS.},
journal = {Blood},
volume = {},
number = {},
pages = {},
doi = {10.1182/blood.2025031858},
pmid = {41785374},
issn = {1528-0020},
abstract = {Briquilimab is a monoclonal antibody inhibiting stem cell factor (SCF) binding to CD117 (c-Kit). Based on preclinical data demonstrating the antibody clears hematopoietic stem and progenitor cells (HSPC) and myeloid malignant cells, we conducted a phase 1 trial examining briquilimab plus non-myeloablative fludarabine (flu) and total body irradiation (TBI) as conditioning for older adults with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) undergoing matched donor allogeneic hematopoietic cell transplantation (HCT). Briquilimab was infused 10-14 days before transplant day (TD) 0; fludarabine 30mg/m2 and TBI 2-3 Gy were administered on TD -4 to -2 and TD0, respectively. Graft-versus-host disease prophylaxis consisted of tacrolimus, sirolimus, and mycophenolate mofetil. Thirty-two patients enrolled (n=13 AML in complete remission [CR], n=3 AML in relapse, n=16 MDS). Median age was 70 years and most had detectable measurable residual disease at screening. There were no briquilimab infusion reactions, dose limiting toxicities, or primary graft failure events; briquilimab clearance was predictable across patients. Among the AML in CR cohort, 1-year EFS was 69.2% (95% CI, 37.3, 87.2); 1-year OS was 75% (95% CI, 40.8, 91.2). Among the MDS cohort, 1-year EFS was 53.8% (26.8, 74.8); 1-year OS was 76.4% (42.7, 91.8). One of 3 AML patients in relapse experienced a transient response. Marrow samples obtained before and after briquilimab and prior to flu/TBI demonstrated AML/MDS HSPC depletion (mean 62.4±22.7%) with resultant 3-fold increase in serum SCF. In summary, we demonstrate the feasibility, safety, and proof of concept of CD117 targeting with briquilimab as HCT conditioning for AML/MDS. The trial is registered at clinicaltrials.gov; using identifier: NCT04429191.},
}

@article {pmid41785305,
year = {2026},
author = {Yan, Y and Chen, W and Ge, X and Sun, J and Yu, L and Garcia-Mansfield, K and Zhang, X and Yu, Y and Xiong, W and Zou, D and An, G and Jia, Z and Pirrotte, P and Li, JJ and Yu, Z and Hao, M and Qiu, L and Qi, J and Wang, L and Yi, S},
title = {Proteogenomic features define subtypes of mantle cell lymphoma.},
journal = {Blood advances},
volume = {},
number = {},
pages = {},
doi = {10.1182/bloodadvances.2025018701},
pmid = {41785305},
issn = {2473-9537},
abstract = {Mantle cell lymphoma (MCL) is a biologically heterogeneous B-cell malignancy. While genomics and transcriptomics have delineated parts of the MCL disease spectrum, the proteomics remains largely unexplored. Here, we conducted a comprehensive proteogenomic analysis integrating genomics, transcriptomics, and proteomics on peripheral blood samples from 27 MCL patients and 4 healthy donors to investigate the translational and post-translational dimensions of MCL. Our study identified 1,296 downregulated and 468 upregulated proteins in MCL cells. The splicing pathways were significantly upregulated at both the mRNA and protein levels, suggesting a critical role for aberrant RNA splicing in MCL pathogenesis. Integration of proteomic data with genetic aberrations revealed IGHV mutational status and CCND1 mutation are associated with distinctive transcriptomic and proteomic profiles, which correspond to significant differences in clinical outcomes. A multi-omics molecular stratification model incorporating proteomic data showed superior predictive power for patient survival compared to single-omics models (concordance index 0.83 vs. 0.74). This study provides the first comprehensive proteogenomic profile of MCL, offering novel insights into its molecular mechanisms and clinical behavior. The identification of molecular subtypes and prognostic protein signatures underscores the potential of proteomics to guide precision medicine strategies for MCL.},
}

@article {pmid41782488,
year = {2026},
author = {Grint, DJ and White, RG and Churchyard, G and Fiore-Gartland, A and Rangaka, M and Garcia-Basteiro, AL and Cobelens, F},
title = {Imprecision in tuberculosis infection outcomes: implications for non-inferiority vaccine trials.},
journal = {International journal of epidemiology},
volume = {55},
number = {2},
pages = {},
doi = {10.1093/ije/dyag034},
pmid = {41782488},
issn = {1464-3685},
mesh = {Humans ; *Tuberculosis/prevention & control ; *Tuberculosis Vaccines ; Sensitivity and Specificity ; *BCG Vaccine ; *Equivalence Trials as Topic ; Infant ; Computer Simulation ; *Randomized Controlled Trials as Topic ; Biomarkers ; Research Design ; Infant, Newborn ; },
abstract = {BACKGROUND: Randomized trials comparing new vaccines against tuberculosis for use in neonates and infants, for whom Bacille Calmette-Guérin vaccination is established practice, are using tuberculosis infection as the primary endpoint in a non-inferiority design. Markers of tuberculosis infection have imperfect sensitivity and specificity. Flaws in the non-inferiority trial design typically bias towards non-inferiority, which may result in falsely declaring non-inferiority.

METHODS: We conducted a statistical simulation study to assess the impact of imperfect markers of tuberculosis infection on the interpretation of tuberculosis vaccine trials testing a non-inferiority hypothesis of an infection primary outcome in a two-arm randomized comparison. Data were generated in three 2-year cumulative risk of tuberculosis infection scenarios (2%, 5%, and 8%). The specificity of tests of tuberculosis infection was assumed to range from 100% to 85%, while the sensitivity was assumed to range from 100% to 64%. Log-binomial regression was used to estimate the relative risk of tuberculosis infection.

RESULTS: With 100% sensitivity and specificity, type I error and power were both approximately equal to the expected values (2.5% and 80%, respectively) in all three cumulative tuberculosis risk scenarios. With modest deviations from perfect sensitivity and specificity (95% for both), the risk of falsely declaring non-inferiority was 96.8%, 53.2%, and 27.8% in the 2%, 5%, and 8% cumulative tuberculosis risk infection scenarios, respectively.

DISCUSSION: Tuberculosis vaccine non-inferiority trials using an infection primary outcome must be designed and interpreted accounting for the specificity of the tools used to measure infection, otherwise they risk declaring non-inferiority by default.},
}

Humans
*Tuberculosis/prevention & control
*Tuberculosis Vaccines
Sensitivity and Specificity
*BCG Vaccine
*Equivalence Trials as Topic
Infant
Computer Simulation
*Randomized Controlled Trials as Topic
Biomarkers
Research Design
Infant, Newborn

@article {pmid41782345,
year = {2026},
author = {Likasitwatanakul, P and Blinka, SM and Zarka, JG and Gebrael, G and Weg, E and Longoria, O and Moore, JA and Sharp, A and de Bono, J and Sternberg, CN and Agarwal, N and Swami, U and Orme, JJ and Schweizer, MT and Sloan, L and Hwang, JH and Antonarakis, ES},
title = {Molecular Landscape of Prostate Cancers with Clival Metastases.},
journal = {The oncologist},
volume = {},
number = {},
pages = {},
doi = {10.1093/oncolo/oyag074},
pmid = {41782345},
issn = {1549-490X},
abstract = {BACKGROUND: Clival metastases are a rare and clinically aggressive manifestation of advanced prostate cancer, associated with cranial nerve palsy and poor survival. The molecular features of prostate cancers giving rise to clivus metastases remain unknown.

PATIENTS AND METHODS: We performed a multi-center retrospective study across six institutions, identifying prostate cancer patients with radiographically confirmed clival metastases and available next-generation sequencing (NGS) data. Baseline characteristics and clinical outcomes were collected. Genomic alterations from tissue- and/or blood-based assays were aggregated at the patient level and compared with a publicly available metastatic castration-resistant prostate cancer (mCRPC) cohort (SU2C/PCF).

RESULTS: Fifty-nine patients with clival metastases contributed 87 molecular assays. More than half of patients had Gleason grade group 5 cancer and presented with de novo metastatic (M1) disease. The median interval from initial prostate cancer diagnosis to clival metastasis was 71.4 months (95%CI 42.0-101.7), while median overall survival following clival involvement was only 15.3 months (95%CI 6.9-22.8). Compared with the SU2C/PCF mCRPC cohort, clival metastases showed significant enrichment of BRAF and CHEK2 alterations, as well as homologous recombination repair (HRR) with relative depletion of AR-related, PI3K pathway, and G2-M pathway alterations.

CONCLUSION: Prostate cancers giving rise to clival metastases exhibit a distinct molecular profile enriched for DNA damage-repair and RAF kinase alterations, suggesting unique metastatic biology and potential therapeutic vulnerabilities.},
}

@article {pmid41781474,
year = {2026},
author = {Naderi, E and Watt, GP and Knight, JA and Malone, KE and Lynch, CF and John, EM and Shu, X and Nguyen, TL and Oh, JH and Woods, M and Liang, X and Derkach, A and Pike, MC and Bernstein, JL},
title = {Evaluating mammographic density polygenic risk score for contralateral breast cancer risk prediction.},
journal = {Scientific reports},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41598-026-42365-7},
pmid = {41781474},
issn = {2045-2322},
}

@article {pmid41780572,
year = {2026},
author = {DeBerg, HA and Baloh, CH and DeGottardi, Q and Hou, J and Johansson, A and Newell, E and Laidlaw, TM and Sanda, S and Shamji, M and Durham, S and Togias, A and Kwok, WW},
title = {Differential effects of subcutaneous and sublingual immunotherapy on Timothy grass-specific Th2 CD4[+] T cell subsets.},
journal = {The Journal of allergy and clinical immunology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jaci.2026.02.026},
pmid = {41780572},
issn = {1097-6825},
abstract = {BACKGROUND: Allergen-specific CD4[+] T cells are a highly heterogenous population. Depletion of these cells has been proposed as essential to achieve allergen desensitization in allergen immunotherapy.

OBJECTIVE: The overall aim of this study was to characterize the heterogeneity of Timothy grass (Phleum pratense, Phl p) allergen-specific CD4[+] T cells and determine how the frequency and phenotype of these cells change in response to sublingual (SLIT) and subcutaneous immunotherapy (SCIT). Correlations between frequencies of these cells with Total Nasal Symptom Score (TNSS) and grass-specific serum immunoglobulin were also investigated.

METHODS: Mass cytometry with lanthanides-tagged pMHCII multimers and CD154 upregulation assays were used to examine changes in the frequency and phenotype of Phl p-specific CD4[+] T cells in longitudinal peripheral blood mononuclear cell samples from a randomized, double-blind, placebo-controlled trial of SLIT and SCIT. Supervised and unsupervised clustering was used for data analysis.

RESULTS: Phenotypes of Phl p-specific T cells were highly heterogenous but can be categorized into two major meta-clusters: CRTH2[Hi]CD27[Lo] and CRTH2[Lo]CD27[Hi] , each with distinct phenotypic profiles. Weak positive correlations between TNSS and frequencies of T cells within both subsets were observed. SCIT preferentially depleted CRTH2[Hi]CD27[Lo] cells whereas SLIT depleted CRTH2[Lo]CD27[Hi] cells. CRTH2[Hi]CD27[Lo] cell frequency correlated with Phl p-specific IgE and IgG4, but not IgA levels.

CONCLUSION: Unsupervised clustering revealed distinct subpopulations of allergen-specific T cells that were differentially targeted and depleted by SCIT and SLIT, suggesting that SCIT and SLIT act through overlapping but distinct immunological pathways.},
}

@article {pmid41780060,
year = {2026},
author = {Daodu, RO and Chang, J and Prescott, J and Reinert, K and Kühnert, D},
title = {Lassa Virus Live Tracking and Lineage Assignment: How Nextstrain Can Enhance Surveillance and Public Health in Africa and Beyond.},
journal = {Emerging microbes & infections},
volume = {},
number = {},
pages = {2640699},
doi = {10.1080/22221751.2026.2640699},
pmid = {41780060},
issn = {2222-1751},
abstract = {Lassa virus (LASV), a zoonotic, bi-segmented arenavirus endemic to West Africa, causes seasonal epidemics with substantial morbidity and mortality. Increasing frequency of exported cases emphasises the need for near real-time genomic surveillance to support outbreak response and clinical decision-making. We developed a suite of open-access resources on the Nextstrain and Nextclade platforms tailored to LASV. These include live phylogenetic and phylogeographic visualization, as well as Nextclade builds for rapid mutation detection and lineage assignment based on the L and S segments and the glycoprotein complex (GPC). A dedicated GPC phylogeny enables tracking of clinically relevant mutations, including immunologically relevant variants such as alanine at position 76 (A76), which is prevalent in lineage II and is implicated in reduced binding of monoclonal antibody 25.10C. The Nextclade tools distinguish LASV from other mammarenaviruses and assign lineages with Matthews correlation coefficients (all >85%). These tools are available at https://nextstrain.org/lassa for immediate use in surveillance, data annotation, outbreak response, and potentially support clinical decision-making in both endemic regions and exported-case scenarios. A key limitation is dependence on genomic data quality and recency. Although sampling-to-submission delays have decreased over the past 40 years, the average delay in the past five years remains ∼2 years. In many endemic LASV regions, challenges, such as limited resources, infrastructure, and previous experiences of stigmatization and political repercussions linked to outbreak reporting, restrict data sharing. The resulting disparities and delays may hinder comprehensive surveillance and timely response, with implications for global public health.},
}

@article {pmid41779867,
year = {2026},
author = {Dosey, A and Dadonaite, B and Gillespie, RA and Leaf, EM and Vukovich, MJ and McGowan, J and Grey, E and Muramatsu, H and Jun, RHJ and Pardi, N and Kanekiyo, M and Bloom, JD and King, NP},
title = {Stabilization of the H5 clade 2.3.4.4b hemagglutinin improves vaccine-elicited neutralizing antibody responses in mice.},
journal = {Science translational medicine},
volume = {18},
number = {839},
pages = {eaea8770},
doi = {10.1126/scitranslmed.aea8770},
pmid = {41779867},
issn = {1946-6242},
mesh = {Animals ; *Antibodies, Neutralizing/immunology ; *Influenza Vaccines/immunology ; *Hemagglutinin Glycoproteins, Influenza Virus/immunology/chemistry ; Mice ; Mutation/genetics ; Antibodies, Viral/immunology ; Female ; Humans ; Protein Stability ; Mice, Inbred BALB C ; Epitope Mapping ; Cryoelectron Microscopy ; },
abstract = {Transmission of highly pathogenic avian influenza from H5 clade 2.3.4.4b has expanded in recent years to infect large populations of birds and mammals, heightening the risk of a human pandemic. Influenza viruses that are adapted to transmission in birds and a variety of mammals tend to have a less stable hemagglutinin (HA) than seasonal influenza viruses, enabling membrane fusion at comparatively higher pH levels. Here, we combined five mutations in the H5 HA that increased its melting temperature and promoted stable closure of the HA trimer. Structural analysis by cryo-electron microscopy revealed that the stabilizing mutations create several new hydrophobic interactions while maintaining the local HA structure. We found that vaccinating mice with stabilized H5 HA immunogens resulted in higher hemagglutination inhibition and neutralization titers than nonstabilized comparators. Epitope mapping of vaccine-elicited polyclonal antibody responses using negative-stain electron microscopy and deep mutational scanning showed that site E on the side of the HA receptor binding domain was immunodominant across all groups; however, the stabilized immunogens shifted responses toward the receptor binding site, which elicited a higher proportion of neutralizing antibodies. Consistent with these findings, stabilized H5 HA immunogens delivered as messenger RNA-lipid nanoparticle (mRNA-LNP) vaccines protected mice against H5N1 challenge. These findings highlight that H5 HA-stabilizing mutations enhance the quality of antibody responses across different vaccine formats, underscoring their potential to improve pandemic preparedness vaccines targeting viruses from this widely circulating clade.},
}

Animals
*Antibodies, Neutralizing/immunology
*Influenza Vaccines/immunology
*Hemagglutinin Glycoproteins, Influenza Virus/immunology/chemistry
Mice
Mutation/genetics
Antibodies, Viral/immunology
Female
Humans
Protein Stability
Mice, Inbred BALB C
Epitope Mapping
Cryoelectron Microscopy

@article {pmid41757067,
year = {2026},
author = {Kikawa, C and Huddleston, J and Turner, SA and Loes, AN and Liu, J and Gang, S and Griffiths, T and Drapeau, EM and Cowling, BJ and Ho, F and Leung, NHL and Englund, JA and Lacombe, K and Watanabe, S and Hasegawa, H and Busch, M and Lanteri, M and Stone, M and Spencer, B and Neher, RA and Smith, DJ and Bedford, T and Hensley, SE and Bloom, JD},
title = {Near real-time data on the human neutralizing antibody landscape to influenza virus as of early 2026 to inform vaccine-strain selection.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {41757067},
issn = {2692-8205},
abstract = {Twice each year, a decision is made on whether to update the strains included in the seasonal influenza vaccine to better match the most recent circulating viral strains. To characterize the antigenic properties of current seasonal influenza A strains to inform the upcoming decision about which strains to include in the 2026-2027 Northern Hemisphere vaccine, here we perform high-throughput sequencing-based neutralization assays using a library of 57 H3N2 and 34 H1N1 influenza hemagglutinins reflecting the circulating diversity of strains in late 2025 to early 2026. We assay this library against 302 human sera collected in late 2025. The resulting data set encompasses 27,409 titers, and provides a near real-time portrait of the human neutralizing antibody landscape against influenza virus. We find that many human sera have lower titers against the K subclade of H3N2 and the D.3.1.1 subclade of H1N1; these subclades have recently become dominant among their respective subtypes. Our measurements also reveal variability in titers to different subvariants within the K subclade of H3N2, with titers especially low to subclade K strains with additional mutations in antigenic regions D and E. We make all our data and accompanying visualizations publicly available to enable their use in vaccine-strain selection and analyses of influenza evolution and immunity.},
}

@article {pmid41727567,
year = {2026},
author = {Termini, C and Woodruff, K and Patel, D and Peplinski, J and Setiawan, N and Hagen, M and Meshinchi, S},
title = {HS6ST1 regulates acute myeloid leukemia chemotherapy resistance via TGF-β1 signaling.},
journal = {Research square},
volume = {},
number = {},
pages = {},
pmid = {41727567},
issn = {2693-5015},
abstract = {Despite therapeutic advances, relapse remains the leading cause of death in patients with acute myeloid leukemia (AML). Growth factor signaling controls AML survival, proliferation, relapse, and chemotherapy resistance. Here, we studied heparan sulfate proteoglycans, a class of molecules that bind growth factors via their heparan sulfate chains to change their signaling ability. Heparan sulfate-growth factor interactions are controlled by the addition of sulfate groups catalyzed by heparan sulfotransferases, such as those encoded by HS2ST1 and HS6ST1. Using AML patient cohort analyses, we demonstrate that increased HS6ST1 expression is associated with worse survival and increased relapse risk for AML patients harboring KMT2A-rearrangements. Using cell line derived xenografts, we show that AML cells depleted of HS2ST1, but not HS6ST1, have increased bone marrow leukemic burden. Further, AML cells depleted of HS6ST1 are more sensitive to cytarabine than Control cells, suggesting that HS6ST1 regulates AML chemotherapy resistance. Heparan sulfate antagonism with surfen synergized with cytarabine to further support AML cell death compared to cytarabine alone. Mechanistically, we demonstrate that HS6ST1 depletion in AML cells reduces TGF-β1-mediated signaling, which diminishes cell survival upon cytarabine treatment. Together, our data show that HS6ST1 promotes AML cell chemotherapy resistance by supporting TGF-β1 signaling.},
}

@article {pmid41727151,
year = {2026},
author = {Simonich, CAL and McMahon, TE and Kampman, L and Chu, HY and Bloom, JD},
title = {Complete definition of how mutations affect antibodies used to prevent RSV.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {41727151},
issn = {2692-8205},
abstract = {New antibodies targeting the F protein of respiratory syncytial virus (RSV) have substantially reduced infant hospitalizations. However, viral resistance is a concern: one antibody failed clinical trials due to emergence of a resistant strain, and sporadic resistance mutations to the most widely used antibody (nirsevimab) have been identified in breakthrough infections. Here we define how RSV F mutations affect antibody neutralization. We first provide a biophysical model of how the buffering effect of bivalent IgG binding combines with differences in monovalent Fab potency to explain why nirsevimab resistance mutations are more common in subtype B than subtype A RSV strains. We then perform pseudovirus deep mutational scanning to safely measure how nearly all mutations to F affect its cell entry function and neutralization by the IgG and Fab forms of nirsevimab, clesrovimab, and several other key antibodies. We use these measurements to enable real-time surveillance of RSV sequences for antibody resistance, and identify rare strains with sporadic resistance mutations. Overall, our work improves understanding of the mechanisms by which viral mutations impact antibody neutralization, enables monitoring for natural RSV strains resistant to antibodies of public-health importance, and can help guide development of future antibodies with resilience to viral escape.},
}

@article {pmid41726900,
year = {2026},
author = {Baraznenok, E and Hsieh, HC and Lan, L and Konnick, EQ and Figiel, S and Rao, SR and Woodcock, DJ and Mills, IG and Hamdy, F and Valk, JE and Carter, KT and Yu, M and Paulson, TG and Dintzis, S and Grady, WM and Liu, JTC},
title = {Assessing the effects of a 3D pathology tissue-processing workflow on downstream molecular analyses.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {41726900},
issn = {2692-8205},
abstract = {Non-destructive 3D pathology methods have emerged in recent years with the potential to enhance standard 2D histopathology by greatly increasing the amount of tissue sampled by imaging and by providing volumetric morphological context. Another key advantage is that tissues remain intact, allowing re-embedding after imaging for potential long-term storage and future histological or molecular analyses. However, the impact of 3D pathology protocols on biomolecules - including DNA, RNA, and proteins - and their compatibility with downstream assays, has not been systematically evaluated. Here, we applied a previously optimized 3D pathology protocol - involving deparaffinization, fluorescent H&E-analog staining, optical clearing, and open-top light-sheet microscopy - to formalin-fixed paraffin-embedded (FFPE) specimens of breast, prostate, and head and neck cancer. Following the protocol, tissues were re-embedded in paraffin and compared with paired FFPE controls that did not undergo 3D pathology processing. DNA and RNA were extracted and subjected to quality assessments. Amplifiability was tested by PCR and reverse transcription quantitative PCR (RT-qPCR) of housekeeping genes. Although the results showed a slight decrease in the average yield and increased fragmentation of both DNA and RNA, amplifiability was largely preserved. Sanger sequencing of the PCR products confirmed accurate sequence determinations, while total RNA sequencing indicated that the global transcriptomic profile was largely unchanged. IHC staining of common biomarkers produced comparable signals, suggesting those proteins are well preserved after the 3D pathology workflow. These results demonstrate the feasibility of combining 3D pathology with downstream molecular applications.},
}

@article {pmid41659542,
year = {2026},
author = {Jiang, M and Hu, C and Hedouin, S and Latino, AA and Arimura, Y and Stergachis, AB and Biggins, S},
title = {Native yeast kinetochore structures identify an essential inner kinetochore interaction.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {41659542},
issn = {2692-8205},
support = {P30 CA015704/CA/NCI NIH HHS/United States ; R35 GM149357/GM/NIGMS NIH HHS/United States ; },
abstract = {Kinetochores must accurately assemble on centromeres every cell cycle for faithful chromosome segregation. Although a conserved centromeric histone variant is essential for inner kinetochore formation, the budding yeast centromeric DNA is a poor template for nucleosome formation in vitro, possibly due to a resistance to bend. To better understand how the yeast inner kinetochore is assembled, we developed a one-step protocol to purify de novo assembled native inner kinetochore subcomplexes for structural studies. We performed cryoelectron microscopy on the purified complexes and generated medium to high resolution density maps of four separate inner kinetochore complexes, two of which had not previously been visualized. We detected differences between native and previously reconstituted structures, suggesting that the de novo assembly assay generated intermediate assemblage states. A strong extra structural density, which corresponds to an Ndc10 trimerization domain, associated with centromeric DNA and a pair of CBF3 complexes to induce significant centromere bending. Its deposition on the CBF3-CEN complex is essential for kinetochore assembly and chromosome segregation. We propose that Ndc10 trimerization facilitates bending of the centromeric DNA, leading to assembly and stabilization of the centromeric nucleosome and inner kinetochore.},
}

@article {pmid26761518,
year = {2016},
author = {Jacobson, JM and Zheng, L and Wilson, CC and Tebas, P and Matining, RM and Egan, MA and Eldridge, J and Landay, AL and Clifford, DB and Luetkemeyer, AF and Tiu, J and Martinez, AL and Janik, J and Spitz, TA and Hural, J and McElrath, J and Frahm, N and , },
title = {The Safety and Immunogenicity of an Interleukin-12-Enhanced Multiantigen DNA Vaccine Delivered by Electroporation for the Treatment of HIV-1 Infection.},
journal = {Journal of acquired immune deficiency syndromes (1999)},
volume = {71},
number = {2},
pages = {163-171},
pmid = {26761518},
issn = {1944-7884},
support = {UM1 AI069494/AI/NIAID NIH HHS/United States ; UM1 AI069503/AI/NIAID NIH HHS/United States ; AI069556/AI/NIAID NIH HHS/United States ; UM1 AI069501/AI/NIAID NIH HHS/United States ; 2UM1AI069511-08/AI/NIAID NIH HHS/United States ; UM1 AI069534-08/AI/NIAID NIH HHS/United States ; 2 UM1 AI068636-08/AI/NIAID NIH HHS/United States ; UM1 AI069424/AI/NIAID NIH HHS/United States ; 2UM1AI069432/AI/NIAID NIH HHS/United States ; UM1 AI069432/AI/NIAID NIH HHS/United States ; 2UM1AI069412-08/AI/NIAID NIH HHS/United States ; U01 AI069439/AI/NIAID NIH HHS/United States ; U01 AI069556/AI/NIAID NIH HHS/United States ; UM1 AI069534/AI/NIAID NIH HHS/United States ; UM1 AI069439/AI/NIAID NIH HHS/United States ; UL1 TR000124/TR/NCATS NIH HHS/United States ; HHSN272200800062C/AI/NIAID NIH HHS/United States ; P30 AI045008/AI/NIAID NIH HHS/United States ; UM1 AI069412/AI/NIAID NIH HHS/United States ; UM1 AI068634/AI/NIAID NIH HHS/United States ; 2UM1AI069501/AI/NIAID NIH HHS/United States ; UM1 AI069496/AI/NIAID NIH HHS/United States ; UL1 RR024160/RR/NCRR NIH HHS/United States ; UM1 AI069556/AI/NIAID NIH HHS/United States ; U01 AI69439/AI/NIAID NIH HHS/United States ; UL1 TR001082/TR/NCATS NIH HHS/United States ; UM1 AI106701/AI/NIAID NIH HHS/United States ; 5-P30-AI-045008-15/AI/NIAID NIH HHS/United States ; F32 AI080062/AI/NIAID NIH HHS/United States ; UM1 AI069511/AI/NIAID NIH HHS/United States ; 2 UM1 AI069503-08/AI/NIAID NIH HHS/United States ; UM1AI068636/AI/NIAID NIH HHS/United States ; UM1 AI068636/AI/NIAID NIH HHS/United States ; },
mesh = {AIDS Vaccines/administration & dosage/*immunology ; Adolescent ; Adult ; CD4-Positive T-Lymphocytes/immunology ; Cytokines/immunology ; Electroporation ; Female ; HIV Antigens/*immunology ; HIV Infections/*drug therapy/immunology ; HIV-1/genetics/*immunology ; Humans ; Interferon-gamma/immunology ; Interleukin-12/*immunology ; Interleukin-2/immunology ; Male ; Middle Aged ; Vaccines, DNA/administration & dosage/*immunology ; Young Adult ; },
abstract = {BACKGROUND: Therapeutic vaccination is being studied in eradication and "functional cure" strategies for HIV-1. The Profectus Biosciences multiantigen (MAG) HIV-1 DNA vaccine encodes HIV-1 Gag/Pol, Nef/Tat/Vif, and Envelope, and interleukin-12 (IL-12) and is delivered by electroporation combined with intramuscular injection (IM-EP).

METHODS: Sixty-two HIV-1-infected patients on antiretroviral therapy (plasma HIV-1 RNA levels ≤ 200 copies/mL; CD4(+) T-cell counts ≥ 500 cells/mm(3)) were randomly allocated 5:1 to receive vaccine or placebo. At weeks 0, 4, and 12, 4 consecutive cohorts received 3000 μg HIV MAG pDNA with 0, 50, 250, or 1000 μg of IL-12 pDNA by IM-EP. A fifth cohort received HIV MAG pDNA and 1000 μg of IL-12 pDNA by standard IM injection.

RESULTS: CD4(+) T cells expressing IL-2 in response to Gag and Pol and interferon-γ responses to Gag, Pol, and Env increased from baseline to week 14 in the low-dose (50-μg) IL-12 arm vs. placebo (P < 0.05; intracellular cytokine staining). The total increase in the IL-2-expressing CD4 T-cell responses to any antigen was also higher in the low-dose IL-12 arm vs. placebo (P = 0.04). Cytokine responses by CD8 T cells to HIV antigens were not increased in any vaccine arm relative to placebo.

CONCLUSIONS: HIV-1 MAG/low-dose IL-12 DNA vaccine delivered by IM-EP augmented CD4(+) but not CD8(+) T-cell responses to multiple HIV-1 antigens.},
}

AIDS Vaccines/administration & dosage/*immunology
Adolescent
Adult
CD4-Positive T-Lymphocytes/immunology
Cytokines/immunology
Electroporation
Female
HIV Antigens/*immunology
HIV Infections/*drug therapy/immunology
HIV-1/genetics/*immunology
Humans
Interferon-gamma/immunology
Interleukin-12/*immunology
Interleukin-2/immunology
Male
Middle Aged
Vaccines, DNA/administration & dosage/*immunology
Young Adult

@article {pmid41779832,
year = {2026},
author = {Rodriguez Chevez, HJ and Remington, AJ and Gray, MD and Alam, R and Gilmour, MW and Morningstar, C and Alencar, GF and Pulliam, T and McClure, EM and Singh, N and Urselli, F and Ouellette, S and Poljakov, K and Smythe, KS and Kulikauskas, RM and Robinson, KL and Moshiri, AS and Yeung, CCS and Lin, M and Shimp, KR and Schwartz, A and Macy, AM and Tooley, MR and Baker, ML and Carter, JJ and Hopwo, K and Singhi, N and Bakhtiari, J and Ruterbusch, M and Shasha, C and Iuliano, M and Mullen, LJ and DeBuysscher, BL and Veatch, JR and Koelle, DM and Galloway, DA and Nghiem, P and Taylor, JJ},
title = {Response of B cells specific for polyomavirus-derived oncoprotein is predictive of Merkel cell carcinoma tumor control.},
journal = {Cancer immunology research},
volume = {},
number = {},
pages = {},
doi = {10.1158/2326-6066.CIR-25-0950},
pmid = {41779832},
issn = {2326-6074},
abstract = {Merkel cell carcinomas (MCC) typically arise from clonal integration of the Merkel cell polyomavirus. Immunogenic viral oncoproteins then lead to tumorigenesis. Oncoprotein-specific T cells are essential for anti-MCC immunity, but it is unclear whether B cells promote tumor control. Here, we analyzed the frequency and phenotype of viral oncoprotein-specific and total B cells in blood samples from 47 patients with MCC and tumor samples from another 19 patients with MCC. The phenotype of blood B cells did not correlate with MCC patient outcomes. In contrast, all 11 patients with robust oncoprotein-specific antibody-secreting and/or germinal center B cells in tumors experienced long-term MCC control. In vitro, B cells engineered to be specific for viral oncoproteins increased the sensitivity of oncoprotein-specific CD4+ T cells by over 50-fold. Together, our findings suggest that cancer-specific B cells promote antitumor immunity via increased responses by T cells and that cancer-specific augmentation of B cells could be therapeutically relevant.},
}