Search Results (11,811)

Autophagy-mitophagy pathways are essential for regulating immune homeostasis. However, their contribution to population-level chronic low-grade systemic inflammation (SI) remains unclear. The objective was to investigate the association between variation in the genes related to the autophagy-mitophagy pathways and SI, and to examine whether lifestyle factors modify this relationship. We conducted genome-wide association studies and gene-set enrichment analyses using data from the Korean Genome and Epidemiology Study (KoGES, n = 28,102) and UK Biobank (UKBB, n = 343,892). SI was defined as an elevated white blood cell count or high-sensitivity C-reactive protein. Using Core Longevity State Vectors (CLSVs)—gene sets representing immune-longevity pathways derived from comparative transcriptomic analysis—we tested six pathways and constructed a weighted genetic risk score (GRS) from significant variants. Gene–lifestyle interactions were examined with respect to major dietary and lifestyle factors. Among six CLSVs, only CLSV-2 (mitophagy and autophagy) showed a significant association with SI (β = 0.425, p = 0.008). Six single nucleotide polymorphisms (SNPs) in autophagy-mitophagy genes (INPP5D, ATG16L1, ATG7, AP3S1, OPTN, and VPS33A) were associated with SI in KoGES (p < 5 × 10⁻⁵), and ten SNPs (genes selected in KoGES plus RAB7A, ATG12, VPS33A, BECN1) reached genome-wide significance in UKBB (p < 5 × 10⁻⁸). A higher GRS was associated with increased SI in both cohorts and was strongly associated with metabolic syndrome (MetS, OR = 1.91 in KoGES; OR = 1.62 in UKBB). SI was characterized by neutrophilia with relative lymphopenia. In UKBB, significant gene–lifestyle interactions were observed for diet, physical activity, smoking, and alcohol (p < 0.01). Favorable lifestyle factors reduced SI most effectively in individuals with protective genotypes. Among individuals with a high vegetable/fruit intake, SI prevalence was 35%, 36%, and 38% in the negative-, zero-, and positive-GRS groups, respectively, compared with 36%, 45%, and 48% in the low-intake groups. In conclusion, genetic variations in autophagy-mitophagy pathways specifically influence SI. Genetic predisposition substantially modifies the benefits of lifestyle, underscoring the importance of integrating genetic and lifestyle factors in understanding SI susceptibility. Full article

To address the challenges in UAV remote sensing imagery, such as small object size, dense occlusion and complex background interference, this paper proposes an enhanced small object detection algorithm based on an improved YOLOv13 model for drone applications in complex weather environments. First, an enhanced feature fusion attention network (EFFA-Net) is designed in the preprocessing stage to reduce image degradation and suppress the interference caused by smoke and haze. Then, in the backbone, a swish-gated convolution (SwiGLUConv) module is designed to adaptively expand the receptive field and enhance multi-scale feature extraction, which strengthens the representation of small targets while maintaining efficient computation. Furthermore, a locally enhanced multi-scale context fusion (LF-MSCF) module is integrated into the feature fusion neck of YOLO, combining multi-head self-attention, channel attention, and spatial attention to suppress background noise and redundant responses, thereby improving detection accuracy. Extensive experiments on the VisDrone-DET2019 dataset, UAVDT dataset, and HazyDet dataset demonstrate that the proposed algorithm outperforms other mainstream methods, showcasing excellent detection accuracy and robustness in complex UAV aerial scenarios. Full article

Human papillomavirus (HPV)-driven oropharyngeal squamous cell carcinoma (OPSCC) has emerged as a biologically distinct entity, typically affecting younger, non-smoking patients and showing improved survival compared to HPV-negative tumors. Accurate HPV status determination is essential for correct staging, prognostic assessment, and treatment de-escalation. Despite advances, substantial variability persists among diagnostic methods and clinical workflows. A narrative review of PubMed, Scopus, and Web of Science databases was conducted up to July 2025. Studies addressing HPV detection techniques in OPSCC—including p16^INK4a^ immunohistochemistry (IHC), HPV DNA and RNA assays, liquid biopsy approaches, and computational surrogates—were critically analyzed regarding diagnostic accuracy, clinical applicability, and emerging innovations. Tissue-based assays remain the diagnostic reference standard. p16 IHC provides high sensitivity but limited specificity and should be confirmed with nucleic acid-based methods such as DNA PCR, in situ hybridization (ISH), or E6/E7 mRNA detection. Combined or “orthogonal” testing minimizes discordance and refines risk stratification. Liquid biopsy detection of circulating HPV DNA using droplet digital PCR or next-generation sequencing has shown high sensitivity and specificity in cohorts of patients with HPV-associated OPSCC, supporting its potential role as a complementary biomarker for treatment monitoring and surveillance. However, circulating HPV DNA alone does not unequivocally identify the anatomic source of HPV DNA and should be interpreted together with clinical, radiologic, and tissue-based findings. Oral rinse and saliva assays show moderate diagnostic performance, while artificial intelligence-based radiomic and histopathologic models are emerging as complementary tools. Reliable HPV attribution in OPSCC requires a multimodal diagnostic strategy integrating p16 IHC, molecular confirmation, and ctHPV-DNA monitoring. Methodological standardization and prospective validation are essential to implement precision-guided, cost-effective workflows in routine clinical practice. Full article

Lung squamous cell carcinoma (LUSC) tends to arise in the setting of interstitial or emphysematous lung diseases, including idiopathic pulmonary fibrosis (IPF), pulmonary emphysema (PE), and smoking-related interstitial fibrosis (SRIF), where field cancerization may extend. DNA methylation of promoter regions of p16, CDH13, and RASSF1A and p16 exon 2 was assessed by methylation-specific PCR. Tumor, adjacent (<3 cm), and distant (≥3 cm) lung tissues were obtained from 25 patients with LUSC (IPF, n = 7; PE, n = 8; SRIF, n = 10). p16 exon 2 methylation was significantly higher in tumors than in non-tumorous tissues in PE and SRIF cases. In contrast, IPF cases showed p16 exon 2 hypermethylation also in distant tissues. Across tumor samples, p16 promoter hypermethylation was frequently observed in stage II or higher. p16 expression in tumors was generally reduced in IPF and PE cases, compared with SRIF cases. No consistent methylation or expression patterns were observed for CDH13 or RASSF1A. p16-associated molecular alterations exhibited disease- and stage-related differences, suggesting heterogeneity in LUSC carcinogenesis. These findings indicate a broader epigenetic field effect, as reflected by p16 exon 2, in IPF-associated LUSC and suggest that complex, elusive mechanisms underlying p16 aberrations may contribute to this phenomenon. Full article

Alpha-1 antitrypsin deficiency (AATD) is a genetic disorder characterized by reduced circulating levels and/or impaired function of alpha-1 antitrypsin (AAT), a key serine protease inhibitor, in which loss of effective antiprotease protection results in unchecked neutrophil elastase activity and progressive lung tissue destruction. Although AATD accounts for approximately 1% of chronic obstructive pulmonary disease (COPD) cases and up to 2% of emphysema, AATD-related COPD remains largely underdiagnosed, despite guideline recommendations for systematic evaluation in patients with COPD, particularly in high-risk clinical settings. Pathologically, AATD-related COPD is not limited to the typical early-onset, lower-lobe-predominant emphysema, also including upper-lobe or mixed emphysema patterns, airway-predominant disease, small airways dysfunction, and bronchiectasis. Clinically, AATD-related COPD is distinguished from smoking-related COPD by its earlier onset, physiological impairment that is often disproportionate to smoking exposure, and its potential presence of certain extrapulmonary manifestations. Diagnosis and monitoring are also challenged by the frequent discordance between airflow limitation and gas transfer impairment, as well as the early involvement of small airways, limiting reliance on spirometry alone. A multimodal assessment incorporating more sensitive functional techniques and CT densitometry may provide a more precise evaluation of disease burden, progression, and prognosis. Management generally follows standard COPD principles, with intravenous AAT augmentation therapy remaining currently the only established disease-modifying therapy for selected patients with severe deficiency. The advent of new pharmacological and gene-based therapies emphasizes the importance of developing personalized management strategies that integrate genotype and longitudinal disease behavior. This narrative review summarizes current evidence on AATD-associated COPD, focusing on its genetic basis and pathophysiological features, clinical and functional heterogeneity, current and emerging diagnostic and monitoring approaches, and disease-specific management considerations. Full article

Background/Objective: Dizziness is managed using various therapies, including lifestyle changes, nutritional supplementation, pharmaceutical therapies, and physical therapy, each offering differing efficacy. With legalization of cannabis in Canada, patients are exploring its use in treating their dizziness and related symptoms. Limited knowledge exists regarding usage patterns, forms, doses, and effects on these symptoms. The current study aims to examine cannabis use in patients experiencing dizziness. Methods: We conducted a cross-sectional study at the Ottawa Hospital outpatient neuro-otology clinic. Eligible participants included new patients presenting with a primary complaint of dizziness and follow-up patients reporting new-onset dizziness. Participants completed a questionnaire capturing demographic data, dizziness and related symptoms, attitudes toward cannabis use, consumption patterns, and its perceived effects on their symptoms. Results: Of 154 participants, 118 (77%) expressed willingness to consider cannabis for dizziness and 78 (51%) reported previous cannabis use. Of those patients, 44 (56%) consumed it recreationally, largely via smoking (29/78, 37%). Approximately 21% of these patients reported a moderate–large subjective relief from dizziness after use of cannabis. The most common diagnoses amongst cannabis users were migraine/vestibular migraine (24%), persistent postural perceptive dizziness (22%), and benign paroxysmal positional vertigo (17%). Other related symptoms relieved by cannabis included sleep (28/78, 36%), emotional difficulties (17/78, 22%), neck pain/stiffness (14/78, 18%) and headaches/migraines (9/78, 12%). Conclusions: There is generally a positive attitude towards cannabis use in treating dizziness amongst patients, with a subset of patients reporting a subjective improvement of dizziness and its related symptoms, such as sleep and emotional difficulties. Full article

Background/Objectives: Peak cough flow (PCF) is an objective measure of cough effectiveness after stroke, but biomarkers reflecting physiological vulnerability related to reduced PCF are not well established. We investigated whether bone turnover markers (BTMs)—C-terminal telopeptide of type I collagen (CTX) and procollagen type 1 N-terminal propeptide (P1NP)—were associated with PCF in subacute ischemic stroke. Methods: In this retrospective study, 112 patients admitted within 21 days of stroke onset had fasting morning CTX and P1NP measured by electrochemiluminescence immunoassay, and PCF measured within 72 h of admission. Associations were assessed using Spearman correlation and multivariable linear regression with BTMs standardized (per 1 standard deviation increase), adjusting for age, sex, body mass index, onset-to-admission days, National Institutes of Health Stroke Scale score, Korean version of the Modified Barthel Index, estimated glomerular filtration rate, smoking status, and brainstem lesion. Results: CTX showed an inverse correlation with PCF (rho = −0.469; p < 0.001) and remained independently associated with lower PCF after multivariable adjustment (β = −42.32 L/min; 95% confidence interval, −56.12 to −28.52; p < 0.001), whereas P1NP showed weaker associations. In secondary outcome analyses, higher CTX was associated with low PCF (PCF < 160 L/min), aspiration pneumonia, and longer length of stay. Conclusions: Higher CTX levels were independently associated with lower peak cough flow and selected respiratory-related outcomes in this retrospective cohort. These findings are hypothesis-generating, do not imply prognostic validation, and warrant confirmation in prospective multicenter studies assessing incremental predictive value. Full article

To investigate the temporal and spatial variations in smoking activities in Shanghai, atmospheric fine particles (aerodynamic diameter ≤ 2.5 μm) were collected at four sites in different functional zones, a central urban site (XJH), an urban site (PD), a suburban site (BS), and a rural site (QP), between 2012 and 2020 with the concentration of nicotine measured by GC-MS. The results showed that smoking activities in Shanghai decreased significantly from 2012 to 2020. The average concentration of nicotine in fine particles at XJH (2012–2013) was 13.86 ng m⁻³, while it was 3.39 ng m⁻³ at BS (2017–2018), and 1.13 ng m⁻³ and 0.58 ng m⁻³ at PD and QP during 2018–2020. Nicotine concentration in Shanghai showed strong spatial variability but generally followed a seasonal trend of high in winter and low in summer. At XJH and BS, where higher nicotine concentrations were detected, positive correlations between nicotine and organic carbon in fine particles were observed, but not at PD and QP. A negative correlation between nicotine and ozone was found at QP, suggesting the influence of transported nicotine at the rural site. In general, the concentration of nicotine in atmospheric fine particles is primarily governed by local smoking activities, but is also influenced by meteorological conditions. Full article

Background: Oral squamous cell carcinoma (OSCC) is an aggressive cancer closely associated with smoking and alcohol consumption, with a higher incidence in men. Despite changes in treatment strategies, poor survival persists in most patients, highlighting the need for novel and improved therapeutic options. Naphthoquinone analogs are being investigated because of their active redox structure and broad pharmacological profile; they demonstrate cytotoxic antitumor activity, making them potential candidates for new drug agents. Objective: This study investigated new benzyl-naphthoquinone compounds as potential anticancer agents for various genotypes of oral squamous cell carcinoma (OSCC) and other cancer cells. Methods: This study reports the synthesis and evaluation of a series of eight benzyl-naphthoquinone compounds against oral squamous cell carcinoma. Results: Four compounds 1–4 showed the best cytotoxic profiles, with a selectivity index ≥ 3 for all OSCC cell lines tested. Compound 1 was the most selective compound in all OSCC models, showing a higher selectivity index than both carboplatin and shikonin. Furthermore, compound 1 induced DNA fragmentation, cell-cycle arrest, and caspase-3/7 activation, changes consistent with apoptosis, and time-lapse imaging corroborated the apoptotic phenotype. Hemolysis assays showed minimal toxicity in human erythrocytes, and acute in vivo evaluation in mice revealed no evident adverse effects under the conditions tested, indicating low acute toxicity, although more detailed histopathological and biochemical studies will be required to fully establish the safety profile. Molecular modeling suggested that compound 1 may interact with topoisomerase II, RSK2, and PKM2, which could contribute to the activation of apoptotic pathways, although these interactions remain predictive and require biochemical validation. Finally, in silico analysis of physicochemical and ADMET parameters indicated properties compatible with oral absorption and systemic exposure, together with predicted low toxicity; however, these results are model-based and should be confirmed experimentally. Conclusions: Based on these findings, compound 1 emerges as a promising lead candidate for the development of a novel chemotherapeutic agent against OSCC, with potential therapeutic efficacy against other cancer types. Full article

Object detection in UAV-based fire rescue scenarios faces multiple challenges, including densely distributed small targets, severe occlusion, and interference from smoke and flames. Existing mainstream detection models, such as the YOLO series, often prioritize inference speed at the expense of modeling global context and spatial positional information, resulting in limited performance in such complex environments. To address these limitations, this paper proposes FirePM-YOLO, an object detection architecture optimized for fire rescue applications. Based on the YOLO framework, the proposed model introduces two key innovations: first, a Position-Aware Enhanced Mamba module (PEMamba) is designed, which incorporates a compact positional encoding mechanism, lightweight spatial enhancement, and an adaptive feature fusion strategy to significantly improve scene perception while maintaining computational efficiency. Second, a PEMBottleneck structure is constructed, which dynamically balances local convolutional features and global PEMamba features via learnable weights. This module is embedded into the shallow layers of the backbone network, forming an enhanced PEM-C3K2 module that captures long-range dependencies with linear complexity while preserving fine local details, thereby enabling holistic contextual understanding of fireground environments. Experimental results on the self-built “FireRescue” dataset demonstrate that compared with the original YOLOv12 and other mainstream detectors, the proposed model achieves improvements in both mean average precision (mAP) and recall while maintaining real-time inference capability. Notably, it exhibits superior detection performance on challenging samples, such as small-scale and partially occluded professional firefighting vehicles. Full article

In Canada, early fire detection is an important component of wildfire management, and it utilizes a combined effort approach including public reports, aviation patrols, and satellite observations. The role of ground-based continuous smoke sensors has not been formally assessed in Canadian wildfire management detection systems. Dense networks of ground-based, internet-enabled continuous smoke sensors were deployed at three locations across southern Canada during 2023 and 2024, in concert with planned prescribed fire in grass fuels as well as incidental wildfire ignitions. Smoke sensor detection of fires was compared to polar orbiting and geostationary fire detection. Large fire events (50–600 ha) with a ground smoke detector distance of 1–2 km were observed on most occasions (n = 7), but the detection rate dropped to 30% for fires 1 ha or smaller. Follow-up smoke monitoring after the initial detection offered valuable information on smoke production and dispersion across multiple sensors. This typically nighttime smoldering smoke production fell below the threshold for geostationary satellite fire observation and is otherwise only captured sparingly by polar orbiting satellites. Thus, ground-based smoke detection systems likely fit an important niche for monitoring low-energy (i.e., smoldering) smoke events from fully contained fires or to monitor fires considered recently extinguished. Full article

Purpose: Low HDL cholesterol (HDL-C) is a common lipid abnormality among East Asian populations, including Koreans, and is closely associated with increased cardiovascular disease risk. This has traditionally been linked to high-carbohydrate dietary patterns. Therefore, it is essential to assess how recent changes in dietary and lifestyle habits in Korea have influenced HDL-C levels. Methods: This study utilized data from the Korea National Health and Nutrition Examination Survey (KNHANES), conducted from 2014 to 2023. Using a complex sampling method, we analyzed annual trends in carbohydrate intake and HDL-C levels in Korean adults (aged 20–59 years), stratified by gender (male and female) and age (20–39 and 40–59 years), and identified determinants such as demographic factors, health behaviors, and dietary intake. Results: The primary factor in the increase in HDL-C levels was a reduction in carbohydrate intake. When analyzed by age and gender, this significant upward trend in HDL-C levels was consistently observed across all four groups: young men, middle-aged men, young women, and middle-aged women. However, the increase in obesity, indicated by increased BMI and waist circumference, had a negative impact on the improvement in HDL-C levels. The recent improvement in HDL-C levels in Korean adults can be attributed to the successful national dietary policy (reducing carbohydrate intake and increasing healthy fat intake). Conclusions: Public health policies should thus continue emphasizing healthy dietary practices, strengthening smoking cessation initiatives, and managing obesity. These findings suggest similar dietary and lifestyle interventions could effectively reduce cardiovascular disease risk in other Asian populations undergoing comparable dietary transitions. Full article

Chronic obstructive pulmonary disease (COPD) is increasingly recognized as a systemic disorder with clinically significant extrapulmonary manifestations. Among these, renal dysfunction—manifesting as chronic kidney disease (CKD) and acute kidney injury (AKI)—is highly prevalent, frequently underdiagnosed, and strongly associated with adverse clinical outcomes. Meta-analytic data indicate that COPD is associated with more than a twofold increase in CKD prevalence, independent of shared risk factors such as age, smoking, hypertension, and diabetes. CKD in COPD is associated with increased mortality, exacerbation burden, and healthcare utilization. AKI represents a particularly severe expression of renal involvement, occurring most commonly during acute exacerbations of COPD (AECOPD). Although the reported incidence of AKI during AECOPD varies widely by clinical setting—from approximately 2% in population-based studies to over 20% in hospitalized cohorts—its presence is consistently associated with marked increases in mortality, respiratory failure, need for mechanical ventilation, and hospital length of stay. This review synthesizes current evidence supporting a lung–kidney interorgan crosstalk framework in COPD, whereby chronic and acute pulmonary pathophysiology generates systemic disturbances that progressively impair renal structure and function. The heart is incorporated as a physiological intermediary, modulating hemodynamic transmission and venous congestion, without constituting the primary disease axis. Recognizing the role of kidney complications in COPD is crucial, as it influences how we diagnose, predict outcomes, and treat patients—especially when there are sudden flare-ups. Full article

Background: E-cigarette use has risen sharply among young never-smokers, largely driven by the availability of several thousand appealing flavours. This narrative review synthesises evidence on the health effects of vaping, flavour toxicology and attractiveness, designs and outcomes of flavour bans, and complementary measures. Methods: Peer-reviewed publications and institutional reports (up to January 2026) were retrieved from PubMed, Web of Science, Google Scholar, and reference lists of included articles. Evidence from about 200 references was synthesised by a multidisciplinary working group. Results: Although flavouring substances are generally considered safe for ingestion, their inhalation toxicity remains uncertain. In vitro and in vivo studies have reported oxidative stress, inflammation, cytotoxicity, impaired ciliary function, transcriptomic changes, genotoxicity, and DNA damage. These findings—along with the strong youth appeal of fruit/sweet flavours, the inconclusive effects of flavours on smoking cessation, and persisting uncertainties—support banning non-tobacco e-cigarette flavours under the precautionary principle. Flavour bans can reduce e-cigarette use and initiation, especially among young adults, although partial substitution towards combustible cigarettes has been reported in some U.S. states. Policy success requires effective enforcement, prevention of industry circumvention, curbing cross-border sales, and closing regulatory loopholes—ideally at the international level (e.g., EU-wide). Conclusions: E-cigarette flavours may increase vaping toxicity and strongly appeal to youth, justifying flavour bans to prioritise youth protection. To maximise effectiveness, accompanying measures and sustained investment in tobacco prevention, youth education, and accessible evidence-based smoking cessation support are essential. Full article

Maternal Smoking During Pregnancy (MSDP) remains a major source of fetal toxicant exposure. We applied adductomics to profile reactive adducts at the human serum albumin cysteine-34 (HSA-Cys³⁴) locus, which integrates longer-term exposures. HSA-Cys³⁴ adducts formed by acrylonitrile and ethylene oxide, two tobacco-related toxicants previously linked to smoking in adults, were quantified and compared with cotinine and MSDP status. Their relationships with other reactive adducts were also examined. Neonatal dried blood spots (DBS) from 110 children were analyzed. Cotinine and 55 Cys³⁴ adducts were measured by Liquid Chromatography–Tandem Mass Spectrometry (LC-MS/MS). Associations were evaluated using linear regression, chi-square tests, and principal component analysis. Eighteen adducts differed significantly by MSDP status after Bonferroni correction (p ≤ 9.1 × 10⁻⁴). S-acrylonitrile was markedly elevated in exposed newborns, including those whose mothers reported smoking cessation after early pregnancy (p < 0.001). S-acrylonitrile correlated with 31 adducts related to oxidative stress and thiol metabolism, whereas cotinine correlated with eight. S-ethylene oxide, though detectable in DBS, showed no consistent association with MSDP. Adductomics analysis of newborn DBS sensitively captures molecular signatures of prenatal tobacco exposure and related oxidative stress. Acrylonitrile adducts appear to better reflect cumulative MSDP exposure than cotinine, highlighting the utility of adductomics for improved exposure assessment and mechanistic insight. Full article