Near-peer teaching (NPT) in medical education supports active learning and peer engagement while fostering professional development. However, the academic benefits for NPT tutors, including effects on performance and graduation timelines, remain underexplored. We evaluated the impact of NPT participation on academic outcomes, including grade point averages (GPAs), final examination performance, and curriculum adherence. A five-year dataset comprising 1544 medical students was analyzed. Academic performance metrics included GPAs from basic sciences and clinical rotations, diploma GPA, final board exam scores, and progression through semesters. Multiple regression and Generalized Additive Models (GAMs), adjusting for baseline performance and confounders, were used to assess associations. NPT tutors were found to have significantly higher diploma GPAs (+0.24, p < .001) and State exam scores (+0.15, p < .001) than non-tutors. They also had fewer passive semesters (-0.25, p < .001) and shorter total study duration (-0.79 semesters, p < .001). Non-linear interactions were observed between early academic performance and later outcomes. Participation as an NPT tutor was associated with higher academic performance and more efficient curricular progression. Academic benefits were most pronounced among students with lower preclinical GPAs, suggesting that NPT may represent a high-impact opportunity to support students who face early academic challenges.

Autoantibody production is a hallmark of systemic sclerosis (SSc) and the most extensively studied role of B cells in the pathogenesis of the disease. However, the potential involvement of innate immune molecules in B-cell dysfunction in SSc is less understood. B-cell activation is an early event in the pathogenesis of SSc and is influenced by complement receptors (CRs) and Toll-like receptors (TLRs), shaping antibody responses. CR2 and CR1 modulate B-cell activation, and the roles of CR3 and CR4 are associated with autoimmune conditions. We investigated the expression of CRs in B cells from patients with the more severe form of the disease, diffuse cutaneous SSc (dcSSc), and the effect of TLR CD180 ligation on their expression. We found no significant difference in the basal expression of CD21 and CD11c in B cells between dcSSc and healthy controls (HCs). However, reduced basal CD11b expression in B cells in dcSSc compared to HCs, accompanied by a decrease in CD35 and an increase in CD11c expression following CD180 ligation may promote plasma cell formation and autoantibody production. Additionally, we searched for correlations between dcSSc-associated anti-DNA topoisomerase I (Scl-70) autoantibody, anti-citrate synthase (CS) natural autoantibody and complement component 3 (C3) levels and found a negative correlation between C3 and anti-CS autoantibody in dcSSc but not in HCs, supporting the hypothesis that natural autoantibodies could activate the complement system contributing to tissue injury in SSc.

Type I interferon (IFN-I) signaling has been shown to be upregulated in systemic sclerosis (SSc). Dysregulated B-cell functions, including antigen presentation, as well as antibody and cytokine production, all of which may be affected by IFN-I signaling, play an important role in the pathogenesis of the disease. We investigated the IFN-I signature in 71 patients with the more severe form of the disease, diffuse cutaneous SSc (dcSSc), and 33 healthy controls (HCs). Activation via Toll-like receptors (TLRs) can influence the IFN-I signaling cascade; thus, we analyzed the effects of the TLR homologue CD180 ligation on the IFN-I signature in B cells. CD180 stimulation augmented the phosphorylation of signal transducer and activator of transcription 1 (STAT1) in dcSSc B cells (p = 0.0123). The expression of IFN-I receptor (IFNAR1) in non-switched memory B cells producing natural autoantibodies was elevated in dcSSc (p = 0.0109), which was enhanced following anti-CD180 antibody treatment (p = 0.0125). Autoantibodies to IFN-Is (IFN-alpha and omega) correlated (dcSSc p = 0.0003, HC p = 0.0192) and were present at similar levels in B cells from dcSSc and HC, suggesting their regulatory role as natural autoantibodies. It can be concluded that factors other than IFN-alpha may contribute to the elevated IFN-I signature of dcSSc B cells, and one possible candidate is B-cell activation via CD180.

Background: Serum C–C motif chemokine ligand 18 (seCCL18) in systemic sclerosis (SSc) has been primarily associated with progressive interstitial lung disease (SSc-ILD) and mortality. However, its relationship with non-pulmonary organ involvement, disease activity, and long-term outcome has not been comprehensively evaluated. We therefore examined the clinical relevance of seCCL18 in a single-center SSc cohort. Methods: A total of 151 patients with SSc (83 diffuse cutaneous (dcSSc), 68 limited cutaneous SSc (lcSSc); median (IQR) disease duration: 9 (4;16) years) and 47 age- and sex-matched healthy controls (HCs) were enrolled. Serum CCL18 concentrations were measured by enzyme-linked immunosorbent assay. Elevated seCCL18 was defined as >130 ng/mL (mean + 2 SD of the healthy control group). Organ involvement and disease activity (EUSTAR Activity Index, EUSTAR-AI) were assessed at baseline, while survival was analysed longitudinally. Results: Patients with SSc had significantly higher seCCL18 levels than HCs (mean ± SD: 99.9 ± 43.2 vs. 75.0 ± 27.5 ng/mL, p < 0.01). Elevated seCCL18 was associated with SSc-ILD (81.1% vs. 60.5%, p = 0.022), reduced forced vital capacity (FVC < 70%: 16.2% vs. 3.5%, p = 0.006), and reduced diffusing capacity for carbon monoxide (DLCO < 70%: 80.6% vs. 54.4%, p = 0.005). Higher seCCL18 levels were observed in patients with myocardial disease (104.8 ± 41.8 vs. 83.8 ± 44.2 ng/mL, p = 0.008), left ventricular diastolic dysfunction (107.1 ± 40.5 vs. 84.5 ± 45.0 ng/mL, p < 0.001), and oesophageal involvement (110.7 ± 38.3 vs. 93.3 ± 43.1 ng/mL, p = 0.009). SeCCL18 levels above the cut-off were more frequently associated with tendon friction rubs (51.4% vs. 27.4%, p = 0.007), active disease (EUSTAR-AI ≥ 2.5: 73% vs. 44%, p = 0.002), and elevated inflammatory markers (CRP > 5 mg/L: 51.4% vs. 19.3%, p < 0.001; ESR > 28 mm/h: 37.8% vs. 18.4%, p = 0.015). During a median follow-up of 87 months, 22 patients (15%) died. Elevated baseline seCCL18 predicted poorer survival in univariate analysis (log-rank p = 0.013) and remained an independent predictor of mortality in multivariable Cox regression (HR 1.789; 95% CI 1.133–2.824; p = 0.013), together with declining DLCO and reduced six-minute walk test performance. Conclusions: Elevated seCCL18 may identify patients with systemic sclerosis who exhibit a more severe multisystem phenotype, including cardiopulmonary, gastrointestinal, and musculoskeletal involvement, increased inflammatory activity, and reduced long-term survival. These findings suggest that seCCL18 may have some clinical utility as a prognostic biomarker reflecting widespread disease involvement beyond the lungs, even in patients with long-standing disease; however, the lack of an established cut-off value requires further validation in prospective, multicentre studies.