Search Results (1,292)

Background: Asymptomatic intracranial atherosclerotic arterial stenosis (ICAS) is an underrecognized entity for which vascular risk-factor optimization is the primary management strategy, with no current indication for routine antiplatelet therapy or endovascular intervention for primary stroke prevention. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) reduce major adverse cardiovascular events, including stroke, in high-risk cardiometabolic populations, but their association with outcomes in asymptomatic ICAS is yet to be evaluated. The present study aims to evaluate the association between GLP-1RA use and cerebrovascular outcomes in adults with asymptomatic ICAS. Materials and Methods: We used the TriNetX US Collaborative Network (71 healthcare organizations) to identify adults (≥18 years) with ICAS between 1 January 2016 and 31 December 2025, and excluded patients with prior cerebral infarction, intracranial hemorrhage, or cerebrovascular ischemic syndromes. Exposure was defined as initiation of any GLP-1 receptor agonist (lixisenatide, semaglutide, liraglutide, tirzepatide, dulaglutide) during the 6 months before or on the date of index ICAS diagnosis. Outcomes were assessed at 1 year, and included ischemic stroke, all-cause mortality, and a composite of ischemic stroke or mortality. Propensity-score matching (1:1) was performed, including demographics, vascular risk factors, comorbidities, antithrombotics, lipid/diabetes therapies, and cardiometabolic laboratory/physiologic measures. Results: Before matching, 1746 GLP-1RA users and 71,792 non-users met inclusion criteria; after matching, 1728 patients remained in each cohort. GLP-1RA use was associated with lower 1-year risk of ischemic stroke (4.40% vs. 6.10%; hazard ratio [HR] 0.70, 95% CI 0.52–0.95; p = 0.044), lower all-cause mortality (3.40% vs. 9.40%; HR 0.35, 95% CI 0.26–0.47; p < 0.001), and lower composite outcome risk (7.50% vs. 15.00%; HR 0.48, 95% CI 0.39–0.59; p < 0.001). Notably, these associations were observed despite matching for HbA1c, LDL cholesterol, BMI, and systolic blood pressure, suggesting potential effects beyond measured cardiometabolic risk profiles. Conclusions: In this large, propensity-matched cohort of adults with a-ICAS, GLP-1RA use was associated with lower ischemic stroke, all-cause mortality, and composite outcome at 1 year. These findings are hypothesis-generating and require further prospective studies to confirm this observation. Full article

Cooperative localization enables teams of robots to maintain better positioning in GNSS-denied environments by sharing state estimates and inter-robot range measurements to reduce the rate of proprioceptive odometry drift. In scenarios without fixed navigation beacons or pre-surveyed reference nodes, each robot functions as both a positioning client and a mobile ranging peer. A critical vulnerability in this architecture is silent fault propagation. A robot with a degraded localization solution may broadcast an incorrect, often overconfident position estimate, corrupting its peers’ localization. Classical Global Navigation Satellite System (GNSS) Receiver Autonomous Integrity Monitoring (RAIM) methods are ineffective in this context because meter-scale inter-robot separations introduce strong geometric nonlinearity and unstable Geometric Dilution of Precision (GDOP), resulting in scattered subset solutions rather than the coherent, biased clusters that RAIM is designed to detect. This paper addresses this vulnerability by proposing a two-stage distributed Fault Detection and Identification (FDI) architecture for peer-to-peer ranging-based cooperative localization. The first stage applies a global chi-square test on Weighted Least-Squares trilateration residuals to detect the presence of a fault. The second stage identifies the faulty robot by computing Leave-One-Out and Leave-Two-Out subset solutions, which are then partitioned using a clustering algorithm. The cluster that exempts measurements from the faulty robot is identified using either a maximum-cardinality or a minimum-variance criterion. A decentralized voting protocol that requires at least two independent corroborations is then employed for network-wide fault declaration. Monte Carlo simulations show that the clustering-based identification method outperforms classical residual-based methods across multiple fault types, with results reported for the planar (2D) case. No single clustering configuration dominates in terms of identification performance across all tested fault conditions, as performance varies with the fault profile. The proposed architecture operates fully in a distributed manner, requiring only the exchange of position estimates, covariances, and binary votes. Full article

Threaded cast iron fittings, including tees and elbows, are commonly used in fire suppression systems to connect piping components due to their simplicity, reliability, and compatibility with National Pipe Thread (NPT) standards. While extensively used in practice, their structural performance under seismic demands, particularly for large-diameter fittings, remains insufficiently understood. Previous studies have primarily focused on smaller-diameter fittings or have idealized the fitting body as rigid, overlooking the potential for internal deformation and rupture. This study addresses this knowledge gap through an experimental investigation of 3-inch and 4-inch gray cast iron threaded elbow and tee fittings subjected to loading. A total of 18 full-scale assemblies were tested across multiple configurations. Results showed that structural rupture of the fitting body was the dominant failure mode, with no specimens reaching the defined threshold for substantial leakage. Limited early-stage leakage was observed in select 3-inch tee configurations prior to rupture. Damage State 3 (DS3), defined as rupture, occurred at rotational capacities ranging from 0.0061 to 0.0179 radians. Fitting stiffness to failure averaged approximately 643 kip-ft/rad. Fragility models were developed within a probabilistic framework, incorporating variability due to material imperfections and assembly tolerances. The findings reveal a size-dependent shift in behavior: 3-inch fittings demonstrated greater pipe rotation prior to failure, while 4-inch fittings exhibited higher internal stiffness but reduced flexibility. These results provide moment–rotation relationships and fragility models to support analytical modeling and seismic vulnerability assessments, advancing the predictive understanding of large-diameter threaded cast iron fittings used in fire suppression systems. Full article

Background/Objectives: General-purpose and domain-specific multimodal foundation models show considerable promise in medical image analysis. In this study, we evaluated the classification accuracy of diabetic retinopathy vs. normal fundus images using general-purpose conversational models (Gemini 3 Flash, GPT-5.2, and Pixtral-Large), a medical conversational model (MedGemma-1.5), and its image-encoder (MedSigLIP), as well as ophthalmology-specific models (RETFound and EyeCLIP). Methods: We applied zero-/few-shot to general-purpose conversational models, linear probing, and fine-tuning approaches to domain-specific models for evaluation purposes. Results: We found that the zero-shot accuracies for Pixtral-Large (70.7%) and fine-tuned RETFound (77.1%) were comparable but lower than those of GPT-5.2 (77.9%), MedGemma-1.5 (88.2%), and Gemini 3 (88.5%) as well as the fine-tuned EyeCLIP (85.8%) and MedSigLIP (94.8%). The accuracy gains from few-shot prompting were substantial for Pixtral-Large (+7.4%) but were limited for GPT-5.2 (+3.6%), Gemini 3 (−3.4%), and MedGemma-1.5 (−1.1%). Embedding-based linear probing further improved accuracy over fine-tuning for RETFound (+9.7%) and yielded only marginal gains for EyeCLIP (+2.3%) but did not benefit MedSigLIP (−0.8%). Overall, with minimal prompting enhancement, general-purpose conversational models such as Gemini 3 and GPT-5.2 achieved performance comparable to ophthalmology-specific models that were either fine-tuned or enhanced via embedding-based linear probing, but remained inferior to MedSigLIP and its conversational counterpart, MedGemma-1.5. Conclusions: The findings highlight a trade-off between specialization and flexibility, where domain-specific models provide higher accuracy and stability, while general-purpose multimodal models offer greater accessibility, adaptability, and interactive reasoning, serving as complementary tools for retinal disease screening and clinical decision support. Full article

Background: Finerenone and sodium–glucose cotransporter-2 inhibitors provide cardiovascular and renal benefits in patients with chronic kidney disease (CKD) and heart failure (HF), but real-world comparative evidence is limited. Methods: This retrospective study used the TriNetX database. Adults ≥ 40 years with CKD stages 1–5 and HF [LVEF > 40%; excluding end-stage renal disease (ESRD) or dialysis] receiving finerenone were compared with those on SGLT2 inhibitors. Propensity score matching (1:1) yielded 333 patients per cohort. Kaplan–Meier and Cox models estimated hazard ratios (HRs) with 95% confidence intervals. Results: After matching, baseline characteristics were reasonably balanced, with some residual imbalance remaining. All-cause mortality was similar between finerenone and SGLT2 inhibitors at 6 months (HR 0.98; 95% CI 0.50–1.90) and 1 year (HR 0.93; 95% CI 0.53–1.66). All-cause hospitalization or ER visits were also comparable at 6 months (HR 1.07; 95% CI 0.84–1.36) and 1 year (HR 1.04; 95% CI 0.83–1.29). Finerenone was associated with a modest, borderline reduction in HF hospitalization at 1 year, without consistent effects across timepoints or a mortality benefit; thus, this finding is hypothesis-generating (HR 0.81; 95% CI 0.66–0.99). Safety outcomes were similar between groups. Conclusions: In this real-world analysis, finerenone was associated with similar all-cause mortality, overall hospitalization, and renal safety outcomes compared with SGLT2 inhibitors, with a modest reduction in HF hospitalization at 1 year that should be interpreted cautiously given the exploratory nature of the study. These findings are hypothesis-generating and underscore the need for prospective head-to-head trials to better define optimal therapy sequencing in patients with HFpEF and CKD. Full article

Background: Negative public attitudes promote undesirable stereotypes and stigma in stutterers. Method: To mitigate negative attitudes, 403 respondents combined from 16 international samples filled out the Public Opinion Survey of Human Attributes–Stuttering (POSHA–S) before and after interventions to improve attitudes and were compared to 249 respondents from seven control groups. Investigators aimed (a) to replicate an extreme case of regression to the mean (i.e., “crossover” effect) reported earlier in larger combined samples in which respondents with high pre-scores ended with low post-scores, respondents with low pre-scores finished with high post-scores, and intermediate scorers were unchanged; and (b) to identify individual POSHA–S items related to overall attitude change and among the high and low scorers. Results: As in previous studies, stuttering attitudes improved in the intervention group but not in the control group. Intervention and control respondents demonstrated “crossover” but less than the earlier samples due to lower pre–post correlations. Item contributions to pre–post change and differences among the three change groups were inconsistent; however, high agreement items by respondents were less likely to vary than low agreement items. Conclusion: The “crossover” effect was replicated, and future research should explore its presence in other measures or conditions. Full article

The EU Regulation on deforestation-free products (EUDR) introduces a new regulatory framework in which the agri-environmental characteristics of production become a prerequisite for access to the European Union market. In this paper, the EUDR is conceptualized as a regulatory framework that renders pre-existing agri-environmental risk drivers economically relevant and, in cases of non-compliance, may translate them into financial risks for agricultural businesses through identifiable transmission channels. The study aims to identify these risk drivers and to assess the institutional and technical readiness of Eastern European countries to implement the Regulation’s requirements. The methodological approach combines an analysis of trade exposure to the EU market, an assessment of countries’ spatial and digital capacities, and the construction of an Institutional and Technical Readiness Index for EUDR implementation. The results indicate an asymmetric impact of the Regulation across the region, driven by cross-country differences in the availability of geospatial data, the maturity of digital traceability systems, and the effectiveness of institutional coordination. The findings further show that broad indicators of digital trade facilitation are insufficient to explain variation in readiness to comply with EUDR requirements. Overall, the study identifies the key institutional and technical constraints shaping EUDR implementation readiness and demonstrates how these constraints translate into financial risks along agricultural supply chains. Full article

Background: Macrophage migration inhibitory factor (MIF) is a critical modulator of the tumor immune microenvironment (TME). Its clinical significance in head and neck squamous cell carcinoma (HNSCC) remains controversial because of HPV-dependent tumor biology and the limitations of single-timepoint biomarker assessments. This preliminary study evaluates whether dynamic changes in circulating MIF (ΔMIF) in an HPV-stratified longitudinal cohort reflect disease severity and treatment response. Methods: Ninety-six serial serum samples were analyzed from 27 HNSCC patients (22 HPV-positive, 5 HPV-negative) from diagnosis through therapy and follow-up. Serum MIF and anti-HPV16 E7 IgG were quantified by ELISA, and ΔMIF was defined as the change in MIF concentration between consecutive visits. Results: Baseline MIF did not correlate with clinical stage in the total cohort (p = 0.63). However, 56% of HPV-positive patients exhibited a positive correlation between elevated MIF and advanced stage. Following chemoradiotherapy, the HPV-negative group showed a consistent and significant decline in MIF (mean ΔMIF = −1.23, p = 0.031), corresponding with no evidence of disease (NED). In contrast, the HPV-positive group showed heterogeneous trajectories (mean ΔMIF = +0.21, p = 0.94), with several patients demonstrating paradoxical declines in MIF during active disease or relapse, followed by recovery upon reaching NED. In select cases, MIF dynamics were closely synchronized with anti-E7 IgG levels. Conclusions: Serum MIF dynamics are strongly dependent on HPV status. While MIF serves as a reliable therapy-monitoring marker in HPV-negative HNSCC, it may play a complex and paradoxical immunomodulatory role in HPV-positive disease. These preliminary findings support the need for larger prospective, HPV-stratified trials. Full article

Mitral valve prolapse represents the most common cause of primary mitral regurgitation in Western countries and has traditionally been viewed as a disorder driven by valvular incompetence and chronic volume overload. Within this paradigm, left ventricular enlargement was expected to correlate with regurgitant severity. However, patients with myxomatous bileaflet prolapse often exhibit left ventricular dilatation disproportionate to the degree of regurgitation, leading to the hypothesis of an intrinsic myocardial disease process. Cardiovascular magnetic resonance imaging has challenged this concept through the identification of doming volume, a previously unrecognized systolic blood compartment located between the mitral annular plane and the ventricular surface of prolapsing leaflets. This volume is mechanically coupled to ventricular contraction and contributes to total ventricular volume load independently of transvalvular regurgitation. Recognition of doming volume provides a physiological explanation for excessive ventricular remodeling observed in bileaflet prolapse and Barlow disease. Doming volume has important implications for imaging assessment. Its common exclusion from echocardiographic volumetric measurements may result in underestimation of left ventricular end-systolic volume, overestimation of ejection fraction, and underestimation of regurgitant burden, contributing to discordance between echocardiographic and cardiovascular magnetic resonance-derived measurements. Cardiovascular magnetic resonance enables comprehensive assessment, allowing accurate quantification of ventricular volumes, mitral regurgitation severity, doming volume, and myocardial tissue characteristics. Integration of doming volume into the evaluation of mitral valve prolapse improves physiological consistency between imaging findings and ventricular remodeling. However, further evidence is required before doming volume assessment can be incorporated into operative clinical indications or decision-making thresholds. Full article

Metabolic dysfunction, a hallmark of diet-induced obesity (DIO), is increasingly attributed to alterations in intestinal nutrient and electrolyte transport. Yet the mechanisms that drive obesity-associated functional alterations of intestinal transporters remain incompletely understood. In this context, the effects of a high-fat diet (HFD) induced obesity on sodium-dependent glucose co-transporter 1 (SGLT1), Na⁺/H⁺ exchanger 3 (NHE3), and Cl⁻/HCO₃⁻ exchangers (DRA/PAT1), the primary glucose, sodium, and chloride absorptive pathways in mice small intestinal villus cells, were investigated. SGLT1 activity significantly increased in intact villus cells and brush border membrane vesicles (BBMV) from HFD-fed mice. Kinetic analysis demonstrated reduced Km without a change in Vmax, indicating enhanced transporter affinity. Notably, SGLT1 mRNA and protein expression, including BBM localization, were unchanged. Basolateral Na⁺/K⁺-ATPase activity was decreased, excluding enhanced Na⁺ gradient generation as the mechanism for SGLT1 stimulation. In contrast, DRA/PAT1 activity was significantly increased in HFD-fed mice, and kinetic studies revealed elevated Vmax without a change in Km, indicating increased transport capacity. DRA/PAT1 mRNA, total protein, and BBM expression were all significantly elevated. NHE3 activity and expression remained unchanged. These findings demonstrate that DIO enhances intestinal glucose absorption by increasing SGLT1 affinity and chloride absorption by upregulating DRA/PAT1 transcription. These transporter-specific alterations may amplify nutrient absorption and contribute to metabolic dysregulation in obesity. Full article

Craniofacial and corneal neuropathic pain are disabling conditions characterized by persistent pain that is frequently refractory to conventional pharmacologic and interventional therapies. These disorders arise from complex interactions between peripheral nerve injury, neuroinflammation, and maladaptive central sensitization within trigeminal pathways, features that span neuropathic and nociplastic pain mechanisms as defined by the International Association for the Study of Pain, thus emphasizing the need for mechanism-based, patient-stratified treatment strategies. Regenerative medicine offers a paradigm shift from symptom suppression toward structural nerve repair and functional restoration. This narrative review examines the pathophysiological mechanisms underlying craniofacial and corneal neuropathic pain and critically evaluates emerging regenerative therapies, including autologous biologics (autologous serum tears and platelet-rich plasma), mesenchymal stem cells and their derivatives, exosomes and extracellular vesicles, and neurotrophic peptides. Particular emphasis is placed on corneal neuropathic pain as a translational model, given the cornea’s dense sensory innervation and the ability to non-invasively quantify nerve regeneration using in vivo confocal microscopy as an objective biomarker of treatment response. Clinical evidence across regenerative modalities varies by indication: cenegermin has demonstrated robust efficacy and regulatory approval for neurotrophic keratitis, while platelet-rich plasma shows growing evidence in temporomandibular disorders, myofascial pain, and occipital neuralgia. Cell-based and cell-free therapies demonstrate strong preclinical promise but remain limited by heterogeneous protocols and a paucity of large-scale randomized trials. Key barriers to translation include regulatory uncertainty, lack of standardized outcome measures, and workforce and implementation challenges. Advancing regenerative therapies for craniofacial and corneal neuropathic pain will require rigorous clinical trials, biomarker-driven patient selection, and multidisciplinary collaboration. Sex as a biological variable remains underexplored across all regenerative modalities and represents a priority for future research. Full article

Biometrics technology is undergoing a paradigm shift from static single-modal authentication to continuous multimodal sensing, combined with higher-performing algorithms powered by new deep learning techniques. This editorial reviews cutting-edge advancements and trends in the field of biometrics in four dimensions—novel sensors, modalities, algorithms, and equipment—as well as summarizes the contributions to this Special Issue, “New Trends in Biometric Sensing and Information Processing” by grouping them into the corresponding aspects of breakthroughs in this field. Full article

Introduction: Cardiovascular disease (CVD) is a leading cause of non-cancer death among cancer survivors, attributable to cardiotoxic therapies and cardiovascular risk factors. General population risk prediction tools, including ASCVD (Atherosclerotic cardiovascular disease), Framingham’s Score, and PREVENT (Predicting Risk of Cardiovascular Disease EVENTS), lack cancer-specific variables. We evaluated whether these models, even after statistical optimization, could predict cardiovascular mortality in cancer survivors. Methods: Using the National Health and Nutrition Examination Survey (NHANES) 2001–2018, linked with National Death Index (NDI) mortality data, we conducted a retrospective analysis of 634 and 429 cancer survivors, respectively, across model-specific cohorts free of baseline cardiovascular disease. Discrimination was assessed for ASCVD, Framingham Score, and PREVENT using standardized thresholds of 7.5% and 20%, as well as Youden-optimized cutoffs. Area under the curve (AUC) comparisons were performed using the DeLong non-parametric method. Results: Standard thresholds showed suboptimal discrimination across all models (AUCs: ASCVD 0.56, Framingham 0.53, PREVENT 0.64). In contrast, Youden-optimized AUCs (ASCVD: 0.68; PREVENT: 0.71; all p < 0.001, DeLong test). Optimization increased the “low-risk” group’s mortality rate from 2.8% to 4.1% (RR = 1.47), suggesting improved statistical fit came at the cost of overestimating the risk. Optimized thresholds outperformed conventional cutoffs, underscoring the necessity for recalibrated, cohort-specific risk stratification in cancer survivors. Conclusions: Standard risk scores have inadequate discrimination for cardiovascular mortality prediction in cancer survivors. Threshold recalibration improves statistical metrics but does not resolve the structural failure of these models to account for cardiotoxic exposure. Development of cardio-oncology-specific risk models incorporating oncologic exposures is therefore warranted. Full article

Vitamin C, also known as ascorbic acid, plays a pivotal role in forming blood vessels, cartilage, muscles, and collagen in bones. We report a 6-year-old non-verbal female with global developmental delay who presented with complaints of lower limb pain and inability to bear weight. Symptoms started five weeks prior to presentation and had progressed from decreased activity to complete loss of weight-bearing. Physical examination showed gingival hyperplasia, perifollicular petechiae, lower limb edema, and corkscrew hair. Initial radiologic findings raised concerns of osteomyelitis, showing bone marrow edema, periosteal reaction, and cortical irregularity. However, correlation with dietary history limited to flavored milk and yogurt and lacking fruits and vegetables, in conjunction with clinical presentation, suggested vitamin C deficiency, and she was started on ascorbic acid. Vitamin C deficiency was later confirmed on day 7 by a low C deficiency level (<0.1 mg/dL). Treatment with ascorbic acid, multivitamins, and supportive therapy led to gradual recovery, and gastrostomy tube placement facilitated supplementation. This case highlights the importance of detailed dietary history and recognition of clinical signs of vitamin C deficiency. Early dietary assessment and clinical correlation can prevent unnecessary invasive procedures and prolonged antibiotic therapy. Early identification enables timely intervention, reducing morbidity and improving quality of life. Full article

Precise control of mitochondrial electron transport is essential to maintain mitochondrial coupling and efficiency in ATP production. Furthermore, disruptions to ETC complex function can drive increased oxidant production, resulting in oxidative damage to the mitochondrion and bioenergetic inefficiency. This is highly relevant in the aging heart, as increased cardiac oxidative stress and mitochondrial dysfunction are hallmarks of age-related cardiovascular disease. Lysine acetylation has recently been characterized as a novel regulator of mitochondrial metabolic and bioenergetic function in the aging heart. In the present study, we investigated how lysine acetylation regulates oxidant production and redox milieu through mitochondrial acetyltransferase GCN5L1. Using a cardiac-specific GCN5L1 knockout mouse model, we observed that age-associated lipid peroxidation and semiquinone radicals were decreased with GCN5L1 KO. RNA sequencing analysis identified mitochondrial bioenergetic and respiratory pathways revolving around the respiratory chain to be enriched in the old KO group. Further, we showed the old KO group to exhibit reduced acetylation of ETC complex and antioxidant proteins, improved ETC complex and antioxidant protein activity. Overall, GCN5L1 regulates redox homeostasis in the aged heart by regulating mitochondrial ETC complex activity, oxidative stress, and mitochondrial bioenergetics. These findings identify GCN5L1 and acetylation as potential therapeutic targets in aging and age-related diseases. Full article