Systematic investigation of allelic regulatory activity of schizophrenia-associated common variants.

Genome-wide association studies (GWASs) have successfully identified 145 genomic regions that contribute to schizophrenia risk, but linkage disequilibrium makes it challenging to discern causal variants. We performed a massively parallel reporter assay (MPRA) on 5,173 fine-mapped schizophrenia GWAS variants in primary human neural progenitors and identified 439 variants with allelic regulatory effects (MPRA-positive variants). Transcription factor binding had modest predictive power, while fine-map posterior probability, enhancer overlap, and evolutionary conservation failed to predict MPRA-positive variants.

Group physical therapy for knee osteoarthritis: protocol for a hybrid type III effectiveness-implementation trial.

Background: Knee osteoarthritis (OA) is a leading cause of chronic pain and disability and one of the most common conditions treated in outpatient physical therapy (PT). Because of the high and growing prevalence of knee OA, there is a need for efficient approaches for delivering exercise-based PT to patients with knee OA. A prior randomized controlled trial (RCT) showed that a 6-session Group Physical Therapy Program for Knee OA (Group PT) yields equivalent or greater improvements in pain and functional outcomes compared with traditional individual PT, while requiring fewer clinician hours per patient to deliver.

The OARSI Joint Effort Initiative: Priorities for osteoarthritis management program implementation and research 2024-2028.

Objective: The Joint Effort Initiative (JEI) is an international collaboration of clinicians, researchers, and consumer organisations with a shared vision of improving the implementation of osteoarthritis management programs (OAMPs). This study aimed to identify JEI's future priorities and guide direction.

Design: A two-part international survey to prioritise topics of importance to our membership and research stakeholders.

Killing tumor-associated bacteria with a liposomal antibiotic generates neoantigens that induce anti-tumor immune responses.

Increasing evidence implicates the tumor microbiota as a factor that can influence cancer progression. In patients with colorectal cancer (CRC), we found that pre-resection antibiotics targeting anaerobic bacteria substantially improved disease-free survival by 25.5%.

Charting Aging Trajectories of Knee Cartilage Thickness for Early Osteoarthritis Risk Prediction: An MRI Study from the Osteoarthritis Initiative Cohort.

Knee osteoarthritis (OA), a prevalent joint disease in the U.S., poses challenges in terms of predicting of its early progression.

Features of Knee and Multijoint Osteoarthritis by Sex and Race and Ethnicity: A Preliminary Analysis in the Johnston County Health Study.

Objective: To evaluate knee osteoarthritis (KOA) and multijoint osteoarthritis (MJOA), and to compare features by sex and race and ethnicity in a population-based cohort.

Methods: Participants (n = 544) enrolled in the Johnston County Health Study (JoCoHS) as of January 2023 were categorized by radiographic and symptomatic KOA and MJOA phenotypes, and frequencies were compared by sex and race and ethnicity. Symptoms were assessed according to the Knee Injury and Osteoarthritis Outcome Score (KOOS) and pain, aching, and stiffness (PAS) scores at various joints.

Chromatin loop dynamics during cellular differentiation are associated with changes to both anchor and internal regulatory features.

Three-dimensional (3D) chromatin structure has been shown to play a role in regulating gene transcription during biological transitions. Although our understanding of loop formation and maintenance is rapidly improving, much less is known about the mechanisms driving changes in looping and the impact of differential looping on gene transcription. One limitation has been a lack of well-powered differential looping data sets.

The Association Between Racialized Discrimination in Health Care and Pain Among Black Patients With Mental Health Diagnoses.

Chronic pain is a costly and debilitating problem in the United States, and its burdens are exacerbated among socially disadvantaged and stigmatized groups. In a cross-sectional study of Black Veterans with chronic pain at the Atlanta VA Health Care System (N = 380), we used path analysis to explore the roles of racialized discrimination in health care settings, pain self-efficacy, and pain-related fear avoidance beliefs as potential mediators of pain outcomes among Black Veterans with and without an electronic health record-documented mental health diagnosis. In unadjusted bivariate analyses, Black Veterans with a mental health diagnosis (n = 175) reported marginally higher levels of pain-related disability and significantly higher levels of pain interference compared to those without a mental health diagnosis (n = 205).

Implementation intensification to disseminate a skills-based caregiver training program: protocol for a type III effectiveness-implementation hybrid trial.

Background: Family caregiver training decreases caregiver psychological burden and improves caregiver depressive symptoms and health-related quality of life. Caregivers FIRST is an evidence-based group skills training curriculum for family caregivers and was announced for national dissemination in partnership with the Veterans Health Administration (VHA) National Caregiver Support Program (CSP). Previous evaluations of Caregivers FIRST implementation highlighted that varying support was needed to successfully implement the program, ranging from minimal technical assistance to intensive assistance and support.

Machine Learning Approaches to the Prediction of Osteoarthritis Phenotypes and Outcomes.

Purpose Of Review: Osteoarthritis (OA) is a complex heterogeneous disease with no effective treatments. Artificial intelligence (AI) and its subfield machine learning (ML) can be applied to data from different sources to (1) assist clinicians and patients in decision making, based on machine-learned evidence, and (2) improve our understanding of pathophysiology and mechanisms underlying OA, providing new insights into disease management and prevention. The purpose of this review is to improve the ability of clinicians and OA researchers to understand the strengths and limitations of AI/ML methods in applications to OA research.

Cartilage-specific deficiency represses IGF-1 and enhances osteoarthritis severity in mice.

Objectives: Prior studies noted that chondrocyte SIRT6 activity is repressed in older chondrocytes rendering cells susceptible to catabolic signalling events implicated in osteoarthritis (OA). This study aimed to define the effect of deficiency on the development of post-traumatic and age-associated OA in mice.

Methods: Male cartilage-specific -deficient mice and intact controls underwent destabilisation of the medial meniscus (DMM) or sham surgery at 16 weeks of age and OA severity was analysed at 6 and 10 weeks postsurgery.

Precision Medicine-Based Machine Learning Analyses to Explore Optimal Exercise Therapies for Individuals With Knee Osteoarthritis: Random Forest-Informed Tree-Based Learning.

Objective: We applied a precision medicine-based machine learning approach to discover underlying patient characteristics associated with differential improvement in knee osteoarthritis symptoms following standard physical therapy (PT), internet-based exercise training (IBET), and a usual care/wait list control condition.

Methods: Participants (n = 303) were from the Physical Therapy vs Internet-Based Training for Patients with Knee Osteoarthritis trial. The primary outcome was the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) total score at 12-month follow-up.

Association Between Severe Nonadherence to Hydroxychloroquine and Systemic Lupus Erythematosus Flares, Damage, and Mortality in 660 Patients From the SLICC Inception Cohort.

Objective: The goals of this study were to assess the associations of severe nonadherence to hydroxychloroquine (HCQ), objectively assessed by HCQ serum levels, and risks of systemic lupus erythematosus (SLE) flares, damage, and mortality rates over five years of follow-up.

Methods: The Systemic Lupus International Collaborating Clinics (SLICC) Inception Cohort is an international multicenter initiative (33 centers throughout 11 countries). The serum of patients prescribed HCQ for at least three months at enrollment were analyzed.

Evidence-Based Dietary Practices to Improve Osteoarthritis Symptoms: An Umbrella Review.

While there is some research investigating whole foods or diets that are easily understood and accessible to patients with osteoarthritis, specific nutrients or nutraceuticals are more commonly identified. Unfortunately, guidelines and evidence surrounding individual nutrients, extracts, and nutraceuticals are conflicting and are more difficult to interpret and implement for patients with osteoarthritis. The purpose of this umbrella review is to provide a comprehensive understanding of the existing evidence of whole foods and dietary patterns effects on osteoarthritis-related outcomes to inform evidence-based recommendations for healthcare professionals and identify areas where more research is warranted.

Proximity-dependent recruitment of Polycomb repressive complexes by the lncRNA Airn.

During mouse embryogenesis, expression of the long non-coding RNA (lncRNA) Airn leads to gene repression and recruitment of Polycomb repressive complexes (PRCs) to varying extents over a 15-Mb domain. The mechanisms remain unclear. Using high-resolution approaches, we show in mouse trophoblast stem cells that Airn expression induces long-range changes to chromatin architecture that coincide with PRC-directed modifications and center around CpG island promoters that contact the Airn locus even in the absence of Airn expression.

Ready, set, go! The role of organizational readiness to predict adoption of a family caregiver training program using the Rogers' diffusion of innovation theory.

Background: Caregivers FIRST is an evidence-based program addressing gaps in caregivers' skills. In 2020, the Veterans Health Administration Caregiver Support Program (CSP) nationally endorsed Caregivers FIRST, offering credit in leadership performance plans to encourage all VA medical centers (VAMCs) to implement locally. This study examines the association of organizational readiness with VAMC adoption of Caregivers FIRST.

Delayed cartilage oligomeric matrix protein response to loading is associated with femoral cartilage composition post-ACLR.

Purpose: To determine associations between immediate and delayed response of serum cartilage oligomeric matrix protein (sCOMP) to loading (i.e., 3000 walking steps) and femoral cartilage interlimb T1ρ relaxation times in individual's post-anterior cruciate ligament reconstruction (ACLR).

Chromatin alternates between A and B compartments at kilobase scale for subgenic organization.

Nuclear compartments are prominent features of 3D chromatin organization, but sequencing depth limitations have impeded investigation at ultra fine-scale. CTCF loops are generally studied at a finer scale, but the impact of looping on proximal interactions remains enigmatic. Here, we critically examine nuclear compartments and CTCF loop-proximal interactions using a combination of in situ Hi-C at unparalleled depth, algorithm development, and biophysical modeling.

Effects of Implementation of a Supervised Walking Program in Veterans Affairs Hospitals : A Stepped-Wedge, Cluster Randomized Trial.

Background: In trials, hospital walking programs have been shown to improve functional ability after discharge, but little evidence exists about their effectiveness under routine practice conditions.

Objective: To evaluate the effect of implementation of a supervised walking program known as STRIDE (AssiSTed EaRly MobIlity for HospitalizeD VEterans) on discharge to a skilled-nursing facility (SNF), length of stay (LOS), and inpatient falls.

Design: Stepped-wedge, cluster randomized trial.

Intestinal Helminth Infection Impairs Oral and Parenteral Vaccine Efficacy.

The impact of endemic parasitic infection on vaccine efficacy is an important consideration for vaccine development and deployment. We have examined whether intestinal infection with the natural murine helminth Heligmosomoides polygyrus bakeri alters Ag-specific Ab and cellular immune responses to oral and parenteral vaccination in mice. Oral vaccination of mice with a clinically relevant, live, attenuated, recombinant Salmonella vaccine expressing chicken egg OVA (Salmonella-OVA) induced the accumulation of activated, OVA-specific T effector cells rather than OVA-specific regulatory T cells in the GALT.

Partner engagement for planning and development of non-pharmacological care pathways in the AIM-Back trial.

Background/aims: Embedded pragmatic clinical trials are increasingly recommended for non-pharmacological pain care research due to their focus on examining intervention effectiveness within real-world settings. Engagement with patients, health care providers, and other partners is essential, yet there is limited guidance for how to use engagement to meaningfully inform the design of interventions to be tested in pain-related pragmatic clinical trials. This manuscript aims to describe the process and impacts of partner input on the design of two interventions (care pathways) for low back pain currently being tested in an embedded pragmatic trial in the Veterans Affairs health care system.

-Gal Syndrome: Busting Paradigms in Food Allergy.

-Gal syndrome, also known as red or mammalian meat allergy, results from immunoglobulin E-mediated hypersensitivity responses to the carbohydrate galactose--1,3-galactose (-gal). Patients with -gal syndrome experience immediate onset of allergic symptoms following the injection of pharmaceutical products containing -gal. However, it typically takes 2 hours or more after dietary -gal ingestion before patients with -gal syndrome experience immunoglobulin E-mediated hypersensitivity responses.