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INTRODUCTION: Adolescents are especially susceptible to the harmful effects of secondhand smoke exposure. Mental health issues may be one of these negative consequences. This study aimed to explore the association between secondhand smoke exposure and anxiety among Korean adolescents. METHODS: This study used the nationwide representative cross-sectional data obtained from the 4-year (2020-2023) Korea Youth Risk Behavior Survey. In total, 214514 individuals aged 12-18 years were included in this study (109910 males and 104604 females). Secondhand smoke exposure was assessed based on responses to questions concerning the days they were exposed (at home and in public places), while anxiety levels were measured using the Generalized Anxiety Disorder 7 scale. Multivariable logistic regression analysis divided by sex was performed to explore the association (p=0.0173 for interaction by secondhand smoke exposure and sex), and adjusted odds ratios (ORs) with 95% confidence intervals (CI) were calculated. RESULTS: Among the study population, 8.8% of the male and 15.6% of the female participants had anxiety. After adjusting for covariates, adolescents with secondhand smoke exposure had a higher likelihood of reporting anxiety than those without the exposure (male, OR=1.23; 95% CI: 1.16-1.29; female, OR=1.27; 95% CI: 1.21-1.33). In additional stratified analyses, this association was more prominent among those who were never smokers, were exposed for more days, and had severe levels of anxiety. CONCLUSIONS: This study found that secondhand smoke exposure was associated with anxiety in adolescents; hence, proper political interventions to reduce secondhand smoke exposure may be required.

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PURPOSE: An early genetic diagnosis can guide the time-sensitive treatment of individuals with genetic epilepsies. However, most genetic diagnoses occur long after disease onset. We aimed to identify early clinical features suggestive of genetic diagnoses in individuals with epilepsy through large-scale analysis of full-text electronic medical records (EMR). METHODS: We extracted 89 million time-stamped standardized clinical annotations using Natural Language Processing from 4,572,783 clinical notes from 32,112 individuals with childhood epilepsy, including 1,925 individuals with known or presumed genetic epilepsies. We applied these features to train random forest models to predict SCN1A-related disorders and any genetic diagnosis. RESULTS: We identified 47,774 age-dependent associations of clinical features with genetic etiologies a median of 3.6 years prior to molecular diagnosis. Across all 710 genetic etiologies identified in our cohort, neurodevelopmental differences between 6-9 months increased the likelihood of a later molecular diagnosis fivefold (P<0.0001, 95% CI=3.55-7.42). A later diagnosis of SCN1A-related disorders (AUC=0.91) or an overall positive genetic diagnosis (AUC=0.82) could be reliably predicted using random forest models. CONCLUSION: Clinical features predictive of genetic epilepsies precede molecular diagnoses by up to several years in conditions with known precision treatments. An earlier diagnosis facilitated by automated EMR analysis has the potential for earlier targeted therapeutic strategies in the genetic epilepsies.

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BACKGROUND: Globally, the rise in single-person households poses a potential risk to mental health, with generalized anxiety disorder (GAD) being a prominent concern. The proliferation of single-person households may exacerbate social isolation and foster loneliness and anxiety. Notably, research investigating the association between single-person households and GAD remains limited. Therefore, this study aimed to investigate the association between single-person households and GAD across sexes in Korea. METHODS: We utilized data from the Korea National Health and Nutrition Examination Survey conducted in 2021 and 2022, comprising a sample of 9936 participants aged 19 or older. The Generalized Anxiety Disorder Screening Tool (GAD-7) was employed to assess anxiety levels in adults. Multiple logistic regression analysis was conducted to investigate the correlation between single-person households and GAD. RESULTS: The reference variable used in the analysis was multi-person households (consisting of two or more individuals). The association between single-person households and GAD was statistically significant across sexes (male: odds ratio [OR]: 1.92, 95 % CI: 1.15-3.20; female: OR: 1.56, 95 % CI: 1.03-2.36). Participants in single-person households exhibited higher scores on the GAD-7 compared with those in multi-person households. Notably, marital status and education level displayed disparate effects based on sex, whereas physical activity demonstrated consistent effects irrespective of sex. LIMITATIONS: Given the use of cross-sectional data, only correlations could be established. CONCLUSION: The findings indicate an elevated risk of GAD in single-person households compared with multi-person households. Furthermore, promoting physical activity emerged as a potential strategy for mitigating GAD in single-person households.

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BACKGROUND: The association between atopic dermatitis and childhood overweight and obesity has been studied extensively, but the results are inconclusive; most studies have focused on body mass index as a measure of obesity, with few investigating the relationship with underweight. Therefore, this study aimed to investigate the association between body mass index levels and atopic dermatitis in Korean adolescents. METHODS: 3-year (2019-2021) of Korea Youth Risk Behavior Web-based Survey were used. Body mass index was used to measure obesity and a recent diagnosis within the past year was used as the criterion for atopic dermatitis. Multiple logistic regression analyses were performed to explore the associations. The odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. RESULTS: A total of 144,183 adolescents aged 12-18 years were included in this study (74,704 males and 69,479 females). Over the past year, 5.4% of males and 7.3% of females were diagnosed with atopic dermatitis in the study population. Adolescents with normal weight (males [OR: 1.19, CI: 1.02-1.38]; females [OR: 1.26, CI: 1.10-1.43]) and overweight (males [OR: 1.37, CI: 1.16-1.61]; females [OR: 1.37, CI: 1.19-1.58]) were more likely to develop atopic dermatitis than underweight. CONCLUSION: Increased degree of obesity may contribute to the development of atopic dermatitis. The normal-weight and obese adolescents had higher likelihood of developing atopic dermatitis compared with the underweight adolescents.

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Evidence for adaptation of human skin color to regional ultraviolet radiation suggests shared and distinct genetic variants across populations. However, skin color evolution and genetics in East Asians are understudied. We quantified skin color in 48,433 East Asians using image analysis and identified associated genetic variants and potential causal genes for skin color as well as their polygenic interplay with sun exposure. This genome-wide association study (GWAS) identified 12 known and 11 previously unreported loci and SNP-based heritability was 23-24%. Potential causal genes were determined through the identification of nonsynonymous variants, colocalization with gene expression in skin tissues, and expression levels in melanocytes. Genomic loci associated with pigmentation in East Asians substantially diverged from European populations, and we detected signatures of polygenic adaptation. This large GWAS for objectively quantified skin color in an East Asian population improves understanding of the genetic architecture and polygenic adaptation of skin color and prioritizes potential causal genes.

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BACKGROUND: Eating habits formed during adolescence greatly influence the maintenance of health in adulthood. With the recent development of social media and easy access to the Internet, adolescents watch plenty of food videos, particularly Mukbang and Cookbnag(eating show)content. This media genre's impact on food choices has been covered in several studies; however, studies on unhealthy eating habits directly related to adolescents' exposure to eating shows are insufficient. METHODS: For this study, we used data from the 18th Korea Youth Risk Behavior Survey conducted in 2022 and finalized 50,451 participants. The extent of exposure to eating show media over the course of a week, as well as the consumption of fast food, sugar-sweetened beverages (SSBs), and high caffeinated beverages within that week were measured through self-reporting questionnaires. We classified the participants into two groups based on their frequency of watching eating shows. A multiple logistic regression analysis was performed to investigate the association between eating show and unhealthy food consumption. RESULTS: For both males and females, eating show exposure was strongly associated with the consumption of fast food (male: OR:1.37, 95% CI:1.26-1.49; female: OR:1.46, 95% CI:1.36-1.57), SSB (male: OR:1.42, 95% CI:1.26-1.60; female: OR:1.51, 95% CI:1.35-1.70), and high caffeinated beverage (male: OR:1.30, 95% CI:1.23-1.37; female: OR:1.24, 95% CI:1.18-1.31). It was observed that both sexes were more likely to frequently eat unhealthy food than students who did not watch eating shows. CONCLUSION: Among Korean adolescents, students exposed to eating shows, which primarily aim to entertain, were more likely to consume fast food, SSBs, and high caffeinated beverages. Therefore, this study's findings suggest that eating show could influence adolescents' food choices, highlighting the need for interest in emerging cultures and corresponding health policies.

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The gut microbiome plays important roles in host function and health. Core microbiomes have been described for different species, and imbalances in their composition, known as dysbiosis, are associated with pathology. Changes in the gut microbiome and dysbiosis are common in aging, possibly due to multi-tissue deterioration, which includes metabolic shifts, dysregulated immunity, and disrupted epithelial barriers. However, the characteristics of these changes, as reported in different studies, are varied and sometimes conflicting. Using clonal populations of Caenorhabditis elegans to highlight trends shared among individuals, we employed 16s rRNA gene sequencing, CFU counts and fluorescent imaging, identifying an Enterobacteriaceae bloom as a common denominator in aging animals. Experiments using Enterobacter hormaechei, a representative commensal, suggested that the Enterobacteriaceae bloom was facilitated by a decline in Sma/BMP immune signaling in aging animals and demonstrated its potential for exacerbating infection susceptibility. However, such detrimental effects were context-dependent, mitigated by competition with commensal communities, highlighting the latter as determinants of healthy versus unhealthy aging, depending on their ability to restrain opportunistic pathobionts.

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Fractions are the gatekeepers to advanced mathematics but are difficult to learn. One powerful learning mechanism is analogy, which builds fraction understanding on a pre-existing foundation of integer knowledge. Indeed, a short intervention that aligned fractions and integers on number lines improved children's estimates of fractions (Yu et al., 2022). The breadth and durability of such gains, however, are unknown, and analogies to other sources (such as percentages) may be equally powerful. To investigate this issue, we randomly assigned 109 fourth and fifth graders to one of three experimental conditions with different analogical sources (integers, percentages, or fractions) or a control condition. During training, children in the experimental conditions solved pairs of aligned fraction number line problems and proportionally-equivalent problems expressed in integers, percentages, or fractions (e.g., 3/8 on a 0-1 number line aligned with 3 on a 0-8 number line). Children in the control group solved fraction number-line problems sequentially. At pretest and a two-week delayed posttest, children completed a broad fraction knowledge battery, including estimation, comparison, categorization, ordering, and arithmetic. Results showed that aligning integers and fractions on number lines facilitated better estimation of fractional magnitudes, and the training effect transferred to novel fraction problems after two weeks. Similar gains were not observed for analogies using percentages. These findings highlight the importance of building new mathematical knowledge through analogies to familiar, similar sources.

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Hyperuricemia is an essential causal risk factor for gout and is associated with cardiometabolic diseases. Given the limited contribution of East Asian ancestry to genome-wide association studies of serum urate, the genetic architecture of serum urate requires exploration. A large-scale cross-ancestry genome-wide association meta-analysis of 1,029,323 individuals and ancestry-specific meta-analysis identifies a total of 351 loci, including 17 previously unreported loci. The genetic architecture of serum urate control is similar between European and East Asian populations. A transcriptome-wide association study, enrichment analysis, and colocalization analysis in relevant tissues identify candidate serum urate-associated genes, including CTBP1, SKIV2L, and WWP2. A phenome-wide association study using polygenic risk scores identifies serum urate-correlated diseases including heart failure and hypertension. Mendelian randomization and mediation analyses show that serum urate-associated genes might have a causal relationship with serum urate-correlated diseases via mediation effects. This study elucidates our understanding of the genetic architecture of serum urate control.

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Cerebral aneurysms are rarely encountered in pregnancy. Their antepartum and intrapartum management remain clinically challenging, primarily due to concern regarding potential rupture. We present a case of a patient in preterm labor at risk for imminent delivery with a 10mm cerebral aneurysm. She was recommended for cesarean section (CS), yet delivered via spontaneous vaginal delivery in the operating room after induction of general anesthesia for the intended CS. Her aneurysm and neurologic function remained intact postpartum. Cerebral aneurysms <5mm are unlikely to undergo significant growth during pregnancy. The presence of a cerebral aneurysm is not automatically a contraindication to the Valsalva maneuver. The recommendation for which patients with unruptured cerebral aneurysms should deliver by CS, operative vaginal delivery, or unassisted vaginal delivery (i.e., which patients should avoid Valsalva maneuver intrapartum), is complex and requires multidisciplinary discussion.

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Creativity is known to be heritable and exhibits familial aggregation with psychiatric disorders; however, the complex nature of their relationship has not been well-established. In the present study, we demonstrate that using an expanded and validated machine learning (ML)-based phenotyping of occupational creativity (OC) can allow us to further understand the trait of creativity, which was previously difficult to define and study. We conducted the largest genome-wide association study (GWAS) on OC with 241,736 participants from the UK Biobank and identified 25 lead variants that have not yet been reported and three candidate causal genes that were previously associated with educational attainment and psychiatric disorders. We found extensive genetic overlap between OC and psychiatric disorders with mixed effect direction through various post-GWAS analyses, including the bivariate causal mixture model. In addition, we discovered a strongly genetic correlation between our original GWAS and the GWAS adjusted for education years (rg = 0.95). Our GWAS analysis via ML-based phenotyping contributes to the understanding of the genetic architecture of creativity, which may inform genetic discovery and genetic prediction in human cognition and psychiatric disorders.

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Obstructive sleep apnea (OSA) is a common sleep disorder characterised by recurrent upper airway collapse during sleep. Alcohol consumption has been linked to an increased risk of OSA due to its effects on the upper airway and body mass index (BMI). We aimed to investigate the correlation between alcohol use disorders and OSA. We used 11,859 participants data from Korean National Health and Nutrition Examination Surveys. The variable of interest was alcohol use disorder, measured using the Alcohol Use Disorders Identification Test, and the dependent variable was the risk of OSA, measured using the Snoring, Tiredness, Observed apnea, high blood Pressure, BMI, age, neck circumference, and male gender questionnaires. Multiple logistic regression was used to assess the association between alcohol use disorder and OSA risk after adjusted analysis. A significant association was found between alcohol use disorder and OSA (adjusted odds ratio [aOR] 2.14, 95% confidence interval [CI] 1.93-2.37). In the unemployed group, those with alcohol use disorder had the highest odds of being at risk of OSA compared with those who did not have this disorder (aOR 2.45, 95% CI 2.04-2.95). The OSA risk increased as the snoring frequency, amount of alcohol consumed, and frequency of binge drinking increased. This study suggests an association between alcohol use disorders and the risk of OSA. The frequency of alcohol consumption, quantity of alcohol consumed, and snoring frequency were associated with the risk of OSA. Therefore, ceasing alcohol consumption is recommended as an effective approach to enhancing sleep quality.

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Objective: This study explored the association between anti-smoking campaign types and smoking cessation attempts. Methods: This study included 4,594 individuals (3,292 male and 1,302 female) from the Korea Youth Risk Behavior Web-based Survey (KYRBWS) in 2018 and 2020. The methods of anti-smoking promotion were divided into online, offline, online and offline, and none. Attempts to quit smoking were classified as yes or no. Multiple logistic regression was performed to examine the association between antismoking campaign type and smoking cessation attempts. Results: Those who saw anti-smoking advertisements both online and offline were found to have tried to quit smoking more than those who did not. (Online & offline: male, odds ratio [OR] 1.36; 95% confidence interval [95% CI], 1.08-1.71; female, OR, 1.75; 95% CI 1.21-2.54) In a subgroup analysis of the independent variables into which smoking cessation advertisements were subdivided, males were found to have the highest OR for smoking cessation attempts when they encountered advertisements in newspapers. (Newspaper: male, OR, 2.25; 95% CI, 1.00-5.02) Females had the highest OR for smoking cessation attempts when accessed via the Internet. (Internet: female, OR, 1.93; 95% CI, 1.07-3.50). Conclusion: This study showed that there is a correlation between smoking cessation advertisements and adolescents' smoking cessation attempts. The possibility of smoking cessation attempts is high when encountering smoking cessation advertisements both online and offline. Although offline smoking cessation advertisements have a great effect on adolescents' smoking cessation attempts, it can be confirmed that the frequency of exposure for offline advertisements is less than that for online advertisements.

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Human activity is altering the environment in a rapid pace, challenging the adaptive capacities of genetic variation within animal populations. Animals also harbor extensive gut microbiomes, which play diverse roles in host health and fitness and may help expanding host capabilities. The unprecedented scale of human usage of xenobiotics and contamination with environmental toxins describes one challenge against which bacteria with their immense biochemical diversity would be useful, by increasing detoxification capacities. To explore the potential of bacteria-assisted rapid adaptation, we used Caenorhabditis elegans worms harboring a defined microbiome, and neomycin as a model toxin, harmful for the worm host and neutralized to different extents by some microbiome members. Worms raised in the presence of neomycin showed delayed development and decreased survival but were protected when colonized by neomycin-resistant members of the microbiome. Two distinct mechanisms facilitated this protection: gut enrichment driven by altered bacterial competition for the strain best capable of modifying neomycin; and host avoidance behavior, which depended on the conserved JNK homolog KGB-1, enabling preference and acquisition of neomycin-protective bacteria. We further tested the consequences of adaptation, considering that enrichment for protective strains may represent dysbiosis. We found that neomycin-adapted gut microbiomes caused increased susceptibility to infection as well as an increase in gut lipid storage, suggesting metabolic remodeling. Our proof-of-concept experiments support the feasibility of bacteria-assisted host adaptation and suggest that it may be prevalent. The results also highlight trade-offs between toxin adaptation and other traits of fitness.

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BACKGROUND: Although three years after the outbreak of SARS-CoV-2, the virus is still having a significant impact on human health and the global economy. Infection through respiratory droplets is the main transmission route, but the transmission of the virus by surface contact cannot be ignored. Hand sanitizers and antiviral films can be applied to control SARS-CoV-2, but sanitizers and films show drawbacks such as resistance of the virus against ethanol and environmental problems including the overuse of plastics. Therefore, this study suggested applying natural substrates to hand sanitizers and antiviral films made of biodegradable plastic (PLA). This approach is expected to provide advantages for the easy control of SARS-CoV-2 through the application of natural substances. METHODS: Antiviral disinfectants and films were manufactured by adding caffeic acid and vanillin to ethanol, isopropyl alcohol, benzalkonium chloride, and PLA. Antiviral efficacies were evaluated with slightly modified international standard testing methods EN 14,476 and ISO 21,702. RESULTS: In suspension, all the hand sanitizers evaluated in this study showed a reduction of more than 4 log within 2 min against HCoV-229E. After natural substances were added to the hand sanitizers, the time needed to reach the detection limit of the viral titer was shortened both in suspension and porcine skin. However, no difference in the time needed to reach the detection limit of the viral titer was observed in benzalkonium chloride. In the case of antiviral films, those made using both PLA and natural substances showed a 1 log reduction of HCoV-229E compared to the neat PLA film for all treatment groups. Furthermore, the influence of the organic load was evaluated according to the number of contacts of the antiviral products with porcine skin. Ten rubs on the skin resulted in slightly higher antiviral activity than 50 rubs. CONCLUSION: This study revealed that caffeic acid and vanillin can be effectively used to control HCoV-229E for hand sanitizers and antiviral films. In addition, it is recommended to remove organic matter from the skin for maintaining the antiviral activity of hand sanitizer and antiviral film as the antiviral activity decreased as the organic load increased in this study.

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Drug targets with genetic support are several-fold more likely to succeed in clinical trials. We introduce a genetic-driven approach based on causal inferences that can inform drug target prioritization, repurposing, and adverse effects of using lipid-lowering agents. Given that a multi-trait approach increases the power to detect meaningful variants/genes, we conduct multi-omics and multi-trait analyses, followed by network connectivity investigations, and prioritize 30 potential therapeutic targets for dyslipidemia, including SORT1, PSRC1, CELSR2, PCSK9, HMGCR, APOB, GRN, HFE2, FJX1, C1QTNF1, and SLC5A8. 20% (6/30) of prioritized targets from our hypothesis-free drug target search are either approved or under investigation for dyslipidemia. The prioritized targets are 22-fold higher in likelihood of being approved or under investigation in clinical trials than genome-wide association study (GWAS)-curated targets. Our results demonstrate that the genetic-driven approach used in this study is a promising strategy for prioritizing targets while informing about the potential adverse effects and repurposing opportunities.

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The gut microbiome plays important roles in host function and health. Core microbiomes have been described for different species, and imbalances in their composition, known as dysbiosis, are associated with pathology. Changes in the gut microbiome and dysbiosis are common in aging, possibly due to multi-tissue deterioration, which includes metabolic shifts, dysregulated immunity, and disrupted epithelial barriers. However, the characteristics of these changes, as reported in different studies, are varied and sometimes conflicting. Using clonal populations of C. elegans to highlight trends shared among individuals, and employing NextGen sequencing, CFU counts and fluorescent imaging to characterize age-dependent changes in worms raised in different microbial environments, we identified an Enterobacteriaceae bloom as a common denominator in aging animals. Experiments using Enterobacter hormachei, a representative commensal, suggested that the Enterobacteriaceae bloom was facilitated by a decline in Sma/BMP immune signaling in aging animals and demonstrated its detrimental potential for increasing susceptibility to infection. However, such detrimental effects were context-dependent, mitigated by competition with commensal communities, highlighting the latter as determinants of healthy versus unhealthy aging, depending on their ability to restrain opportunistic pathobionts.

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Alzheimer's disease (AD) is a neurodegenerative disease that causes a gradual loss of normal motor and cognitive function. The complex AD pathophysiology involves various factors such as oxidative stress, neuroinflammation, amyloid-beta (Aß) aggregation, disturbed neurotransmission, and apoptosis. The available drugs suffer from a range of side effects and are not able to cover different aspects of the disease. Therefore, finding a safer therapeutic approach that can affect multiple targets at a time is highly desirable. In the present study, the underlying neuroprotective mechanism of an important culinary spice, Syzygium aromaticum (Clove) extract, and major bioactive compounds were studied in hydrogen peroxide-induced oxidative stress in human neuroblastoma SH-SY5Y cell lines as a model. The extracts were subjected to GC-MS to identify important bioactive components. The extracts and key bio-actives reduced reactive oxygen species (ROS), restored mitochondrial membrane potential (MMP), and provided neuroprotection from H2O2-induced oxidative stress in cell-based assays due to the antioxidant action. They also reduced lipid peroxidation significantly and restored GSH content. Clove extracts have also displayed anti-acetylcholinesterase (AChE) activity, anti-glycation potential, and Aß aggregation/fibrilization inhibition. The multitarget neuroprotective approach displayed by Clove makes it a potential candidate for AD drug development.

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CUDC­907 is a novel inhibitor of phosphoinositide 3­kinase and histone deacetylase. It exerts anticancer activities by inducing apoptosis and inhibiting the growth and metastases of various tumors. However, the anticancer effects of CUDC­907 on bladder cancer have not been previously reported. Thus, the present study aimed to examine the anticancer effects of CUDC­907 on 2D monolayer and 3D spheroid models of T24 cells established from highly malignant human grade III urinary bladder carcinoma and cisplatin­resistant T24R2 cells generated by 17 months of exposure to cisplatin, starting at 0.01 µg/ml and increasing stepwise to 2 µg/ml. CUDC­907 treatment significantly reduced the cell viabilities of the monolayer and spheroid cultures in a concentration­dependent manner. The IC50 value of CUDC­907 was higher in the bladder cancer spheroids than in the monolayers. Treatment with CUDC­907 suppressed epithelial­mesenchymal transition via decreasing vimentin and E­cadherin and consequently inhibited the migration and invasion of the bladder cancer spheroids. In addition, it promoted apoptosis and increased the expression of apoptosis­related genes, such as Bax and caspases. In conclusion, CUDC­907 exerted anticancer effects by reducing the viability, migration and invasion, and inducing apoptosis of bladder cancer spheroids. These results suggest that CUDC­907 is a potent agent for the treatment of bladder cancer.

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