For the first time, imaging photoplethysmography synchronized with an electrocardiogram was used to study and diagnose systemic lupus erythematosus. It was found that patients experience significant changes in the photoplethysmographic characteristics of the microvasculature of the facial skin in the cheeks compared with the control. Therefore, the proposed technique can pretend to be an objective instrumental criterion of the disease.
BACKGROUND:TMEM43 (transmembrane protein 43) is a ubiquitously expressed 4-transmembrane-protein localized in the endoplasmic reticulum and nuclear lamina. The missense mutation TMEM43-p.S358L causes fully penetrant ARVC5 (arrhythmogenic right ventricular cardiomyopathy type 5) especially in males. The TMEM43 function of the protein and the pathomechanisms of TMEM43-p.S358L remain poorly understood. We analyzed carrier-derived human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs), human myocardial tissue from TMEM43-wild-type, and TMEM43-p.S358L and identified differentially interacting proteins. Here we provide evidence for a novel pathomechanism contributing to the onset of ARVC5. METHODS:Microsomes of human wild-type myocardium were separated by sucrose-gradient ultracentrifugation and characterized by mass-spectrometry to identify potential interacting proteins. Proteome and metabolome analyses of a TMEM43-p.S358L explanted human myocardium were performed. hiPSC-derived cardiomyocytes of TMEM43-p.S358L carrier and a corresponding isogenic control were generated. A 3'-end HA-Tag was introduced in TMEM43 for pull-down experiments under optimized conditions. Lipidomics, proteomics, contractility, and ATP-content were measured in hiPSC-CMs. RESULTS:Pull-down analyses of TMEM43-WT and mutant showed altered interacting proteins involved in metabolic pathways. Lipidomics revealed the accumulation of lipids and decreased lipid metabolism capacity in mutant hiPSC-CMs. The ATP to ADP ratio was lower in mutant hiPSC-CMs and could be associated with diminished contraction frequency. The human TMEM43-p.S358L myocardial proteome revealed altered protein-expression of metabolic pathways comparable to mutant hiPSC-CMs. Metabolic remodeling was also found in the mutant human myocardium. Ultracentrifugation fraction with the highest protein amount of TMEM43 and pull-down experiments of hiPSC-CMs revealed differentially interacting proteins of TMEM43-p.S358L from endoplasmic reticulum and mitochondrial membranes. CONCLUSIONS:We suggest differential interaction of mutant TMEM43 with proteins of mitochondria and endoplasmic reticulum influences endoplasmic reticulum-mitochondrial contact sites. TMEM43-p.S358L primarily contributes to changes in mitochondrial function affecting lipid homeostasis and energy supply.
Children with invasive aspergillosis (IA) experience significant morbidity and mortality. Posaconazole is a broad-spectrum triazole antifungal agent indicated for IA treatment in adolescents and adults. A phase 2, open-label, noncomparative, multinational clinical trial in pediatric participants (2-to-<18 years old, body weight ≥10 kg) with possible, probable, or proven IA was conducted. Participants received intravenous posaconazole for ≥1 week, after which they could switch to oral posaconazole for a total treatment duration <12 weeks. Posaconazole dosing and selection of oral formulation (tablet or oral suspension [PFS]) were weight-based. The primary endpoint was safety, assessed as treatment-related adverse events (TRAE) through 14 days after treatment cessation. Global clinical response was a secondary and all-cause mortality an exploratory endpoint. PFS palatability was assessed using a 5-point scale. Thirty-one participants (proven/probable IA n = 9, possible invasive fungal disease n = 22) received ≥1 dose of posaconazole; 14 were 2 to <12 years, and 17 were 12 to <18 years old. Median treatment duration was 49 (range: 2-88) days. Seven participants (22.6%; 95% confidence interval [CI]: 9.6, 41.1) had ≥1 TRAE (grade 1 or 2, all resolved). One participant discontinued treatment due to a nonserious TRAE. Favorable global clinical response rates through weeks 6 and 12 were 67.7% (95% CI: 48.6, 83.3) and 77.4% (95% CI: 58.9, 90.4), respectively (no relapses). Day 114 all-cause mortality was 12.9%. No participants experienced problems taking PFS, and 90.0% rated PFS palatability as very good to neutral. Posaconazole was well tolerated and associated with high clinical response rates in pediatric patients with IA.CLINICAL TRIALSThis study is registered with ClinicalTrials.gov as NCT04218851.
Post-COVID-19 syndrome (PCS), also referred to as post-acute sequelae of SARS-CoV-2 infection (PASC), represents a heterogeneous set of persistent clinical manifestations developing after acute infection. These conditions are associated with immune dysregulation, autonomic imbalance, impaired thymic function, and possible viral persistence. Objective: This study aims to systematically synthesise current evidence on the immunopathogenesis of PCS and to critically evaluate the application of artificial intelligence (AI) and machine learning (ML) approaches for its prediction and clinical stratification. Methods: A PRISMA 2020–informed systematic review was conducted using PubMed/MEDLINE, Scopus, Web of Science, elibrary.ru and Embase databases (January 2020–December 2025). Studies addressing immunopathological mechanisms and AI/ML applications in PCS were selected based on predefined eligibility criteria. Risk of bias in prediction studies was assessed using the PROBAST tool. Due to heterogeneity, a structured qualitative synthesis was performed. Current evidence indicates that PCS may result from sustained systemic inflammation, cytokine dysregulation, autoimmunity, and delayed restoration of T-cell homeostasis, including reduced thymic output of naïve T lymphocytes. Persistent thymic dysfunction may contribute to prolonged immune imbalance, increased susceptibility to secondary infections, and reactivation of latent viruses. AI/ML approaches—including gradient boosting, ensemble learning, deep neural networks, and natural language processing—have demonstrated promising performance across multimodal datasets. However, significant limitations were identified, including small sample sizes, overfitting, lack of external validation, and heterogeneity in outcome definitions. Conclusions: The integration of immunopathological insights with data-driven modelling highlights the potential of combined approaches for improving PCS risk stratification. However, current AI models remain insufficiently validated for clinical implementation. Future research should prioritise methodological standardisation, external validation, and incorporation of mechanistically informed biomarkers.
INTRODUCTION: The increasing number of patients requiring prolonged mechanical ventilation (MV) is associated with a higher risk of complications, including ventilator-associated pneumonia and diaphragm dysfunction. Timely assessment of a patient's readiness for weaning from respiratory support helps minimize the risks associated with prolonged MV; however, existing predictive criteria require comprehensive evaluation due to their variable diagnostic significance. OBJECTIVE: Analysis of the clinical efficacy of predictive indicators for discontinuing MV. MATERIALS AND METHODS: A literature search was performed in PubMed and eLibrary databases in Russian and English. Inclusion criteria: randomized controlled trials, meta-analyses, clinical guidelines; studies with MV duration of less than 24 hours were excluded. RESULTS: The analysis showed that the Rapid Shallow Breathing Index (RSBI) remains the most extensively studied predictor of successful weaning from MV. However, its predictive value varies significantly depending on the etiology of respiratory failure and the methodology of the spontaneous breathing trial. Parameters such as P0.1 (airway occlusion pressure) and NIF (negative inspiratory force), which reflect respiratory effort, demonstrated a strong correlation with successful weaning but require careful interpretation considering the underlying disease and current ventilator settings. Promising approaches include ultrasound assessment of diaphragm function and metabolic marker analysis. Clinical studies confirm the importance of a comprehensive patient evaluation, including fluid balance and echocardiography data, to predict potential hemodynamic complications. Special attention should be paid to the cough reflex, which serves as a significant additional criterion for weaning readiness. CONCLUSIONS: Optimizing the weaning process from MV requires a comprehensive assessment of respiratory, hemodynamic, and metabolic parameters. The development of standardized algorithms with a personalized approach is a priority for future research.
