Search Results (130,742)

Background: Early-onset Alzheimer’s disease (EOAD) caused by autosomal dominant mutations provides a deterministic framework for investigating genetic modifiers of neurodegeneration. Telomere biology has emerged as a central regulator of genomic stability, cellular ageing, and stress response integration, yet its role in EOAD, particularly in under-represented populations, remains poorly defined. Methods: We conducted a cross-sectional case–control study to evaluate the genetic distribution, disease association, and predicted regulatory consequences of common variants in the telomere maintenance genes TERT and TERC in individuals from Western Mexico. The EOAD group comprised genetically confirmed carriers of the PSEN1 p.Ala431Glu (A431E) founder mutation with clinical EOAD (n = 69), and controls were unrelated individuals without dementia (n = 179). Five common variants were analyzed: rs2242652, rs2853677, rs2736100, and rs10069690 (TERT), and rs12696304 (TERC). Results: Genotype distributions in controls conformed to the Hardy–Weinberg equilibrium. Single-variant analyses showed no significant allele-level associations. Most TERT variants did not show significant allele-level associations with EOAD. However, a preliminary genotype-level enrichment for the GC allele at rs12696304 (TERC) was observed among EOAD cases compared with controls; allele-level associations were not significant. Linkage disequilibrium analysis revealed low r² values (<0.20), supporting variant independence. Population-level allele frequency comparisons revealed ancestry-dependent divergence across loci; in silico functional annotation localised all variants to non-coding regulatory regions. GTEx-based analyses indicated that rs12696304 acts as an eQTL for ACTRT3 in whole blood and pituitary, as well as for LRRC34 in the cerebellar hemisphere, suggesting a potential regulatory network within the TERC locus (3q26.2). Conclusions: Overall, common regulatory variants in TERT did not show strong independent effects on EOAD susceptibility in PSEN1 A431E carriers. However, the convergence of association patterns, functional annotation, and regulatory evidence provides hypothesis-generating support for the TERC locus (3q26.2), particularly rs12696304, as a candidate region for further investigation. Additional studies integrating telomere dynamics, functional validation, and multi-omics analyses are needed to clarify the role of telomere biology in the pathogenesis of autosomal dominant EOAD. Full article

Suicide is a global and public health crisis that impacts people of all ages and backgrounds. The literature supports that individuals with serious mental illness are at a higher risk of suicide compared with those without a serious mental illness. It is also well-documented that individuals are at particularly high risk of suicide immediately post-hospitalization for a psychiatric illness. Our narrative review synthesizes and analyzes the existing literature on this phenomenon, the rates of suicide post-hospitalization, the risk factors for suicide during that time, and the interventions and strategies developed to reduce the rates. Current risk assessments struggle to identify individual patients who are at the highest risk of suicide post-discharge. Research has shifted towards focusing on brief crisis interventions to target this high-risk period. Other interventions in the literature include those that attempt to increase engagement with mental health services and increase institutional resources. We also synthesize literature on the iatrogenic risk of hospitalization, the impact hospitalization itself can have on patients, and their risk of suicide once discharged. Future directions could include further exploration of the impact these interventions have on specific populations, such as those with comorbid psychiatric and substance use conditions. Full article

Background: Eosinophilic granulomatosis with polyangiitis (EGPA), formerly Churg–Strauss syndrome, is a rare necrotizing vasculitis characterized by asthma, eosinophilia, and systemic granulomatosis vasculitis. Perioperative risk is primarily driven by airway hyperreactivity, potential cardiac disease, chronic immunosuppressive therapy, and reported alterations in plasma cholinesterase activity. Evidence specifically addressing anesthetic management remains scarce and largely limited to case-based reports. Methods: A focused narrative review was conducted by searching MEDLINE (via PubMed), Scopus, and Embase from inception to January 2026 for publications reporting perioperative anesthetic management in patients with EGPA/Churg–Strauss syndrome. Case reports and case-based descriptions providing explicit anesthetic details were qualitatively synthesized. Results: Available evidence consists predominantly of isolated case reports across heterogeneous surgical settings, including ENT, abdominal, orthopedic, ambulatory, pediatric, and rare cardiac procedures. Recurring perioperative principles include optimization of bronchial disease and continuation of inhaled therapy; minimization of airway stimulation and avoidance of histamine-releasing drugs; selection of induction agents preserving hemodynamic stability in the presence of myocardial involvement; preference for non-depolarizing neuromuscular blockade with quantitative monitoring (and consideration for sugammadex when appropriate); individualized corticosteroid management and multimodal, opioid-sparing analgesia, often supported by regional techniques. Conclusions: In the absence of dedicated perioperative guidelines, anesthetic care for EGPA should be individualized based on clinical phenotype and organ involvement. A structured approach targeting airway protection, cardiovascular stability, safe neuromuscular management, and opioid-sparing analgesia may represent a pragmatic risk-mitigation framework. These considerations are illustrated by an institutional experience in mitral valve surgery. Full article

Background and Objectives: Sentinel lymph node biopsy (SLNB) is increasingly used for high-risk, clinically node-negative cutaneous squamous cell carcinoma (cSCC), yet pathological reporting remains binary, lacking morphological stratification. The prognostic relevance of nodal tumor burden subtypes—isolated tumor cells (ITC), micrometastases, and macrometastases—is well established in melanoma and breast cancer but remains uncharacterized in cSCC. We aimed to describe the morphological spectrum of sentinel lymph node involvement in a consecutive institutional cohort and determine whether primary tumor characteristics predict the extent of nodal colonization. Materials and Methods: We conducted a retrospective-observational study at Clinical Center Niš (Serbia) including 35 consecutive clinically N0 high-risk cSCC patients who underwent SLNB using a dual-tracer protocol (⁹⁹mTc-labeled albumin and methylene blue). Sentinel nodes were processed by serial sectioning with hematoxylin-eosin and pancytokeratin (AE1/AE3) immunohistochemistry. Deposits were classified as ITC (≤0.2 mm), micrometastases (>0.2–2.0 mm), or macrometastases (>2.0 mm). Clinicopathologic predictors were evaluated using the Mann–Whitney U test, Fisher’s exact test, the Kruskal–Wallis test, and the Spearman rank correlation test. Results: SLN involvement was identified in 12 of 35 patients (34.3%). Among positive cases, ITC accounted for 6 patients (50.0%), micrometastases for 5 (41.7%), and macrometastasis for 1 (8.3%)—minimal nodal disease constituting 91.7% of positive findings. No primary tumor feature—including diameter, thickness, grade, perineural invasion, or lesion multiplicity—significantly distinguished ITC from overt metastatic deposits. Patients with ITC showed numerically higher median tumor thickness (8.0 mm) than those with micrometastases (4.0 mm), though this did not reach significance (Kruskal–Wallis p = 0.065). Conclusions: SLN positivity in high-risk cSCC is morphologically heterogeneous, with minimal nodal disease predominating. Primary tumor features do not reliably stratify the extent of nodal colonization. Structured tumor-burden reporting—distinguishing ITC, micrometastases, and macrometastases—should be adopted as standard practice to enable meaningful prognostic comparisons and inform individualized management. Full article

Traumatic spinal cord injury (TSCI) frequently necessitates prolonged ventilatory support, raising the clinical dilemma of early versus late tracheostomy. Despite decades of debate, no randomized controlled trials (RCTs) have been conducted exclusively in TSCI populations, and evidence remains largely observational. This review synthesizes contemporary evidence on the timing and outcomes of tracheostomy in acute TSCI. Across multiple cohort studies and meta-analyses, early tracheostomy (≤7 days) is consistently associated with shorter mechanical ventilation duration, shorter ICU length of stay, reduced sedation exposure, and fewer immobility-related complications. Data suggested a lower incidence of ventilator-associated pneumonia, though mortality outcomes remain unchanged. Importantly, cervical-level injuries appear to derive the most significant benefit, while variability in defining “early” versus “late” complicates direct comparisons. Despite methodological limitations, including reliance on retrospective data, inconsistent definitions, and lack of long-term follow-up, cumulative evidence indicates that early tracheostomy improves short-term outcomes. The optimal timing of tracheostomy in TSCI remains uncertain. Current observational evidence suggests that early tracheostomy in cervical SCI is associated with a reduction in the duration of mechanical ventilation, ICU stay, and respiratory complications. These benefits might come from better access to the airways, less anatomical dead space, better clearance of secretions, less need for sedation, together with earlier mobilization and rehabilitation. Mortality outcomes remain inconclusive. In the absence of randomized trials and long-term data, individualized decisions based on injury level, clinical course, and institutional expertise are essential. Full article

Multiple sclerosis (MS) is an inflammatory disease of the central nervous system (CNS) that impacts nearly 3 million people worldwide. While the etiology and pathogenesis of MS are not yet fully understood, current evidence suggests that it results from complex interactions between genetic and environmental conditions. Clarifying the autoimmune mechanisms underlying MS remains a central objective in the development of effective therapeutic strategies. Interferon-beta (IFN-$\beta$) is one of the most frequently prescribed disease-modifying treatments for individuals with MS. However, despite its established efficacy, recent studies report that approximately 30–50% of patients exhibit inadequate response to IFN-$\beta$, largely due to genetic variability. Machine learning (ML), a branch of artificial intelligence (AI), employs data-driven computational models to enhance predictive accuracy and classification. In recent MS research, unsupervised learning techniques such as hierarchical clustering and K-means have been applied for classification purposes. However, these methods often fail to yield optimal solutions because they require numerous arbitrary decisions and perform adequately only when datasets contain clusters of similar sizes and lack significant outliers. Fuzzy systems (FSs) are designed to model complex, ambiguous real-world phenomena. In this study, an AI algorithm incorporating a fuzzy system, informed by expert neurologist input, is proposed to enhance the assignment of unknown class labels related to IFN-$\beta$ response in MS patients. Additionally, a genetic algorithm (GA) is introduced to identify optimal solutions within the search space, facilitating hyperparameter optimization of a deep learning (DL) model trained with genetic biomarkers to identify patients likely to benefit from this therapy. Experimental results demonstrate that the fuzzy system achieved $80\%$ classification efficiency, in contrast to $64\%$ with conventional hierarchical clustering. Furthermore, an artificial neural network (ANN) model, with hyperparameters optimized by the GA, achieved an accuracy of 0.8–1.0, surpassing the multi-layer perceptron (MLP), which achieved 0.6–0.8 accuracy using conventional tuning methods. Full article

Understanding forest dynamics requires reliable inventories that assess tree- and stand-level characteristics. Traditionally, this has relied on field measurements such as diameter at breast height (DBH), height, and crown attributes, but these methods are labor-intensive and spatially limited. Remote sensing, particularly Light Detection and Ranging (LiDAR), has expanded forest inventory capacity by generating three-dimensional structural information. Mobile laser scanning (MLS), a recent adaptation, offers flexible, high-resolution data collection, though its performance across complex forests is still being evaluated. This study assessed the effectiveness of MLS in detecting individual trees and estimating DBH in mixed-species forests of the Northeastern United States. We also evaluated the influence of tree- and plot-level characteristics on detection accuracy and DBH estimation. Results showed an 85.2% tree detection rate, a 23.5% commission rate, and a DBH root mean square error (RMSE) of 1.98 cm (9.65%). Among the variables tested, tree DBH was the only significant predictor of detection probability; tree density and relative density had minimal effect. These findings demonstrate that MLS can achieve precise DBH estimation when trees are correctly identified, but false detections remain a limitation. Further methodological improvements are needed to enhance accuracy in structurally complex forests and advance MLS for operational forest monitoring. Full article

Background: Pediatric septic shock remains a major cause of morbidity and mortality and requires timely recognition and management across multiple hospital settings. Although intensive care support is critical, outcomes are also influenced by earlier phases of care, including emergency department recognition, first-hour treatment, inpatient monitoring, and timely escalation to the pediatric intensive care unit (PICU). Objective: We aimed to review pediatric septic shock across the full hospital trajectory, from emergency department recognition to PICU management and outcomes, with emphasis on diagnostic challenges, early treatment, escalation of care, and prognostic assessment. Methods: This narrative review was based on a structured literature search of PubMed/MEDLINE, Scopus, and the Cochrane Library, with emphasis on international guidelines, consensus statements, systematic reviews, and clinically relevant pediatric studies addressing recognition, resuscitation, escalation, intensive care management, and outcomes in pediatric septic shock. Results: Pediatric septic shock is best approached as a dynamic continuum rather than a single event. Early recognition is complicated by age-dependent physiology, nonspecific presentation, and delayed hypotension. Timely antimicrobial therapy, individualized fluid resuscitation, early vasoactive support, and repeated reassessment during the first hours are central to management. Ward surveillance and prompt escalation to PICU are critical, as delayed recognition of deterioration may worsen organ dysfunction and resource use. In the PICU, phenotype-informed hemodynamic support, fluid stewardship, respiratory support, and organ support are essential. Outcomes should be evaluated beyond mortality to include organ dysfunction burden, duration of support, length of stay, and longer-term functional recovery. Conclusions: Pediatric septic shock outcomes are shaped by the entire hospital care pathway rather than PICU treatment alone. A trajectory-based, continuum-of-care approach may improve timely diagnosis, escalation, and short- and longer-term outcomes. Full article

Rapid urbanization in plateau mountain regions exacerbates the tension between rigid resource demands and fragile ecological carrying capacities. Enhancing the resilience of the Water–Energy–Food (W–E–F) nexus is therefore essential for coping with external shocks. This study constructs a multidimensional resilience evaluation framework based on the Pressure-State-Response (PSR) model, taking the Kunming Metropolitan Area—a typical plateau mountain region—as a case study. Integrating the TOPSIS model, Coupling Coordination Degree (CCD) model, and spatial autocorrelation analysis, we systematically assessed both individual subsystem and comprehensive W–E–F nexus resilience from 2005 to 2020. Results show that W–E–F nexus resilience generally improved from 2005 to 2020, but subsystem development remained uneven across space, with water resilience characterized by a peripheral-high/central-low pattern, energy resilience by a core-high/periphery-low structure, and food resilience by the strongest spatial heterogeneity and volatility. By 2020, the mean comprehensive resilience reached 0.67, with 58.3% of counties above the average, exhibiting significant spatial clustering. Based on resilience levels and limiting subsystems of 2020, the metropolitan area was classified into Enhancement, Adjustment, and Maintenance zones, comprising 6, 16, and 2 counties respectively, to support differentiated regional governance. This study provides a spatially explicit regulation paradigm to bolster urban resilience against resource constraints and climate uncertainty. Full article

Background: Femoral pseudoaneurysms are clinically heterogeneous, with substantial variability in anatomical features and patient-related bleeding risk. Standard treatment algorithms may be inadequate, particularly in patients receiving anticoagulation or presenting with altered coagulation profiles. A personalized, risk-adapted interventional strategy may optimize outcomes while preserving procedural safety. This study compares ultrasound-guided compression with endovascular and percutaneous therapies and evaluates the safety of minimally invasive approaches across different risk profiles to support individualized management. Methods: This single-center retrospective cohort study included 65 consecutive patients treated for femoral pseudoaneurysms between January 2019 and May 2025. Treatment modalities comprised ultrasound-guided compression, endovascular embolization (coils, covered stents, NBCA–Lipiodol), percutaneous glue injection, and hybrid approaches. Primary endpoints were technical and clinical success. Safety was assessed using pre- and post-procedural INR, platelet count, and hemoglobin levels. High-risk status was defined as ongoing anticoagulation or antiplatelet therapy, INR > 1.5, or platelet count <50 × 10⁹/L. Results: Endovascular and percutaneous approaches achieved significantly higher technical (100% vs. 68.5%, p = 0.006) and clinical success rates (100% vs. 77.8%, p = 0.009) compared with ultrasound-guided compression. In minimally invasive cohorts, INR and platelet counts remained stable after treatment, while hemoglobin showed an expected post-procedural decrease (p < 0.001). High-risk patients demonstrated technical success rates comparable to standard-risk patients, with no significant differences in laboratory trends. Favorable outcomes were observed across different embolic materials. Conclusions: Endovascular and percutaneous therapies provide superior effectiveness compared with ultrasound-guided compression while maintaining a reassuring safety profile, even in patients at increased bleeding risk. These findings support a personalized, patient-tailored interventional approach based on individual anatomical and clinical characteristics. Full article

Background: Mega-events like the FIFA World Cup (FWC) present unique and substantial challenges for individuals in recovery from substance use disorders (SUDs), primarily by increasing the risk of relapse. We employed a qualitative design using reflexive thematic analysis to explore the behavior of patients with SUDs during the 2022 FWC and to evaluate institutional strategies for mitigating related risks. Methods: We purposively sampled 32 participants who were present at the Naufar Center during the 2022 FWC: (i) thirteen adult patients with SUDs who were receiving treatment, and (ii) nineteen healthcare practitioners. Semi-structured patient interviews were conducted, and focus group discussions were held with a multidisciplinary team, including psychologists, nurses, and physicians. Individuals’ experiences regarding patterns in substance use behavior, environmental triggers, and the effects of institutional interventions were examined. Thematic analysis was employed to identify patterns, risks, and effective strategies. Results: Most patients maintained abstinence and only had cravings for alcohol. Triggers included public celebrations, emotional excitement, and the increased availability of addictive substances. Psychologists and physicians reported signs of behavioral destabilization; nurses observed some behavioral changes and noted logistical challenges. The participants acknowledged the supportive measures provided by Naufar, including the accessibility of clinical services, individualized therapy, social and recreational programming, and protective fan zones, which enabled them to participate in various activities during the event. Conclusions: The 2022 FWC created considerable psychological and environmental triggers for high exposure to alcohol and other substances. The supportive structured activities and tailored interventions were helpful in mitigating the risk of relapse, maintaining treatment engagement and ensuring recovery. Further research is required to explore the implications for recovery-oriented practices during culturally and socially high-risk events. Full article

Background: The Danish National Survey of Diet and Physical Activity (DANSDA) is Denmark’s national dietary surveillance system, providing population-level data to support evidence-based government advisory tasks and policymaking, research, and education. Methods: DANSDA 2021–2024 is a cross-sectional survey based on a simple random sample of citizens aged 4–80 years from the Danish Civil Registration System. Home visits included structured interviews covering socio-economic status, family composition, ethnicity, lifestyle behaviors and attitudes, health and non-communicable diseases, dietary supplement use, and measurements of anthropometrics and blood pressure. Dietary intake was recorded using a digital or paper-based seven-day food record and a food frequency questionnaire. Physical activity was measured with a pedometer and a seven-day step diary. Participants aged 40–70 years were offered blood sampling for glucose and lipid analyses. Results: A total of 4223 individuals participated, with 3824 providing valid food records (97.4% were digital). The response rate was 26.3%. The overall underreporting rate was 24%. The sample was skewed by age, education, income, household type, and region; these variables and sex were used to generate weighting factors. Nearly 1000 blood samples were analyzed for glucose and lipids, with surplus material stored in a biobank. Conclusions: DANSDA 2021–2024 provides comprehensive data on diet, physical activity, anthropometry, blood pressure, and blood glucose and lipids. Despite declining response rates and underrepresentation of individuals with lower education and income, weighting procedures support its continued use for national monitoring and research. Strengthening participation and representativeness should be a priority in future survey cycles. Full article

This study presents research on optimizing the parameters of the passivation process for precipitation-hardening stainless steels (PHSS) to improve the corrosion resistance of AM350 and CUSTOM 450 alloys, which are extensively utilized in the aerospace and aviation sectors, since, as this is a complex process, it requires the implementation of a robust methodological approach that allows for multi-response optimization. Experiments were designed using the Taguchi method, which offered a strong framework for examining the impact of material, type of passivation solution, concentration, temperature, and passivation process time on the corrosion resistance of both PHSS alloys. To confirm the ideal PHSS passivation process parameters and measure the significance of each component, gray relational analysis (GRA) and analysis of variance (ANOVA) were also employed. The combined use of the Taguchi/GRA represents a robust and efficient methodological approach to the multi-response optimization of complex processes, overcoming the limitations inherent in the individual application of each technique. It was determined that the optimized parameters were a PHSS AM 350, a solution composed of a combination of citric acid and oxalic acid, acid concentration of 25% v/v, temperature of 50 °C, and time of 120 min. This combination of parameters resulted in significant improvements of up to 55% in corrosion resistance in the H₂SO₄ and NaCl evaluation solutions, demonstrating the effectiveness of the optimized conditions. This work emphasizes the efficacy of integrating Taguchi, GRA, and ANOVA techniques to significantly reduce the corrosion rate of PHSS undergoing the passivation process using alternatives to nitric acid. The integration of the Taguchi methodology with GRA enables the normalization and combination of responses with different scales and performance criteria into a single gray relational index, facilitating the overall evaluation of the system. Full article

Tree detection is a core task in forest inventory and mapping, yet reliable stem identification remains difficult in dense and structurally complex forests. This study systematically reviews the literature on terrestrial laser scanning (TLS)-based tree detection to summarize methodological development, identify persistent challenges, and highlight research gaps. Records were retrieved from Scopus and Web of Science (WoS). Following PRISMA 2020, 39 articles were included and analyzed using Bibliometrix v 5.2.1 package in R Studio 2026.01.1 and qualitative content coding. The reviewed studies were published between 2011 and 2025 in 20 peer-reviewed journals and involved 169 authors from 73 institutions across 24 countries. The literature was organized into three developmental phases: foundational development (2011–2015), rapid growth (2016–2020), and refinement and integration (2021–2025). Across these phases, methods evolved from geometric fitting and clustering to voxel-based and increasingly integrated workflows. Reported performance varied markedly with scan configuration, forest structure, and algorithm design, ranging from very low detection rates to near-complete detection under favorable conditions. Overall, TLS shows strong potential for forest inventory; however, dense stands, multilayered forests, and regeneration-rich environments remain major challenges. Full article

Navigating extensive legislative corpora is often impeded by the linguistic complexity inherent in legal texts. To address this, we present a novel topic representation learning method designed to facilitate the systematic exploration of legislative content. We demonstrate the efficacy of this approach by applying it to the vast corpus of Italian legislation comprising about 74 k laws with more than 300 k articles. While current topic models group documents by latent semantic similarity, they often lack the granularity required for precise navigation. Our approach augments these representations by integrating our topic modeling framework with multi-label profiles. We enrich the representation of individual laws by extracting and ranking the top 10 keywords based on their relevance to the enclosing topic, subsequently aggregating these rankings to construct a comprehensive, alternative description of the broader legal themes. By bridging latent semantic clusters with explicit, LLM-generated labels, this method yields a highly interpretable representation of the corpus, significantly enhancing the profiling and navigability of complex legislative content. We improve over our baseline representation in 74.67% of cases, showing potential for re-use in highly specialized text corpora. Full article