3D chromatin structure in chondrocytes identifies putative osteoarthritis risk genes.

Genome-wide association studies have identified over 100 loci associated with osteoarthritis risk, but the majority of osteoarthritis risk variants are noncoding, making it difficult to identify the impacted genes for further study and therapeutic development. To address this need, we used a multiomic approach and genome editing to identify and functionally characterize potential osteoarthritis risk genes. Computational analysis of genome-wide association studies and ChIP-seq data revealed that chondrocyte regulatory loci are enriched for osteoarthritis risk variants.

Tibiofemoral knee osteoarthritis progresses symmetrically by knee compartment in the GOGO cohort.

Objective: To evaluate the degree of symmetry of knee osteoarthritis (OA) structural severity and progression of participants with a mean follow-up time of 3.8 years.

Design: Participants from the Genetics of Generalized Osteoarthritis (GOGO) study (n = 705) were selected on the basis of radiographic evidence of OA in at least 1 knee, availability of radiographs at baseline and follow-up, and no history of prior knee injury or surgery.

Early ablation of Ccr2 in aggrecan-expressing cells following knee injury ameliorates joint damage and pain during post-traumatic osteoarthritis.

Objective: To investigate whether Ccr2 inactivation in aggrecan-expressing cells induced before post-traumatic OA (PTOA) onset or during progression, improves joint structures, synovial thickness and pain.

Design: We induced a Ccr2 deletion in aggrecan-expressing cells (CCR2-AggKO) in skeletally mature mice using a tamoxifen-inducible Ccr2 inactivation. We stimulated PTOA changes (destabilization of medial meniscus, DMM) in CCR2-AggKO and CCR2+/+ mice, inducing recombination before DMM or 4 wks after DMM (early-vs late-inactivation).

The Disparities in Patient Portal Use Among Patients With Rheumatic and Musculoskeletal Diseases: Retrospective Cross-sectional Study.

Background: During the COVID-19 pandemic, the shift to virtual care became essential for the continued care of patients. Individuals with rheumatic and musculoskeletal diseases (RMDs) especially require frequent provider visits and close monitoring. To date, there have been limited studies examining inequities in health technology use among patients with RMDs.

Association of Biomarkers with Individual and Multiple Body Sites of Pain: The Johnston County Osteoarthritis Project.

Introduction: Biochemical biomarkers may provide insight into musculoskeletal pain reported at individual or multiple body sites. The purpose of this study was to determine if biomarkers or pressure-pain threshold (PPT) were associated with individual or multiple sites of pain.

Methods: This cross-sectional analysis included 689 community-based participants.

Comet assay for quantification of the increased DNA damage burden in primary human chondrocytes with aging and osteoarthritis.

It is known that chondrocytes from joints with osteoarthritis (OA) exhibit high levels of DNA damage, but the degree to which chondrocytes accumulate DNA damage during "normal aging" has not been established. The goal of this study was to quantify the DNA damage present in chondrocytes obtained from cadaveric donors of a wide age range, and to compare the extent of this damage to OA chondrocytes. The alkaline comet assay was used to measure the DNA damage in normal cartilage from the ankle (talus) and the knee (femur) of cadaveric donors, as well as in OA chondrocytes obtained at the time of total knee replacement.

Biomarker clusters differentiate phenotypes of lumbar spine degeneration and low back pain: The Johnston County Osteoarthritis Project.

Objective: Describe the association between biomarkers and lumbar spine degeneration (vertebral osteophytes [OST], facet joint osteoarthritis [FOA], and disc space narrowing [DSN]), for persons with and without low back pain (LBP) and determine whether clusters based on biomarkers differentiate lumbar spine structure with and without LBP.

Methods: Using data from the Johnston County Osteoarthritis Project (2006-2010), we measured serum N-cadherin, Keratin-19, Lumican, CXCL6, RANTES, HA, IL-6, BDNF, OPG, and NPY, and urinary CTX-II. Biomarkers were used to group participants using k-means cluster analysis.

Construction of an Administrative Osteoarthritis Severity Index.

Objective: Electronic health record (EHR) databases are a powerful resource to investigate clinical trajectories of osteoarthritis (OA). There are no existing EHR tools to evaluate risk for knee arthroplasty (KA). We developed an OA severity index (OASI) using EHR data and demonstrate the index's association with time to KA.

Osteoarthritis Treatment Guidelines from Six Professional Societies: Similarities and Differences.

Despite the high prevalence and burden of osteoarthritis (OA) worldwide, management of OA continues to primarily focus on symptom management due to the lack of approved pharmacologic agents that halt disease progression. Recent recommendations from 6 professional societies support the importance of education, self-management approaches, weight loss, and physical modalities in managing OA. These recent guidelines also highlight the paucity of effective and safe treatment options, with recommendations against ineffective therapies outnumbering those for effective ones.

Remission and low disease activity (LDA) prevent damage accrual in patients with systemic lupus erythematosus: results from the Systemic Lupus International Collaborating Clinics (SLICC) inception cohort.

Objective: To determine the independent impact of different definitions of remission and low disease activity (LDA) on damage accrual.

Methods: Patients with ≥2 annual assessments from a longitudinal multinational inception lupus cohort were studied. Five mutually exclusive disease activity states were defined: remission off-treatment: clinical Systemic Lupus Erythematosus Disease Activity Index (cSLEDAI)-2K=0, without prednisone or immunosuppressants; remission on-treatment: cSLEDAI-2K score=0, prednisone ≤5 mg/day and/or maintenance immunosuppressants; low disease activity Toronto cohort (LDA-TC): cSLEDAI-2K score of ≤2, without prednisone or immunosuppressants; modified lupus low disease activity (mLLDAS): Systemic Lupus Erythematosus Disease Activity Index-2K score of 4 with no activity in major organ/systems, no new disease activity, prednisone ≤7.

Foot pain and inflammatory markers: a cross sectional study in older adults.

Background: Foot disorders may limit independence and reduce quality of life for older adults. Obesity is a risk factor for foot conditions; both mechanical load and metabolic effects may contribute to these conditions. This study determined cross-sectional associations between inflammatory markers and foot disorders.

Adapting to CONNECT: modifying a nursing home-based team-building intervention to improve hospital care team interactions, functioning, and implementation readiness.

Background: Clinical interventions often need to be adapted from their original design when they are applied to new settings. There is a growing literature describing frameworks and approaches to deploying and documenting adaptations of evidence-based practices in healthcare. Still, intervention modifications are often limited in detail and justification, which may prevent rigorous evaluation of interventions and intervention adaptation effectiveness in new contexts.

A multi-omic dissection of super-enhancer driven oncogenic gene expression programs in ovarian cancer.

The human genome contains regulatory elements, such as enhancers, that are often rewired by cancer cells for the activation of genes that promote tumorigenesis and resistance to therapy. This is especially true for cancers that have little or no known driver mutations within protein coding genes, such as ovarian cancer. Herein, we utilize an integrated set of genomic and epigenomic datasets to identify clinically relevant super-enhancers that are preferentially amplified in ovarian cancer patients.

Identifying Family and Unpaid Caregivers in Electronic Health Records: Descriptive Analysis.

Background: Most efforts to identify caregivers for research use passive approaches such as self-nomination. We describe an approach in which electronic health records (EHRs) can help identify, recruit, and increase diverse representations of family and other unpaid caregivers.

Objective: Few health systems have implemented systematic processes for identifying caregivers.

Narrative Review of Machine Learning in Rheumatic and Musculoskeletal Diseases for Clinicians and Researchers: Biases, Goals, and Future Directions.

There has been rapid growth in the use of artificial intelligence (AI) analytics in medicine in recent years, including in rheumatic and musculoskeletal diseases (RMDs). Such methods represent a challenge to clinicians, patients, and researchers, given the "black box" nature of most algorithms, the unfamiliarity of the terms, and the lack of awareness of potential issues around these analyses. Therefore, this review aims to introduce this subject area in a way that is relevant and meaningful to clinicians and researchers.

Increased Wnt/β-catenin signaling contributes to autophagy inhibition resulting from a dietary magnesium deficiency in injury-induced osteoarthritis.

Background: Dietary magnesium deficiency, which is common in modern diet, has been associated with osteoarthritis (OA) susceptibility. Despite this clinical association, no study has addressed if dietary magnesium deficiency accelerates OA development, especially at molecular level. This study aimed to explore aggravating effects of dietary magnesium deficiency on cartilage damage in an injury-induced murine OA model and to determine the underlying mechanism.

Biclustering reveals potential knee OA phenotypes in exploratory analyses: Data from the Osteoarthritis Initiative.

Objective: To apply biclustering, a methodology originally developed for analysis of gene expression data, to simultaneously cluster observations and clinical features to explore candidate phenotypes of knee osteoarthritis (KOA) for the first time.

Methods: Data from the baseline Osteoarthritis Initiative (OAI) visit were cleaned, transformed, and standardized as indicated (leaving 6461 knees with 86 features). Biclustering produced submatrices of the overall data matrix, representing similar observations across a subset of variables.

Synthetic amyloid beta does not induce a robust transcriptional response in innate immune cell culture systems.

Background: Alzheimer's disease (AD) is a progressive neurodegenerative disease that impacts nearly 400 million people worldwide. The accumulation of amyloid beta (Aβ) in the brain has historically been associated with AD, and recent evidence suggests that neuroinflammation plays a central role in its origin and progression. These observations have given rise to the theory that Aβ is the primary trigger of AD, and induces proinflammatory activation of immune brain cells (i.