Differential phagocytosis induces diverse macrophage activation states in malignant gliomas.

Background: Diffuse midline glioma (DMG) and glioblastoma (GBM) are aggressive brain tumors with limited treatment options. Macrophage phagocytosis is a complex, tightly regulated process governed by competing pro-phagocytic and anti-phagocytic signals. CD47-SIRPα signaling inhibits macrophage activity, while radiotherapy (RT) can enhance tumor immunogenicity.

Neonatal striatal volume is associated with infant anhedonia.

Anhedonia is increasingly recognized as a transdiagnostic risk factor for psychopathology. New evidence demonstrates that anhedonia is present in infancy and early childhood. Structural variability in striatal regions involved in reward processing and pleasure seeking is concurrently linked to anhedonia, yet few studies have examined whether striatal differences presage anhedonia, and none have examined prospective associations before middle childhood.

Developmental auditory deprivation in one ear impairs brainstem binaural processing and reduces spatial hearing acuity.

Early sensory experience can exert lasting perceptual consequences. For example, a brief period of auditory deprivation early in life can lead to persistent spatial hearing deficits. Some forms of hearing loss (i.

Chronic Ocular Surface Pain: An Optometrist and Ophthalmologist Survey.

Introduction: Chronic ocular surface pain (COSP) is defined as ocular pain that is perceived to originate from the ocular surface and persists for more than 3 months. Clear epidemiological data on COSP prevalence are lacking.

Methods: In 2025, a total of 100 eye care providers were surveyed, including 50 optometrists and 50 ophthalmologists.

The Role of Selection for Function in Aging and Chronic Diseases: A Novel Evolutionary Perspective.

Aging, and by extension age-related diseases, has traditionally been understood through classical evolutionary genetic models, such as the mutation accumulation and antagonistic pleiotropy theories. However, these frameworks primarily focus on the declining efficacy of organismal-level selection against mutations with deleterious effects in late life. Here, we propose a novel hypothesis: many chronic diseases associated with aging may emerge, at least in part, as a result of selection acting at lower organizational levels, including non-replicative biological entities, enabled by the relaxation of selective pressures that constrained within-organism evolutionary processes in early life.

Multi-Trait Polygenic Scores for COPD and COPD Exacerbations Implicate Druggable Proteins.

Objectives: To construct multi-trait polygenic scores (PRS) predicting chronic obstructive pulmonary disease (COPD) and exacerbations, validate their performance in diverse cohorts, and identify PRS-related proteins for potential therapeutic targeting.

Design: Prospective cohort studies.

Setting: Genetic Epidemiology of COPD (COPDGene; 2007-present), Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE; 2005-2008), Mass General Brigham Biobank (MGBB; 2010-present), All of Us (2016-present), and UK Biobank (UKB; 2006-present).

An Efficient Lasso Framework for Admixture-Aware Polygenic Scores.

Polygenic scores (PGS) have promising clinical applications for risk stratification, disease screening, and personalized medicine. However, most PGS are trained on predominantly European ancestry cohorts and have limited portability to external populations. While cross-population PGS methods have demonstrated greater generalizability than single-ancestry PGS, they fail to properly account for individuals with recent admixture between continental ancestry groups.

Rbm8a deficiency causes hematopoietic defects by modulating Wnt/PCP signaling.

Thrombocytopenia-Absent Radius (TAR) syndrome is a rare congenital condition with reduced platelets, forelimb anomalies, and variable heart and kidney defects. TAR syndrome is caused by mutations in RBM8A/Y14, a component of the exon junction complex. How perturbing a general mRNA-processing factor causes the selective TAR Syndrome phenotypes remains unknown.

Importance of responder criteria for reporting health-related quality-of-life data in clinical trials for advanced cancer: recommendations of Common Sense Oncology and the European Organisation for Research and Treatment of Cancer.

The goals of treatment for people with advanced cancer are to prolong survival and improve symptoms and health-related quality of life (HRQOL). Although many phase 3 randomised clinical trials seek to evaluate HRQOL during treatment, informing individual patients about expected HRQOL outcomes is challenging, as the common method of analysis and reporting compares averages for randomised groups, and clinicians find these data difficult to apply in clinical practice. Symptomatic patients with advanced cancer would like to know the probability that a proposed treatment might improve their survival or their dominant symptoms, and the probability of having treatment-related side-effects.

Prospective assessment of prognostic significance of malignant peritoneal cytology in endometrial cancer: An NRG Oncology / Gynecologic Oncology Group study on GOG-210 protocol.

Objective: To examine the association between malignant peritoneal cytology and survival outcomes in endometrial cancer.

Methods: This was an ancillary analysis of prospectively collected surgical-pathological data in the NRG Oncology / Gynecologic Oncology Group study on GOG-210 protocol. The study population included 2383 patients with stage I-III endometrial cancer from 2003 to 2011.

Development and Evaluation of Sleep Disorder Decision Aids for Veterans With Mild Traumatic Brain Injury.

Objective: First, to summarize the design of novel decision aid prototypes aimed at facilitating shared decision-making for Veterans with co-morbid mild traumatic brain injury (mTBI) and sleep disorders (insomnia, obstructive sleep apnea [OSA]) in the Veterans Health Administration (VHA) Polytrauma/TBI System of Care (PSC). Second, to elicit feedback regarding usability, acceptability, and feasibility of prototypes to inform future implementation.

Setting: Nationwide VHA PSC sites.

Sentinel Injuries in Emergency Departments and Subsequent Serious Injury in Children.

Study Objective: Sentinel injuries in young children are minor injuries that can raise suspicion of physical abuse. Although early identification is critical, widespread screening of patients can incur unintended harm to both children and their families. We determined the frequency of serious abusive injury within 12 months following an emergency department (ED) encounter for a sentinel injury.

Homologous recombination deficiency and survival in ovarian high-grade serous carcinoma by self-reported race.

Background: Half of ovarian high-grade serous carcinomas (HGSC) have homologous recombination deficiency (HRD). However, HRD is not well-characterized in Black individuals who experience worse survival after a diagnosis of HGSC. The objective of this study was to characterize ovarian HGSC HRD and examine its association with survival by self-reported race.

Circulating TNF-α levels in rheumatoid arthritis: a systematic review and meta-analysis and comparison to TNF-α levels in sepsis.

Background: Tumor necrosis factor-alpha (TNF-α) is implicated in the pathogenesis of autoimmune conditions and sepsis. Although anti-TNF-α therapies have demonstrated clinical efficacy in rheumatoid arthritis (RA), there is no established evidence for benefit in patients with sepsis.

Objectives: We sought to quantify circulating TNF-α in patients with RA and compare results to TNF-α levels in sepsis.

Cardiorespiratory Fitness, Physical Activity, Sedentary Behavior, and Diabetes Risk Among Breast Cancer Survivors Treated with Endocrine Therapies.

Endocrine therapies for breast cancer (BC) (i.e., selective estrogen receptor modulators (SERMs) or aromatase inhibitors (AI)) lower the risk for cancer recurrence but are linked to an increased risk of type 2 diabetes (T2D).

Virtual radiotherapy plan quality education: Perspectives from a global setting.

Purpose: Evaluation of treatment plan quality is a critical element of training for radiotherapy professionals. With the increased adoption of intensity modulated radiotherapy internationally, this training is crucial to address patient care inequity. We aim to evaluate learning outcomes from a 14-session remote training course targeting critical elements of plan quality with advanced modalities.

Bordetellae colonization oligosaccharide (b-Cool), a glycan crucial for nasal colonization.

Respiratory tract infections pose considerable global health challenges. Upper airway colonization is pivotal to these infections, including those caused by species. We identified an oligosaccharide, bordetellae colonization oligosaccharide (b-Cool), crucial for early nasal colonization of .

High-throughput synthesis and specificity characterization of natively paired influenza hemagglutinin antibodies with oPool display.

Antibody discovery is crucial for developing therapeutics and vaccines and for understanding adaptive immunity. However, the lack of approaches to synthesize antibodies with defined sequences in a high-throughput manner represents a major bottleneck in antibody discovery. Here, we present oPool display, a high-throughput cell-free platform that combined oligo pool synthesis and mRNA display to rapidly construct and characterize hundreds to thousands of natively paired antibodies in parallel.

Integrating Continuing Professional Development, Continuing Education, and Quality Improvement: A Case Study and Implications for Practice.

Continuing professional development (CPD) and quality improvement (QI) are both dedicated to improving clinical practice and health outcomes. Although leaders in both disciplines have long recommended closer alignment, few case studies have demonstrated how such alignment can be developed and sustained within a health care system. Kaiser Permanente Colorado is an integrated health care delivery system in the United States that has worked toward coordination of CPD and QI for >20 years.

Severe Cerebral Palsy and Short Stature Predict Absent Baseline IONM Signals in Pediatric Neuromuscular Scoliosis Surgery.

Background: Intraoperative neurophysiological monitoring (IONM) is essential for detecting potential neurological injury during scoliosis surgery, but obtaining recordable baseline signals can be challenging in neuromuscular scoliosis (NMS) patients. Absent baseline IONM signals, characterized by unattainable initial IONM responses despite technical and anesthetic optimization, present significant challenges to intraoperative neurological assessment and surgical risk stratification. This study aims to identify predictive factors for absent baseline IONM signals in pediatric NMS patients and establish a clinically applicable risk prediction model.

IL15/IL15Ra complex induces an anti-tumor immune response following radiation therapy only in the absence of Tregs and fails to expand progenitor TCF1+ CD8 T cells.

In this work, we show that the combination of radiation therapy (RT) and an IL15/IL15Rα fusion complex (denoted IL15c) fails to confer anti-tumor efficacy; however, a CD8-driven anti-tumor immune response can be elicited with the concurrent administration of an aCD25 Treg-depleting antibody. Using IL15-/- and Rag1-/- knockout mouse models, we show that the response to RT + IL15c + aCD25 is dependent on both IL15 and CTLs. Furthermore, despite an equivalent survival benefit following treatment with RT + IL15c + aCD25 and combination RT and PD1-IL2v, a novel immunocytokine with PD-1 and IL2Rbg binding domains, CTL immunophenotyping and phospho-proteomic analysis of intracellular metabolites showed a significant upregulation of activation and functionality in CD8 T cells in the RT + PD1-IL2v regimen.

Longitudinal Effects of Mild Traumatic Brain Injury on the Gut Microbiome and Acoustic Startle Response in Male and Female Rats.

Traumatic brain injuries (TBI) frequently occur and can lead to lasting negative cognitive, physical, and mental health outcomes. The biological response to even mild TBIs (mTBI) includes well-characterized inflammatory sequelae that start immediately post-injury, remain for weeks, and can develop into long-term systemic inflammation. Studies have shown that TBI influences multiple physiological systems, including the gastrointestinal tract, through bidirectional communication modulated, in part, by the gut microbiome.