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Scharf, M.

Publications and source records attributed to Scharf, M..

2 recordsLinked to original sources

Social Jet Lag Estimated From CPAP Adherence Data in Two Obstructive Sleep Apnea Cohorts

BackgroundSocial jet lag (SJL), the discrepancy timing between work nights and free nights, reflects schedule-related circadian misalignment. Time-stamped CPAP adherence records may provide objective, longitudinal estimates of sleep timing and could augment conventional CPAP reports by adding information on sleep regularity and weekday-weekend misalignment. ObjectivesTo quantify CPAP-derived SJL in two independent clinical cohorts, characterize its behavioral correlates and age-related patterns, and assess cross-site reproducibility. MethodsWe analyzed CPAP-derived sleep timing in patients from Rutgers-RWJ Health (RWJ, N = 1,437) and Hackensack Meridian Health (HMH, N = 1,510) with at least 31 valid nights and at least one valid work night and free night. Mid-sleep on work nights (MSW) and free nights (MSF) was estimated using circular statistics. SJL was defined as the absolute circular difference between MSF and MSW and categorized as none (<1 h), moderate (1-2 h), or severe ([&ge;]2 h). Sleep duration, free-night rebound, age-stratified prevalence, and cross-site differences were evaluated using nonparametric and categorical tests. ResultsSJL was right-skewed at both sites, with median values below 0.5 h at RWJ and HMH. SJL >1 h was present in 21.2% and 16.4% of patients, respectively; severe SJL occurred in 4.0% and 2.8%. Moderate and severe SJL were associated with shorter work-night sleep and greater free-night rebound, consistent with weekday restriction and weekend compensation. SJL prevalence and variability were highest in younger and middle-aged adults, particularly those aged 26-50 years, and declined markedly after age 65. Core timing phenotypes, including MSW, MSF, and free-night rebound, were highly reproducible across sites despite modest differences in absolute sleep duration and overall SJL prevalence. ConclusionsIn CPAP-treated cohorts, SJL is common but usually modest, is associated with weekday sleep restriction and free-night rebound, and declines substantially with age. These findings support the use of routinely collected CPAP data as a scalable, low-burden source of device-anchored circadian screening phenotypes. CPAP-derived SJL may augment standard adherence reports by helping identify patients who warrant further behavioral, circadian, or activity-based assessment.

physiology↗

CSF single-cell RNA sequencing reveals clonally expanded CD4+ stem cell-like memory T cells in GAD65-antibody associated neurological syndromes

BackgroundGlutamic acid decarboxylase (GAD) antibody-associated autoimmune neurological syndromes (AINS) are a spectrum of autoimmune-mediated CNS disorders. While antibodies targeting the 65 kDa isoform of GAD are of high diagnostic value, T cell mediated cytotoxicity has been identified as a key component of disease pathogenesis. The precise pathophysiological mechanisms by which the disease is triggered and maintained, however, remain incompletely understood. MethodsWe performed single-cell transcriptome and immune repertoire sequencing (sc-seq) in CSF and blood of 8 anti-GAD65 AINS patients compared to 8 non-inflammatory controls. Monoclonal antibodies (mAbs) were synthesized from B cell receptor (BCR) data to evaluate the B cellular immune response. FindingsWe identified an increase and expansion of activated CD4+ stem cell-like memory T cells (TSCM) in the CSF of anti-GAD65 AINS patients. Expanded T cells showed increased expression of proinflammatory genes. The mAb analysis revealed a high frequency of GAD65-reactive BCRs in the CSF of anti-GAD65 AINS patients with increased somatic hypermutations compared to non-GAD-reactive BCRs and BCRs from controls. ConclusionsSc-seq identified clonally expanded CD4+ TSCM in the CSF of anti-GAD65 AINS patients harboring cytotoxic properties likely contributing to disease pathogenesis. GAD-reactive B cells circulate in the CSF of anti-GAD65 AINS patients further supporting the concept of an antigen-specific intrathecal immune response. Future studies need to clarify the actual pathogenicity of these immune cells and the link between T and B cellular immune mechanisms in the pathogenesis of anti-GAD65 AINS. FundingGerman Research Foundation (ERARE18-202 UltraAIE), German Federal Ministry of Education and Research (CONNECT GENERATE (2.0); 01GM1908A and 01GM2208A).

immunology↗