Genetic analysis of psychosis Biotypes: shared Ancestry-adjusted polygenic risk and unique genomic associations.

The Bipolar-Schizophrenia Network for Intermediate Phenotypes (B-SNIP) created psychosis Biotypes based on neurobiological measurements in a multi-ancestry sample. These Biotypes cut across DSM diagnoses of schizophrenia, schizoaffective disorder, and bipolar disorder with psychosis. Two recently developed post hoc ancestry adjustment methods of Polygenic Risk Scores (PRSs) generate Ancestry-Adjusted PRSs (AAPRSs), which allow for PRS analysis of multi-ancestry samples.

Brain derived β-interferon is a potential player in Alzheimer's disease pathogenesis and cognitive impairment.

Background: Recent research has postulated that the activation of cGAS-STING-interferon signalling pathways could be implicated in the pathogenesis of Alzheimer's disease (AD). However, the precise types of interferons and related cytokines, both from the brain and periphery, responsible for cognitive impairment in patients with AD remain unclear.

Methods: A total of 131 participants (78 [59.

Effectiveness of dolutegravir-based regimens compared to raltegravir-, elvitegravir-, bictegravir, and darunavir-based regimens among older adults with HIV in the Veterans Aging Cohort Study (VACS).

Background: Real-world data on treatment patterns and clinical outcomes for newer drugs, including integrase strand transfer inhibitors, among older people with human immunodeficiency virus (PWH) are limited.

Methods: This cohort study included PWH enrolled in the Veterans Aging Cohort Study (VACS) who were prescribed a standard 3-drug antiretroviral therapy (ART) regimen containing dolutegravir (DTG), bictegravir (BIC), cobicistat boosted elvitegravir (EVG), raltegravir (RAL), or darunavir/ritonavir (DRV) plus 2 nucleoside reverse transcriptase inhibitors between January 1, 2014, and March 31, 2020, and who were ≥50 years at regimen initiation. The association between regimen and virologic effectiveness or discontinuation was assessed using logistic regression models with inverse probability of treatment weights.

International workshop: what is needed to ensure outcome measures for Rett syndrome are fit-for-purpose for clinical trials? June 7, 2023, Nashville, USA.

Introduction: The clinical, research and advocacy communities for Rett syndrome are striving to achieve clinical trial readiness, including having fit-for-purpose clinical outcome assessments. This study aimed to (1) describe psychometric properties of clinical outcome assessment for Rett syndrome and (2) identify what is needed to ensure that fit-for-purpose clinical outcome assessments are available for clinical trials.

Methods: Clinical outcome assessments for the top 10 priority domains identified in the Voice of the Patient Report for Rett syndrome were compiled and available psychometric data were extracted.

Genomic Biomarkers Associated with Enfortumab Vedotin Outcomes for Patients with Advanced Urothelial Carcinoma: Analysis of UNITE Study Data.

Enfortumab vedotin (EV) is used as monotherapy or combined with pembrolizumab in advanced urothelial carcinoma (aUC), but biomarker data associated with EV outcomes are limited. We identified 170 patients in the UNITE study who received EV monotherapy and had molecular biomarker data available. Outcomes for groups with and without a particular biomarker were compared using logistic regression (unadjusted) for the objective response rate (ORR), and a log-rank test and Cox proportional-hazard models (CPHMs) for progression-free survival (PFS) and overall survival (OS) from EV initiation.

Family Caregiver Knowledge in the Outpatient Management of Pediatric Tracheostomy-Related Emergencies.

Tracheostomy-related emergencies (TREs) contribute significantly to preventable mortality. The retention of caregiver knowledge and skills acquired through simulation-based training (SBT) is unknown. This study aimed to assess the management of TREs by caregivers who did and did not receive SBT.

Maximizing insights from longitudinal epigenetic age data: simulations, applications, and practical guidance.

Background: Epigenetic age (EA) is an age estimate, developed using DNA methylation (DNAm) states of selected CpG sites across the genome. Although EA and chronological age are highly correlated, EA may not increase uniformly with time. Departures, known as epigenetic age acceleration (EAA), are common and have been linked to various traits and future disease risk.

Low expression of CCKBR in the acinar cells is associated with insufficient starch hydrolysis in ruminants.

Unlike monogastric animals, ruminants exhibit significantly lower starch digestibility in the small intestine. A better understanding of the physiological mechanisms that regulate digestion patterns in ruminants could lead to an increased use of starch concentrates. Here we show more robust pancreatic exocrine function in adult goats (AG) than in neonatal goats (NG) by combining scRNA-seq and proteomic analysis.

Increasing Life Expectancy in Patients with Genitourinary Malignancies: Impact of Treatment Burden on Disease Management and Quality of Life.

Background And Objective: Treatment burden refers to the overall impact of medical treatments on a patient's well-being and daily life. Our objective is to evaluate the impact of treatment burden on quality of life (QoL) in patients with genitourinary (GU) malignancies, highlighting the importance of patient-reported outcomes (PROs) in clinical trials to inform treatment decisions and improve patient care.

Methods: We conducted a narrative review of clinical trials focused on GU malignancy (prostate, bladder, and kidney) between January 2000 and June 2024, analyzing related PROs and findings regarding treatment burden.

Smoking Status Impacts Mitochondrial Function and Synthetic Function in Mesenchymal Stem Cells Derived from Diabetics with Arterial Insufficiency.

Diabetes and smoking are frequently co-morbid conditions leading to arterial insufficiency, significantly increasing the risk of non-healing wounds and subsequent major amputation. Autologous patient-specific mesenchymal stem cells (MSCs) present a novel tool for regenerative therapy to treat advanced stages of arterial insufficiency. The regenerative performance of cells from diabetics with impaired arterial perfusion is known to be reduced, but the impact of additional patient factors such as smoking remains poorly understood.

Acute Kidney Injury Among Florida Construction Workers: A Pilot Study.

Background: While construction workers have the second highest rate of heat-related mortality, less is known about the prevelance of heat-related illness (HRI) symptoms, dehydration and kidney dysfunction. The aim of this study was to conduct a biomedical field-based study with construction workers to characterize HRI symptoms, dehydration, and kidney dysfunction, and analyze relationships between post-work urine specific gravity (USG) percentiles and predictors such as work hours, water consumption, and sugary beverage consumption.

Methods: In collaboration with the Farmworker Association of Florida, 58 construction workers in Central Florida were monitored pre- and post-work shift on one workday.

Vagus nerve stimulation in treatment-resistant depression: A one-year, randomized, sham-controlled trial.

Background: Few treatments are available for individuals with marked treatment-resistant depression (TRD).

Objective: Evaluate the safety and effectiveness of FDA-approved adjunctive vagus nerve stimulation (VNS) in patients with marked TRD.

Methods: This 12-month, multicenter, double-blind, sham-controlled trial included 493 adults with marked treatment-resistant major depression who were randomized to active or no-stimulation sham VNS for 12 months.

The role of the psychedelic experience in psilocybin treatment for treatment-resistant depression.

Objective: To determine the relationships between psilocybin dose, psychedelic experiences, and therapeutic outcome in treatment-resistant depression.

Methods: For treatment-resistant depression, 233 participants received a single dose of 25, 10, or 1 mg of COMP360 psilocybin (a proprietary, pharmaceutical-grade synthesized psilocybin formulation, developed by the sponsor, Compass Pathfinder Ltd.) with psychological support.

Randomized trial investigating the utility of a liver tissue transcriptional biomarker in identifying adult liver transplant recipients not requiring maintenance immunosuppression.

The maintenance of stable allograft status in the absence of immunosuppression, known as operational tolerance, can be achieved in a small proportion of liver transplant recipients, but we lack reliable tools to predict its spontaneous development. We conducted a prospective, multi-center, biomarker-strategy design, immunosuppression withdrawal clinical trial to determine the utility of a predictive biomarker of operational tolerance. The biomarker test, originally identified in a patient cohort with high operational tolerance prevalence, consisted of a 5-gene transcriptional signature measured in liver tissue collected before initiating immunosuppression weaning.

The direct and urinary electrolyte-mediated effects of ambient temperature on population blood pressure: A causal mediation analysis.

High ambient heat can directly influence blood pressure (BP) through the vasodilation of the skin vasculature and indirectly by affecting urinary volume and electrolyte levels. We evaluated the direct and urine electrolyte-mediated effects of ambient temperature on BP. We pooled 5,624 person-visit data from a community-based stepped-wedge randomized control trial in southwest coastal Bangladesh from December 2016 to May 2017.

Determining the association of hyperoxia while on extracorporeal life support with mortality in neonates following Norwood operation.

Background: Patients requiring extracorporeal life support (ECLS) support post-Norwood operation constitute an extremely high-risk group.

Materials And Methods: We retrospectively aimed to evaluate the relationship of hyperoxia with mortality and other clinical outcomes in patients who required ECLS following Norwood operation between January/2010 and December/2020 in a large volume center.

Results: During the study period 65 patients required ECLS post-Norwood.

Trop-2 and Ephrin B2 expression in urothelial carcinoma with divergent differentiation and aggressive urothelial carcinoma subtypes.

Objectives: Urothelial carcinomas (UCs) encompass a heterogeneous group of tumors. Several histopathologic features are associated with poor clinical outcomes and limited treatment options. With new rising therapeutic modalities, we aimed to determine the pattern of expression of Trop-2 and ephrin B2 in UC with aggressive subtype histology and/or divergent differentiation (SH/DD).