Identification of drug repurposing candidates for amyotrophic lateral sclerosis using electronic health records: a retrospective cohort study.

Clinical outcomes and prognostic determinants of dehydrated human amnion/chorion membrane for refractory venous leg ulcers.

Study design/settingRetrospective longitudinal study.PurposeOsteoporotic vertebral fractures (OVF) are common in middle-aged and elderly populations. However, few studies have predicted the risk of OVF from the perspective of the bone heterogeneity. This study conducted a longitudinal study to predict the risk of OVF in individuals over 50years old based on habitat radiomics which can quantify heterogeneity of vertebral trabecular bone.MethodsIndividuals aged over 50years who had not experienced OVF and underwent CT scans between 2016 and 2023 were enrolled and followed up until 2024. During the follow-up period, 107 cases developed new OVF, and 270 individuals without fractures were selected as the control group. Radiomic features of each pixel within the vertebra were extracted, and the optimal segmentation of vertebral sub-regions was determined using the K-means unsupervised clustering method.ResultsThe habitat radiomics model significantly outperformed the CT value model (AUC = 0.702, DeLong test P-value = 0.001) and also surpassed the traditional radiomics model. The Cox proportional hazards analysis showed that the habitat radiomics risk score could serve as an independent predictor of vertebral fractures (hazards ratio = 1.092, 95% confidence interval (CI): 1.074 - 1.111, P < 0.001). The C-index of the habitat radiomics nomogram model was 0.803 in the training set (95% CI: 0.752 - 0.854) and 0.748 in the validation set (95% CI: 0.667 - 0.829).ConclusionThe habitat radiomics model can predict vertebral fractures based on vertebral heterogeneity, with better performance than traditional bone density prediction methods.

Ensuring safe operation of autonomous vehicle: A comprehensive survey of Operational Design Condition.

Sepsis, involving systemic inflammation and organ failure, presents significant challenges due to its complex and heterogeneous immunological reactions. T-helper 17 (Th17) cells contribute significantly to immune regulation, and their dysregulation is implicated in sepsis pathogenesis. Understanding how Th17 cell differentiation-related genes contribute to sepsis heterogeneity and prognosis is crucial for improving patient prognosis. We retrieved mRNA expression and clinical datasets (GSE65682, GSE95233, and GSE28750) from the Gene Expression Omnibus repository for subsequent analyses, and Th17 cell differentiation-related genes were obtained from the Molecular Signatures Database (MSigDB). We applied Weighted Gene Coexpression Network Analysis to identify sepsis-connected gene modules. Consensus clustering divided sepsis patients into subtypes. We established a prognostic model using Least Absolute Shrinkage and Selection Operator followed by multivariate Cox proportional hazards analysis. Immune infiltration, gene set enrichment analysis, gene ontology, and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were applied to characterize subtypes and risk groups. Weighted Gene Coexpression Network Analysis identified a sepsis-associated turquoise module. Our analysis revealed the existence of two distinct molecular categories within sepsis, named Cluster 1 and Cluster 2, with Cluster 2 showing significantly poorer survival. We formulated a reliable eight-gene prognostic model, including DENND2D, CD74, BCL11A, FCER1A, LTB, TGFBI, ERAP2, and VSIG4, that effectively categorized patients into high- and low-risk groups. The low-risk group exhibited higher immune cell infiltration and enrichment in immune-related pathways, while the high-risk group showed enrichment in metabolic and stress pathways. Our investigation identified novel Th17 cell differentiation-connected molecular subtypes of sepsis and established a reliable prognostic model. These observations shed light on the molecular variability associated with sepsis and hold the prospect of personalized therapeutic strategies and improved patient management.

Applying demographic and epidemiological models in challenging situations: Grappling with a small sample size and complex sociopolitical contexts among the ancient Maya at Lower Dover.

Higher incidence of HBeAg seroclearance with tenofovir alafenamide fumarate than entecavir in HBeAg-positive patients with chronic hepatitis B.

Tuberculosis and increased risk of cardio-cerebrovascular disease: A nationwide cohort study.

Lenvatinib is widely used to treat several malignancies. Proteinuria is a frequent adverse event associated with lenvatinib; however, limited evidence exists regarding risk factors for severe proteinuria-specifically, a urine protein-to-creatinine ratio (UPCR) ≥3.5 g/g creatinine (g/gCre)-across multiple cancer types. This study aimed to identify risk factors for UPCR ≥3.5 g/gCre in patients with thyroid cancer, hepatocellular carcinoma, and endometrial cancer treated with lenvatinib. This retrospective study examined the incidence and risk factors for UPCR ≥3.5 g/gCre in patients treated with lenvatinib between January 2018 and December 2022. Of 195 patients screened, 131 met the inclusion criteria (thyroid cancer: 55; hepatocellular carcinoma: 55; endometrial cancer: 21). Ethics approval was obtained from the institutional review board. UPCR ≥3.5 g/gCre occurred in 34 patients (26.0%), with the highest rate in patients with thyroid cancer (45.5%). Univariate Cox proportional hazards analysis identified an initial lenvatinib dose of ≥20 mg/day [hazard ratio (HR)=2.54; 95% confidence interval (CI)=1.10-5.89; p=0.030] and the onset of grade 3 hypertension after treatment initiation (HR=2.65; 95% CI=1.10-6.40; p=0.031) as significant risk factors. Multivariate analysis also confirmed these factors as independent predictors: initial lenvatinib dose ≥20 mg/day (HR=2.62; 95% CI=1.12-6.14; p=0.027) and grade 3 hypertension after treatment initiation (HR=2.70; 95% CI=1.11-6.57; p=0.029). These findings emphasize the need for intensive blood pressure management and regular UPCR monitoring during lenvatinib therapy to reduce the risk of severe proteinuria, regardless of cancer type.

Pavement deterioration modeling plays a critical role in modern pavement management systems by enabling accurate prediction of performance and supporting maintenance and rehabilitation planning. Pavement deterioration results from the combined effects of traffic loading, environmental conditions, material characteristics, and maintenance strategies. This paper presents a comprehensive review of pavement deterioration models, categorizing them into deterministic, probabilistic, Machine learning and AI techniques and hybrid approaches. Deterministic models, including empirical, mechanistic, and ME formulations, use predefined mathematical relationships to predict pavement condition. Probabilistic models, particularly those based on Markov processes and hazard analysis, account for uncertainty and are suitable for long-term forecasting. Machine learning and AI techniques such as ANN, SVM, genetic programming, and ensemble learning have recently demonstrated superior performance by capturing nonlinear and multivariate deterioration behavior. Hybrid models integrating deterministic, probabilistic, and data-driven approaches further enhance prediction reliability by combining the strengths of multiple modeling paradigms. Key performance indicators such as the IRI, PCI, and PSI are reviewed in terms of their evolution, use, and limitations. ME sensitivity studies are discussed to identify influential parameters, including layer thickness, resilient modulus, asphalt stiffness, and cumulative traffic loading. The review also highlights persistent challenges such as limited data availability, lack of globally adaptable models, and inconsistent integration of maintenance effects. Future directions include the development of transferable models calibrated for diverse conditions, real-time monitoring using sensor-based data, and explainable AI frameworks for transparent decision-making. This representative synthesis provides a structured understanding of current pavement deterioration modeling practices and offers guidance for advancing predictive accuracy and infrastructure management efficiency.

Objective In 2018, Veterans Health Administration (VHA) mandated adoption of the Columbia-Suicide Severity Rating Scale (C-SSRS) for health system suicide screens. This study evaluates the predictive validity of C-SSRS screens in VHA specialty mental health (SMH) and emergency department (ED) settings. Methods For 867,023 patients screened in SMH clinics from 10/1/2018-11/30/2020 and 1,035,317 screened in EDs from 11/1/2019-11/30/2020, proportional hazards analyses evaluated whether C-SSRS screens (rated as minimal, low, moderate, or high risk) were associated with non-fatal suicide attempts and with suicide deaths within the subsequent 7, 30, and 365 days. Analyses adjusted for patient characteristics, prior year mental health treatment, prior year suicide attempts, and most recent VHA REACH VET suicide prediction algorithm risk score. Results For the SMH cohort, 61.27% of those who died by suicide and 78.29% of those who attempted suicide within a year initially screened as low, moderate, or high risk; for the ED cohort, 15.39% of those who died by suicide and 46.29% of those who attempted suicide within a year initially screened low, moderate, or high. In both settings, C-SSRS risk level was positively associated with risk of suicide attempts and deaths (hazard ratios ranged from 1.76 to 6.62 depending on outcome, setting, and risk level), adjusting for covariates. Conclusion In VHA SMH and ED populations, the C-SSRS identifies patients who are at increased risk of suicide deaths and attempts. Follow-up should be completed for patients who screen at low risk or higher on the C-SSRS, particularly in EDs.

The competing risk of nonstroke mortality may limit the potential benefit of stroke prophylaxis therapy in patients with atrial fibrillation or atrial flutter AF. Using a Medicare 20% sample, we identified a cohort of beneficiaries diagnosed with atrial fibrillation or atrial flutter from 2006 to 2019 using International Classification of Diseases, Ninth Revision (ICD-9) and Tenth Revision (ICD-10) codes. Fine and Gray regression analysis determined the hazard of stroke with a competing risk of nonstroke mortality, and Cox proportional hazard analysis determined risk of nonstroke mortality. A scoring tool stratified patients into low or high potential benefit for thromboembolic prophylaxis. Among a total of 1 883 759 Medicare beneficiaries, 330 136 patients were included with median age of 79.7 years. 54% of patients had prior bleeding episodes. The median CHA2DS2-VASc score was 5. Of these patients, 211 791 (64%) died and 77 717 (24%) experienced an embolic stroke over median follow-up of 7.3 years. In the high potential benefit group (26.1%), the risk of stroke was much higher than the risk of nonstroke mortality at 1 year (12.2% versus 7.1%); 3 years (22.7% versus 16.9%); 5 years (31.9% versus 26.1%). In the low potential benefit group (73.9%), the risk of stroke was much lower than the risk of nonstroke mortality at 1 year (11.5% versus 39.2%); 3 years (23.2 versus 57.2%); and 5 years (34.3% versus 69.4%). We propose a scoring tool to identify the potential benefit of thromboembolic prophylaxis therapy in older patients diagnosed with atrial fibrillation or atrial flutter. This tool can be used in shared decision-making settings. Further studies to improve and validate this scoring tool are warranted.

Lower Household Income Is Associated With Higher Cardiac and Vascular Mortality After Endovascular Abdominal Aortic Aneurysm Repair.

Landslides are among the most frequent geological hazards worldwide and cause significant loss of life and extensive damage to homes, infrastructure, and services (Caleca, Tofani, Raspini, Segoni, &amp; Casagli, 2025). This paper presents an epistemological analysis of natural hazards, with an emphasis on the risk of landslides in Mexico, approached from the perspective of critical thinking on environmental issues proposed by Enrique Leff and Edgar Morin, opening the discussion on addressing environmental issues in a cross-cutting and holistic manner, avoiding the closure of scientific knowledge, as well as a brief critique of the institutionalization of risk management in Mexico in its early stages, based on the history of disasters that occurred up to the 1980s and 1990s. Finally, conclusions are drawn about the cross-cutting nature of environmental studies, particularly the identification of areas susceptible to landslides, with the aim of achieving comprehensive risk management.

Investigation of Coca-Cola products (Coke and Fanta Orange) involving (the raw materials, simple syrup, final syrup and final products) was carried out using the hazard analysis critical control point concept. The production environment was also monitored for microbial quality. The total viable counts (TVCs) of the water samples varied from raw water to water obtained from polishing filter with the highest (7.5 x l02 cfu ml-1) occurring in the former. Coliform counts of the water samples also showed variations ranging from 1.0 x 102 cfu m1-1 to 5.0 x 102 cfuml-1 The total viable counts (TVCs) of the sugar samples (2.0 x 102 cfug-1) while the fungal counts 1.5 x 102 cfumg-1. The total viable counts (TVCs) of simple syrup ranged from 5.0 x102 cfum-2 to 7.0 x 102 cfuml-1 while the fungal loads ranged from 5.0 x 102 cfuml-1’ to 8.0 x 102 cfum-l. The total viable counts (TVCs) of final syrup were different for Coke and Fanta Orange, with the higher counts of 2.0 x 102 cfum-1 occurring in Fanta Orange while the fungal counts were 4.0 x 102 cfuml-1’. The total viable counts of the final products (Coke and Fanta Orange) differed on the day of production with the former (Coke) showed higher populations of 5.0 x 102 cfuml-1. The total viable counts and fungal loads were higher in Fanta than in Coke ten days of ambient storage after production. The production environment (simple syrup room, final syrup room, washer II outlet and filler line II area) showed variations in microbial profiles with filler line II showing the maximum (14.0 x 102 cfum3 for fungal counts, 7.0 x 102 cfum-3 for coliform and 25.0 x 102 cfum-3 for total viable counts respectively) and the minimum in simple syrup room 1.1 x 102 cfum3 for fungi; 5.0 x 102 cfum-3 for coliform and 1.0 x 102 cfum3 for total viable counts respectively. The carbonation level of the product (Coke! Fanta) differed also with Coke having 3.80 and Fanta 2.80. The isolated samples were identified as Bacillus spp, Leuconotsoc spp and Lactobacillus spp with Bacilis spp being more predominant in the environment. The fungi were identified as Fusarium spp, Penicilliurn spp, Aspergillus spp and Geotrichum spp with Fusariurn spp being more predominant. The pH of raw water (Borehole water) to final product (Coke and Fanta) ranged from 5.00 borehole water, 6.60 sand filtered water, 6.80 carbon filtered water, 4.00 Coke and 4.11 for Fanta Orange respectively. This work has shown that the microbial characteristics of the final product (Coke and Fanta Orange) are influenced by the quality of the raw materials and the measures employed in the production process.

Split-thickness skin grafting is a common procedure for the treatment of complicated wounds. Predictors of skin graft failure are not fully understood. The study aimed to identify baseline predictors of skin graft failure and delayed healing. Consecutive adult patients with wounds treated using split-thickness skin grafting between 2009 and 2019 were included in a retrospective single-center study. Failures referred to total graft loss or the need of a new operation. In total, 1484 wounds in 1011 patients were analyzed. Graft failure occurred in 384 (25.9%) cases and reoperation was required in 297 (20.0%) cases. At 1 year, the wound was healed in 91.5% of the cases. Logistic regression analysis showed that peripheral arterial disease, diabetes, use of immunosuppressive medication, and wounds located in the foot significantly increased the risk of graft failure, while wounds located in the chest and those secondary to trauma, burn, or cancer excision had significantly lower graft failure risk. Cox proportional hazards analysis showed that wounds of the hand, forearm, and thigh as well as those secondary to trauma and burns were associated with higher rates of wound healing at 1 year. Wounds in feet, wound duration, lower limb edema, peripheral arterial disease, use of antipsychotic medication as well as wounds secondary to surgical complications, venous insufficiency, diabetes, and other comorbidities were associated with lower wound healing at 1 year. The present study identified several risk factors associated with poor outcome after skin grafting. These findings highlight the importance of recognizing patient comorbidities and wound etiology in preoperative planning.

The global immune-nutrition inflammation index (GINI) is a new indicator that integrates blood biochemistry and complete blood count components, offering a comprehensive assessment of immunity, inflammation, and nutritional status. The in-hospital mortality rates for GINI and post-primary percutaneous coronary intervention (pPCI) in patients with ST-elevation myocardial infarction (STEMI) are still unclear, despite evidence indicating the GINI's prognostic value in different types of cancer. This study examined the link between GINI, measured at admission, and in-hospital death rates in STEMI patients. This retrospective study included 1459 consecutive patients diagnosed with STEMI who underwent pPCI. Following the application of exclusion criteria, the 1090 patients left were split into two groups based on the median GINI value of 192. In-hospital mortality rates during follow-up were recorded from the registry. The study's primary outcome, in-hospital mortality, was notably higher in patients with a GINI ≥ 192 compared to those with a GINI < 192 (38 [7%] vs. 7 [1.3%], p < 0.001). Univariate and multivariate Cox proportional hazard analyses revealed that the GINI is independently associated with in-hospital mortality. GINI optimal cut-off value of > 688 predicted in-hospital mortality with 66.7% sensitivity and 86.7% specificity. Univariate logistic regression analysis revealed significant correlations between in-hospital mortality, age, systolic blood pressure (SBP), left ventricular ejection fraction (LVEF), and GINI. Further analysis of these variables using the multivariate logistic regression analysis indicated that age, SBP, LVEF, and GINI (OR: 0.882, 95% CI: 0.849-0.916; p < 0.001) were independent predictors for the development of in-hospital mortality. This study's results suggest that GINI could be an important independent predictor of in-hospital mortality among STEMI patients treated with pPCI. Patients with a higher GINI are at increased risk of in-hospital mortality.

In seismic hazard analyses, it is common practice to consider only earthquakes with magnitudes greater than 5 while assuming that smaller events cannot damage engineered structures. However, this assumption may not hold for induced seismicity, where earthquakes often occur at very shallow depths with rupture distances of only a few kilometers. The steep attenuation of ground motions within the first 10 km in small-magnitude events can yield median short-period accelerations that exceed those predicted by conventional ground-motion models. The combination of higher ground-motion amplitudes and elevated earthquake rates challenges the assumption that earthquakes smaller than magnitude 5 cannot cause damage to earth structures. This study evaluates the damage potential of small-to-moderate (magnitudes 3–5) induced earthquakes occurring at shallow depths on the seismic performances of earth canal dykes. The earthquake scenarios and ground motions selected for the assessments represent features expected from induced seismicity associated with wastewater injection. For dykes with a yield acceleration of 0.1 g , the results indicate that significant deformations (&amp;gt;10 cm) may occur during earthquakes with magnitudes between 3.0 and 4.0 at a rupture distance of about 3 km. The methodology presented herein also provides a framework for assessing the minimum threshold magnitudes of other engineered systems in regions affected by induced seismicity.

Foodborne illnesses represent a major global public health and economic challenge. According to WHO estimates for the year 2010, approximately 600 million people fell ill and 420,000 died as a result of contaminated food. This narrative review summarizes the main bacterial, viral and parasitic agents responsible for foodborne disease worldwide, with a particular focus on key bacterial pathogens (Salmonella, Campylobacter, pathogenic Escherichia coli, Listeria monocytogenes, Staphylococcus aureus, Clostridium perfringens, Bacillus cereus and others). For each pathogen group, we outline microbiology, epidemiology, pathogenesis, clinical manifestations and selected outbreak examples. The review further discusses the farm-to-fork continuum, microbiological risk assessment, and critical control points, emphasizing evidence-based prevention strategies such as Good Agricultural Practices, Good Manufacturing Practices, Hazard Analysis and Critical Control Points systems and consumer education. Emerging challenges—including antimicrobial resistance, climate change and globalization of food supply chains—are analysed within a One Health framework. This synthesis aims to inform food safety professionals, public health practitioners and policymakers in designing more effective interventions to reduce the global burden of foodborne diseases. Asian Australas. J. Food Saf. Secur. 2026, 10(1), 20-42

Patients with multiple myeloma (MM) often use cardiovascular medications due to their increased risk of cardiovascular diseases. This study investigated the associations of baseline use of these drugs with survival and adverse events in MM patients initiating daratumumab, lenalidomide, or bortezomib combination treatments. Data from Phase III trials (CASTOR, MAIA, and POLLUX) were analysed, focusing on beta-blockers, calcium channel blockers, ACE inhibitors (ACEI), angiotensin II receptor blockers (ARBs), diuretics, and statins. Cox proportional hazard analysis and logistic regression were used to assess associations with survival and grade ≥ 3 adverse events. Among 1804 patients, ACEI/ARBs were most common (31%), followed by beta-blockers (23%), statins (21%), calcium channel blockers (17%), and diuretics (16%). ACEI/ARBs was associated with better progression-free survival (adjusted hazard ratio (aHR) [95% CI] = 0.84 [0.71-0.99], P = 0.034) but also higher odds of grade ≥ 3 adverse events (adjusted odds ratio (aOR) = 1.45 [1.06-1.97], P = 0.019). Diuretics were similarly associated with grade ≥ 3 adverse events (aOR = 1.53 [1.01-2.34], P = 0.047). Other cardiovascular drugs showed no significant associations. While ACEI/ARBs may improve progression-free survival, they pose safety concerns. It is reassuring that other cardiovascular drugs were not significantly associated with MM treatment outcomes. Further research is essential to fully understand the implications of these medications.