Search Results (170)

Congenital factor V (FV) deficiency is a rare autosomal recessive bleeding disorder caused by pathogenic variants in F5 gene and characterized by heterogeneous clinical manifestations. The aim of this study was to define the mutational spectrum of F5 in Russian patients with congenital FV deficiency. We analyzed 16 unrelated patients with different disease severity and 9 relatives from five families. All functionally relevant regions of F5 were examined by Sanger sequencing. Multiplex ligation-dependent probe amplification (MLPA) was used to detect large deletions and duplications. Whole-genome sequencing and functional cDNA analysis were performed in selected cases. This study represents the first description of the F5 mutational spectrum in a Russian cohort. We identified 12 novel variants and demonstrated the functional effect of two previously unreported variants located outside canonical splice-site dinucleotides, leading to aberrant splicing. Notably, the proportion of variants undetectable by routine diagnostic approaches was higher than that reported in other populations. No clear genotype–phenotype correlation was observed. Despite the limited sample size, our findings expand current knowledge of the molecular basis of congenital FV deficiency and may improve genetic diagnostics in Russia. Full article

The Vehicle-to-Grid (V2G) technology is considered one of the best solutions for integrating renewable energy systems; however, most literature reports favorable economic results using synthetic data, without accounting for seasonal or market limitations. The current research presents the results of the MATLAB R2023b (Version 23.2, MathWorks, Natick, MA, USA) simulation of the 100-household energy community in Debrecen, Hungary, with 30 electric vehicles (EVs) using entirely simulation-based Lithium Iron Phosphate (LiFePO4) batteries, a simulation-based 150 kW solar photovoltaic (PV) system, and a simulation-based 200 kW wind power system, using real meteorological data for January 2024. The optimization of charging/discharging for electric vehicles was performed using a multi-objective genetic algorithm (GA) over 30 days at a 15 min time resolution, accounting for stochastic loads and temperature effects on battery degradation, with a sensitivity analysis of key parameters. The results of the optimized solution for the electric vehicle charging/discharging were unexpected: the total energy cost increased by 68.9% ($4337.65 to $7327.54), the peak demand increased by 266.2% (31.9 to 116.9 kW), the degradation cost was $479.63, the load factor was reduced from 0.847 to 0.722, and the SOC constraint was violated for 0.758% of measurements. The V2G is not economically viable under current Hungarian pricing and Central Europe winter conditions. Results are robust for varying parameters using sensitivity analysis and Pareto front tracing. The break-even point is achieved when ratios of peak-to-off-peak prices are above 3.5:1. Seasonal policies and market reforms are critical for V2G viability. Importantly, the influence of inherent design deficiencies in the optimization model on the reported results cannot be ruled out. Full article

To unveil the underlying risk structures in complex industrial systems, this paper proposes a hybrid analytical framework that integrates BERTopic modeling, a large language model (LLM), and social network analysis (SNA). This framework aims to extract systemic safety intelligence from unstructured accident reports. It first employs BERTopic to identify latent causal topics based on 745 Chinese accident investigation reports and utilizes DeepSeek-V3.1 (LLM) for semantic refinement and causal mapping of these topics. Subsequently, a semantic network of causal keywords based on positive pointwise mutual information (PPMI) is constructed, and its topological structure is analyzed using SNA methods. The study identifies and analyzes five major risk communities: confined spaces, fire, mining, construction, and road traffic. It reveals that accident causation exhibits the small-world characteristics of multi-factor coupling and non-linearity, with core risk nodes concentrated in systemic inducements such as organizational management and compliance deficiencies. The results demonstrate that this framework effectively identifies the latent systemic risk patterns embedded within the texts, providing methodological support for developing sustainable safety management mechanisms based on design for safety. Full article

Background: Thrombotic thrombocytopenic purpura (TTP) is a life-threatening condition resulting from a disintegrin and metalloproteinase with thrombospondin type 1 motif, member 13 (ADAMTS13) deficiency, leading to the accumulation of ultra-large von Willebrand factor (vWF) multimers and widespread microvascular thrombosis. While therapeutic plasma exchange and immunosuppression have significantly improved response, refractory and relapsed disease are significant challenges. N-acetylcysteine (NAC) has emerged as a biologically plausible adjunctive therapy due to its potential to reduce disulfide bonds in vWF multimers. However, its clinical role is unclear. This systematic review aimed to evaluate the clinical evidence regarding the efficacy and safety of N-acetylcysteine in patients with immune-mediated TTP. Methods: We performed a systematic review in accordance with the PRISMA guidelines. PubMed/MEDLINE, Google Scholar, and ClinicalTrials.gov were searched until January 2026. Studies involving patients with immune-mediated TTP treated with NAC were included. Case reports, case series, and observational studies involving patients with immune-mediated TTP treated with NAC were included. Risk of bias was evaluated using adapted quality assessment tools. Results: Sixteen studies encompassing 69 patients met the inclusion criteria. Most reports were case reports or small case series; two were larger observational cohorts. NAC was predominantly used as adjunctive therapy in relapsed or refractory TTP. Dose regimens varied. Platelet recovery following NAC was reported within 1–15 days in responding cases. Predominantly positive haematological responses were observed in small series. Significant heterogeneity in patient populations, timing of initiation, concomitant therapies, and outcome reporting limited causal inference. Conclusions: The current evidence suggests that NAC has a biologically rational and potentially adjunctive value in TTP, particularly in refractory disease or resource-constrained settings. However, current data are largely heterogeneous and derived from low-level evidence. Well-designed prospective studies and randomized controlled trials are needed to determine whether NAC provides significant clinical benefit beyond standard therapy. Full article

Autoimmune thyroiditis (AIT) is characterized by dysregulated endocrine–immune interactions, and vitamin D has been proposed as a potential immunomodulatory factor influencing vaccine-induced immune responses. This study investigated the association between serum vitamin D status and humoral responses to SARS-CoV-2 vaccination in patients with AIT, while exploring potential molecular mechanisms using network pharmacology, molecular docking and Molecular Dynamics (MD) simulations. Patients were stratified according to serum 25-hydroxyvitamin D levels as deficient, insufficient, or sufficient. Anti–spike receptor-binding domain (RBD) IgG titers, thyroid autoantibodies, and thyroid-stimulating hormone levels were measured. In parallel, vitamin D₃ related molecular targets were integrated with AIT-associated genes, followed by protein–protein interaction analysis, molecular docking and MD simulations were performed to assess the interactions between vitamin D₃ (cholecalciferol) and selected key proteins. An inverse correlation was observed between serum vitamin D levels and anti-RBD IgG titers (p = 0.0013), with higher antibody responses detected in vitamin D-deficient patients. Network pharmacology analysis highlighted CYP19A1, CYP17A1, and ESR1 as prioritized targets associated with steroid hormone biosynthesis and endocrine signaling pathways. Molecular docking showed compatible binding of vitamin D₃ to these proteins, while MD simulations supported the structural stability of the complexes over time. Collectively, these findings suggest that vitamin D status may influence post-vaccination humoral immune responses in AIT, potentially through modulation of endocrine–immune crosstalk. Further longitudinal and mechanistic studies are required to clarify causality and clinical relevance. Full article

Vitamin D is a secosteroid hormone traditionally recognized for its role in bone and mineral metabolism, but it is increasingly understood to also function as an important immunomodulator influencing susceptibility to and outcomes of infectious diseases. This narrative review summarizes current evidence on the immunological, clinical, and preventive effects of vitamin D in the context of novel coronavirus disease (COVID-19), post-acute sequelae of SARS-CoV-2 infection (long COVID), and influenza. Mechanistically, vitamin D enhances innate immune defenses through the induction of antimicrobial peptides, including cathelicidin and defensins, and modulates adaptive immunity by suppressing maladaptive Th1/Th17 responses while promoting regulatory T-cell activity. Observational studies have frequently associated vitamin D deficiency with more severe COVID-19 outcomes; however, these associations may be influenced by confounding factors and reverse causality. Some meta-analyses suggest that vitamin D supplementation reduced rates of intensive care unit admission and ventilatory support, particularly among older adults and individuals with low baseline serum 25-hydroxyvitamin D concentrations. Emerging evidence also indicates that inadequate vitamin D status may be associated with an increased risk and symptom burden of long COVID, although causality has not been established. In the case of influenza, a limited number of randomized controlled trials (RCTs) and meta-analyses report a modest but statistically significant reduction in infection risk, especially with daily or weekly vitamin D supplementation in populations with low baseline vitamin D levels. Clinical guidelines consistently recommend maintaining adequate vitamin D status for general health but do not endorse high-dose vitamin D as a treatment for COVID-19 due to inconsistent trial findings. Overall, vitamin D should not be considered a standalone therapeutic agent; rather, maintaining sufficient vitamin D levels represents a low-risk, potentially beneficial strategy to support immune resilience against respiratory viral infections. Full article

Metabolic bariatric surgery (MBS) induces substantial metabolic, inflammatory, and nutritional changes that can alter hemostatic balance through redox-dependent mechanisms. This systematic review evaluated coagulation disturbances after MBS with emphasis on oxidative stress and micronutrient deficiencies. A structured search of PubMed, Scopus, and Web of Science (2000–2025) identified 1707 records; 21 studies met inclusion criteria. Available evidence suggests that although MBS reduces obesity-related inflammation and oxidative burden in many patients, a proportion of individuals may present with persistent redox imbalance, elevated D-dimer or vWF (von Willebrand Factor), and delayed normalization of fibrinolysis. Micronutrient deficiencies—particularly vitamins K, B12, folate, selenium, zinc, and copper—are common after malabsorptive procedures and contribute to both thrombotic and hemorrhagic complications by impairing antioxidant defenses, endothelial function, and vitamin K-dependent coagulation pathways. Postoperative venous thromboembolism (VTE) incidence ranges from 0.3 to 0.5%, with higher risk after Roux-en-Y gastric bypass than sleeve gastrectomy, while bleeding is primarily associated with vitamin K deficiency, marginal ulcers, and anticoagulant exposure. The findings underscore the interdependence of oxidative stress, nutritional status, and hemostasis after MBS. Individualized thromboprophylaxis, routine detection of micronutrient deficiencies, and long-term biochemical monitoring are essential to maintain hemostatic stability. Standardized redox–hemostasis biomarker panels are needed to clarify mechanistic pathways and improve postoperative preventive strategies. Full article

Clonal hematopoiesis of indeterminate potential (CHIP) is defined by the expansion of hematopoietic stem cells harboring leukemogenic mutations in the absence of overt malignancy. Strongly associated with advancing age, CHIP is detected by next-generation sequencing of peripheral blood in more than 20% of individuals over 80, most commonly through mutations in DNMT3A, TET2, ASXL1, and PPM1D. While CHIP confers over a four-fold increased risk of hematologic malignancy, it has recently emerged as a key determinant of cardiometabolic health. Epidemiological data indicated a 40% higher cardiovascular disease (CVD) risk events and a 34% increase in all-cause mortality among CHIP carriers, with specific mutations and larger clone sizes conferring greater cardiovascular burden. Preclinical studies have shown that macrophages deficient in TET2 or DNMT3A drive interleukin (IL)-1β/IL-6 inflammasome activation, thereby promoting atherosclerosis and metabolic dysfunction, whereas the JAK2V617F mutation accelerates thrombosis. CHIP integrates into a broader network of dysregulation encompassing adiposity and inflammaging, which underlies its association with diverse comorbidities, including type 2 diabetes (T2D), chronic kidney disease (CKD), and chronic obstructive pulmonary disease (COPD). Multi-omics approaches have identified epigenetic and proteomic signatures correlated with CHIP expansion, providing potential biomarkers for risk stratification. Despite growing evidence of its systemic impact, CHIP screening remains limited to research settings. Emerging therapeutic strategies, including inflammasome inhibition, STING modulation, and epigenetic restoration, highlight its potential as a modifiable risk factor. This narrative review synthesizes current epidemiological, mechanistic, and translational insights, framing CHIP as an emerging causal factor in cardiometabolic disease and as a promising target for precision medicine in aging populations. Full article

Background/Objectives: Machine learning is an extremely important issue, considering the potential to prevent the onset of long-term complications from coronavirus disease or to ensure timely detection and effective treatment. The aim of our study was to develop an algorithm and mathematical model to predict the risk of developing long COVID in children who have had acute SARS-CoV-2 viral infection, taking into account a wide range of demographic, clinical, and laboratory parameters. Methods: We conducted a cross-sectional study involving 305 pediatric patients aged from 1 month to 18 years who had recovered from acute SARS-CoV-2 infection. To perform a detailed analysis of the factors influencing the development of long-term consequences of coronavirus disease in children, two models were created. The first model included basic demographic and clinical characteristics of the acute SARS-CoV-2 infection, as well as serum levels of vitamin D and zinc for all patients from both groups. The second model, in addition to the aforementioned parameters, also incorporated laboratory test results and included only hospitalized patients. Results: Among 265 children, 138 patients (52.0%) developed long COVID, and the remaining 127 (48.0%) fully recovered. We included 36 risk factors of developing long COVID in children (DLCC) in model 1, including non-hospitalized patients, and 58 predictors in model 2, excluding them. These included demographic characteristics of the children, major comorbid conditions, main symptoms and course of acute SARS-CoV-2 infection, and main parameters of complete blood count and coagulation profile. In the first model, which accounted for non-hospitalized patients, multivariate regression analysis identified obesity, a history of allergic disorders, and serum vitamin D deficiency as significant predictors of long COVID development. In the second model, limited to hospitalized patients, significant risk factors for long-term sequelae of acute SARS-CoV-2 infection included fever and the presence of ≥3 symptoms during the acute phase, a history of allergic conditions, thrombocytosis, neutrophilia, and altered prothrombin time, as determined by multivariate regression analysis. To assess the acceptability of the model as a whole, an ANOVA analysis was performed. Based on this method, it can be concluded that the model for predicting the risk of developing long COVID in children is highly acceptable, since the significance level is p < 0.001, and the model itself will perform better than a simple prediction using average values. Conclusions: The results of multivariate regression analysis demonstrated that the presence of a burdened comorbid background—specifically obesity and allergic pathology—fever during the acute phase of the disease or the presence of three or more symptoms, as well as laboratory abnormalities including thrombocytosis, neutrophilia, alterations in prothrombin time (either shortened or prolonged), and reduced serum vitamin D levels, are predictors of long COVID development among pediatric patients. Full article

Background/Objectives: β-Carotene oxygenase-2 (BCO2) is a mitochondrial carotenoid-cleaving enzyme expressed in multiple tissues, including the lungs. While BCO2 regulates carotenoid handling, its role in shaping pulmonary immune architecture and antiviral responses is unknown. We hypothesized that BCO2 deficiency reprograms epithelial–innate circuits and alters antiviral outcomes. Methods: BCO2-knockout (KO) and C57BL/6J wild-type (WT) mice underwent lung single-cell RNA sequencing (scRNA-seq), immunoblotting, and intranasal SARS-CoV-2 challenge to assess cell-type heterogeneity, pathway programs (by gene set variation analysis, GSVA), and antiviral responses. Results: scRNA-seq resolved 14 major lung cell populations with cell-type-specific pathway shifts. Compared with WT, BCO2 KO lungs showed increased conventional dendritic cells and natural killer (NK) cells, with reductions in macrophages, B cells, and endothelial cells. In KO alveolar type II cells, GSVA indicated a stress-adapted metabolic program. Ciliated epithelium exhibited vitamin-K-responsive and axoneme-remodeling signatures with attenuated glucocorticoid and very-low-density lipoprotein remodeling. Innate lymphoid type 2 cells favored fatty acid oxidation and chromatin dynamics with reduced mitochondrial activity. NK cells were biased toward constitutive chemokine/cytokine secretion and counter-inflammatory signaling. Immunoblotting confirmed the elevated level of interferon regulatory factor-3 protein in BCO2-KO lungs. Functionally, BCO2-KO mice had improved outcomes after intranasal SARS-CoV-2 exposure. Conclusions: Loss of BCO2 reconfigures the pulmonary immune landscape and enhances antiviral responsiveness in mice. These findings identify BCO2 as a nutrient-linked enzyme with immunomodulatory impact and highlight cell-state changes as candidate mechanisms for improved antiviral tolerance. Full article

Background: As the member of the B7 family, V-set and immunoglobulin domain-containing 4 (VSIG4) plays an essential role in regulating immune responses against bacterial infection, autoimmune disease, and chronic viral infection. However, the role of VSIG4 in acute viral infections remains largely unclear. Methods: Here, we constructed a gene-targeted VSIG4-deficient mouse model and then infected it with influenza to explore the detailed VSIG4-involved mechanism. Results: Our results demonstrated that the gene-deficient mice exhibited reduced survival rates, ranging from 25% to 50%, after being infected with different influenza virus strains. At the sites of infection, an increased number of CD8⁺ T cells, along with heightened expression of pro-inflammatory cytokines, e.g., Il-6 and TNFα, may have contributed to tissue damage. The recombinant VSIG4 protein slightly improved protection from the influenza challenge, suggesting regulatory functions of VSIG4 during infection. Using in vitro cell models, we show that the type C lectin receptor pathway member DC-SIGNR1 (CD209) is an essential factor during acute virus infection. The affinity and CO-IP tests indicated an interaction between CD209 and VSIG4, but not through protein modification. Conclusions: Therefore, VSIG4 functionally protected mice by regulating the type C lectin receptor pathway to inhibit excessive Th1 immune responses and inflammation. Our findings highlight the importance of considering immune homeostasis in the development of therapies for severe infections. Full article

Water stress represents one of the most critical limiting factors affecting plant distribution, growth rate, biomass accumulation, and crop yield across diverse growth stages. Variations in species’ drought tolerance fundamentally shape global biodiversity patterns by influencing survival rates, distribution ranges, and community composition under changing environmental conditions. This study investigated the physiological responses of six plant species (Haloxylon ammodendron (H.A.), Nitraria tangutorum Bobr. (N.T.B.), Sympegma regelii Bge. (S.R.B.), Tamarix chinensis (T.C.), Potentilla fruticosa (P.F.R.), and Sabina chinensis (Linn.) Ant. (S.C.A.)) to varying water stress levels through controlled water gradient experiments. Four treatment levels were established: W1 (full water supply, >70% field water holding capacity); W2 (mild stress, 50–55%); W3 (moderate stress, 35–40%); and W4 (severe stress, 20–25%). Height growth and leaf mass per area decreased significantly with increasing water stress across all species. S.C.A. consistently exhibited the highest leaf mass per area among the six species, while H.A. showed the lowest values across all treatments. Leaf water content declined progressively with intensifying water stress, with T.C. and P.F.R. showing the most pronounced reductions (T.C.: 16.53%, 18.07%, and 33.37% under W2, W3, and W4, respectively; P.F.R.: 19.45%, 28.52%, and 36.08%), whereas N.T.B. and H.A. demonstrated superior water retention capacity (N.T.B.: 2.44%, 6.64%, and 9.76%; H.A.: 1.44%, 4.39%, and 5.52%). Water saturation deficit increased correspondingly with declining soil moisture. Diurnal leaf water potential patterns exhibited a characteristic V-shaped curve under well-watered (W1) and mildly stressed (W2) conditions, transitioning to a double-valley pattern with unstable fluctuations under moderate (W3) and severe (W4) stress. Leaf water potential showed linear relationships with air temperature and relative humidity, and a quadratic relationship with atmospheric water potential. For all six species, the relationship between pre-dawn leaf water potential and soil water content followed the curve equation y = a + b/x. Under water-deficient conditions, S.C.A. exhibited the greatest water physiological changes, followed by P.F.R. Both logarithmic and power function relationships between leaf and soil water potentials were highly significant (all F > 55.275, all p < 0.01). T.C. leaf water potential was the most sensitive to soil water potential changes, followed by S.C.A., while H.A. demonstrated the least sensitivity. These findings provide essential theoretical foundations for selecting drought-resistant plant species in arid regions of the Qaidam Basin. This study elucidates the response mechanisms of six distinct drought-tolerant plant species under water stress. It provides critical theoretical support for selecting drought-tolerant species, designing community configurations, and implementing water management strategies in vegetation restoration projects within the arid Qaidam Basin. Furthermore, it contributes empirical data at the plant physiological level to understanding the mechanisms sustaining species diversity in arid ecosystems. Full article

Background and Clinical Significance: Chronic Myeloid Leukemia (CML) management has been revolutionized by tyrosine kinase inhibitors (TKIs), though cardiovascular and thrombotic complications remain a concern, especially in patients with underlying risk factors. Inherited thrombophilia, including protein S deficiency and Factor V Leiden mutation, poses a substantial risk for venous thromboembolism (VTE). Managing CML in patients with such prothrombotic predispositions presents complex therapeutic challenges, particularly in selecting an appropriate TKI and managing anticoagulation. Case Presentation: A 33-year-old woman with congenital thrombophilia (type I protein S deficiency and heterozygous Factor V Leiden mutation) and a history of VTE on long-term anticoagulation with acenocoumarol presented with CML. She exhibited primary resistance to first-line imatinib and poor tolerance with suboptimal response to second-line bosutinib. Third-line treatment with asciminib led to a rapid and sustained major molecular response (MR4.5) without bleeding or thrombotic complications. Conclusions: This case highlights the importance of individualized, multidisciplinary management in CML patients with coexisting thrombophilia. Asciminib, with its favorable cardiovascular safety profile, represents a promising therapeutic option in high-risk patients where other TKIs may be contraindicated due to resistance, intolerance, or thrombotic risk. Full article

Sustainable construction has evolved into a global priority to mitigate the impacts of climate change, as the construction industry significantly contributes to environmental degradation and the overexploitation of resources. This study considers the effects on sustainability, particularly the inadequate management of resources, the ecological impact, and the anticipated degradation of the structures, all of which are due to the omission of the structural analysis during the design phase of the reinforced concrete (RC) structure. A methodical survey was conducted in three major cities among 258 professionals in the construction sector in Burundi, a developing country that has suffered socio-political and infrastructural challenges. The study examines the impact of these challenges on construction results. Quantitative analysis was carried out using SPSS v.30 and Amos 26 Software. For this research, reliability analysis, Kaiser-Meyer-Olkin test (KMO), Bartlett test, Exploratory Factor Analysis (EFA), Principal Component Analysis (PCA), and the Relative Importance Index (RII) were used to ensure the reliability and accuracy of the data. The results indicate that many projects are taking place in the absence of proper structural analysis due to financial constraints, poor quality materials, lack of qualified personnel, poor enforcement of regulations, and insufficient monitoring. These parameters have led to structural deficiencies compromising sustainability. The study recommends that government agencies, professional construction workers, and building owners improve regulation, teaching effectiveness, and professional responsibility to ensure that fundamental practices, such as structural analysis and the use of right sustainable materials, are logically applied to improve public safety and environmental resilience. Full article

Background and Objectives: Congenital thrombophilias are biologically plausible contributors to chronic thromboembolic pulmonary hypertension (CTEPH), yet their frequency and clinical impact remain uncertain. We undertook a systematic review to (i) estimate the pooled prevalence of specific hereditary defects among adults with CTEPH, (ii) characterise associated demographic and haemodynamic phenotypes, and (iii) summarise peri-operative and survival outcomes after pulmonary endarterectomy (PEA) or balloon pulmonary angioplasty (BPA) in genetically defined subgroups. Methods: A protocol compliant with PRISMA-2020 was registered prospectively on the Open Science Framework (OSF). PubMed/MEDLINE, Scopus, and Web of Science were searched from inception to 1 June 2025 using validated, PRESS-reviewed strings combining CTEPH and thrombophilia terms. Observational cohorts, case–control studies and trials reporting laboratory-confirmed congenital thrombophilias in adults with right-heart-catheter-defined CTEPH were eligible. Results: Eight studies encompassing 677 unique CTEPH patients met the inclusion criteria. Among the 400 individuals screened for deficiencies of the natural anticoagulant pathways, 56 possessed a defect: protein S deficiency 5.3% (21/400; 95% CI 3.3–8.0), protein C deficiency 4.3% (17/400; 2.5–6.8), and antithrombin deficiency 1.5% (6/400; 0.6–3.3). In 520 genotyped patients, factor V Leiden and prothrombin G20210A were infrequent (1.3% and 1.0%, respectively) and confined to European/North American cohorts. Baseline haemodynamics were uniformly severe (mean mPAP 46.7 mm Hg; pulmonary vascular resistance ≈ 9 WU). Definitive reperfusion therapy was common (PEA 63%; BPA 18%), reducing mPAP to 20.5 mm Hg and yielding a weighted one-year survival of 96.2%. No study demonstrated a thrombophilia-specific effect on surgical candidacy or early survival. Conclusions: Approximately one in seven patients with CTEPH harbours a congenital thrombophilia, most often protein S or protein C deficiency, whereas classic venous-thrombo-embolism mutations are rare and ethnically restricted. Current evidence indicates that genetic status does not materially influence haemodynamic severity, uptake of PEA/BPA, or short-term survival, supporting guideline recommendations for universal referral to specialist reperfusion centres. Future multicentre registries integrating systematic genotyping and long-term outcome capture are needed to clarify genotype-specific prognostic and therapeutic implications. Full article