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The diversity in our genome is crucial to understanding the demographic history of worldwide populations. However, we have yet to know whether subtle genetic differences within a population can be disentangled, or whether they have an impact on complex traits. Here we apply dimensionality reduction methods (PCA, t -SNE, PCA- t -SNE, UMAP, and PCA-UMAP) to biobank-derived genomic data of a Japanese population ( n  = 169,719). Dimensionality reduction reveals fine-scale population structure, conspicuously differentiating adjacent insular subpopulations. We further enluciate the demographic landscape of these Japanese subpopulations using population genetics analyses. Finally, we perform phenome-wide polygenic risk score (PRS) analyses on 67 complex traits. Differences in PRS between the deconvoluted subpopulations are not always concordant with those in the observed phenotypes, suggesting that the PRS differences might reflect biases from the uncorrected structure, in a trait-dependent manner. This study suggests that such an uncorrected structure can be a potential pitfall in the clinical application of PRS. Population structure, even subtle differences within seemingly homogenous populations, can have an impact on the accuracy of polygenic prediction. Here, Sakaue et al. use dimensionality reduction methods to reveal fine-scale structure in the Biobank Japan cohort and explore the performance of polygenic risk scores.

Systemic inflammation in rheumatoid arthritis (RA) is associated with metabolic changes. We used nuclear magnetic resonance (NMR) spectroscopy-based metabolomics to assess the relationship between an objective measure of systemic inflammation [C-reactive protein (CRP)] and both the serum and urinary metabolome in patients with newly presenting RA. Serum (n=126) and urine (n=83) samples were collected at initial presentation from disease modifying anti-rheumatic drug naïve RA patients for metabolomic profile assessment using 1-dimensional H-NMR spectroscopy. Metabolomics data were analysed using partial least square regression (PLS-R) and orthogonal projections to latent structure discriminant analysis (OPLS-DA) with cross validation. Using PLS-R analysis, a relationship between the level of inflammation, as assessed by CRP, and the serum (p=0.001) and urinary (p<0.001) metabolome was detectable. Likewise, following categorisation of CRP into tertiles, patients in the lowest CRP tertile and the highest CRP tertile were statistically discriminated using OPLS-DA analysis of both serum (p=0.033) and urinary (p<0.001) metabolome. The most highly weighted metabolites for these models included glucose, amino acids, lactate, and citrate. These findings suggest increased glycolysis, perturbation in the citrate cycle, oxidative stress, protein catabolism and increased urea cycle activity are key characteristics of newly presenting RA patients with elevated CRP. This study consolidates our understanding of a previously identified relationship between serum metabolite profile and inflammation and provides novel evidence that there is a relationship between urinary metabolite profile and inflammation as measured by CRP. Identification of these metabolic perturbations provides insights into the pathogenesis of RA and may help in the identification of therapeutic targets.

Digital health technology (DHT) plays an increasingly vital role in managing chronic diseases by enabling patients to actively manage their health. These tools have been shown to improve self-management and adherence to medical advice. However, for DHT to be fully effective, patients with chronic conditions must be digitally literate. The eHealth Literacy Scale (eHEALS), an 8‑item tool with scores ranging from 8 to 40, was developed to assess individuals' perceived ability to find, evaluate, and apply digital health information. Assessing patients' digital health literacy (DHL) and understanding the factors influencing it are essential for improving the accessibility and usability of health resources. This study aimed to assess DHL in patients with diabetes mellitus (DM), hypertension, and rheumatoid arthritis (RA) through a systematic review and meta‑analysis using eHEALS. We sought to determine average DHL scores, examine demographic and socioeconomic factors influencing DHL, and explore its impact on disease management to inform future strategies for enhancing DHL and improving chronic disease outcomes. Following PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, we conducted a systematic review across 7 databases (PubMed, SCOPUS, Embase, ERIC, CINAHL, Library Literature and Information Science Index, and Google Scholar) from inception to August 14, 2022, with an updated search in October 2024. Eligible studies included adults (≥18 years) with DM, hypertension, or RA who reported DHL data using eHEALS (8-40) and were original research published in English. Exclusion criteria included studies involving participants younger than 18 years, reviews, meta‑analyses, studies not addressing the target diseases, or non‑English publications. Study quality was evaluated using the Newcastle‑Ottawa Scale (NOS). Eight studies involving 2527 participants were included. The pooled mean eHEALS score was 27.03 (95% CI 25.08-28.98), indicating high overall DHL. Stratified by disease, scores were higher for DM (27.79) and hypertension (28.48) but lower for RA (24.74). Quality assessment indicated a high standard of included studies. Factors influencing DHL included age, education, employment, and perception of the internet as a health resource. Due to the limited number of studies, meta‑regression analysis could not be performed. DHL is critical for individuals with chronic conditions, empowering them to make informed decisions and manage their health effectively. However, the scarcity of studies limits comprehensive analysis of DHL determinants. While the internet offers abundant health information, unequal DHL and health skills remain barriers. More inclusive research is needed to fully understand DHL's impact on health outcomes and mitigate disparities, ensuring equitable access to digital health resources and improving disease management.

Background Communication skills is a core area of competency for healthcare practitioners. However, trainees deficient in those skills are not identified early enough to address the deficiency. Furthermore, faculty often struggle to identify effective remediation strategies for those who fail to meet expectations. We undertook a systematic review to determine which assessment methods are appropriate to identify learners that struggle with communication skills and the strategies used to remediate them. Methods The literature was searched from January 1998 through to May 2019 using academic databases and grey literature. Trainees were defined as healthcare practitioners in undergraduate, graduate and continuing education. Characteristics of studies, assessment and intervention strategies and outcomes were synthesized qualitatively and summarized in tables. Results From an initial 1636 records, 16 (1%) studies met the review criteria. Majority of the learners were medical students. A few studies (44%) included students from other disciplines, residents and physicians in practice. The remediation programs, in the studies, ranged from 1 week to 1 year. Around half of the studies focused solely on learners struggling with communication skills. The majority of studies used a format of a clinical OSCE to identify struggling learners. None of the studies had a single intervention strategy with the majority including an experiential component with feedback. Conclusions A few studies collectively described the diagnosis, remediation intervention and the assessment of the outcomes of remediation of communication skills. For a remediation strategy to be successful it is important to ensure: (i) early identification and diagnosis, (ii) the development of an individualized plan and (iii) providing reassessment with feedback to the learner.

 Behçet's syndrome (BS) is a chronic systemic inflammatory disorder with vascular involvement representing a severe complication. Despite its high prevalence along the Silk Route, data on vascular Behçet's in Middle Eastern populations remain limited. This study evaluates the prevalence, clinical features, and treatment outcomes of vascular BS in Qatar's multinational cohort. A retrospective analysis was conducted on 82 BS patients (2016-2024) meeting the International Criteria for Behçet's Disease (ICBD). Vascular involvement was confirmed via imaging (Doppler, CTA/MRA). Demographics, clinical manifestations, and treatment responses were characterized using descriptive analyses, and intervariable associations were statistically examined. Vascular involvement was identified in 20.7% (17/82) of patients, with a male predominance (76.5%) and earlier diagnosis among Arab patients (29.3 vs. 44.3 years, p=0.02). Multivascular involvement was the most common pattern (35.3%), followed by isolated venous thrombosis (29.4%) and isolated arterial involvement (11.8%). Overall, venous disease was the predominant vascular manifestation, occurring either as isolated venous thrombosis or as part of combined arterial-venous involvement. The favorable clinical outcomes observed with corticosteroid-immunosuppressant combination therapy strongly support the early initiation of aggressive immunomodulatory treatment in patients with vascular Behçet's disease. In Qatar, about 1 in 5 patients with Behçet's disease show signs of vascular involvement, with notable differences based on ethnicity and gender. Venous and multivascular involvement are more common, making comprehensive imaging essential. Immunosuppression, particularly steroid-biologic combinations, appears superior to anticoagulation alone. These findings highlight the need for region-specific management protocols in this high-risk population.

There is limited information on the epidemiology and treatment patterns of rheumatoid arthritis (RA) across the Arab region. We aim in this study to describe the demographic characteristics, clinical profile, and treatment patterns of patients of Arab ancestry with RA. This is a cross sectional study of 895 patients with established rheumatoid arthritis enrolled from five sites (Jordan, Lebanon, Qatar, Kingdom of Saudi Arabia (KSA), and United Arab Emirates). Demographic characteristics, clinical profile, and treatment patterns are compared between the five countries. The majority of our patients are women, have an average disease duration of 10 years, are married and non-smokers, with completed secondary education. We report a high (>80%) ever-use of methotrexate (MTX) and steroids among our RA population, while the ever-use of disease modifying anti-rheumatic drugs (DMARDs) and TNF-inhibitors average around 67% and 33%, respectively. There are variations in RA treatment use between the five country sites. Highest utilization of steroids is identified in Jordan and KSA (p-value < 0.001), while the highest ever-use of TNF-inhibitors is reported in KSA (p-value < 0.001). Disparities in usage of RA treatments among Arab patients are noted across the five countries. National gross domestic product (GDP), as well as some other unique features in each country likely affect these. Developing treatment guidelines specific to this region could contribute in delivering standardized therapies to RA patients.

Established in 2015, the Multi-Stakeholder Engagement (MuSE) Consortium is an international network of over 120 individuals interested in stakeholder engagement in research and guidelines. The MuSE group is developing guidance for stakeholder engagement in the development of health and healthcare guideline development. The development of this guidance has included multiple meetings with stakeholders, including patients, payers/purchasers of health services, peer review editors, policymakers, program managers, providers, principal investigators, product makers, the public, and purchasers of health services and has identified a number of key issues. These include: (1) Definitions, roles, and settings (2) Stakeholder identification and selection (3) Levels of engagement, (4) Evaluation of engagement, (5) Documentation and transparency, and (6) Conflict of interest management. In this paper, we discuss these issues and our plan to develop guidance to facilitate stakeholder engagement in all stages of the development of health and healthcare guideline development. Plain English summary A group of international researchers, patient partners, and other stakeholders are working together to create a checklist for when and how to involve stakeholders in health guideline development. Health guidelines include clinical practice guidelines, which your healthcare provider uses to determine treatments for health conditions. While working on this checklist, the team identified key issues to work on, including: (1) Definitions, roles, and settings (2) Stakeholder identification and selection (3) Levels of engagement, (4) Evaluation of engagement, (5) Documentation and transparency, and (6) Conflict of interest management. This paper describes each issue and how the team plans to produce guidance papers to address them.

Recent metabolomics studies of Rheumatoid Arthritis (RA) reported few metabolites that were associated with the disease, either due to small cohort sizes or limited coverage of metabolic pathways. Our objective is to identify metabolites associated with RA and its cofounders using a new untargeted metabolomics platform. Moreover, to investigate the pathomechanism of RA by identifying correlations between RA-associated metabolites. 132 RA patients and 104 controls were analyzed for 927 metabolites. Metabolites were tested for association with RA using linear regression. OPLS-DA was used to discriminate RA patients from controls. Gaussian Graphical Models (GGMs) were used to identify correlated metabolites. 32 metabolites are identified as significantly (Bonferroni) associated with RA, including the previously reported metabolites as DHEAS, cortisol and androstenedione and extending that to a larger set of metabolites in the steroid pathway. RA classification using metabolic profiles shows a sensitivity of 91% and specificity of 88%. Steroid levels show variation among the RA patients according to the corticosteroid treatment; lowest in those taking the treatment at the time of the study, higher in those who never took the treatment, and highest in those who took it in the past. Finally, the GGM reflects metabolite relations from the steroidogenesis pathway.

The Medical Student Performance Evaluation (MSPE) is an important tool of communication used by program directors to make decisions in the residency application process. To understand the perspective and usage of the MSPE across multiple medical specialties now and in anticipation of the planned changes in USMLE Step 1 score-reporting. A survey instrument including quantitative and qualitative measures was developed and piloted. The final survey was distributed to residency programs across 28 specialties in 2020 via the main contact on the ACGME listserv. Of the 28 specialties surveyed, at least one response was received from 26 (93%). Eight percent of all programs (364/4675) responded to the survey, with most respondents being program directors. Usage of the MSPE varied among specialties. Approximately 1/3 of end-users stated that the MSPE is very or extremely influential in their initial screening process. Slightly less than half agreed or strongly agreed that they trust the information to be an accurate representation of applicants, though slightly more than half agree that the MSPE will become more influential once USMLE Step 1 becomes pass/fail. Professionalism was rated as the most important component and noteworthy characteristics among the least important in the decision-making process. Performance in the internal medicine clerkship was rated as the most influential while neurology and psychiatry performances were rated as less influential. Overwhelmingly, respondents suggested that including comparative performance and/or class rank would make the MSPE more useful once USMLE Step 1 becomes pass/fail. MSPE end-users across a variety of specialties utilize this complex document in different ways and value it differentially in their decision-making processes. Despite this, continued mistrust of the MSPE persists. A better understanding of end-users' perceptions of the MSPE offers the UME community an opportunity to transform the MSPE into a highly valued, trusted document of communication.

Background It has been hypothesized that adaptation of health practice guidelines to the local setting is expected to improve their uptake and implementation while cutting on required resources. We recently adapted the published American College of Rheumatology (ACR) Rheumatoid Arthritis (RA) treatment guideline to the Eastern Mediterranean Region (EMR). The objective of this paper is to describe the process used for the adaptation of the 2015 ACR guideline on the treatment of RA for the EMR. Methods We used the GRADE-Adolopment methodology for the guideline adaptation process. We describe in detail how adolopment enhanced the efficiency of the following steps of the guideline adaptation process: (1) groups and roles, (2) selecting guideline topics, (3) identifying and training guideline panelists, (4) prioritizing questions and outcomes, (5) identifying, updating or conducting systematic reviews, (6) preparing GRADE evidence tables and EtD frameworks, (7) formulating and grading strength of recommendations, (8) using the GRADEpro-GDT software. Results The adolopment process took 6 months from January to June 2016 with a project coordinator dedicating 40% of her time, and the two co-chairs dedicating 5% and 10% of their times respectively. In addition, a research assistant worked 60% of her time over the last 3 months of the project. We held our face-to-face panel meeting in Qatar. Our literature update included five newly published trials. The certainty of the evidence of three of the eight recommendations changed: one from moderate to very low and two from low to very low. The factors that justified a very low certainty of the evidence in the three recommendations were: serious risk of bias and very serious imprecision. The strength of five of the recommendations changed from strong to conditional. The factors that justified the conditional strength of these 5 recommendations were: cost ( n  = 5 [100%]), impact on health equities ( n  = 4 [80%]), the balance of benefits and harms ( n  = 1 [20%]) and acceptability (n = 1 [20%]). Conclusion This project confirmed the feasibility of GRADE-Adolopment. It also highlighted the value of collaboration with the organization that had originally developed the treatment guideline. We discuss the implications for both guideline adaptation and future research to advance the field.