One score to rule them all: regularized ensemble polygenic risk prediction with GWAS summary statistics.

Ensemble learning has been increasingly popular for boosting the predictive power of polygenic risk scores (PRS), with almost every recent multi-ancestry PRS approach employing ensemble learning as a final step. Existing ensemble approaches rely on individual-level data for model training, which severely limits their real-world applications, especially in non-European populations without sufficient genomic samples. Here, we introduce a statistical framework to construct regularized ensemble PRS, which allows us to combine a large number of candidate PRS models using only summary statistics from genome-wide association studies.

"Inverse" shape memory effect in energetic electron crosslinked methylcellulose hydrogels: Programming, demonstration and quantification.

Shape memory hydrogels constitute a highly attractive materials class that bears enormous potential within a broad range of areas - from engineering to medicine. Within the present contribution we demonstrate that energetic electron crosslinked methylcellulose-only hydrogels exhibit an "inverse" shape memory effect that transforms from a secondary shape to its primary shape upon cooling. The primary shape can conveniently be "programmed" by application of energetic electrons.

Pervasive biases in proxy genome-wide association studies based on parental history of Alzheimer's disease.

Almost every recent Alzheimer's disease (AD) genome-wide association study (GWAS) has performed meta-analysis to combine studies with clinical diagnosis of AD with studies that use proxy phenotypes based on parental disease history. Here, we report major limitations in current GWAS-by-proxy (GWAX) practices due to uncorrected survival bias and nonrandom participation in parental illness surveys, which cause substantial discrepancies between AD GWAS and GWAX results. We demonstrate that the current AD GWAX provide highly misleading genetic correlations between AD risk and higher education, which subsequently affects a variety of genetic epidemiological applications involving AD and cognition.

Controlling for polygenic genetic confounding in epidemiologic association studies.

Epidemiologic associations estimated from observational data are often confounded by genetics due to pervasive pleiotropy among complex traits. Many studies either neglect genetic confounding altogether or rely on adjusting for polygenic scores (PGS) in regression analysis. In this study, we unveil that the commonly employed PGS approach is inadequate for removing genetic confounding due to measurement error and model misspecification.

Comparative single-cell transcriptional and proteomic atlas of clinical-grade injectable mesenchymal source tissues.

Bone marrow aspirate concentrate (BMAC) and adipose-derived stromal vascular fraction (ADSVF) are the most marketed stem cell therapies to treat a variety of conditions in the general population and elite athletes. Both tissues have been used interchangeably clinically even though their detailed composition, heterogeneity, and mechanisms of action have neither been rigorously inventoried nor compared. This lack of information has prevented investigations into ideal dosages and has facilitated anecdata and misinformation.

Pharmacokinetics, Fecal Output, and Grimace Scores in Rabbits Given Long-acting Buprenorphine or Fentanyl for Postsurgical Analgesia.

The New Zealand white rabbit (Oryctolagus cuniculus) is a frequently used surgical model. Pain management after surgery is a critical aspect of animal welfare. Recently, a long-acting buprenorphine formulation (Ethiqa XR; EXR) was approved for use in rats and mice but has not yet been investigated in rabbits.

Controlling for polygenic genetic confounding in epidemiologic association studies.

Epidemiologic associations estimated from observational data are often confounded by genetics due to pervasive pleiotropy among complex traits. Many studies either neglect genetic confounding altogether or rely on adjusting for polygenic scores (PGS) in regression analysis. In this study, we unveil that the commonly employed PGS approach is inadequate for removing genetic confounding due to measurement error and model misspecification.

Relationship of Age And Mobility Levels During Physical Rehabilitation With Clinical Outcomes in Critical Illness.

Objective: To determine whether age, mobility level, and change in mobility level across the first 3 physical rehabilitation sessions associate with clinical outcomes of patients who are critically ill.

Design: Retrospective, observational cohort study.

Setting: Medical Intensive Care Unit (MICU).

Effect of Heat Treatment on Mechanical Properties of Nickel-Titanium Instruments.

Introduction: The aim of this study was to evaluate the torsional resistance, cyclic fatigue resistance, and bending stiffness of nickel-titanium (NiTi) file systems with different heat treatments and cross-sectional designs.

Methods: WaveOne Primary treated with memory-triple (MT) heat treatment (WOMT) was compared with WaveOne Primary (WO) and WaveOne Gold Primary (WOG). Torsional resistance test was performed using a customized device, and the distortion angle, ultimate strength, and toughness were evaluated.

Pervasive biases in proxy GWAS based on parental history of Alzheimer's disease.

Almost every recent Alzheimer's disease (AD) genome-wide association study (GWAS) has performed meta-analysis to combine studies with clinical diagnosis of AD with studies that use proxy phenotypes based on parental disease history. Here, we report major limitations in current GWAS-by-proxy (GWAX) practices due to uncorrected survival bias and non-random participation of parental illness survey, which cause substantial discrepancies between AD GWAS and GWAX results. We demonstrate that current AD GWAX provide highly misleading genetic correlations between AD risk and higher education which subsequently affects a variety of genetic epidemiologic applications involving AD and cognition.

Plecanatide Improves Symptoms of Irritable Bowel Syndrome with Constipation: Results of an Integrated Efficacy and Safety Analysis of Two Phase 3 Trials.

Purpose: Patients with irritable bowel syndrome with constipation (IBS-C) experience abdominal pain with altered bowel movements. Plecanatide is indicated as IBS-C treatment in adults. This integrated analysis further characterizes plecanatide efficacy and safety in IBS-C.

Assessment of Stakeholder Perceptions and Cost of Implementing a Telemedicine Specialty Program at Correctional Facilities in North Carolina.

Background Delivering in-person health care to the more than 1.2 million incarcerated adults can be expensive, logistically challenging, fragmented, and pose security risks. The purpose of this study was to evaluate the implementation of a specialty care telemedicine program in statewide prisons in North Carolina during the COVID-19 pandemic.

Examining Sanction Type and Drug Offender Recidivism: A Register-Based Study in Finland.

Nordic countries incarcerate offenders at much lower rates in comparison with incarceration rates in the United States, and reincarcerate fewer people per capita. Noncustodial alternatives to sanctions, including fines and community service, are used extensively in Finland to reduce negative effects of institutionalization and subsequent disadvantage caused by incarceration. The nature of drug-involved offenders within the Finnish system is reviewed in light of current research about the effectiveness of incarceration and deterrence-based approaches for drug offenders.

Cooperative Pd/Cu Catalysis for Alkene Arylboration: Opportunities for Divergent Reactivity.

A preeminent challenge in alkene difunctionalization is the control of regio-, diastereo-, and enantioselectivity. In this Perspective, a Pd/Cu-cooperative catalytic system for alkene arylboration is highlighted that allows for the controlled introduction of substituents. In particular, examples that allowed for divergent reactivity from a single substrate based on the tuning of catalysts and reaction conditions are emphasized.

Implementing Collaborative Care Management of Behavioral Health for Patients with Inflammatory Bowel Disease.

Background: Individuals with inflammatory bowel disease (IBD) are up to twice as likely to suffer from anxiety and/or depression. Collaborative care management (CoCM) is an evidence-based approach to treating behavioral health disorders that have proven effective for a range of conditions in primary care and some specialty settings. This model involves a team-based approach, with care delivered by a care manager (case reviews and behavioral therapy), psychiatrist (case reviews and psychopharmacological recommendations), and medical provider (ongoing care including psychopharmacological prescriptions).

Occupational Exposure among Electronic Repair Workers in Ghana.

Electronic repair workers may be exposed to lead, mercury, cadmium and other elements including rare earth elements used in electronic equipment. In this study, repair work took place in small repair shops where, e.g.

The "Second Hit" of Repair in a Rabbit Model of Chronic Rotator Cuff Tear.

The rabbit supraspinatus is a useful translational model for rotator cuff (RC) repair because it recapitulates muscle atrophy and fat accumulation observed in humans after a chronic tear (the "first hit"). However, a timeline of RC tissue response after repair, especially with regard to recent evidence of muscle degeneration and lack of regeneration, is currently unavailable. Thus, the purpose of this study was to characterize the progression of muscle and fat changes over time after the repair of a chronic RC tear in the rabbit model.

Supraspinatus muscle architecture and physiology in a rabbit model of tenotomy and repair.

Chronic rotator cuff tears can cause severe functional deficits. Addressing the chronic fatty and fibrotic muscle changes is of high clinical interest; however, the architectural and physiological consequences of chronic tear and repair are poorly characterized. We present a detailed architectural and physiological analysis of chronic tear and repair (both over 8 and 16 wk) compared with age-matched control rabbit supraspinatus (SSP) muscles.

Implementation and Evaluation of a Telemedicine Program for Specialty Care in North Carolina Correctional Facilities.

This cross-sectional study evaluates the implementation of a telemedicine program in North Carolina prisons based on responses from individuals who were incarcerated, health care practitioners, and telepresenters.

Modular Synthesis of a Versatile Double-Allylation Reagent for Complex Diol Synthesis.

Double-allylation reagents allow for the construction of highly complex molecules in an expedient fashion. We have developed an efficient, modular, and enantioselective approach towards accessing novel variants of these reagents through Cu/Pd-catalyzed alkenylboration of alkenylboron derivatives. Importantly, we demonstrate novel use of an allylBdan reagent directly in a stereocontrolled allylation without initial deprotection to the boronic ester.

Acetabular Bone Marrow Aspiration During Total Hip Arthroplasty.

Biologically augmented surgical treatments of orthopaedic conditions are increasingly popular. Bone marrow aspirate concentrate is a key orthobiologic tissue source, and the field is moving from the standard iliac crest marrow aspiration toward local aspirations of marrow depots that are accessible during the standard-of-care procedures in an attempt to reduce morbidity, surgery time, and cost. Here, we present the aspiration of the standard iliac marrow depot, but through a novel acetabular approach during total hip arthroplasty.

Assessing the oxidative potential of PAHs in ambient PM using the DTT consumption assay.

The oxidative potential (OP) of atmospheric fine particulate matter (PM) has been linked to organic content, which includes polycyclic aromatic hydrocarbons (PAHs). The OP of 135 individual PAHs (including six subclasses) was measured using the dithiolthreitol (DTT) consumption assay. The DTT assay results were used to compute the concentration of each PAH needed to consume 50% of the DTT concentration in the assay (DTT), and the reduction potential of the PAHs (ΔG).

Backslide or forward progress? Virtual care at U.S. healthcare systems beyond the COVID-19 pandemic.

The COVID-19 pandemic forced most U.S. healthcare systems to quickly pivot to virtual care.