Search Results (4,976)

Malaria is one of the major global public health issues. An estimated 282 million malaria cases occurred worldwide in 2024, and the overall prevention and control progress has stagnated or even reversed in some regions. Mass drug administration (MDA), as a potential strategy to accelerate malaria elimination, has regained attention. This paper reviews the evidence base, controversial focuses, and application strategies of MDA in malaria prevention and control. It aims to promote its scientific application in the elimination phase. MDA plays an important role in malaria prevention and control. However, this strategy is accompanied by core limitations such as long-term drug resistance risks, insufficient implementation sustainability, and a high failure rate of regional adaptation. It also faces challenges from multiple common malaria species, as well as the newly discovered Plasmodium knowlesi. We therefore propose an “MDA+” collaborative strategy integrating vaccines, digital monitoring, and cross-border cooperation, so as to optimize resource allocation, achieve full coverage control over various malaria parasites, and advance the global malaria elimination process. Full article

Deep reinforcement learning (DRL) for autonomous mobile robot navigation faces several inherent limitations. The stochastic nature of actions generated by DRL policies can undermine performance consistency, while inefficient exploration frequently delays the learning process or prevents the discovery of optimal solutions. This research aims to enhance the robustness of path planning by addressing these challenges. To achieve this goal, we propose a hybrid approach that integrates the flexible decision-making capabilities of deep reinforcement learning with the stability of traditional path planning. The proposed model adopts the Twin Delayed Deep Deterministic Policy Gradient (TD3) network as its base. Notably, we pre-process LiDAR point cloud data to extract only essential features for the state representation, thereby preventing performance degradation from high-dimensional inputs and improving computational efficiency. Our model optimizes the learning process through two core strategies. First, it prioritizes experience data generated during training based on negative rewards, guiding the model to learn more frequently from critical failures rather than redundant successes. Second, it dynamically compares the action proposed by the TD3 network with a goal-oriented action from a classical path-planning algorithm in real time. By selecting the action with the higher estimated value, the model guides the policy toward a stable and effective trajectory from the earliest stages of training. To validate the efficacy of our approach, we conducted simulation-based experiments comparing the performance of the proposed model with existing reinforcement learning networks. To ensure statistical significance and mitigate the impact of random initialization, all reported results are averaged over 10 independent runs with different random seeds. The results quantitatively demonstrate that our model achieves significantly higher and more stable reward values, confirming a robust improvement in the path-planning process. Full article

In this study, the microstructure and mechanical properties of ultrasonic welded joints between large-diameter aluminum wire and Cu (Ni-plated copper) terminals were systematically investigated, to reveal the underlying fracture mechanisms. The cross-sectional morphology, interfacial microstructure, and mechanical properties of the two types of welded joints are investigated. The results indicate that ultrasonic welding produces well-structured Al-Cu and Al-Ni joints. Under the same welding process parameters, the Al-Cu joint exhibits many pores, while the Al-Ni joint has no pores in its microstructure. The interfacial region of the Al-Cu joint presents various morphologies, such as flat bonding, interlocking, and eddy current patterns, whereas the Al-Ni joint interface is flat. No significant atomic diffusion phenomenon occurs between the interfaces of the two types of joints. The tensile strength of the Al-Cu joint is 53 MPa, with fracture modes including ductile fracture and brittle fracture, whereas the tensile strength of the Al-Ni joint is 50 MPa, with a failure mode of pull-out fracture. In working conditions requiring ultrasonic welding of aluminum and copper, nickel-plated copper can be used as a substitute for copper to prevent electrochemical corrosion between aluminum and copper. Full article

Eastern deciduous forests are undergoing directional compositional shifts, marked by the progressive replacement of Quercus-dominated canopies with generalists and shade-tolerant taxa. These shifts are increasingly interpreted within a regeneration debt framework, in which canopy composition persists despite recruitment failure and regeneration mismatch in smaller size classes. We evaluated 30 years (1995–2025) of compositional and structural change in adjacent upland and cove forests on the southern Cumberland Plateau, Tennessee, using a permanent nested circular plot design to determine whether previously observed upland resistance reflects durable resilience or delayed demographic transition. Both habitats exhibited continued Quercus decline while remaining compositionally distinct. As documented in prior analyses, reductions in small-diameter stems were more pronounced in the cove forest, but now reveal demographic mismatches between canopy and regeneration layers in both habitats. Upland forests maintained a higher representation of species capable of basal sprouting and clonal growth via root suckering, indicating that vegetative regeneration buffered short-term demographic change. However, recruitment into larger size classes declined in both habitats, demonstrating that buffering facilitated by vegetative regeneration delayed but did not prevent the accumulation of regeneration debt. What appeared as differential resistance through 2014 is more accurately interpreted as temporal offset in regeneration debt accumulation. Full article

Background and Objectives: Total femoral replacement (TFR) was originally developed for limb salvage following the resection of malignant tumors. Over time, its indications have expanded, now serving as a reconstructive option for failed endoprosthetic replacements and severe trauma cases. Despite its advantages, TFR is a highly complex surgical procedure associated with significant complication rates. This study aims to analyze the management of complications and propose strategies to mitigate associated risks. Materials and Methods: This is a retrospective study conducted on patients from two independent hospitals who underwent TFR for different reasons. Results: Nineteen patients were included: eight underwent TFR for oncological indications, while 11 had the procedure as a revision following failed endoprosthetic arthroplasty or trauma. Postoperative complications were observed in 10 patients (53%), including hip dislocation (21%), mechanical implant failure (11%), infection (21%), wound healing complications (26%), and metal allergy symptoms (5%). Revision surgery was required in six patients (32%), but no cases necessitated amputation. Conclusions: TFR is associated with a high risk of complications, with infection and wound healing issues being the most prevalent. In our experience effective complication management strategies should include early intervention, considering TFR at an earlier stage in non-oncological patients to minimize multiple revision surgeries; allergy screening, assessing for potential metal hypersensitivity preoperatively; dislocation prevention, implementing dual mobility bearings to reduce instability; infection control, utilizing intraoperative local antibiotic therapy in revision cases; and wound management, applying vacuum-assisted closure (VAC) therapy postoperatively to enhance wound healing. Implementing these strategies may improve patient outcomes and reduce the burden of complications associated with TFR. Full article

The taxane family of compounds, including paclitaxel, docetaxel (Taxotere), and cabazitaxel (Jevtana), are common drugs used in chemotherapy for the frontline treatment of most major types of cancer. Alopecia, the dramatic loss of hair, is a common side effect that became a symbol of the suffering of many cancer patients. Concerted efforts have been made to understand the mechanism of taxane toxicity to hair follicles and, thus, prevention methods. Taxanes act by stabilizing cellular microtubules, which consequently cause mitotic arrest and then failure, as microtubules play critical functions in chromosome segregation. Hair follicle matrix cells are highly proliferative and thus are exceedingly sensitive to taxanes. We review the cellular mechanism-based strategies under investigation to counter taxane-induced hair follicle damage. These include the application of cyclin kinase inhibitors to block mitotic entry, the practical method using scalp cooling to reduce exposure of scalp hair follicles to drugs during infusion, the requirement of p53 action for hair follicle damage, and the recently discovered method of using low-intensity ultrasound to break taxane-stabilized microtubules and thus reverse taxane toxicity in hair follicle matrix cells. The concept of low-intensity ultrasound as an antidote to taxanes may have the potential to provide a practical and compelling strategy to counter alopecia in cancer treatment using taxanes. Tweet: Taxanes (paclitaxel/docetaxel) are powerful microtubule-stabilizing cancer drugs, but they also cause adverse effects, including alopecia. New research discoveries of temporary microtubule disruption by low-intensity ultrasound may counteract taxane toxicity and prevent alopecia during cancer chemotherapy. “Mechanistic-based strategies for the prevention of taxane-induced hair follicle damage in cancer chemotherapy” OUTLINE: 1. Taxane/paclitaxel mechanism of action in cancer therapy. 2. Taxane side effects: Alopecia (hair loss). 3. p53 dependence of taxane-induced hair follicle damage. 4. Research efforts to counter taxane -induced alopecia by CDK4/6i. 5. Prevention of taxane chemotherapy side effects using scalp cooling. 6. Discovery of low-intensity ultrasound as an antidote for taxane cytotoxicity, and potential prevention of alopecia in chemotherapy using taxanes. 7. Summary and prospective. Full article

At around 8:40 a.m. on 17 July 2024, the Wanshuitian landslide in the Three Gorges Reservoir Area (TGRA) experienced a deformation failure characterized by thrust load-caused deformations and high-speed sliding. Using geological surveys and unmanned aerial vehicle (UAV) photography, this study divided the Wanshuitian landslide area into five zones: sliding initiation (A1), secondary disintegration (A2), main accumulation (B1), right falling (B2), and left falling (B3) zones. Through monitoring data analysis and GeoStudio-based numerical simulations, this study revealed the mechanisms behind the landslide failure mode characterized by slope sliding approximately along the strike of the rock formation under the coupling effect of hydrological and geological conditions. The results indicate that factors inducing the landslide failure include the geomorphic feature of alternating grooves and ridges, the lithologic assemblage characterized by interbeds of soft and hard rocks, the slope structure with well-developed joints, and the sustained heavy rains in the preceding period. In the Wanshuitian landslide area, mudstone valleys are prone to accumulate rainwater, which can infiltrate directly into the weak interlayers of rock masses and soften the rock masses. Multi-peak rain events with a short time interval serve as a critical factor in groundwater recharge. Within 17 days preceding its failure, the Wanshuitian landslide experienced a superimposed process of heavy and secondary rain events with a short interval (four days). Rainwater from the first heavy rain event failed to completely discharge during the short interval, while the secondary rain event also caused rainwater accumulation. These led to a continuous rise in the groundwater table, a constant decrease in the shear strength of the slope, and ultimately the landslide instability. Since the landslide sliding in the dip direction of the rock formation was impeded, the main sliding direction of the landslide formed an angle of 88° with this direction. This led to a unique failure mode characterized by slope sliding approximately along the strike of the rock formation. Based on these findings, this study proposed characteristics for the early identification of the failure of similar landslides, aiming to provide a robust scientific basis for the monitoring, early warning, and prevention and control of the failure of similar landslides. Full article

Background: Oxidative liver damage, fibrosis, cirrhosis and liver failure are caused by reactive oxygen species and inflammatory responses triggered by bile retention during prolonged cholestasis. Pomegranate and persimmon fruits, which are loaded with bioactive compounds that have anti-inflammatory and antioxidant properties, were evaluated separately for their efficacy in preventing oxidative stress and inflammation in cholestasis. Methods: Pomegranate and persimmon juices were analyzed for their vitamin C, carotenoids and organic acid levels, phenolic profile, and antioxidant activity. Liver protection against oxidative stress and inflammation brought on by cyclosporine-induced cholestasis in rats was verified by biochemical measurements, metabolite identification, and histopathologic examination. To forecast the mechanism of pomegranate and persimmon anti-inflammatory action, an in silico assessment was also carried out. Results: Vitamin C levels in pomegranate and persimmon juices were 99.55 and 51.75 µg/g, respectively. In both pomegranate and persimmon juices, gallic acid was the most prevalent phenolic compound (123.20 and 50.69 µg/g, respectively). Pomegranate and persimmon juices significantly (p < 0.05) reduced the rise in liver values of MDA, NO, TNF-α, IL-6, IL-1β, and TLR4, as well as serum values of total and direct bilirubin caused by cyclosporine. Additionally, the alteration of metabolites, particularly amino acids, demonstrated the inhibitory effect of pomegranate and persimmon juices on liver damage. Gallic acid’s and catechin’s substantial binding affinities with target inflammatory cytokines (TNF-α and TLR4) were further validated by molecular docking. Conclusions: These results showed that pomegranate and persimmon juices mainly modulated inflammation and oxidative stress to provide hepato-protective benefits against cyclosporine-induced cholestatic liver injury. Full article

This study presents a multi-period Generalized Cell Formation Problem with Machine Availability (GCFP-MA) aimed at designing manufacturing cells that explicitly account for equipment reliability, maintainability, and temporal degradation. The proposed model extends classical formulations by introducing (i) availability-based constraints derived from Mean Time Between Failures (MTBF) and Mean Time to Repair (MTTR) and Markov-Chain models, (ii) downtime penalty costs reflecting non-production losses, and (iii) a multi-period horizon that captures system dynamics over time. To solve the resulting NP-hard problem, the Black Widow Optimizer (BWO)—a population-based metaheuristic inspired by cannibalistic reproduction—is implemented and validated against an exhaustive search benchmark. Computational experiments confirm that the BWO attains the global optimum with substantially reduced computational effort, achieving a balanced trade-off between exploration and exploitation. Results highlight that incorporating availability and repair dynamics prevents infeasible or over-optimistic configurations and yields cost-effective, robust cell layouts. The proposed approach provides both theoretical and practical contributions by integrating availability engineering and production system design within a unified optimization framework. Full article

Bilirubin, historically recognized solely as a waste product of heme catabolism, has recently gained attention for its potential protective role in the cardiovascular system. Experimental and clinical studies suggest that bilirubin exhibits potent antioxidant, anti-inflammatory, anti-apoptotic, and cytoprotective properties that may protect the heart against oxidative stress, ischemia–reperfusion injury, and the progression of cardiovascular diseases, such as heart failure. As an endogenous hormone, bilirubin activates peroxisome proliferator-activated receptor-α (PPARα), a nuclear receptor that controls energy balance and lipid metabolism. Moderately elevated circulating bilirubin levels have been associated with a reduced risk of coronary artery disease, heart failure, and myocardial infarction; however, the mechanisms underlying bilirubin’s protective effects remain incompletely understood. Conversely, the gut microbiota’s metabolism of bilirubin to urobilin is detrimental, given urobilin’s association with cardiometabolic dysfunction. The therapeutic potential of bilirubin in the management of cardiovascular disease is becoming increasingly apparent, supported by preclinical research and emerging technologies that enhance bilirubin delivery via nanoparticles and methods to elevate plasma bilirubin levels. Collectively, these scientific advancements position bilirubin as a promising, biologically plausible endogenous therapeutic for the prevention and treatment of heart disease. Full article

Chronic diseases increasingly reflect a shared biological origin: persistent cellular stress. This review summarizes the biochemical mechanisms that normally preserve cellular homeostasis, namely redox regulation, endoplasmic reticulum proteostasis, mitochondrial quality control, autophagy, and DNA damage response, and explains how they fail under sustained lifestyle-related overload. Repeated exposure to psychological stress, sleep disruption, hypercaloric intake, and physical inactivity shifts adaptive signaling toward maladaptation, promoting oxidative damage, protein misfolding, mitochondrial dysfunction, low-grade inflammation, and genomic instability. These interconnected processes contribute to the development and progression of major chronic non-communicable diseases, including obesity, type 2 diabetes, cardiovascular disease, neurodegeneration, and cancer. Particular emphasis is placed on circadian and neuroendocrine regulation, especially overactivation of the hypothalamic–pituitary–adrenal axis and impaired nocturnal regenerative pathways such as glymphatic clearance and DNA repair. Together, the evidence supports a unifying model in which chronic pathology emerges from cumulative failure of cellular resilience systems rather than isolated organ-specific defects. This perspective highlights sleep optimization, stress reduction, and metabolic regulation as mechanistically grounded strategies for prevention and supportive interventions for chronic disease. Full article

Background/Objectives: Early neurological deterioration (END) is a frequent and clinically relevant complication in patients with a single small subcortical infarction (SSI), including lacunar infarction and branch atheromatous disease (BAD). Despite initially mild symptoms, END occurs in approximately 20–25% of cases and is strongly associated with poor functional outcomes. However, definitions, mechanisms, predictors, and therapeutic strategies remain heterogeneous. This review aims to synthesize current evidence regarding the incidence, pathophysiology, predictors, and management of END in SSI. Methods: We performed a narrative review of published studies addressing END in patients with lacunar stroke or SSI. We analyzed data on END definitions and incidence, imaging and clinical predictors, proposed pathophysiological mechanisms, and preventive and rescue therapeutic strategies. Results: END definitions vary across studies, most commonly defined as a ≥2-point increase in the National Institutes of Health Stroke Scale within 48–72 h. Hemodynamic compromise due to proximal perforator pathology, particularly in BAD, appears central to END development. Advanced imaging studies demonstrate perfusion abnormalities beyond the infarct core, supporting the concept of a “lacunar penumbra.” Lesion topology, proximal infarct patterns, parent artery plaques, larger infarct size, and vertical extension are consistent imaging predictors. Clinical factors such as diabetes mellitus, higher baseline severity, systemic inflammation, and increased arterial stiffness further modulate risk. Preventive strategies, including early dual antiplatelet therapy and intensified antithrombotic regimens, show promising signals, while induced hypertension may benefit selected patients as a rescue therapy. However, evidence remains largely observational or derived from subgroup analyses. Conclusions: END in SSI is a multifactorial and potentially modifiable process driven by interactions between proximal vascular pathology, hemodynamic failure, and tissue vulnerability. Standardized definitions, MRI-based phenotyping, and mechanism-driven trials are needed to optimize risk stratification and develop targeted preventive and rescue strategies. Full article

Urban transportation systems are facing increasingly severe threats from extreme weather events such as rainstorms, which can trigger cascading failures and lead to regional traffic paralysis. The strategic location of emergency facilities to enhance system resilience has emerged as a critical proactive prevention strategy. This study proposes a multi-objective hierarchical coverage location model that integrates point and flow demands to improve the resilience of urban road traffic systems under rainstorm conditions. First, the resilience risk levels of road nodes were quantified using an entropy-weighted TOPSIS method that combines topological attributes, traffic flow performance, and indirect propagation intensity. Second, a flow-capturing mechanism was introduced to address the dynamic rescue demands of stranded vehicles in motion, enabling the pre-positioning of “safe havens” along critical travel routes. The model balances two objectives: maximizing the resilience risk value of the covered demands and minimizing facility construction costs. A case study was conducted in Jianghan District, Wuhan, a flood-prone area, and the NSGA-II algorithm was employed to solve the multi-objective optimization problem. The results demonstrate that the proposed model significantly outperforms traditional single-demand location models in terms of coverage effectiveness and cost efficiency, achieving improvements in resilience risk coverage of up to 311.6% and cost reductions of up to 63.6%. This study provides a systems science perspective for pre-disaster emergency resource allocation, shifting the paradigm from infrastructure-centric protection to human-centered rescue. Full article

Objective: To determine the publication bias of the reported prevalence of malocclusions in Mexican children and adolescents. Background: Publication bias determination is crucial in a systematic review, helping to ensure the conclusions’ validity and reliability. Nevertheless, without accurate knowledge of disease prevalence and patterns, the health system risks inefficiency, inequity, and failure to meet the population’s needs. On the other hand, malocclusions can impair proper chewing efficiency, contributing to digestive alterations, and nutritional deficiencies among other functional, psychological, and social problems. The data of the prevalence of malocclusion is imperative to implement early interventions in health services that prevent more severe skeletal discrepancies and reduce the need for invasive treatments in adolescence or adulthood. Methods: Studies were collected from five databases, following the PRISMA and Cochrane guidelines for systematic reviews. Eligibility criteria were full-text research in which the prevalence of malocclusions was reported. The risk of bias (Hoy tool), publication bias (the Doi plot and the Luis Furuya-Kanamori (LFK) index), and quality assessments (GRADE tool) were performed. The data were combined using a random-effects meta-analysis. Results: The result of the meta-analysis suggests a high prevalence of malocclusions in mixed dentition was 50.2% (95% confidence interval [CI]: 38.9–61.5%). However, the studies showed a risk of bias and publication bias. Conclusions: In Mexico, there is a high prevalence of malocclusions among children and adolescents. However, these results are not robust enough to draw solid conclusions, due to the low certainty of the evidence. Full article

Background: In the paediatric intensive care unit (PICU), certain drugs should be avoided or administered with strict precautions and close monitoring. This is due to their potential for toxicity or adverse effects or a lack of safety data, especially for critically ill children with organ failure. Additionally, practitioners must assess the unique pharmacokinetic and pharmacodynamic properties of drugs when treating critically ill children. In this narrative review, we highlight the risks, advantages, and disadvantages of three exemplary cases of drugs for paediatric patients hospitalised in the PICU: chloramphenicol, acetylsalicylic acid, and propofol. Methods: Apart from key papers on these drugs, a retrospective analysis of the English literature on chloramphenicol, acetylsalicylic acid (ASA), and propofol was performed on PubMed for papers from January 2014 to December 2025. Results: Chloramphenicol should be avoided in neonates due to the risk of grey baby syndrome. Acetylsalicylic acid (ASA) is contraindicated in children ≤18 years with suspected viral illness because of the risk of Reye’s syndrome, but remains essential for Kawasaki disease and post-cardiac surgery antiplatelet therapy. Propofol should be avoided when used for a longer period at high doses. With proper dosing and monitoring, propofol-related infusion syndrome (PRIS) is preventable, but high-risk patients should receive alternative treatment. Conclusions: This narrative review highlights the significant risks associated with the use of chloramphenicol, ASA, and propofol in paediatric intensive care settings. Their potential for life-threatening and severe adverse reactions emphasises the need for cautious and informed use. Clinicians must carefully consider the risks and benefits of these drugs. To minimise adverse events, strict monitoring, dose adjustments, and the use of safer alternatives are essential. However, it appears that their use in well-defined circumstances in acute illness in children is still warranted. The findings of this narrative review underscore the need for further research to focus on identifying high-risk biomarkers, genetic predispositions, and safer alternatives to improve evidence-based guidelines and reduce morbidity and mortality in paediatric intensive care. Full article