Purpose: Smoking is causally related to alcohol use disorder. Although polycyclic aromatic hydrocarbons (PAHs) are major neurotoxic pollutants in tobacco smoke, evidence is lacking on the role of PAHs in the relationship between smoking and alcohol use disorder. This study investigated the types of PAHs associated with smoking and whether exposure to those PAHs mediated the effect of smoking on alcohol use disorder. Materials and Methods: A total of 968 male firefighters were analyzed. Smoking history and cumulative pack-years were obtained using self-reported questionnaires. Alcohol use disorder was defined using the Alcohol Use Disorder Identification Test.PAH exposure was assessed by urinary metabolites. Regression analyses were performed between exposure (smoking), outcome (alcohol use disorder), and mediator (PAH metabolites) variables. A mediation analysis was performed to test the indirect effect of PAH metabolites on the association between smoking and alcohol use disorder. All analyses were repeated for 770 participants who were followed up after 2 years, while alcohol use disorder was redefined from follow-up data ensuring the temporal sequence of the variables. Results: Both 2-naphthol [β=0.78, 95% confidence interval (CI): 0.59–0.98] and 2-hydroxyfluorene (β=0.69, 95% CI: 0.56–0.82) were associated with smoking history. Furthermore, 2-naphthol and 2-hydroxyfluorene mediated the associations of smoking history (proportion mediated: 14.2%, 23.6% respectively) or cumulative pack-years (proportion mediated: 14.4%, 25.4% respectively) with alcohol use disorder. The results were consistent in longitudinal settings. Conclusion Exposure to PAHs mediated the association between tobacco smoking and alcohol use disorder. PAH exposure from tobacco may increase the risk of addictive disorders.

Purpose: Smoking is causally related to alcohol use disorder. Although polycyclic aromatic hydrocarbons (PAHs) are major neurotoxic pollutants in tobacco smoke, evidence is lacking on the role of PAHs in the relationship between smoking and alcohol use disorder. This study investigated the types of PAHs associated with smoking and whether exposure to those PAHs mediated the effect of smoking on alcohol use disorder. Materials and Methods: A total of 968 male firefighters were analyzed. Smoking history and cumulative pack-years were obtained using self-reported questionnaires. Alcohol use disorder was defined using the Alcohol Use Disorder Identification Test.PAH exposure was assessed by urinary metabolites. Regression analyses were performed between exposure (smoking), outcome (alcohol use disorder), and mediator (PAH metabolites) variables. A mediation analysis was performed to test the indirect effect of PAH metabolites on the association between smoking and alcohol use disorder. All analyses were repeated for 770 participants who were followed up after 2 years, while alcohol use disorder was redefined from follow-up data ensuring the temporal sequence of the variables. Results: Both 2-naphthol [β=0.78, 95% confidence interval (CI): 0.59–0.98] and 2-hydroxyfluorene (β=0.69, 95% CI: 0.56–0.82) were associated with smoking history. Furthermore, 2-naphthol and 2-hydroxyfluorene mediated the associations of smoking history (proportion mediated: 14.2%, 23.6% respectively) or cumulative pack-years (proportion mediated: 14.4%, 25.4% respectively) with alcohol use disorder. The results were consistent in longitudinal settings. Conclusion Exposure to PAHs mediated the association between tobacco smoking and alcohol use disorder. PAH exposure from tobacco may increase the risk of addictive disorders.

Purpose: Smoking is causally related to alcohol use disorder. Although polycyclic aromatic hydrocarbons (PAHs) are major neurotoxic pollutants in tobacco smoke, evidence is lacking on the role of PAHs in the relationship between smoking and alcohol use disorder. This study investigated the types of PAHs associated with smoking and whether exposure to those PAHs mediated the effect of smoking on alcohol use disorder. Materials and Methods: A total of 968 male firefighters were analyzed. Smoking history and cumulative pack-years were obtained using self-reported questionnaires. Alcohol use disorder was defined using the Alcohol Use Disorder Identification Test.PAH exposure was assessed by urinary metabolites. Regression analyses were performed between exposure (smoking), outcome (alcohol use disorder), and mediator (PAH metabolites) variables. A mediation analysis was performed to test the indirect effect of PAH metabolites on the association between smoking and alcohol use disorder. All analyses were repeated for 770 participants who were followed up after 2 years, while alcohol use disorder was redefined from follow-up data ensuring the temporal sequence of the variables. Results: Both 2-naphthol [β=0.78, 95% confidence interval (CI): 0.59–0.98] and 2-hydroxyfluorene (β=0.69, 95% CI: 0.56–0.82) were associated with smoking history. Furthermore, 2-naphthol and 2-hydroxyfluorene mediated the associations of smoking history (proportion mediated: 14.2%, 23.6% respectively) or cumulative pack-years (proportion mediated: 14.4%, 25.4% respectively) with alcohol use disorder. The results were consistent in longitudinal settings. Conclusion Exposure to PAHs mediated the association between tobacco smoking and alcohol use disorder. PAH exposure from tobacco may increase the risk of addictive disorders.

Purpose: Smoking is causally related to alcohol use disorder. Although polycyclic aromatic hydrocarbons (PAHs) are major neurotoxic pollutants in tobacco smoke, evidence is lacking on the role of PAHs in the relationship between smoking and alcohol use disorder. This study investigated the types of PAHs associated with smoking and whether exposure to those PAHs mediated the effect of smoking on alcohol use disorder. Materials and Methods: A total of 968 male firefighters were analyzed. Smoking history and cumulative pack-years were obtained using self-reported questionnaires. Alcohol use disorder was defined using the Alcohol Use Disorder Identification Test.PAH exposure was assessed by urinary metabolites. Regression analyses were performed between exposure (smoking), outcome (alcohol use disorder), and mediator (PAH metabolites) variables. A mediation analysis was performed to test the indirect effect of PAH metabolites on the association between smoking and alcohol use disorder. All analyses were repeated for 770 participants who were followed up after 2 years, while alcohol use disorder was redefined from follow-up data ensuring the temporal sequence of the variables. Results: Both 2-naphthol [β=0.78, 95% confidence interval (CI): 0.59–0.98] and 2-hydroxyfluorene (β=0.69, 95% CI: 0.56–0.82) were associated with smoking history. Furthermore, 2-naphthol and 2-hydroxyfluorene mediated the associations of smoking history (proportion mediated: 14.2%, 23.6% respectively) or cumulative pack-years (proportion mediated: 14.4%, 25.4% respectively) with alcohol use disorder. The results were consistent in longitudinal settings. Conclusion Exposure to PAHs mediated the association between tobacco smoking and alcohol use disorder. PAH exposure from tobacco may increase the risk of addictive disorders.

Purpose: Smoking is causally related to alcohol use disorder. Although polycyclic aromatic hydrocarbons (PAHs) are major neurotoxic pollutants in tobacco smoke, evidence is lacking on the role of PAHs in the relationship between smoking and alcohol use disorder. This study investigated the types of PAHs associated with smoking and whether exposure to those PAHs mediated the effect of smoking on alcohol use disorder. Materials and Methods: A total of 968 male firefighters were analyzed. Smoking history and cumulative pack-years were obtained using self-reported questionnaires. Alcohol use disorder was defined using the Alcohol Use Disorder Identification Test.PAH exposure was assessed by urinary metabolites. Regression analyses were performed between exposure (smoking), outcome (alcohol use disorder), and mediator (PAH metabolites) variables. A mediation analysis was performed to test the indirect effect of PAH metabolites on the association between smoking and alcohol use disorder. All analyses were repeated for 770 participants who were followed up after 2 years, while alcohol use disorder was redefined from follow-up data ensuring the temporal sequence of the variables. Results: Both 2-naphthol [β=0.78, 95% confidence interval (CI): 0.59–0.98] and 2-hydroxyfluorene (β=0.69, 95% CI: 0.56–0.82) were associated with smoking history. Furthermore, 2-naphthol and 2-hydroxyfluorene mediated the associations of smoking history (proportion mediated: 14.2%, 23.6% respectively) or cumulative pack-years (proportion mediated: 14.4%, 25.4% respectively) with alcohol use disorder. The results were consistent in longitudinal settings. Conclusion Exposure to PAHs mediated the association between tobacco smoking and alcohol use disorder. PAH exposure from tobacco may increase the risk of addictive disorders.

Background: Although influenza poses substantial mortality burden, most studies have estimated excess mortality using time-aggregated data. Here, we estimated mortality risk and population attributable fraction (PAF) attributed to seasonal influenza using individual-level data from a nationwide matched cohort. Methods: Individuals with influenza during four consecutive influenza seasons (2013–2017) (n = 5,497,812) and 1:4 age- and sex-matched individuals without influenza (n = 20,990,683) were identified from a national health insurance database. The endpoint was mortality within 30 days after influenza diagnosis. All-cause and cause-specific mortality risk ratios (RRs) attributed to influenza were estimated. Excess mortality, mortality RR, and PAF of mortality were determined, including for underlying disease subgroups. Results: Excess mortality rate, mortality RR, and PAF of all-cause mortality were 49.5 per 100,000, 4.03 (95% confidence interval [CI], 3.63–4.48), and 5.6% (95% CI, 4.5–6.7%). Cause-specific mortality RR (12.85; 95% CI, 9.40–17.55) and PAF (20.7%; 95% CI, 13.2– 27.0%) were highest for respiratory diseases. In subgroup analysis according to underlying disorders, PAF of all-cause mortality was 5.9% (95% CI, 0.6–10.7%) for liver disease, 5.8% (95% CI, 2.9–8.5%) for respiratory disease, and 3.8% (95% CI, 1.4–6.1%) for cancer. Conclusion Individuals with influenza had a 4-fold higher mortality risk than individuals without influenza. Preventing seasonal influenza may lead to 5.6% and 20.7% reductions in all-cause and respiratory mortality, respectively. Individuals with respiratory disease, liver disease, and cancer may benefit from prioritization when establishing influenza prevention strategies.

Background: Numerous studies have shown the effect of particulate matter exposure on brain imaging markers. However, little evidence exists about whether the effect differs by the level of low-grade chronic systemic inflammation. We investigated whether the level of c-reactive protein (CRP, a marker of systemic inflammation) modifies the associations of particulate matter exposures with brain cortical gray matter thickness and white matter hyperintensities (WMH). Methods: We conducted a cross-sectional study of baseline data from a prospective cohort study including adults with no dementia or stroke. Long-term concentrations of particulate matter ≤ 10 µm in diameter (PM10) and ≤ 2.5 µm (PM2.5) at each participant’s home address were estimated. Global cortical thickness (n = 874) and WMH volumes (n = 397) were estimated from brain magnetic resonance images. We built linear and logistic regression models for cortical thickness and WMH volumes (higher versus lower than median), respectively. Significance of difference in the association between the CRP group (higher versus lower than median) was expressed as P for interaction. Results: Particulate matter exposures were significantly associated with a reduced global cortical thickness only in the higher CRP group among men (P for interaction = 0.015 for PM10 and 0.006 for PM2.5). A 10 μg/m3 increase in PM10 was associated with the higher volumes of total WMH (odds ratio, 1.78; 95% confidence interval, 1.07–2.97) and periventricular WMH (2.00; 1.20–3.33). A 1 μg/m3 increase in PM2.5 was associated with the higher volume of periventricular WMH (odds ratio, 1.66; 95% confidence interval, 1.08–2.56). These associations did not significantly differ by the level of high sensitivity CRP. Conclusion Particulate matter exposures were associated with a reduced global cortical thickness in men with a high level of chronic inflammation. Men with a high level of chronic inflammation may be susceptible to cortical atrophy attributable to particulate matter exposures.

Microplastics are environmental pollutants that prevail in the oceans, remote islands, and polar regions. Exposure to microplastics presents a major emerging threat to the ecosystems due to their potential adverse effects. Herein, we reviewed the literature to provide an up-to-date synopsis of the current understanding of the sources, compositions, and adverse effects of microplastics in humans and the environment. Most studies on microplastics have focused on developing standardized methods for monitoring the occurrence, distribution, and movement of microplastics in the environment, as well as developing microplastic substitutes; however, although humans are exposed to microplastics via various routes, research on the adverse effects of microplastics in humans remains limited. Little is known about the impact of microplastics on human health and the toxic effects that may vary depending on the type, size, shape, and concentration of microplastics. Therefore, more research is needed to understand the cellular and molecular mechanisms of microplastic toxicity and related pathologies.

Objective: To develop and test a machine learning model for classifying human papillomavirus (HPV) status of patients with oropharyngeal squamous cell carcinoma (OPSCC) using 18 F-fluorodeoxyglucose ( 18 F-FDG) PET-derived parameters in derived parameters and an appropriate combination of machine learning methods in patients with OPSCC. Materials and Methods: This retrospective study enrolled 126 patients (118 male; mean age, 60 years) with newly diagnosed, pathologically confirmed OPSCC, that underwent 18 F-FDG PET-computed tomography (CT) between January 2012 and February 2020. Patients were randomly assigned to training and internal validation sets in a 7:3 ratio. An external test set of 19 patients (16 male; mean age, 65.3 years) was recruited sequentially from two other tertiary hospitals. Model 1 used only PET parameters, Model 2 used only clinical features, and Model 3 used both PET and clinical parameters. Multiple feature transforms, feature selection, oversampling, and training models are all investigated. The external test set was used to test the three models that performed best in the internal validation set. The values for area under the receiver operating characteristic curve (AUC) were compared between models. Results: In the external test set, ExtraTrees-based Model 3, which uses two PET-derived parameters and three clinical features, with a combination of MinMaxScaler, mutual information selection, and adaptive synthetic sampling approach, showed the best performance (AUC = 0.78; 95% confidence interval, 0.46–1). Model 3 outperformed Model 1 using PET parameters alone (AUC = 0.48, p = 0.047) and Model 2 using clinical parameters alone (AUC = 0.52, p = 0.142) in predicting HPV status. Conclusion Using oversampling and mutual information selection, an ExtraTree-based HPV status classifier was developed by combining metabolic parameters derived from 18 F-FDG PET/CT and clinical parameters in OPSCC, which exhibited higher performance than the models using either PET or clinical parameters alone.

Purpose: Atrial fibrillation (AF) patients with low to intermediate risk, defined as non-gender CHA2DS2-VASc score of 0–1, are still at risk of stroke. This study verified the usefulness of ABCD score [age (≥60 years), B-type natriuretic peptide (BNP) or N-terminal pro-BNP (≥300 pg/mL), creatinine clearance (<50 mL/min/1.73 m2 ), and dimension of the left atrium (≥45 mm)] for stroke risk stratification in non-gender CHA2DS2-VASc score 0–1. Materials and Methods: This multi-center cohort study retrospectively analyzed AF patients with non-gender CHA2DS2-VASc score 0–1. The primary endpoint was the incidence of stroke with or without antithrombotic therapy (ATT). An ABCD score was validated. Results: Overall, 2694 patients [56.3±9.5 years; female, 726 (26.9%)] were followed-up for 4.0±2.8 years. The overall stroke rate was 0.84/100 person-years (P-Y), stratified as follows: 0.46/100 P-Y for an ABCD score of 0; 1.02/100 P-Y for an ABCD score ≥1. The ABCD score was superior to non-gender CHA2DS2-VASc score in the stroke risk stratification (C-index=0.618, p=0.015; net reclassification improvement=0.576, p=0.040; integrated differential improvement=0.033, p=0.066). ATT was prescribed in 2353 patients (86.5%), and the stroke rate was significantly lower in patients receiving non-vitamin K antagonist oral anticoagulant (NOAC) therapy and an ABCD score ≥1 than in those without ATT (0.44/100 P–Y vs. 1.55/100 P-Y; hazard ratio=0.26, 95% confidence interval 0.11–0.63, p=0.003). Conclusion The biomarker-based ABCD score demonstrated improved stroke risk stratification in AF patients with non-gender CHA2DS2-VASc score 0–1. Furthermore, NOAC with an ABCD score ≥1 was associated with significantly lower stroke rate in AF patients with non-gender CHA2DS2-VASc score 0–1.