👤 Evgenii Gusev

Social context modulates stress physiology and resilience, yet preclinical rat paradigms vary widely in stressor type, timing of social exposure, contact modality, and endpoint definitions. We synthesized rat studies to quantify directional and, where feasible, standardized effect-size evidence for social buffering and to outline translational implications. PubMed, Scopus, and Web of Science were searched (2008-2025) for in vivo rat studies comparing conspecific (pair/group housing or conspecific presence) versus solitary conditions across validated stress and PTSD-like paradigms (e.g., fear conditioning/extinction, CUS/CMS, social defeat, predator threat). Data extraction and reporting followed PRISMA 2020 and SYRCLE guidance. Synthesis followed a two-tier approach: (i) all eligible contrasts were direction-coded as beneficial, neutral/mixed, or detrimental under conspecific conditions based strictly on reported statistical contrasts; and (ii) for domains with sufficient coded contrasts, the proportion of beneficial comparisons was estimated with exact binomial tests and 95% confidence intervals. Standardized mean-difference meta-analysis (Hedges' g; random-effects REML) was conducted only for predefined outcomes with adequate numerical reporting. Forty studies met inclusion criteria, yielding 89 extracted comparisons. Overall, 69/89 comparisons (≈78%) favored conspecific conditions. Domain-level directional syntheses supported predominance of beneficial outcomes for hormonal (0.72; 95% CI 0.50-1.00; p = 0.048) and neurotrophic/plasticity markers (0.89; 95% CI 0.57-1.00; p = 0.020), whereas inflammatory/oxidative outcomes were more variable (0.71; 95% CI 0.39-0.94; p = 0.227). For predefined behavioral endpoints with sufficient data, effect-size pooling showed a large reduction in conditioned fear (Hedges' g = -1.22 [-1.53; -0.91], p < 0.0001). Social buffering is robust at behavioral and neuroendocrine levels and often aligns with neurotrophic/plasticity markers, while peripheral immune/redox readouts are more context-dependent. Show less

Tumor-induced osteomalacia (TIO) is a rare disorder caused by a phosphaturic mesenchymal tumor (PMT) secreting fibroblast growth factor 23 (FGF23). The aim of this study was to analyze PMTs for their transcriptomic characteristics. We performed single-cell RNA (n = 3) alongside bulk RNA sequencing of PMTs (n = 5) and surrounding bone tissue (n = 4) obtained during tumor removal in 10 patients (age 44 (41;64), serum phosphate (Pi)- 0.54 (0.43; 0.59) mM/L, FGF23-113 (40; 205) pg/ml). We revealed a total of 22,449 cells divided into 13 different categories. We identified the heterogeneity of the PMT cell cluster and subsequently divided it into two tumor clusters 1 and 2 characterized by the deeper epithelial-mesenchymal phenotype transition, higher FGF23 expression as well as various SNP and CNV. We further identified tumor cell differentiation driving regulons ERG and EGR3, based on scoring by allele expression and velocity based pseudotime on a trajectory that may play a critical role in the tumorigenesis of PMTs. In both single-cell and bulk transcriptome analysis we found upregulation of vesicle-specific and exocytosis associated genes (SLC30A3, SYT1, STX1A and SNAP25) which most likely represent molecular mechanisms of active secretion in all PMT samples. We report transmembrane protein coding genes expressed in all PMTs specifically in tumor cell clusters (PHEX, ERBB4, PCDH7, LRRFIP2) which are suggested as potential diagnostic targets. We confirmed the presence of FN1-FGFR1 fusion genes and Klotho expression in most PMTs (6 out of 8). Conclusion: specific SNARE proteins gene upregulation along with transcriptional signatures of PMT offer new insights into its pathogenesis which may be further studied for diagnostic and therapeutic interventions. Show less

We sought to identify susceptibility genes for high-grade serous ovarian cancer (HGSOC) by performing a transcriptome-wide association study of gene expression and splice junction usage in HGSOC-relevant tissue types (N = 2,169) and the largest genome-wide association study available for HGSOC (N = 13,037 cases and 40,941 controls). We identified 25 transcriptome-wide association study significant genes, 7 at the junction level only, including LRRC46 at 19q21.32, (P = 1 × 10 Show less