Search Results (1,536)

Semiconductor manufacturing relies heavily on automatic test equipment (ATE), and yet thermal aging poses a critical risk to equipment reliability. This study proposes a novel anomaly detection framework for ATE driver boards by integrating cumulative degradation time (CDT)—derived from accelerated life testing (ALT)—with artificial intelligence models. Specifically, the approach quantifies the cumulative effects of thermal stress as CDT and utilizes it as a key input feature to enable the early detection of degradation under prolonged high-temperature conditions. The proposed framework successfully demonstrates the capability to diagnose real-time anomalies before critical CDT thresholds are reached. Consequently, this approach allows for efficient management, significantly contributing to reduced maintenance costs, minimized downtime, and enhanced equipment reliability, serving as a foundational strategy for condition-based maintenance (CBM) strategies in semiconductor manufacturing. Full article

Age-related macular degeneration (AMD) is an increasingly prevalent source of permanent visual impairment in the aging population and is widely accepted as a multi-factorial neurodegenerative disorder of the retina. While there has been significant progress in treating neovascular AMD, there are currently no effective disease-sparing treatments for dry AMD and geographic atrophy. To date, research has begun to reveal the complex relationship between the environment and genetic predisposition in AMD pathogenesis. Various environmental factors responsible for AMD include oxidative stress, mitochondrial dysfunction, inflammation, abnormal complement activation, and epigenetic regulation, which interact dynamically to drive disease progression. This review summarizes recent data and provides a comprehensive model for understanding how these interacting factors lead to the progression of AMD from an early stage to advanced stages with complications associated with the disease. We highlight the central role of retinal pigment epithelial mitochondrial failure and impaired stress resilience as upstream drivers that amplify inflammation and complement-mediated injuries. We also discuss how dysregulated miRNAs and proteomic network remodeling contribute to disease heterogeneity. Emerging therapeutic strategies are reviewed in the context of molecular endotyping and personalized intervention. Finally, we outline future directions toward precision medicine in AMD, emphasizing early disease modification, rational combination therapies, and the need to bridge the translational gaps between molecular discovery and clinical trial design. Full article

Objective: This study evaluated the effects of a 12-week High-Intensity Functional Training (HIFT) program combined with thylakoid supplementation on plasma adipo-myokine levels (Decorin, Myostatin, Follistatin, Activin A, and TGF-β1) in men with obesity. Secondary outcomes included anthropometric indices, lipid profiles, and insulin resistance markers. Methods: Sixty men with obesity (age: 27.6 ± 8.4 years; BMI: 32.6 ± 2.6 kg/m²) were randomly assigned to four groups (n = 15 per group): Placebo (PG), Supplement (SG), HIFT + placebo (TPG), and HIFT + supplement (TSG). To ensure robustness against the 27% attrition rate, statistical analyses included both per-protocol and intention-to-treat (ITT) models. HIFT was performed for 3 sessions/week (Borg scale: 15–17). Results: Following Bonferroni correction for multiple endpoints, repeated-measures ANOVA showed significant Time × Group interactions for most adipo-myokines and metabolic markers. Both training groups (TPG and TSG) demonstrated improvements in body composition and insulin sensitivity compared to PG (p < 0.05). While no significant differences were observed between TPG and TSG for systemic metabolic markers, preliminary data suggested that thylakoid supplementation might provide modest complementary modulations in specific myokines (e.g., decorin and follistatin). However, these observed trends did not reach clinical superiority over exercise alone in the broader metabolic profile. Conclusions: Twelve weeks of HIFT is an effective primary driver for modulating the adipo-myokine network in obese men. Although thylakoid supplementation showed potential for selective complementary effects on certain myokines, these findings are exploratory given the small sample size. The clinical significance and long-term complementary value of thylakoid-exercise interactions require further validation in larger, more diverse cohorts. Full article

Huizhou covered bridges represent a unique and irreplaceable component of China′s architectural heritage, yet they are increasingly threatened by flash floods. In the Huizhou region, complex mountainous terrain, concentrated intense rainfall, and structural aging jointly exacerbate flood damage risks. Existing flood risk assessment approaches often prioritize external hydrodynamic hazards or assume linear additive effects, overlooking the complex interactions among inherent structural and physical attributes. To address this limitation, this study integrates Random Forest (RF) and fuzzy-set Qualitative Comparative Analysis (fsQCA) to develop a flood risk assessment framework capable of capturing both nonlinear relationships and configurational (asymmetric) causal mechanisms. Based on field investigations of 89 covered bridges and 116 documented damage cases from 2020 to 2024, the RF model identifies six key risk factors (ACC = 0.79, AUC = 0.87), several of which exhibit pronounced nonlinear and threshold effects. Building on these results, fsQCA further reveals eight equivalent configurational pathways leading to covered bridge damage (solution coverage = 0.66, solution consistency = 0.94), highlighting multiple causal combinations rather than a single dominant driver. The results demonstrate that the disaster resilience of covered bridges emerges from interactions among structural characteristics, management conditions, and spatial scale attributes, rather than from any individual factor alone. Accordingly, this study advocates a shift in protection strategies from conventional “one-size-fits-all” structural reinforcement toward risk-pattern-oriented, precision-based non-structural interventions. By combining predictive modeling with configurational causal analysis, this research provides a system-level understanding of flood-induced damage mechanisms and offers actionable insights for flood risk mitigation and sustainable conservation of covered bridge heritage in Huizhou and comparable regions worldwide. Full article

In the rapidly urbanizing Global South, megacities face a perplexing “paradox of idleness”: acute land scarcity in the urban core coexisting with inefficient rural homesteads in the hinterland. Using Shanghai as a representative case, this study integrates spatial autocorrelation analysis with Geographical Detector modeling to quantify the spatial differentiation patterns and driving mechanisms of this phenomenon. The results reveal a distinct core-periphery gradient, with vacancy density increasing from the inner suburbs to the remote hinterland. Four regional typologies were identified: dispersed-inefficient, high-density accumulation, sparse-stable, and intensive-efficient. Quantitative analysis identifies demographic aging and low agricultural efficiency as dominant drivers. Counter-intuitively, the study finds that top-down institutional pilots alone exert a negligible direct impact. Instead, interaction analysis confirms a significant policy-bundling effect, in which institutional tools promote revitalization only when coupled with economic and locational incentives. These findings expose a mechanism of “involuntary vacancy” trapped by institutional rigidity, distinct from the market-driven abandonment seen in shrinking or remote Western contexts. Consequently, a gradient-based governance framework is proposed to transition from “one-size-fits-all” regulation to targeted spatial restructuring pathways. Full article

High Mobility Group ^{Box 1} (HMGB1) and S100 proteins are major ligands of Receptor for Advanced Glycation End-products (RAGE) and have causal roles in endometriosis lesions. Yet the AGE–RAGE pathway that unifies Advanced Glycation End-products (AGEs) with these ligands has not been assessed in endometriosis. In diabetes, atherosclerosis, and chronic kidney disease, AGE–RAGE links insulin resistance and oxidative stress to inflammation, fibrosis, and organ harm. Endometriosis shares key drivers of AGE accumulation, including insulin resistance, oxidative stress, and chronic inflammation. Endometriosis is also linked to higher vascular risk and arterial stiffness. We asked whether AGE–RAGE could bridge metabolic stress to pelvic lesions and systemic risk. We did a focused review of mechanisms and an evidence map of studies on AGEs, RAGE, or known RAGE ligands in endometriosis. We grouped findings as most consistent with a driver, amplifier, consequence, or parallel role. We included 29 studies across human samples, cell systems, and animal models. Few studies measured AGE adducts directly. Most work tracked RAGE ligands (mainly HMGB1 and S100 proteins) and downstream immune and angiogenic programs. Across models, this pattern fits best with a self-reinforcing loop after lesions form. RAGE expression often aligned with lesion remodeling, especially fibrosis. Blood and skin readouts of AGE burden were mixed and varied by cohort and sample type. A central gap is receptor proof. Many models point to shared Toll-like receptor 4 (TLR4)/ nuclear factor kappa B (NF-κB) signaling, but few test RAGE dependence. Overall, current evidence supports AGE–RAGE as a disease-amplifying loop involved in chronic inflammation and fibrosis rather than an initiating trigger. Its effects likely vary by stage and site. Priorities now include direct lesion AGE measurement, paired systemic–pelvic sampling over time, receptor-level studies, and trials testing diet or drug interventions against clear endpoints. Outcomes could include fibrosis, angiogenesis, immune state, pain, and oocyte and follicle function. Full article

The human microbiome is often presented as “the next genetics,” with the expectation that microbial profiles will explain complex diseases and yield new therapies. Yet for most conditions, it remains unclear whether microbiome changes act as causal drivers or primarily mirror underlying host biology and pathology. In this narrative review, we argue that microbiome causality is frequently overstated relative to the roles of host genetics and the environment, and we explore the implications for molecular pathology. We outline a simple framework in which the microbiome can act as (i) a primary driver, (ii) a conditional mediator or effect modifier or (iii) an association biomarker that mainly reflects upstream processes. We then use marital and household studies as natural experiments to test whether chronic diseases track more strongly with a shared microbiome or with a shared lifestyle and host susceptibility. Across metabolic, inflammatory, neurodegenerative and ageing-related outcomes, spouses show only low to modest disease concordance, which is difficult to reconcile with a universally strong, transmissible microbiome causality. Adult microbiomes instead appear mostly host-constrained and context-dependent, acting more as destabilisers of homeostasis and amplifiers of allostatic load than as independent disease-causing factors. For molecular pathology, this suggests that microbiome features are often most informative as biomarkers integrated alongside host genomics, immune context and histopathology, rather than as standalone targets. Study designs and diagnostic workflows should therefore jointly model the host genome, environment, behaviour and microbiome within broader systems medicine frameworks. Full article

Forests face significant pressures from human activities, mainly through deforestation and land-use changes driven by agricultural expansion. This study aims to conduct a literature review to identify and analyze the primary factors that have driven farmers to engage in deforestation and agricultural expansion over the past 25 years. The review followed the methodology proposed by Arksey and O’Malley, with an initial broad search followed by article selection and exclusion. The analysis of the results revealed interacting factors with varying intensities by region, extending to different levels. At the demographic level, factors such as gender, age, household composition, and education play a significant role. At the social level, factors are mainly related to migration, population growth, and the phenomenon of “imitation”. At the economic level, poverty, unemployment, the need for supplementary income, and the growing demand for cash crops are key drivers of agricultural expansion in forests. At the political level, state licensing of deforestation, either as part of poverty reduction strategies or to meet market demand, and the inability to impose sanctions, reinforce deforestation for agricultural cultivation. Finally, at the environmental level, factors such as climate change and soil fertility decline constitute another critical area of pressure on forest ecosystems. Full article

Unsafe disposal of pesticide waste remains a critical environmental and public health issue in developing agricultural systems. This study examined cocoa farmers’ disposal behaviours and their determinants across Nigeria’s major cocoa-producing regions using an explanatory sequential mixed-methods design. Quantitative data were collected from 391 farmers, followed by 23 in-depth interviews to contextualise behavioural drivers. Results showed that knowledge of pesticide risks and availability of disposal facilities significantly predicted safer disposal practices (R² = 0.469, p < 0.05), whereas age had a negative influence. Qualitative findings revealed that negative attitudes, social norms, and limited infrastructure reinforced unsafe behaviours, while membership in farmers’ associations promoted safer practices through peer learning. A joint display demonstrated convergence between structural enablers (collection cages, extension support) and behavioural factors (knowledge, attitudes, norms). The study identifies a dual challenge of systemic shortcomings and behavioural inertia, suggesting that regulatory action alone is insufficient without farmer engagement and education. Policy and extension programmes should prioritise collection infrastructure, association-based training, and Integrated Pest Management to promote sustainable pesticide waste management. These insights advance understanding of pesticide disposal behaviour and offer actionable guidance for environmental governance in low- and middle-income agricultural contexts. Full article

Problem Statement: Two global trends, including aging populations and the acceleration of global warming, are increasing the risk of heat-related illness, challenging the health of populations, and the sustainability of healthcare systems. Global warming refers to the increase in the Earth’s average surface temperature, generally attributed to the greenhouse effect, which is occurring at three times the rate of the pre-industrial era. The global population of older adults, defined here as individuals aged 60 and over, is expected to reach over 2 billion by mid-century. This population is particularly vulnerable to heat-related illness, specifically disruption of thermoregulation from excessive exposure to environmental heat due to metabolic and cognitive changes associated with aging. Objectives: This review examines heat-related illness and its impact on older adults within a socio-ecological framework, considering both drivers and mitigation strategies related to global warming, the built environment, social determinants of health, healthcare system responses, and the individual. The authors were motivated to create a conceptual model within this framework drawing on their lived experiences as healthcare providers interacting with older adults in a large urban area of the southwestern US, known for its extreme heat and extensive heat island effects. Based on this framework, the authors suggest actionable strategies supported by the literature to reduce the risks of morbidity and mortality. Methods: The literature search utilized a wide lens to identify evidence supporting various aspects of the hypothesized framework. In this sense, this review differs from systematic and scoping reviews, which seek a complete synthesis of the available literature or a mapping of the evidence. The first author conducted the literature search and synthesis, while the second and third authors reviewed and added publications to the initial search and conceptualized the socio-ecological framework. Discussion: This study is unique in its focus on a global trend that threatens the well-being of a growing population. The population health focus underscores social determinants of health and limitations of existing healthcare systems to guide healthcare providers in reducing older adults’ vulnerability to heat-related illness. This includes patient education regarding age-related declines in extreme heat tolerance, safe and unsafe physical activity habits, the impact of prescription drugs on heat tolerance, and, importantly, identifying the symptoms of heatstroke, which is a medical emergency. Additional strategies for improving survivability and quality of life for this vulnerable population include improved emergency response systems, better social support, and closer attention to evidence-based treatment for heat-related health conditions. Full article

Vehicular emissions are a major contributor to air pollution and respiratory morbidity in Ecuador’s urban centers. Despite increasing evidence of traffic-related health impacts, national research remains fragmented and unevenly distributed. This narrative review synthesizes 26 peer-reviewed studies published between 2000 and 2024 to characterize vehicular air pollution sources, pollutants, and respiratory health effects in Ecuador. The evidence shows a strong geographic concentration, with more than half of the studies conducted in Quito, followed by Guayaquil and Cuenca. National inventories indicate that the transport sector accounts for approximately 41.7% of Ecuador’s CO₂ emissions. Across cities, PM_2.5, PM₁₀, NO₂, CO, and SO₂ were the most frequently assessed pollutants and were repeatedly reported to approach or exceed international guideline values, particularly during traffic peaks and under low-dispersion conditions. Health-related studies documented substantial impacts, including up to 19,966 respiratory hospitalizations in Quito, with short-term PM_2.5 exposure associated with increased hospitalization risk in children. Among schoolchildren attending high-traffic schools, carboxyhemoglobin levels above 2.5% were linked to a threefold increase in the risk of acute respiratory infections. Occupationally exposed adults, such as drivers, traffic police officers, and outdoor workers with regular exposure to traffic-related air pollution, also showed a higher prevalence of chronic respiratory symptoms. Environmental evidence further highlighted the accumulation of traffic-related heavy metals (Zn, Cu, Pb, Cr) and pronounced spatial inequalities affecting low-income neighborhoods. Overall, the review identifies aging vehicle fleets and diesel-based transport as dominant contributors to observed pollution and health patterns, while underscoring methodological limitations such as the scarcity of longitudinal studies and uneven monitoring coverage. These findings provide integrated and policy-relevant evidence to support sustainable urban planning, cleaner transport strategies, and targeted respiratory health policies in Ecuador. Full article

Background: Altered lipid metabolism has been reported in several malignancies, but its clinical relevance in non-small cell lung cancer (NSCLC) remains uncertain. This study aimed to compare serum lipid parameters between NSCLC patients and healthy controls and to explore their association with histological subtype and selected driver mutations. Methods: We retrospectively analyzed serum total cholesterol (TC), low-density lipoprotein (LDL), high-density lipoprotein (HDL), and triglycerides (TG) in patients diagnosed with adenocarcinoma or squamous cell carcinoma from 2021 to 2024, alongside a control group of 100 healthy individuals. Statistical comparisons were performed using appropriate parametric or nonparametric tests after normality assessment (Shapiro–Wilk), and p-values were adjusted using the Benjamini–Hochberg false discovery rate (FDR). Results: A total of 160 NSCLC patients were included. Most were male (75.5%) and current or former smokers (96.1%), with a mean age of 70.4 ± 10.3 years. Squamous cell carcinoma was the predominant subtype (64.4%). Hypocholesterolemia was observed in 59.9% of patients, while hypercholesterolemia was less frequent (40.1%). Compared with controls, patients had significantly lower HDL levels (p = 0.007, FDR-adjusted p = 0.024), while other lipid markers showed no statistically significant differences after correction for multiple testing. Differences between adenocarcinoma and squamous cell carcinoma were not statistically significant. Squamous cell carcinoma patients had higher TG but lower TC, LDL, and HDL levels compared with adenocarcinoma. A negative correlation between TG and ROS1 expression remained significant (r = −0.223, FDR-adjusted p = 0.004). Conclusions: In this retrospective, real-world cohort, only HDL levels demonstrated a robust difference between NSCLC patients and controls. Observed associations should be interpreted cautiously due to potential confounding factors and incomplete clinical data inherent to retrospective analyses. Prospective studies are needed to clarify whether lipid alterations play a biological or prognostic role in NSCLC. Full article

Age-related osteoporosis is driven in part by senescence-associated rewiring of bone marrow mesenchymal stem cells (MSCs) from osteogenic toward adipogenic fates. Accumulating evidence indicates that epigenetic drift and reduced autophagy are not isolated lesions but are mechanistically coupled through a bidirectional DNA methylation and autophagy axis. Here, we summarize how promoter hypermethylation of genes involved in autophagy and osteogenesis suppresses autophagic flux and osteoblast lineage transcriptional programs. Conversely, autophagy insufficiency reshapes the methylome by limiting methyl donor availability, most notably S-adenosylmethionine (SAM), and by reducing the turnover of key epigenetic regulators, including DNA methyltransferases (DNMTs), ten-eleven translocation (TET) dioxygenases, and histone deacetylases (HDACs). This self-reinforcing circuitry exacerbates mitochondrial dysfunction, oxidative stress, and inflammation driven by the senescence-associated secretory phenotype (SASP), thereby stabilizing adipogenic bias and progressively impairing marrow niche homeostasis and bone remodeling. We further discuss therapeutic strategies to restore balance within this axis, including selective modulation of epigenetic enzymes; activation of AMP-activated protein kinase (AMPK) and mechanistic target of rapamycin (mTOR) signaling with downstream engagement of Unc-51-like autophagy-activating kinase 1 (ULK1) and transcription factor EB (TFEB); targeting sirtuin pathways; mitochondria- and autophagy-supportive natural compounds; and bone-targeted delivery approaches or rational combination regimens. Full article

Aging is accompanied by progressive gastrointestinal structural and functional decline, increased intestinal permeability, dysbiosis, and impaired mucosal immunity, collectively elevating susceptibility to infections, chronic inflammation, and multimorbidity. These age-related changes are further exacerbated by polypharmacy, metabolic disorders, and lifestyle factors, positioning the gastrointestinal tract as a central driver of systemic physiological decline. Gut-centered interventions have emerged as critical strategies to mitigate these vulnerabilities and support healthy aging. Dietary modulation, prebiotic and probiotic supplementation, and microbiota-targeted approaches have demonstrated efficacy in improving gut microbial diversity, enhancing short-chain fatty acid production, restoring epithelial integrity, and modulating immune signaling in older adults. Beyond nutritional strategies, non-nutritional interventions such as molecular hydrogen and medical ozone offer complementary mechanisms by selectively neutralizing reactive oxygen species, reducing pro-inflammatory signaling, modulating gut microbiota, and promoting mucosal repair. Hydrogen-based therapies, administered via hydrogen-rich water or inhalation, confer antioxidant, anti-inflammatory, and cytoprotective effects, while ozone therapy exhibits broad-spectrum antimicrobial activity, enhances tissue oxygenation, and stimulates epithelial and vascular repair. Economic considerations further differentiate these modalities, with hydrogenated water positioned as a premium wellness product and ozonated water representing a cost-effective, scalable option for geriatric gastrointestinal care. Although preclinical and early clinical studies are promising, evidence in older adults remains limited, emphasizing the need for well-designed, age-specific trials to establish safety, dosing, and efficacy. Integrating dietary, microbiota-targeted, and emerging non-nutritional gut-centered interventions offers a multimodal framework to preserve gut integrity, immune competence, and functional health, potentially mitigating age-related decline and supporting overall health span in older populations. Full article

As chatbot technology becomes increasingly prevalent across a wide range of industries, it is crucial to explore the factors that shape user satisfaction with this AI-driven innovation. This research provides insights into how age and gender impact user perceptions and engagement with AI-driven health technologies in Saudi Arabia. The information systems success model has been utilised to determine the effect of age and gender on user satisfaction. A self-administered questionnaire was distributed in two hospitals in Makkah City, Saudi Arabia, and 527 responses were collected from chatbot users. Structural equation modelling via analysis of moment structures validated the model constructs. The findings revealed that the privacy issue on user satisfaction has been significantly greater with males than with females. However, the correlation between user satisfaction and continuance usage intention, as well as net benefits, has been much higher among the females. Also, notable differences were found between user satisfaction and net benefits and continuance usage intention and net benefits, especially when comparing younger and older participants. Across all age groups, user satisfaction consistently emerged as a central driver of continuance usage intention and net benefits, underscoring the importance of fostering satisfaction to enhance the effectiveness of AI-driven chatbots in digital health services. This study can serve as a guide to highlight the importance of chatbot user satisfaction and provide implications, limitations, and future research opportunities. Full article