Multiancestry brain pQTL fine-mapping and integration with genome-wide association studies of 21 neurologic and psychiatric conditions.

To understand shared and ancestry-specific genetic control of brain protein expression and its ramifications for disease, we mapped protein quantitative trait loci (pQTLs) in 1,362 brain proteomes from African American, Hispanic/Latin American and non-Hispanic white donors. Among the pQTLs that multiancestry fine-mapping MESuSiE confidently assigned as putative causal pQTLs in a specific population, most were shared across the three studied populations and are referred to as multiancestry causal pQTLs. These multiancestry causal pQTLs were enriched for exonic and promoter regions.

Multigenerational proteolytic inactivation of restriction upon subtle genomic hypomethylation in Pseudomonas aeruginosa.

Restriction-modification (R-M) systems protect against phage infection by detecting and degrading invading foreign DNA. However, like many prokaryotic anti-phage defences, R-M systems pose a major risk of autoimmunity, exacerbated by the presence of hundreds to thousands of potential cleavage sites in the bacterial genome. Pseudomonas aeruginosa strains experience the temporary inactivation of restriction endonucleases following growth at high temperatures, but the reason and mechanisms for this phenomenon are unknown.

Outcomes of robot-assisted radical prostatectomy with novel robotic platforms vs da Vinci multiport systems: a systematic review and network meta-analysis.

Introduction: The introduction of novel robotic platforms has expanded surgical options for robot-assisted radical prostatectomy (RARP). However, comparative outcomes with da Vinci multiport (MP) system remain unclear. This systematic review and network meta-analysis aimed to compare perioperative, early oncological, and functional outcomes of RARP performed with novel robotic platforms versus the da Vinci MP system.

Hemodialysis access planning and outcomes in older adults.

The rate of end-stage kidney disease (ESKD) is steadily rising in the United States, and older adults (ie, 65 years and older) represent the fastest-growing segment in need of hemodialysis. This demographic shift presents unique challenges due to age-related comorbidities, frailty, and increased procedural risks. Despite these challenges, there is limited guidance for risk stratification and management of renal replacement therapy in older patients with ESKD.

The Impact of Transfemoral Adjustable-Volume Sockets on Socket Comfort and Quality of Life: A Randomized Clinical Trial.

Objective: To determine if adjustable-volume sockets affect patient comfort and quality of life.

Design: Randomized clinical trial SETTING: Two prosthetics clinics and two research laboratories.

Participants: A convenience sample of 29 individuals with unilateral transfemoral amputation who used prescribed conventional laminated sockets or adjustable volume sockets.

A Macroporous Cyclodextrin Monolith for Continuous Removal of Per- and Polyfluoroalkyl Substances from Water.

Per- and polyfluoroalkyl substances (PFASs) are environmentally persistent, bioaccumulative, and toxic chemicals that contaminate global drinking water resources. Their ubiquity and potential impact on human health motivate large-scale remediation. Conventional materials used to remove PFASs during drinking water production are functionally inefficient or energetically expensive, motivating the discovery of new materials and technologies.

Clinical applications of mass spectrometry in multiple myeloma.

Mass spectrometry (MS) is an emerging tool in multiple myeloma that detects and quantifies monoclonal proteins in the peripheral blood with sensitivity several orders of magnitude greater than conventional serum protein electrophoresis and immunofixation. Both intact light chain (top-down) and clonotypic peptide (bottom-up) MS approaches have demonstrated sensitivity comparable to-or even surpassing-BM-based assessments using next generation flow cytometry or sequencing. However, due to the delayed clearance of paraproteins, MS may be less informative for early response assessment, underscoring the need to define the optimal timing for evaluation.

Neutrophil-to-Lymphocyte Ratio (NLR) as a Biomarker in Clinically Stable Chronic Obstructive Pulmonary Disease: SPIROMICS cohort.

Rationale: Inflammation is central to chronic obstructive pulmonary disease (COPD) pathogenesis but incompletely represented in COPD prognostic models. Neutrophil to lymphocyte ratio (NLR) is a readily available inflammatory biomarker.

Objectives: To explore the associations of NLR with smoking status, clinical features of COPD, and future adverse outcomes.

CUX1 restrains latent hematopoietic stem cell plasticity by suppressing stem cell-intrinsic inflammatory pathways.

Long-term maintenance of somatic stem cells relies on precise regulation of self-renewal and differentiation. Understanding the molecular framework for these homeostatic processes is essential for improved cellular therapies and treatment of myeloid neoplasms. CUX1 is a widely expressed, dosage-sensitive transcription factor crucial in development and frequently deleted in myeloid neoplasia in the context of -7/(del7q).

Platelet Factor 4 (PF4) Regulates Hematopoietic Stem Cell Aging.

Hematopoietic stem cells (HSCs) responsible for blood cell production and their bone marrow regulatory niches undergo age-related changes, impacting immune responses and predisposing individuals to hematologic malignancies. Here, we show that the age-related alterations of the megakaryocytic niche and associated downregulation of Platelet Factor 4 (PF4) are pivotal mechanisms driving HSC aging. PF4-deficient mice display several phenotypes reminiscent of accelerated HSC aging, including lymphopenia, increased myeloid output, and DNA damage, mimicking physiologically aged HSCs.

Posterior Shoulder Instability in Athletes.

» Posterior shoulder instability (PSI) constitutes approximately 10% of all shoulder instability cases and is prevalent among contact sport athletes because of recurrent blunt trauma to the shoulder.» PSI presents as persistent pain and can be diagnosed using clinical tests such as the Kim test and the Jerk test.» Surgical intervention is recommended for athletes who have exhausted nonoperative treatment.

Interferon-gamma 1b-induced gene expression alters neutrophil function in patients with chronic granulomatous disease.

ClinicalTrials.gov NCT03548818.

The impact of driving versus undistracted listening on podcast knowledge acquisition and retention using a driving simulator: A randomized, cross-over trial.

Introduction: Research on listening to podcasts while driving suggested no significant difference compared to undistracted listening. However, these studies were conducted in non-controlled driving environments, limiting the evaluation of the environment's impact. This study aimed to compare knowledge acquisition and retention among resident physicians and undergraduate students while listening to medical education podcasts in a controlled, simulator-based, driving environment versus an undistracted listening condition.

Fixed-Duration Epcoritamab Plus R2 Drives Favorable Outcomes in Relapsed or Refractory Follicular Lymphoma.

Epcoritamab is a subcutaneous CD3xCD20 bispecific antibody approved as monotherapy for relapsed/refractory (R/R) follicular lymphoma (FL). We evaluated fixed-duration epcoritamab with rituximab plus lenalidomide (R2) in R/R FL in arm 2 of EPCORE® NHL-2 (phase 1b/2; NCT04663347). Patients received epcoritamab (2 step-up doses, then 48-mg full doses) for up to 2 years and R2 for up to 12 cycles (28 days/cycle).

Does Seed Funding by the Plastic Surgery Foundation Progress to National Institutes of Health Grants? An Analysis of 20 Years of Funded Grants.

Background: One of the goals of the Plastic Surgery Foundation (PSF) is to initiate a pathway by which researchers can develop national extramurally-funded grants. The present study investigates the effectiveness of seed PSF grants in aiding researchers to obtain grant funding through the National Institutes of Health (NIH).

Methods: The NIH RePORTER database was queried with the names of all American Society of Plastic Surgeons (ASPS) members.

Measures of family process: Psychometric properties and invariance testing across South Koreans, Korean Chinese, and Korean Americans.

Using data from three interrelated studies of Korean adolescents in South Korea ( = 524; = 14.98), China ( = 267; = 15.24), and the United States ( = 408; = 14.

Gonorrhea and Chlamydia Screening for Adolescents and Young Adults in Emergency Departments.

Importance: Adolescents account for almost half of the 2.5 million diagnosed sexually transmitted infections in the US annually, and the emergency department functions as the primary source of health care for many adolescents. No recommendations exist for emergency department gonorrhea and chlamydia screening.

Elinzanetant for the Treatment of Vasomotor Symptoms Associated With Menopause: A Phase 3 Randomized Clinical Trial.

Importance: There is an unmet need for long-term, safe, effective, and hormone-free treatments for menopausal symptoms, including vasomotor symptoms (VMS) and sleep disturbances.

Objective: To evaluate the 52-week efficacy and safety of elinzanetant, a dual neurokinin-targeted therapy, for treating moderate to severe VMS associated with menopause.

Design, Setting, And Participants: OASIS-3 was a double-blind, placebo-controlled, randomized phase 3 clinical trial that was conducted at 83 sites in North America and Europe from August 27, 2021, to February 12, 2024, and included postmenopausal women aged 40 to 65 years who were seeking treatment for moderate to severe VMS (no requirement for a minimum number of VMS events per week).

Decentralized Clinical Trials in the Era of Real-World Evidence: A Critical Assessment of Recent Experiences.

Since the first decentralized clinical trial (DCT) was conducted in 2011, there has been an increased usage of DCT due to its benefits of patient-centricity and generalizability of findings. This trend was further expedited by the global COVID-19 pandemic. We identified 23 case studies across various therapeutic areas and grouped them into different categories according to their purposes-by necessity, for operational benefits, to address unique research questions, to validate innovative digital endpoints, or to validate decentralization as a clinical research platform.

Real -World Evidence of the Long-Term Clinical Utility of a Vibrating Capsule in the Management of Chronic Idiopathic Constipation.

Introduction: Pharmacological therapies for chronic idiopathic constipation (CIC) are useful, but many patients report dissatisfaction from a lack of efficacy and occurrence of adverse events. The vibrating capsule (VC) is an FDA approved non-pharmacologic, treatment for CIC. However, its long-term usefulness in a community setting is unknown.

Methods to Validate Digital Health Technologies for Dermatology.

The integration of wearable medical devices and digital health technologies (DHTs) in health care has grown significantly during the past 2 decades, particularly in dermatology, in which objective measurement of symptoms such as itch remains challenging. This review examines the evolution of DHTs in dermatology, focusing on the validation frameworks necessary for their implementation in clinical trials and research. We discuss the key stages of validation: hardware validation to ensure device reliability, analytical validation to transform raw sensor data into meaningful metrics, and clinical validation to demonstrate utility in specific patient populations.