Search Results (269)

Background/Objectives: Rabies is a fatal zoonotic disease caused by the rabies virus (RABV), and effective therapeutic treatments are currently lacking. Vaccination remains the primary strategy for rabies control. The Semliki Forest virus-rabies virus glycoprotein (SFV-RVG), a virus-like vesicle rabies vaccine combining Semliki Forest virus replicase and rabies glycoprotein, has shown potential as a promising vaccine candidate. This study aimed to optimize the production of SFV-RVG and evaluate adjuvant formulations to improve its immunogenicity in both mice and dogs. Methods: SFV-RVG production was optimized by determining the optimal multiplicity of infection (MOI) at 0.03 and cell density at 1 × 10⁶–1.3 × 10⁶ cells/mL, followed by scaling up the process in bioreactors. Eleven adjuvant formulations were tested in mice and dogs to assess their effects on immunogenicity. Cytokine analysis and antibody responses were measured, including IFN-γ, IL-4, IgG2a/IgG1 ratios, and neutralizing antibody titers. Results: The optimized SFV-RVG production was successfully scaled up, and M103 adjuvant induced rapid early antibody titers in mice. In dogs, GEL02 led to the highest neutralizing antibody levels, exceeding 40 IU/mL by 28 days post-immunization. Cytokine analysis indicated that both M103 and GEL02 significantly enhanced IFN-γ and IL-4 expression, balancing the Th1/Th2 immune response. SFV-RVG with GEL02 demonstrated stronger immunogenicity than a commercial vaccine, and challenge studies confirmed robust protection against lethal RABV in mice. Conclusions: This study establishes GEL02 as a superior adjuvant for rabies vaccines and provides a scalable SFV-RVG production process. These findings highlight SFV-RVG with GEL02 as a promising rabies vaccine candidate for dogs, offering significant potential for rabies control. Full article

Transorbital penetrating intracranial injuries are a rare but life-threatening subset of penetrating head traumas. While isolated cases caused by bicycle brake handles have been reported, often with fatal outcomes, this is the first documented case of such an injury caused by an electric scooter (e-scooter) brake handle. The objective is to present the unique management and clinical course of this unusual case. A case of a 76-year-old male is presented. The patient sustained a transorbital intracranial injury after a same-level fall onto a parked e-scooter, which resulted in the brake handle penetrating his left orbit and reaching the third ventricle. A combined maxillofacial and neurosurgical team performed a frontal craniotomy for foreign body removal, followed by duraplasty. No cerebrospinal fluid leakage was detected postoperatively. Imaging and clinical follow-up at six months and one year revealed significant post-traumatic encephalomalacia in the frontal lobes, ventricular enlargement, and persistent neurocognitive deficits, including memory impairment and executive dysfunction. Visual acuity in the affected eye was reduced, with associated orbital fat atrophy and mild ptosis. E-scooter brake handles pose a previously unrecognized risk for severe transorbital penetrating intracranial injuries. This case underscores the critical importance of a multidisciplinary surgical approach to manage complex craniofacial trauma. Despite successful acute management, patients can suffer substantial long-term neurological and functional sequelae, necessitating comprehensive follow-up care. Full article

Background/Objectives: Overkill is generally defined as violence demonstrably exceeding the force required to cause death, often involving a disproportionate number of inflicted injuries. Typically linked to specific mental states, this phenomenon can serve diverse perpetrator purposes, from expressing sadistic impulses to deliberately contaminating forensic evidence. This study re-examines the historical case of Mary Jane Kelly, the canonical final victim of Jack the Ripper, to offer a historical perspective on extreme violence and its influence on modern forensic frameworks. Methods: We employed a retrospective analysis, combining a systematic literature review with application of the Homicide Injury Scale to documented autopsy findings from 1888. Results: The autopsy revealed systematic post-mortem mutilation following a fatal neck laceration. Application of the Homicide Injury Scale confirmed violence exceeding lethal force. Conclusions: This case represents a foundational example of organized overkill behavior, demonstrating the value of applying modern forensic frameworks to historical cases to inform comprehensive overkill analysis. Full article

Fetal lower urinary tract obstruction (LUTO) and pleural effusion are conditions that can disrupt fetal growth and lead to fetal death. LUTO inhibits the formation of amniotic fluid, which is vital for lung development, while pleural effusions can compress the fetal heart, potentially causing fatal cardiac failure. To manage these conditions, a fetal shunt (vesico-amniotic shunt) is placed inside the fetal bladder. This paper presents a study on a new design incorporating a Tesla valve in the shunt. Six groups of Tesla valves with loop angles of 50 degrees and 60 degrees, and different end dimensions, are examined and evaluated in terms of the urine flow rate from the fetal bladder into the amniotic cavity, the pressure buildup between the two sides, and their potential in developing fetal bladder muscles. A mathematical method is used to compare diode characteristics, analyze flow rates, identify the Tesla valve angle, determine the Reynolds number, and assess diodicity. The Computational Fluid Dynamics (CFD) method is also employed to verify calculation results and simulate fluid behavior inside the Tesla valve. Combining the calculations and simulations, a 50-degree Tesla valve with specific dimensions showed the best performance and will be the optimal design for the fetal shunt. Full article

Porcine deltacoronavirus (PDCoV) is an emerging pathogen that causes severe, often fatal, diarrhea in suckling piglets and has zoonotic potential. Its nonstructural protein 12 (Nsp12), functioning as the RNA-dependent RNA polymerase (RdRp), is a central component of the viral replication–transcription complex and a critical target for host antiviral mechanisms. Here, we identified eukaryotic elongation factor 1 gamma (eEF1G) as a host interactor of PDCoV Nsp12 by immunoprecipitation-coupled mass spectrometry in IPEC-J2 cells. This interaction was confirmed by co-immunoprecipitation, pull-down assays, and confocal microscopy. Functional analyses involving siRNA knockdown and overexpression of eEF1G, combined with viral titration, strand-specific real-time quantitative PCR, and RNA immunoprecipitation assays, demonstrated that eEF1G directly binds to Nsp12. Knockdown of eEF1G significantly enhanced viral replication and increased negative-stranded RNA synthesis, whereas overexpression did not affect viral proliferation. Furthermore, eEF1G was found to bind PDCoV genomic RNA and competitively disrupt the interaction between Nsp12 and viral RNA, thereby impairing RdRp activity. Our results indicate that eEF1G acts as a novel host restriction factor that inhibits PDCoV replication by competing with Nsp12 for genomic RNA binding, ultimately blocking negative-stranded RNA synthesis. This study unveils a new antiviral mechanism and highlights a potential target for developing interventions against PDCoV. Full article

Background: Monkeypox (Mpox) is a re-emerging zoonotic disease caused by the monkeypox virus (MPXV). Transmission occurs primarily through direct contact with lesions or contaminated materials, with sexual transmission playing a significant role in recent outbreaks. In 2022, Mpox triggered a major global outbreak and was declared a Public Health Emergency of International Concern (PHEIC) by the World Health Organization (WHO), prompting renewed interest in effective control strategies. Methods: This study developed a compartmental SEIR-based model to assess the epidemiological impact of key interventions, including vaccination and isolation, while incorporating critical epidemiological parameters. Sensitivity analyses were conducted to examine (1) disease dynamics in relation to the basic reproduction number, and (2) how different parameters influence the curve of symptomatic infections. Real-world continental-scale data were used to validate the model and identify the parameters that most significantly affect epidemic progression and potential control of Mpox. Results: Results showed that the basic reproduction number was most influenced by the recovery rate, vaccination rate, vaccine effectiveness, and transmission rates of symptomatic and asymptomatic individuals. In contrast, the progression of symptomatic cases was highly sensitive to the case fatality rate and incubation rate. Conclusions: These findings highlight the importance of integrated public health strategies combining vaccination, isolation, and early transmission control to mitigate future Mpox outbreaks. Full article

Landslides represent a recurrent hazard in tropical mountain environments, where rapid urbanization and extreme rainfall amplify disaster risk. The Sentani region of Papua, Indonesia, is highly vulnerable, as demonstrated by the catastrophic debris flows of March 2019 that caused fatalities and widespread losses. This study developed high-resolution landslide susceptibility maps for Sentani using an ensemble machine learning framework. Three base learners—Random Forest, eXtreme Gradient Boosting (XGBoost), and CatBoost—were combined through a logistic regression meta-learner. Predictor redundancy was controlled using Pearson correlation and Variance Inflation Factor/Tolerance (VIF/TOL). The landslide inventory was constructed from multitemporal satellite imagery, integrating geological, topographic, hydrological, environmental, and seismic factors. Results showed that lithology, Slope Length and Steepness Factor (LS Factor), and earthquake density consistently dominated model predictions. The ensemble achieved the most balanced predictive performance, Area Under the Curve (AUC) > 0.96, and generated susceptibility maps that aligned closely with observed landslide occurrences. SHapley Additive Explanations (SHAP) analyses provided transparent, case-specific insights into the directional influence of key factors. Collectively, the findings highlight both the robustness and interpretability of ensemble learning for landslide susceptibility mapping, offering actionable evidence to support disaster preparedness, land-use planning, and sustainable development in Papua. Full article

Background: Acute lung injury (ALI) and its severe form, acute respiratory distress syndrome (ARDS), remain major causes of morbidity and mortality, yet no targeted pharmacological therapy is available. Excessive neutrophil and macrophage infiltration drives reactive oxygen species (ROS) production and cytokine release, leading to alveolar–capillary barrier disruption and fatal respiratory failure. Methods: We applied an integrative multi-omics strategy combining single-cell transcriptomics, peripheral blood proteomics, and lung tissue proteomics in a lipopolysaccharide (LPS, 10 mg/kg)-induced mouse ALI model to identify key signaling pathways. Harpagide, an iridoid glycoside identified from our natural compound screen, was evaluated in vivo (40 and 80 mg/kg) and in vitro (0.1–1 mg/mL). Histopathology, oxidative stress markers (SOD, GSH, and MDA), cytokine levels (IL-6 and IL-1β), and signaling proteins (HIF-1α, p-PI3K, p-AKT, Nrf2, and HO-1) were quantitatively assessed. Direct target engagement was probed using surface plasmon resonance (SPR), the cellular thermal shift assay (CETSA), and 100 ns molecular dynamics (MD) simulations. Results: Multi-omics profiling revealed robust activation of HIF-1, PI3K/AKT, and glutathione-metabolism pathways following the LPS challenge, with HIF-1α, VEGFA, and AKT as core regulators. Harpagide treatment significantly reduced lung injury scores by ~45% (p < 0.01), collagen deposition by ~50%, and ROS accumulation by >60% relative to LPS (n = 6). The pro-inflammatory cytokines IL-6 and IL-1β were reduced by 55–70% at the protein level (p < 0.01). Harpagide dose-dependently suppressed HIF-1α and p-AKT expression while enhancing Nrf2 and HO-1 levels (p < 0.05). SPR confirmed direct binding of Harpagide to HIF-1α (KD = 8.73 µM), and the CETSA demonstrated enhanced thermal stability of HIF-1α. MD simulations revealed a stable binding conformation within the inhibitory/C-TAD region after 50 ns. Conclusions: This study reveals convergent immune–microenvironmental regulatory mechanisms across cellular and tissue levels in ALI and demonstrates the protective effects of Harpagide through multi-pathway modulation. These findings offer new insights into the pathogenesis of ALI and support the development of “one-drug, multilayer co-regulation” strategies for systemic inflammatory diseases. Full article

Road traffic crashes (RTCs) have emerged as a major global cause of fatalities, with the number of accident-related deaths rising rapidly each day. To mitigate this issue, it is essential to develop early prediction methods that help drivers and riders understand accident statistics relevant to their region. These methods should consider key factors such as speed limits, compliance with traffic signs and signals, pedestrian crossings, right-of-way rules, weather conditions, driver negligence, fatigue, and the impact of excessive speed on RTC occurrences. Raising awareness of these factors enables individuals to exercise greater caution, thereby contributing to accident prevention. A promising approach to improving road traffic accident severity classification is the stacking ensemble method, which leverages multiple machine learning models. This technique addresses challenges such as imbalanced datasets and high-dimensional features by combining predictions from various base models into a meta-model, ultimately enhancing classification accuracy. The ensemble approach exploits the diverse strengths of different models, capturing multiple aspects of the data to improve predictive performance. The effectiveness of stacking depends on the careful selection of base models with complementary strengths, ensuring robust and reliable predictions. Additionally, advanced feature engineering and selection techniques can further optimize the model’s performance. Within the field of artificial intelligence, various machine learning (ML) techniques have been explored to support decision making in tackling RTC-related issues. These methods aim to generate precise reports and insights. However, the stacking method has demonstrated significantly superior performance compared to existing approaches, making it a valuable tool for improving road safety. Full article

Background and Objectives: Severe combined immunodeficiency (SCID) represents a group of rare and potentially fatal monogenic disorders arising from pathogenic variants in a broad spectrum of genes. Diagnostic delays beyond the first few months of life have been associated with poor overall survival and hematopoietic stem cell transplantation (HSCT) outcomes. Therefore, the aim of our study was to apply an NGS assay enabling the rapid and reliable diagnosis of SCID. Materials and Methods: We developed a targeted NGS panel of 30 genes implicated in the pathogenesis of most SCID cases and we applied it to three Greek infants with suspected SCID. Results: Each patient displayed a distinct immunophenotype—T⁻B⁻NK⁻, T⁻B⁻NK⁺ and T⁻B⁺NK⁻, respectively—and was found to harbor pathogenic or likely pathogenic variants in the analyzed SCID-related genes. In particular, patient 1 carried two heterozygous ADA variants (c.58G>A, p.Gly20Arg and c.956_960del, p.Glu319Glyfs); patient 2 harbored two discrete pathogenic variants in the DCLRE1C gene (a large deletion of exons 1–3 and the nonsense mutation c.241C>T, p.Arg81*), causing Artemis deficiency; and patient 3 carried a hemizygous IL2RG missense variant (c.437T>C, p.Leu146Pro), associated with X-linked SCID. All variants were confirmed by Sanger sequencing. Conclusions: Our method successfully identified the underlying genetic defects in all patients, thereby establishing a molecular diagnosis of SCID. These findings highlight the potential of targeted NGS assays for achieving rapid and accurate molecular diagnosis of SCID, which is crucial for the timely treatment of life-threatening conditions in affected children. Full article

Drowning constitutes the leading cause of injury-related fatalities among adolescents. In swimming pool environments, traditional manual surveillance exhibits limitations, while existing technologies suffer from poor adaptability of wearable devices. Vision models based on YOLO still face challenges in edge deployment efficiency, robustness in complex water conditions, and multi-scale object detection. To address these issues, we propose YOLO11-LiB, a drowning object detection model based on YOLO11n, featuring three key enhancements. First, we design the Lightweight Feature Extraction Module (LGCBlock), which integrates the Lightweight Attention Encoding Block (LAE) and effectively combines Ghost Convolution (GhostConv) with dynamic convolution (DynamicConv). This optimizes the downsampling structure and the C3k2 module in the YOLO11n backbone network, significantly reducing model parameters and computational complexity. Second, we introduce the Cross-Channel Position-aware Spatial Attention Inverted Residual with Spatial–Channel Separate Attention module (C2PSAiSCSA) into the backbone. This module embeds the Spatial–Channel Separate Attention (SCSA) mechanism within the Inverted Residual Mobile Block (iRMB) framework, enabling more comprehensive and efficient feature extraction. Finally, we redesign the neck structure as the Bidirectional Feature Fusion Network (BiFF-Net), which integrates the Bidirectional Feature Pyramid Network (BiFPN) and Frequency-Aware Feature Fusion (FreqFusion). The enhanced YOLO11-LiB model was validated against mainstream algorithms through comparative experiments, and ablation studies were conducted. Experimental results demonstrate that YOLO11-LiB achieves a drowning class mean average precision (DmAP50) of 94.1%, with merely 2.02 M parameters and a model size of 4.25 MB. This represents an effective balance between accuracy and efficiency, providing a high-performance solution for real-time drowning detection in swimming pool scenarios. Full article

Although cannabinoids have proven therapeutic benefits, they are increasingly known for their capacity to disturb cardiac electrophysiology, particularly in individuals with hidden genetic issues such as channelopathies. This review consolidates molecular, clinical, epidemiological, and forensic findings linking cannabinoid exposure to arrhythmias and sudden cardiac death. It examines how phytocannabinoids, synthetic analogs, and endocannabinoids influence calcium and potassium currents through cannabinoid receptor-dependent and -independent pathways, affect autonomic regulation, and contribute to adverse conditions such as oxidative stress and inflammation in heart tissue. Genetic variants in key genes linked to SCD (SCN5A, KCNH2, KCNQ1, RYR2, and NOS1AP) can reduce repolarization reserve, transforming otherwise subclinical mutations into lethal substrates when combined with cannabinoid-induced electrical disruptions. Forensic research highlights the importance of comprehensive toxicological testing and postmortem genetic analysis in distinguishing between actual causes and incidental findings. There is an urgent need to re-evaluate the cardiovascular safety of cannabinoids, and this is underscored by the findings presented. The merging of molecular, clinical, and forensic evidence reveals that cannabinoid exposure—especially from high-potency synthetic analogs—can reveal latent channelopathies and precipitate fatal arrhythmias. Accordingly, this review advocates for a paradigm shift toward personalized risk stratification. If genetic screening is integrated with ECG surveillance and controlled cannabinoid dosing, risk assessment can be personalized. Ultimately, forensic and epidemiological data highlight the heart’s vulnerability, emphasizing its role as a target of cannabinoid toxicity and as a crucial aspect of public health monitoring. Full article

This review examines South Africa’s escalating flood vulnerability through a synthesis of over 80 peer-reviewed articles, historical records, policy reports, and case studies. Using a PRISMA-guided analysis, the study identifies key climatic drivers, including extreme rainfall from tropical–temperate interactions, cut-off lows, and La Niña conditions that interact with structural weaknesses such as inadequate drainage, poorly maintained stormwater systems, and rapid urban expansion. Apartheid-era spatial planning has further entrenched risk by locating marginalised communities in floodplains. Governance failures like weak disaster risk reduction (DRR) policies, fragmented institutional coordination, and insufficient early warning systems intensify flood vulnerabilities. Catastrophic events in KwaZulu-Natal (KZN) and the Western Cape (WC) illustrate the consequences exemplified by the April 2022 KZN floods alone, which caused over 450 deaths, displaced more than 40,000 people, and generated damages exceeding ZAR 17 billion. Nationally, more than 1500 flood-related fatalities have been documented in the past two decades. Emerging resilience pathways include ecosystem-based adaptation, green infrastructure, participatory governance, integration of Indigenous knowledge, improved hydrological forecasting, and stricter land-use enforcement. These approaches can simultaneously reduce physical risks and address entrenched socio-economic inequalities. However, significant gaps remain in spatial flood modelling, gender-sensitive responses, urban–rural disparities, and policy implementation. The review concludes that South Africa urgently requires integrated, multi-scalar strategies that combine scientific innovation, policy reform, and community-based action. Embedding these insights into disaster management policy and planning is essential to curb escalating losses and build long-term resilience in the face of climate change. Full article

Hepatitis A virus (HAV) infection sometimes results in the occurrence of acute liver failure and acute-on-chronic liver failure (ACLF), which is often fatal, especially in patients with diabetes mellitus or elderly individuals. ACLF is observed in patients with cirrhosis who occasionally have zinc deficiency. However, effective drugs for hepatitis A are currently unavailable. Glucose-regulated protein 78 (GRP78) is an antiviral agent that has been reported to prevent HAV replication. The effects of zinc acetate on HAV HA11-1299 genotype IIIA replication and changes in GRP78 levels in human hepatocytes with or without HAV infection were examined. Zinc acetate inhibited HAV HA11-1299 genotype IIIA replication in both Huh7 and GL37 cells. Zinc acetate also inhibited HAV replication in both low- and high-glucose media. Zinc acetate increased the expression of GRP78, in response to HAV replication. The combination of zinc acetate with ribavirin led to greater suppression of both HAV HA11-1299 genotype IIIA and HAV HM175/18f genotype IB replication in Huh7 cells than that of ribavirin alone. In conclusion, zinc acetate inhibits HAV replication in accompany with the elevation of GRP78 expression without causing cellular toxicity. Zinc compounds may be useful for the treatment of ACLF caused by HAV infection. Full article

Edwardsiella tarda is a zoonotic facultative intracellular bacterium whose impact on farm-raised amphibians is still poorly defined. We recovered seven strains from American bullfrogs (Aquarana catesbeiana) on four farms in Guangdong, China, and combined field surveillance with molecular and pathological investigations. Phylogenetic analysis of 16S rRNA and rpoB sequences confirmed species identity. Quantitative PCR of 192 apparently healthy frogs revealed intestinal carriage at every farm, with prevalence ranging from 39 to 77 percent and bacterial loads of 10⁵–10⁶ CFU/mL, indicating widespread subclinical colonisation. Virulence profiling demonstrated a conserved core gene set (gadB, mukF, citC, fimA, ompA) and accessory variation confined to the flagellar gene fliC. The strains resisted trimethoprim, ampicillin, and tetracyclines, yet remained susceptible to third generation cephalosporins, carbapenems, and most aminoglycosides. Infection trials showed that although very high inocula caused acute fatalities, an inoculum of 10⁸ CFU/mL was sufficient to induce persistent enteritis characterised by suppressed tight junction proteins, elevated cytokine expression, and marked intestinal damage. These findings demonstrate that E. tarda circulates silently in bullfrog culture, carries an amphibian adapted virulence profile and still responds to key antimicrobials, providing a baseline for risk assessment, surveillance, and targeted control in amphibian aquaculture. Full article