A triad of somatic mutagenesis converges in self-reactive B cells to cause a virus-induced autoimmune disease.

The unexplained association between infection and autoimmune disease is strongest for hepatitis C virus-induced cryoglobulinemic vasculitis (HCV-cryovas). To analyze its origins, we traced the evolution of pathogenic rheumatoid factor (RF) autoantibodies in four HCV-cryovas patients by deep single-cell multi-omic analysis, revealing three sources of B cell somatic mutation converged to drive the accumulation of a large disease-causing clone. A method for quantifying low-affinity binding revealed recurring antibody variable domain combinations created by V(D)J recombination that bound self-immunoglobulin G (IgG) but not viral E2 antigen.

Uncovering the boundary conditions of the association between concerns about falling and physical activity in adult populations: a scoping review protocol.

Introduction: Despite evidence of variation in how concerns about falling influence physical activity, many of the currently available knowledge syntheses merely assume that this relation is uniform across populations and contexts. Therefore, we propose a scoping review protocol to guide a summary of the bodywork that has examined the association between concerns about falling and physical activity in adult populations, with an eye on the availability of empirical evidence of moderation.

Methods And Analyses: Studies reporting on both the concepts of concerns about falling and physical activity among samples with a mean age≥18 years will be included.

Organizational Determinants to Hypertension Management: Adapting a Health Equity Framework to Examine Processes at Two Academic Health Systems.

Background: Hypertension management is a national priority. However, hypertension control rates are suboptimal and vary across clinics, even among those in the same health system and geographic region.

Objective: To identify organizational barriers and facilitators that impact hypertension management at the provider, clinic, and health system level.

Physical activity, sedentary behaviour, and cardiovascular disease risk factors in Canadians living with and without cardiovascular disease.

Background: To describe and compare the proportion of adult Canadians living with and without cardiovascular disease (CVD) meeting the physical activity (PA) and sedentary behaviour (SB) recommendations from the Canadian 24-Hour Movement Guidelines using accelerometer and self-reported measures.

Methods: Using adult (aged 18-79 years) accelerometer data (Actical worn during waking hours for 7 consecutive days) as well as chronic condition, socio-demographic, recreational screen time, and PA questions from three combined cycles of the Canadian Health Measures Survey, the PA, SB, and CVD risk factors of adults living with and without CVD were compared.

Results: A total of 7,035 Canadian adults who reported living with (n=363) and without (n=6,672) CVD were included.

Proteome profiling of cerebrospinal fluid using machine learning shows a unique protein signature associated with APOE4 genotype.

Proteome changes associated with APOE4 variant carriage that are independent of Alzheimer's disease (AD) pathology and diagnosis are unknown. This study investigated APOE4 proteome changes in people with AD, mild cognitive impairment, and no impairment. Clinical, APOE genotype, and cerebrospinal fluid (CSF) proteome and AD biomarker data was sourced from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database.