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We retrospectively examined current trends in ordering for erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) testing. All claims corresponding to ESR and CRP testing for hospital visits in 2022 were obtained from a platform operated by the Health Insurance and Review Agency. The annual (2018-2022) utilization and cost of ESR and CRP, total inpatient days, and patient encounters with outpatients were retrieved. The number of ESR and CRP tests gradually increased over 5 years, except a slight decrease in 2020. The proportion of claims with co-ordering of ESR and CRP tests was 46.64%. More than 60% co-ordering claims were observed in orthopedic surgery, neurosurgery, and plastic surgery departments. The proportion of co-orders was relatively high in inpatient setting and primary hospitals. This study indicated frequent co-ordering patterns of ESR and CRP tests, highlighting an urgent need for diagnostic stewardship programs on ESR and CRP testing in Korea., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2024 The Korean Academy of Medical Sciences.)

In this study, the seed germination and dormancy characteristics of three Ranunculus species native to Korea (R. cantoniensis, R. chinensis, and R. sceleratus) were determined to establish an effective dormancy-breaking protocol. The results revealed that the R. cantoniensis, R. chinensis, and R. sceleratus seeds responded differently to treatment with gibberellins (GAs) and stratification. Warm stratification at 20℃ increased the germination percentage and partially broke the dormancy of the R. cantoniensis seeds; moreover, the germination temperature range of the seeds expanded upon treatment with high-concentration GA 4 + 7 . Meanwhile, neither cold nor warm stratification was effective at breaking the dormancy of R. chinensis seeds; however, high-concentration GA 4 + 7 treatment broke the dormancy of the seeds by expanding the germination temperature range. Lastly, the R. sceleratus seeds did not respond to the treatment with GAs; however, their germination percentage increased after undergoing warm stratification at 25℃. The seeds of these three species were characterized as exhibiting nondeep morphophysiological dormancy. The findings of this study enhance our understanding of the temperature-related germination responses of the three Ranunculus species, offering valuable insights into their conservation and utilization., Competing Interests: Declarations Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

This study retrospectively reviewed the microbiological and clinical characteristics of patients diagnosed with bacteremia. Results from the first positive blood cultures were consecutively collected from July 2022 to June 2023 at a public secondary hospital, a university-affiliated tertiary hospital, and a university-affiliated secondary hospital in the Seoul metropolitan area. Antibiotic spectrum coverage (ASC) scores were calculated on the day the blood culture was performed (B0) and on two days after the blood culture results were reported (R+2). A total of 3,397 isolates were collected from 3,094 patients. Among these, 949 isolates obtained from 893 patients were classified as multidrug-resistant organisms (MDRO), including 170 imipenem-resistant gram-negative bacteria, 714 methicillin-resistant staphylococci, and 65 vancomycin-resistant enterococci. Interestingly, 13 and 42 gram-positive isolates were resistant to linezolid and quinupristin/dalfopristin, respectively. Moreover, 44 and 181 gram-negative isolates were resistant to amikacin and tigecycline, respectively. The proportion of ASC scores corresponding to broad or extremely broad-spectrum coverage was not significantly different between MDRO and non-MDRO groups at B0 (p = 0.0925). However, it increased in the MDRO group at R+2 (p <0.001). This study found that resistance to last-resort antimicrobials is emerging. Therefore, developing and incorporating molecular diagnostics using a wide range of resistance targets may facilitate rapid, tailored antimicrobial treatments., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Yoo et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: The discovery of viruses in small mammalian populations, particularly rodents, has expanded the family Paramyxoviridae. The overlap in habitats between rodents and humans increases the risk of zoonotic events, underscoring the importance of active surveillance. Rodent species, such as Apodemus agrarius, are natural hosts for Paramyxoviridae in the Republic of Korea (ROK). However, it is unknown whether Paramyxoviridae is present in Micromys minutus, another common rodent., Method: Here, we screened M. minutus collected from the Gangwon Province in the ROK for paramyxoviruses using nested polymerase chain reaction and confirm positive samples by next-generation metagenomic sequencing. Complete paramyxovirus genomes were further characterized by phylogenetic analysis, amino acid similarity, secondary structure, and cophylogeny., Result: Overall, 57 of 145 (39.3%) M. minutus kidney samples tested positive for paramyxoviruses. Among them, four whole genome sequences were identified and clustered within the genus Jeilongvirus. One sequence was determined as Samak Micromys paramyxovirus 1 (SMPV-1; 19,911 nucleotides long) and three sequences as Samak Micromys paramyxovirus 2 (SMPV-2; 18,199 nucleotides long). SMPV-1 has a smaller hydrophobic gene and a longer glycoprotein gene than SMPV-2. Cophylogenetic analysis suggests that SMPV-1 evolved through co-divergence, whereas SMPV-2 was inferred to have undergone transfer events., Conclusion: These findings highlight the prevalence of paramyxoviruses in the wild and the potential of M. minutus as a natural viral reservoir. The discovery of SMPV-1 and SMPV - 2 also reveals the genetic diversity and evolutionary history of the genus Jeilongvirus in the Paramyxoviridae., (© 2024. The Author(s).)

Acute kidney injury (AKI) is a common complication of bites by Viperidae snakes. The main venomous snakes in South Korea are members of the Viperidae family, but there is limited information on snake-bite induced AKI in South Korea. Therefore, we investigated snake envenomation-related AKI and the performance of surrogate baseline creatinine to diagnose true AKI. This retrospective, case-control study divided 71 patients with baseline serum creatinine into two groups according to the development of envenomation-related AKI determined based on Kidney Disease Improving Global Outcome Classification. The incidence of AKI was 14.1% with 10% having stage-3 AKI. During hospitalization, the AKI group did not develop venom-induced consumption coagulopathy more frequently than did the non-AKI group. Only one patient needed renal replacement therapy, and no patients died. The serum creatinine concentration at presentation underestimated the incidence of AKI, while the lowest creatinine concentration during hospitalization overestimated the incidence of AKI. After discharge, the incidence of chronic kidney disease did not increase in the AKI group. Snake envenomation-related AKI is characterized by a relatively lower incidence and severity, has no correlation with coagulation disturbance, and has favorable short- and long-term outcomes in South Korea. Based on this study, it is recommended that future envenomation-related AKI studies would utilize the baseline creatinine for diagnosing AKI. If not, envenomation-related AKI studies should include the definition of baseline creatinine used to diagnose AKI and report bias if a baseline creatinine surrogate is used., (© 2024. The Author(s).)

This study evaluates the composition and seasonal characteristics of fine particulate matter (PM 2.5 ) during winter and summer through simultaneous measurements conducted at the Gwangju Institute of Science and Technology in South Korea and the Changping campus of Peking University in China. PM 2.5 samples were concurrently collected at both sites, and chemical analyses were conducted to quantify various components, including carbonaceous materials, ionic species, and metals. Although the average PM 2.5 concentrations were comparable between the two sites, there were distinct differences in the concentrations of major components. Organic indicator compounds were analyzed to discern the contributions of primary and secondary pollution sources. Changping displayed a mix of primary and secondary pollution, characterized by higher concentrations of primary organic carbon (POC) such as polycyclic aromatic hydrocarbons and hopanes, compared to Gwangju. In contrast, Gwangju demonstrated a higher prevalence of secondary organic carbon (SOC), particularly water-soluble organic carbon not related to biomass burning (WSOC nbb ) and various polar organic compounds. The organic mass to organic carbon (OM/OC) ratios estimated using the mass balance method revealed significant differences, with Gwangju showing a higher ratio of 2.3 compared to 1.9 at Changping, indicating a greater influence of secondary pollutants at Gwangju. Additionally, both Changping and Gwangju exhibited higher OM/OC ratios in summer (Changping: 2.0, Gwangju: 2.5) compared to winter (Changping: 1.8, Gwangju: 2.2), indicating seasonal differences in organic mass contributions to PM 2.5 . These findings underscore the importance of accounting for spatial and seasonal variations in air pollution studies and suggest that updating commonly used OM/OC ratios could enhance the reliability of research outcomes., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: To assess the appropriateness of laboratory testing intervals and antiphospholipid syndrome (APS) incidence., Methods: Between January 2010 and August 2022, insurance claims data of patients with disease codes for other thrombophilia (D68.6) and APS (V253) were retrieved in South Korea. Patients who received antiphospholipid antibody tests more than twice were classified as having suspected APS. The interval between the first 2 antiphospholipid antibody tests was evaluated in the patients with suspected APS. Patients with suspected APS who received anticoagulants for >180 days were classified as having APS., Results: Overall, 8656 patients were classified as having suspected APS. The testing interval for the first 2 tests in patients with suspected APS was <6 and <12 weeks in 11.1% and 20.6% of cases, respectively, in 2010, gradually increasing to 21.0% and 35.4%, respectively, in 2021. Subsequently, 4344 patients were classified as having APS, with 65.0% being female. Only 330 patients were diagnosed with APS in 2021, down from 436 in 2020., Conclusion: This study showed a gradual increase in patients receiving antiphospholipid antibody testing with an inappropriate short-term interval, underscoring the need for laboratory stewardship to ensure an appropriate interval for APS testing., (© The Author(s) 2024. Published by Oxford University Press on behalf of American Society for Clinical Pathology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Despite previous efforts to build statistical models for predicting the risk of suicidal behavior using machine-learning analysis, a high-accuracy model can lead to overfitting. Furthermore, internal validation cannot completely address this problem. In this study, we created models for predicting the occurrence of suicide attempts among Koreans at high risk of suicide, and we verified these models in an independent cohort. We performed logistic and penalized regression for suicide attempts within 6 months among suicidal ideators and attempters in The Korean Cohort for the Model Predicting a Suicide and Suicide-related Behavior (K-COMPASS). We then validated the models in a test cohort. Our findings indicated that several factors significantly predicted suicide attempts in the models, including young age, suicidal ideation, previous suicidal attempts, anxiety, alcohol abuse, stress, and impulsivity. The area under the curve and positive predictive values were 0.941 and 0.484 after variable selection and 0.751 and 0.084 in the test cohort. The corresponding values for the penalized regression model were 0.943 and 0.524 in the original training cohort and 0.794 and 0.115 in the test cohort. The prediction model constructed through a prospective cohort study of the suicide high-risk group showed satisfactory accuracy even in the test cohort. The accuracy with penalized regression was greater than that with the "classical" logistic model., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Phytochemicals found in fruits, vegetables, and plant-based foods have potential protective effects against various diseases, including gastric disorders. This study aimed to analyze the longitudinal association between phytochemical intake and the risk of gastritis/gastric ulcer in Korean adults. This was a prospective cohort study, a community-based cohort conducted as part of the Korean Genome and Epidemiology Study, examining the association between phytochemical intake and the risk of gastritis/gastric ulcer in Korean adults. Dietary information was collected using a validated semi-quantitative food frequency questionnaire, and the phytochemical index (PI) was calculated. The study included 7377 Korean men and women aged 40-69 years without gastritis/gastric ulcer at baseline of the Korea Association Resource study in Korea. The incidence of gastritis/gastric ulcer was determined using a survey questionnaire administered by trained staff. Multivariate Cox proportional hazards regression was used to calculate the hazard ratio and 95% confidence interval to determine the association between PI and risk of gastritis/gastric ulcer. During the median follow-up period of 9.50 years, 729 cases were reported. The fully adjusted model showed a significantly lower risk of gastritis/gastric ulcer in the highest PI quartile compared to the lowest (hazard ratio: 0.78, 95% confidence interval: 0.61-0.98), and this association was linear ( p for trend = 0.01). This research indicates that incorporating foods abundant in phytochemicals into one's diet could be associated with a reduced risk of developing gastritis/gastric ulcers. These findings underscore the importance of further investigating the role of phytochemical-rich diets in gastrointestinal health, as demonstrated in this study.

In Korea and other Asian countries, traditional high-carbohydrate diets are increasingly associated with metabolic syndrome (MetS) and its complications. As dietary patterns shift, there is a growing need to assess the effect of these changes on health outcomes related to MetS. This study aimed to investigate the prospective relationship between carbohydrate consumption and the risk of MetS and its components. We analyzed data from 7902 participants from the Korean Association Resource, part of the Korean Genome and Epidemiology Study Dietary intakes, including carbohydrates and fiber, were assessed using a validated semi-quantitative food frequency questionnaire, allowing for the calculation of the proportion of total energy from carbohydrates (P&#95;CARB) and the carbohydrate-to-fiber ratio to assess carbohydrate quality. Blood samples were collected after at least eight hours of fasting for laboratory analysis. We employed Cox proportional hazards models to estimate hazard ratios and 95% confidence intervals, focusing on the relationship between the P&#95;CARB and the risk of developing MetS and its individual components, while adjusting for carbohydrate quality. In the fully adjusted model, which accounted for carbohydrate quality as a covariate, individuals in the highest percentile of the P&#95;CARB showed a significantly increased risk of MetS, hypertriglyceridemia, hypo-high density lipoprotein cholesterolemia, dyslipidemia, and high blood pressure, compared to those in the lowest P&#95;CARB group. Spline curve analyses indicated that the risks for MetS and its components consistently escalated with increasing P&#95;CARB, with all p -values for nonlinearity exceeding 0.05. The findings suggest that higher levels of P&#95;CARB are associated with an increased risk of MetS and related conditions, except for high fasting glucose. These results highlight the importance of dietary awareness and potential adjustments for populations consuming high-carbohydrate diets.

Conflicting findings have been reported regarding the association between Agent Orange (AO) exposure and type 2 diabetes. This study aimed to examine whether AO exposure is associated with the development of type 2 diabetes and to verify the causal relationship between AO exposure and type 2 diabetes by combining DNA methylation with DNA genotype analyses. An epigenome-wide association study and DNA genotype analyses of the blood of AO-exposed and AO-unexposed individuals with type 2 diabetes and that of healthy controls were performed. Methylation quantitative trait locus and Mendelian randomisation analyses were performed to evaluate the causal effect of AO-exposure-identified CpGs on type 2 diabetes. AO-exposed individuals with type 2 diabetes were associated with six hypermethylated CpG sites (cg20075319, cg21757266, cg05203217, cg20102280, cg26081717, and cg21878650) and one hypo-methylated CpG site (cg07553761). Methylation quantitative trait locus analysis showed the methylation levels of some CpG sites (cg20075319, cg20102280, and cg26081717) to be significantly different. Mendelian randomisation analysis showed that CpG sites that were differentially methylated in AO-exposed individuals were causally associated with type 2 diabetes; the reverse causal effect was not significant. These findings reflect the need for further epigenetic studies on the causal relationship between AO exposure and type 2 diabetes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Seo, Kim, Lee, Kim, Kim, An, Jin, Do, Park, Won and Seo.)

Purpose: This study aimed to provide the basic data needed to estimate future urologist supply and demand by applying various statistical models related to healthcare utilization., Materials and Methods: Data from multiple sources, including the Yearbook of Health and Welfare Statistics, Korean Hospital Association, Korean Medical Association, and the Korean Urological Association, were used for supply estimation. Demand estimation incorporated data on both clinical and non-clinical urologists, along with future population estimates. In-and-out moves and demographic methods were employed for supply estimation, while the Bureau of Health Professions model was utilized for demand estimation. Supply estimation assumptions included fixed resident quotas, age-specific death rates, migration rates, and retirement age considerations. Demand estimation assumptions included combining clinical and nonclinical urologist demands, adjusting population size for age-related healthcare usage variations. Urologist productivity was determined by adjusting productivity levels to 100%, 90%, and 80% of the base year based on actual clinical practice volumes., Results: Estimations of both demand and supply consistently indicate an oversupply of urologists until 2025, followed by an expected shortage by 2035 owing to increased deaths and retirements attributed to the aging urologist population. This shortage becomes more pronounced when employing more reliable models, such as logit or ARIMA (autoregressive integrated moving average), underscoring the growing need for urologists in the future., Conclusions: All estimation models estimated an oversupply of urologists until 2025, transitioning to a deficit due to reduced supply thereafter. However, considering potential unaccounted factors, greater effort is needed for accurate predictions and corresponding measures., Competing Interests: The authors have nothing to disclose., (© The Korean Urological Association.)

Background: External apical root resorption (EARR) is a common undesirable outcome of orthodontic treatment, this study aimed to identify genetic polymorphisms associated with the susceptibility to extreme orthodontic-induced EARR in a Korean population using extreme phenotype analysis sampling., Methods: Genomic DNA was isolated from the saliva of 77 patients who underwent orthodontic treatment involving two maxillary premolar extractions. The patients were divided into two groups based on EARR values measured on periapical radiographs: The significant resorption group (SG, EARR ≥ 4 mm) and the normal group (NG, EARR < 2 mm). In the NG group, patients with EARR < 1 mm were named the non-resorption group (NonG). Targeted next-generation sequencing was performed using the screened single nucleotide polymorphisms (SNPs), and firth logistic regression analysis was used to determine genetic associations with EARR. Haplotype-based association analysis was performed for specific SNPs., Results: SNPs related to genes TNFSF11, TNFRSF11B, WNT3A, SFRP2, LRP6, P2RX7, and LRP1 were found to be significantly associated with severe EARR (p < 0.05, pre-Bonferroni correction p-values). Additionally, the haplotype CCA of rs17525809, rs208294, and rs1718119 P2RX7 had a higher frequency in the SG group., Conclusion: Extreme phenotype analysis has identified eleven SNPs related to genes TNFSF11, TNFRSF11B, WNT3A, SFRP2, LRP6, P2RX7, and LRP1 that are associated with severe root resorption in the Korean population. These findings will contribute to the development of predictive diagnostic tools for identifying severe root resorption that may occur during orthodontic treatment., (© 2024. The Author(s).)

Background: Despite significant advancements in treatments such as surgery, radiotherapy, and chemotherapy, the survival rate for patients with asbestos-related cancers remains low. Numerous studies have provided evidence suggesting that air pollution induces oxidative stress and inflammation, affecting acute respiratory diseases, lung cancer, and overall mortality. However, because of the high case fatality rate, there is limited knowledge regarding the effects of air pollution exposures on survival following a diagnosis of asbestos-related cancers. This study aimed to determine the effect of air pollution on the survival of patients with malignant mesothelioma and asbestos-related lung cancer., Methods: We followed up with 593 patients with malignant mesothelioma and 998 patients with lung cancer identified as asbestos victims between 2009 and 2022. Data on five air pollutants-sulfur dioxide, carbon monoxide, nitrogen dioxide, fine particulate matter with a diameter < 10 μm, and fine particulate matter with a diameter < 2.5 μm-were obtained from nationwide atmospheric monitoring stations. Cox proportional hazard models were used to estimate the association of cumulative air pollutant exposure with patient mortality, while adjusting for potential confounders. Quantile-based g-computation was used to assess the combined effect of the air pollutant mixture on mortality., Results: The 1-, 3-, and 5-year survival rates for both cancer types decreased with increasing exposure to all air pollutants. The estimated hazard ratios rose significantly with a 1-standard deviation increase in each pollutant exposure level. A quartile increase in the pollutant mixture was associated with a 1.99-fold increase in the risk of malignant mesothelioma-related mortality (95% confidence interval: 1.62, 2.44). For lung cancer, a quartile increase in the pollutant mixture triggered a 1.87-fold increase in the mortality risk (95% confidence interval: 1.53, 2.30)., Conclusion: These findings support the hypothesis that air pollution exposure after an asbestos-related cancer diagnosis can negatively affect patient survival., (© 2024. The Author(s).)

Objectives: High incidences of haemorrhagic fever with renal syndrome (HFRS) have been reported in the southern Republic of Korea (ROK). A distinct southern genotype of Orthohantavirus hantanense (HTNV) was identified in Apodemus agrarius chejuensis on Jeju Island. However, its association with HFRS cases in southern ROK remains elusive. We investigated the potential of the southern HTNV genotype as an etiological agent of HFRS., Methods: Samples from 22 patients with HFRS and 193 small mammals were collected in the southern ROK. The clinical characteristics of patients infected with the southern HTNV genotype were analysed. Amplicon-based MinION sequencing was employed for southern HTNV from patients and rodents, facilitating subsequent analyses involving phylogenetics and genetic reassortment., Results: High-throughput sequencing of HTNV exhibited higher coverage with a cycle of threshold value below 32, acquiring nearly whole-genome sequences from six patients with HFRS and seven A. agrarius samples. The phylogenetic pattern of patient-derived HTNV demonstrated genetic clustering with HTNV from Apodemus species on Jeju Island and the southern Korean peninsula, revealing genetic reassortment in a single clinical sample between the M and S segments., Discussion: These findings imply that the southern HTNV genotype has the potential to induce HFRS in humans. The phylogenetic inference demonstrates the diverse and dynamic characteristics of the southern HTNV tripartite genomes. Therefore, this study highlights the significance of active surveillance and amplicon sequencing for detecting orthohantavirus infections. It also raises awareness and caution for physicians regarding the emergence of a southern HTNV genotype as a cause of HFRS in the ROK., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Nonalcoholic fatty liver disease (NAFLD) is a highly prevalent condition in the general population. Although recent studies have demonstrated a link between NAFLD and lipoprotein(a), a low-density lipoprotein-like particle synthesized in the liver, its precise physiological role and mechanism of action remain unclear. This study aimed to investigate the relationship between lipoprotein(a) levels and development of NAFLD and hepatic fibrosis in Korean adults. A total of 1501 subjects who underwent abdominal ultrasonography at least twice as part of a health checkup program were enrolled. Biochemical and ultrasonography results were analyzed longitudinally, and the degree of hepatic fibrosis was calculated in subjects with NAFLD using serum biomarkers, such as fibrosis-4 (FIB-4). During the 3.36-year follow-up period, 352 patients (23.5%) were diagnosed with NAFLD. The subjects were categorized into 4 groups based on their lipoprotein(a) levels. Remarkably, the incidence of NAFLD decreased as the lipoprotein(a) levels increased. Following logistic regression analysis and adjustment for various risk factors, the odds ratio for the development of NAFLD was 0.625 (95% CI 0.440-0.888; P = .032) when comparing the highest to the lowest tertile of lipoprotein(a). However, no significant association was observed between the occurrence of hepatic fibrosis and lipoprotein(a) levels in subjects with NAFLD. Lipoprotein(a) levels have been identified as a significant predictor of NAFLD development. Additional large-scale studies with extended follow-up periods are required to better understand the effect of lipoprotein(a) on NAFLD and hepatic fibrosis., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background/aims: To investigate a reported outbreak of presumed hepatitis E virus (HEV) infection in a Korean food manufacturing facility and to explore the association between anti-HEV immunoglobulin M (IgM) positivity and coronavirus disease 2019 (COVID-19) infection or vaccination., Methods: Twenty-four cases of anti-HEV IgM positivity were reported among 646 workers at the facility in 2022. An epidemiological investigation was conducted, comprising HEV-RNA testing of blood and environmental samples, analysis of group meal records, and an association between anti-HEV IgM positivity and confirmed COVID-19 infection or vaccination., Results: All 24 patients were asymptomatic, with cases spread sporadically across the facility. HEV RNA was not detected in the serum or environmental samples. Four out of 340 meals (1.2%) showed a significantly higher proportion of anti-HEV positivity in each meal intake group than in the non-intake group on certain days. Although the cumulative rate of COVID-19 infection showed no difference, the anti-HEV IgM positive group showed significantly higher proportions of >2 doses of COVID-19 vaccination (83.3% vs 48.7%, p=0.021), vaccination within 90 days (45.8% vs 19.7%, p=0.008), and having the Moderna vaccine administered as the last vaccine (75.0% vs 14.5%, p<0.001) than those of the anti-HEV negative group. In four multivariable models, three or more COVID-19 vaccinations and the Moderna vaccine as the last vaccine were consistently associated with anti-HEV IgM positivity, while the specific day group meal intake was also a significant factor., Conclusions: This epidemiological investigation showed that anti-HEV IgM positivity may occur as a false-positive result related to COVID-vaccination over three times and use of the Moderna vaccine, although a portion of true HEV infection may not be excluded.

Objective: With the recent reports of additional alleles of the CYP2C19 gene with decreased or no function, the clinical utility of real-time polymerase chain reaction (PCR)-based testing that detects only a small number of variant targets needs to be evaluated., Method: We retrospectively reviewed 7-year data for real-time PCR test records from a single hospital and analyzed CYP2C19 genotypes from publicly available whole-genome or whole-exome data from a healthy Korean population., Results: Of the 2327 test results in this hospital, the *1 allele was most common (60.5%), followed by *2 (28.0%), *3 (10.1%), and *17 (1.4%). Among 5305 healthy Korean individuals, the frequencies of the *2, *3, and *17 alleles were 28.6%, 9.9%, and 1.0%, respectively, which were not statistically different from those of the hospital data (P = .4439, P = .6025, and P = .1142, respectively). Interestingly, the total frequency of additional nonfunctional alleles (*4, *6, *22, and *24) that could not be detected using real-time PCR was only 0.1%, with a total allele count of 8., Conclusion: Our study shows that the clinical utility of real-time PCR for CYP2C19 genotyping remains satisfactory. However, caution should be exercised because the test can miss patients with decreased CYP2C19 function., (© The Author(s) 2023. Published by Oxford University Press on behalf of American Society for Clinical Pathology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Aims: This study was conducted to develop a population pharmacokinetic (PK) model of methotrexate in Korean patients with haematologic malignancy, identify factors affecting methotrexate PK, and propose an optimal dosage regimen for the Korean population., Methods: Data were retrospectively collected from 188 patients with acute leukaemia or non-Hodgkin's lymphoma who were admitted to Severance Hospital during the period from November 2005 to January 2016. Using demographic factors and laboratory results as potential covariates for PK parameters, model development was performed using NONMEM and optimal dosing regimens were developed using the final PK model., Results: A two-compartment model incorporating body weight via allometry best described the data, yielding typical parameter values of 25.09 L for central volume of distribution ( V 1 ), 17.65 L for peripheral volume of distribution ( V 2 ), 12.89 L/h for clearance (CL) and 0.655 L/h for inter-compartmental clearance in a 50 kg patient. Covariate analyses showed that, at the weight of 50 kg, CL decreased by 0.11 L/h for each 1-year increase in age above 14 years old and decreased 0.8-fold when serum creatinine level doubled, indicating the importance of age-specific dose individualization in methotrexate treatment. Volume of distribution at steady state derived from PK parameters (=  V 1  +  V 2 ) was 0.85 L/kg, which was similar to those in the Western or Chinese populations. Optimal doses simulated from the final model successfully produced the PK measures close to the target chosen., Conclusions: The population PK model and optimal dosage regimens developed in this study can be used as a basis to achieve precision dosing in Korean patients with haematologic malignancy., (© 2023 British Pharmacological Society.)

Although depression is an emerging disorder affecting many people worldwide, most genetic studies have been performed in European descent populations. Herein, a genome-wide association study (GWAS) was conducted in Korean population to elucidate the genomic loci associated with depressive symptoms. Two independent cohorts were used as discovery datasets, which consisted of 6474 (1484 cases and 4990 controls) and 1654 (557 cases and 1097 controls) Korean participants, respectively. The participants were divided into case and control groups based on the Beck Depression Inventory (BDI). Meta-analysis using the two cohorts revealed that rs6945590 was significantly associated with the risk of depressive symptoms [P = 2.83 × 10 -8 ; odds ratio (OR) = 1.23; 95% confidence interval (CI): 1.15-1.33]. This association was validated in other independent cohorts which were another Korean cohort (258 cases and 1757 controls) and the East Asian study of the Psychiatric Genomics Consortium (PGC) (12,455 cases and 85,548 controls). The predicted expression levels of thromboxane A synthase 1 gene (TBXAS1), which encodes the enzyme thromboxane A synthase 1 and participates in the arachidonic acid (AA) cascade, was significantly decreased in the whole blood tissues of the participants with depressive symptoms. Furthermore, Mendelian randomization (MR) analysis showed a causal association between TBXAS1 expression and the risk of depressive symptoms. In conclusion, as the number of risk alleles (A) of rs6945590 increased, TBXAS1 expression decreased, which subsequently caused an increase in the risk of depressive symptoms., (© 2024. The Author(s).)

Hepatitis E virus (HEV), an emerging zoonotic pathogen, poses a significant public health concern worldwide. Recently, rat HEV (Rocahepevirus ratti genotype C1; HEV-C1) has been reported to cause zoonotic infections and hepatitis in humans. Human infections with HEV-C1 are considered to be underestimated worldwide due to limited knowledge of transmission routes, genome epidemiology, and the risk assessment of zoonosis associated with these viruses. A total of 186 wild Norway rats (Rattus norvegicus) were collected from the Republic of Korea (ROK) between 2011 and 2021. The prevalence of HEV-C1 RNA was 8 of 180 (4.4%) by reverse-transcription polymerase chain reaction. We first reported three nearly whole-genome sequences of HEV-C1 newly acquired from urban rats in the ROK. Phylogenetic analysis demonstrated that Korea-indigenous HEV-C1 formed an independent genetic group with those derived from R. norvegicus rats in other countries, indicating geographical and genetic diversity. Our findings provide critical insights into the molecular prevalence, genome epidemiology, and zoonotic potential of Rocahepevirus. This report raises awareness of the presence of Rocahepevirus-related hepatitis E among physicians in the ROK., (© 2024 Wiley Periodicals LLC.)

Orthohantaviruses, etiological agents of hemorrhagic fever with renal syndrome (HFRS) and hantavirus cardiopulmonary syndrome, pose a critical public health threat worldwide. Hantaan orthohantavirus (HTNV) outbreaks are particularly endemic in Gyeonggi Province in northern area of the Republic of Korea (ROK). Small mammals were collected from three regions in the Gyeonggi Province during 2017 and 2018. Serological and molecular prevalence of HTNV was 25/201 (12.4%) and 10/25 (40%), respectively. A novel nanopore-based diagnostic assay using a cost-efficient Flongle chip was developed to rapidly and sensitively detect HTNV infection in rodent specimens within 3 h. A rapid phylogeographical surveillance of HTNV at high-resolution phylogeny was established using the amplicon-based Flongle sequencing. In total, seven whole-genome sequences of HTNV were newly obtained from wild rodents collected in Paju-si (Gaekhyeon-ri) and Yeoncheon-gun (Hyeonga-ri and Wangnim-ri), Gyeonggi Province. Phylogenetic analyses revealed well-supported evolutionary divergence and genetic diversity, enhancing the resolution of the phylogeographic map of orthohantaviruses in the ROK. Incongruences in phylogenetic patterns were identified among HTNV tripartite genomes, suggesting differential evolution for each segment. These findings provide crucial insights into on-site diagnostics, genome-based surveillance, and the evolutionary dynamics of orthohantaviruses to mitigate hantaviral outbreaks in HFRS-endemic areas in the ROK., (© 2024 Wiley Periodicals LLC.)

Purpose: While previous retrospective or phase II studies in Western populations showed that dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin (ddMVAC) as neoadjuvant chemotherapy (NAC) was beneficial, no studies have been reported in Asian populations. This prospective phase II study aimed to evaluate efficacy and safety of ddMVAC in Korean patients with muscle-invasive bladder cancer (MIBC) or locally advanced urothelial cancer (UC)., Materials and Methods: Patients with MIBC (cT2-4aN0M0) or locally advanced UC (cTanyN1-3M0) eligible for radical cystectomy (RC) were enrolled prospectively. The participants were treated with four cycles of ddMVAC with pegfilgrastim every 2 weeks. The primary endpoint was pathologic response rate (≤ypT1N0). Secondary endpoints were pathologic complete response (pCR, ypT0N0), relapse-free survival (RFS), overall survival (OS), and safety., Results: Among 24 patients enrolled between December 2019 and August 2021, 23 were evaluable (52%, cT2-4aN0; 48%, cTanyN1-3). Eighteen patients (78%) completed four cycles of ddMVAC, while remaining five patients experienced early discontinuation. Dose modification (91%) and dose delay (70%) occurred, and the dose intensity of ddMVAC was 79%. Nineteen patients underwent RC and four patients declined. Of 19 patients who underwent RC, eight patients (42%) achieved ≤ypT1N0. With a median follow-up of 22.8 months, the median RFS was 13.5 months (95% CI, not yet evaluable) and the median OS was 28.9 months (95% confidence interval, 19.9-37.9)., Conclusion: Our study showed substantial efficacy and safety of ddMVAC, even in patients with locally advanced UC. The ddMVAC still should be a promising option as NAC in Asian patients with UC., (© 2023 John Wiley & Sons Australia, Ltd.)

Background: More than 200 asthma-associated genetic variants have been identified in genome-wide association studies (GWASs). Expression quantitative trait loci (eQTL) data resources can help identify causal genes of the GWAS signals, but it can be difficult to find an eQTL that reflects the disease state because most eQTL data are obtained from normal healthy subjects., Methods: We performed a blood eQTL analysis using transcriptomic and genotypic data from 433 Korean asthma patients. To identify asthma-related genes, we carried out colocalization, Summary-based Mendelian Randomization (SMR) analysis, and Transcriptome-Wide Association Study (TWAS) using the results of asthma GWASs and eQTL data. In addition, we compared the results of disease eQTL data and asthma-related genes with two normal blood eQTL data from Genotype-Tissue Expression (GTEx) project and a Japanese study., Results: We identified 340,274 cis-eQTL and 2,875 eGenes from asthmatic eQTL analysis. We compared the disease eQTL results with GTEx and a Japanese study and found that 64.1% of the 2,875 eGenes overlapped with the GTEx eGenes and 39.0% with the Japanese eGenes. Following the integrated analysis of the asthmatic eQTL data with asthma GWASs, using colocalization and SMR methods, we identified 15 asthma-related genes specific to the Korean asthmatic eQTL data., Conclusions: We provided Korean asthmatic cis-eQTL data and identified asthma-related genes by integrating them with GWAS data. In addition, we suggested these asthma-related genes as therapeutic targets for asthma. We envisage that our findings will contribute to understanding the etiological mechanisms of asthma and provide novel therapeutic targets., (© 2023. BioMed Central Ltd., part of Springer Nature.)

This study aimed to verify the relationship between the level of understanding of health information and health behaviors among Korean adults. In total, 228 984 adults who participated in the 2021 Korea Community Health Survey were included. Participants were divided into three groups according to age (19-44, 45-64 and 65+). The ability to understand verbal and written health information was included, and its association with health behaviors, including smoking, alcohol consumption and preventive health service uptake, was assessed. Associations between the ability to understand health information and health behaviors were analyzed using chi-squared tests and multiple logistic regression analyses. Approximately 22.7% and 20% of the participants responded that verbal and written health information were easy to understand, respectively, with significant differences by age group. Compared to those with easy-to-understand verbal health information, those with difficulty in understanding had a higher risk of current cigarette smoking and monthly drinking and were less likely to engage in more than moderate physical activity, walking, influenza vaccination in 1 year, cancer examination in 2 years and medical examination in 2 years. Difficulty in understanding or no interest in written health information was also associated with unhealthy behaviors. A strong ability to understand health information is related to positive health behaviors. However, there are differences in the associations by age group, which should be considered when establishing a health literacy improvement strategy. These findings could promote health literacy and ultimately contribute to helping individuals make better choices for positive health behaviors., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Heat waves are generally known to deteriorate air quality. However, the impacts of heat waves on air quality can substantially vary depending on the characteristics of heat waves. In this study, we examine air quality changes in Seoul during heat waves and their associations with large-scale atmospheric patterns. For this, air quality data from 25 stations and meteorological data from 23 weather stations and reanalysis datasets during July and August of 2001-2021 are used. Under heat waves, the mean daily PM 10 , NO 2 , and CO concentrations decrease by 7.9 %, 6.1 %, and 4.6 %, respectively, whereas the mean daily PM 2.5 , O 3 , and SO 2 concentrations increase by 4.1 %, 17.2 %, and 2.9 %, respectively. The atmospheric circulation under heat waves is less favorable for long-range transport of air pollutants to Seoul. The PM 2.5 /PM 10 ratio increases under heat waves, indicating that the secondary formation of aerosols becomes more important under heat waves. 37 % of the heat wave days are accompanied by severe O 3 pollution exceeding the O 3 concentration standard in South Korea. There is a significant variability of air quality in Seoul within heat waves. The heat wave days with higher concentrations of PM 2.5 , PM 10 , O 3 , NO 2 , and CO than their non-heat wave means exhibit a prominent difference in large-scale atmospheric pattern from the heat wave days with lower concentrations. This difference is characterized by a zonal wave-like pattern of geopotential height, which is similar to the circumglobal teleconnection pattern known as one of the major patterns for heat waves in South Korea. This zonal wave-like pattern produces more stagnant conditions over Seoul., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

A proton linac based boron neutron capture therapy system (A-BNCT, 10MeV, 4mA) was successfully developed in Korea. We performed in vitro experiments with U87 and SAS cells and revealed the efficacy of a binary therapy BNCT using epithermal neutrons and boronophenylalanine (BPA). The results revealed that BNCT showed cancer cell selectivity and caused cell death. Further in vitro studies can be a valuable method to characterize an A-BNCT system. We expect BNCT to become a treatment option for cancer patients., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Ltd.)

(1) Background and Objectives : There were two distinct coronavirus disease 2019 (COVID-19) outbreaks in 2020 and 2022 at a long-term mental health facility (LTMHF) in Gyeonggi Province, Korea. We aimed to compare the two outbreaks and identify differences in epidemiological and clinical outcomes due to changes in epidemic timing and management methods. (2) Materials and Methods : The structural, operational, and case-specific LTMHF data of COVID-19-confirmed patients during these outbreaks in 2020 and 2022 were retrospectively analyzed. (3) Results : Forty individuals (37 residents) in 2020 and thirty-nine (32 residents) in 2022 were confirmed to have COVID-19, and ten were infected twice. Facility isolation was implemented as an infection control measure, and one COVID-19-related death occurred in 2020. All residents and staff were vaccinated at least twice in 2022; moreover, in 2022, 38 patients (97.4%) received a third vaccination less than months before infection. The average Ct value of the cases in 2022 was significantly higher than that in 2020; however, vaccine-breakthrough (V-BT) and reinfection after vaccination rates were similar. (4) Conclusions : COVID-19 vaccination could help lower the viral load of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which was inversely correlated with Ct values, and ventilation system improvements in health facilities might reduce transmissibility.

Evidence on the association between serum 25-hydroxyvitamin D (25(OH)D) concentration and all-cause and cause-specific mortality in Asians, especially Koreans, is limited. We hypothesized that high concentrations of 25(OH)D are associated with lower all-cause and cause-specific mortality in the general Korean population. This study included 27,846 adults participating in the Fourth and Fifth Korean National Health and Nutrition Examination Survey 2008-2012, followed up through December 31, 2019. Hazard ratios (HR) and 95% confidence intervals (CIs) for mortality from all causes, cardiovascular disease (CVD), and cancer were estimated using multivariable-adjusted Cox proportional hazards regression. The weighted mean serum 25(OH)D of study participants was 17.77 ng/mL; 66.5% had vitamin D deficiency (<20 ng/mL) and 94.2% had insufficient vitamin D (<30 ng/mL). During a median follow-up of 9.4 years (interquartile range, 8.1-10.6 years), 1680 deaths were documented, including 362 CVD deaths and 570 cancer deaths. Serum 25(OH)D levels ≥30 ng/mL were inversely associated with all-cause mortality (HR, 0.57; 95% CI, 0.43-0.75) compared with serum 25(OH)D levels <10 ng/mL. Based on the quartile cutoffs of serum 25(OH)D concentration, the highest quartile of serum 25(OH)D concentration (≥21.8 ng/mL) was associated with the lowest all-cause mortality (HR, 0.72; 95% CI, 0.60-0.85; P trend < .001), and CVD mortality (HR, 0.60; 95% CI, 0.42-0.85; P trend = .006). No association with cancer mortality outcome was found. In conclusion, higher serum 25(OH)D levels were associated with lower all-cause mortality in the general Korean population. An additional association was found between higher quartile of serum 25(OH)D and lower CVD mortality., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023. Published by Elsevier Inc.)

Purpose: Leflunomide is an immunosuppressive drug indicated for the treatment of rheumatoid arthritis (RA). While the pharmacokinetics (PK) of its active metabolite A771726 reportedly show large interindividual variability, no efficient dose individualization strategy is currently available. The goal of this work was to develop a population PK model for A771726 and propose an optimal individualized dosing strategy., Methods: A771726 plasma concentration data were collected from 50 healthy male volunteers participating in two leflunomide PK studies given a single oral dose of 40 mg. Concentrations were elevated in low body weight (WT) subjects and showed multiple peaks. Thus, A771726 PK modeling was conducted incorporating allometry scaling and enterohepatic circulation (EHC). For dose optimization, simulating a set of 1000 virtual subjects from the developed model and dividing the subjects into 5 groups with WT of 50, 60, 70, 80, 90 kg, respectively, the optimal dose was explored that achieves the drug concentration most similar to the target, which was defined as the concentration for the 70 kg subject treated with the current standard dosage regimen (the loading dose of 100 mg QD for 3 days, followed by the maintenance dose of 20 mg QD)., Results: The data were best described by a two compartment model with first order absorption incorporating EHC with the bile released into the intestine. None of the covariates tested was found to be significant other than WT used in allometry. Simulation showed that the optimal loading dose increased by 15 mg for every 10 kg increment in WT while the optimal maintenance dose was 15 and 25 mg for 50 and 90 kg groups, respectively, and the same (= 20 mg) for the others. Large concentration differences from the target observed in low and high WT groups disappeared when optimal doses were given., Conclusions: This work demonstrates the importance of a population PK model-based dose optimization approach in maintaining drug therapeutic concentrations in leflunomide treatment., Competing Interests: Declaration of Competing Interest The authors declared no conflict of interest, (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Osteoporosis is a prevalent issue among postmenopausal women, who have a higher incidence of the condition than men. This study aimed to examine the relationship between phytochemical-rich food intake and osteoporosis incidence in premenopausal and postmenopausal women. The data analyzed included 4600 women aged 40-69 who were free of osteoporosis at baseline, with dietary intake evaluated through a semi-quantitative food frequency questionnaire and osteoporosis prevalence determined using interviewer-administered questionnaires and bone mineral density tests. The phytochemical index (PI) was calculated to reflect the intake levels of phytochemical-rich foods. Postmenopausal women in the highest PI quartile had a 16% lower risk of osteoporosis (95% confidence interval (CI): 0.71 to 0.99, p for trend = 0.02) than those in the lowest quartile, while no significant association was observed among premenopausal women (hazard ratio: 0.98, 95% CI: 0.78 to 1.24, p for trend = 0.8). These findings suggest that consuming phytochemical-rich foods may have a protective effect against osteoporosis in postmenopausal women, offering valuable scientific insights. However, additional research is needed to validate these findings using biochemical data. Overall, this study highlights the potential of dietary interventions to reduce the risk of osteoporosis in postmenopausal women.

Importance: Over the past 10 years, treatment of non-small cell lung cancer (NSCLC) has been continually revolutionized. However, standard clinical trials may not reflect current multiple lines of treatment and corresponding outcomes in a timely manner., Objective: To investigate outcomes associated with new treatment of NSCLC in a clinical setting., Design, Setting, and Participants: This cohort study included patients with NSCLC between January 1, 2010, and November 30, 2020, who received any anticancer treatment at Samsung Medical Center in Korea. Data were analyzed from November 2021 through February 2022., Exposures: Clinical and pathological stage, histology, and major druggable sequence variation, including epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), ROS1, RET, MET exon 14 skipping, BRAF V600E, KRAS G12C, and NTRK between 2 periods (period I: 2010-2015 vs period II: 2016-2020)., Main Outcomes and Measures: The primary outcome was the 3-year survival rate of NSCLC. Secondary outcomes included median overall survival, progression-free survival, and recurrence-free survival., Results: Among 21 978 patients with NSCLC (median [range] age at diagnosis, 64.1 [57.0-71.0] years; 13 624 males [62.0%]), there were 10 110 patients in period I and 11 868 patients in period II; adenocarcinoma (AD) was the predominant histology (7112 patients [70.3%] in period I and 8813 patients [74.3%] in period II). There were 4224 never smokers [41.8%] in period I and 5292 never smokers [44.6%] in period II. Compared with patients in period I, patients during period II were more likely to undergo molecular tests in the AD (5678 patients [79.8%] vs 8631 patients [97.9%]) and non-AD (1612 of 2998 patients [53.8%] and 2719 of 3055 patients [89.0%]) groups. In patients with AD in period I, 3-year survival rates were 92.8% (95% CI, 91.8%-93.7%), 72.4% (95% CI, 68.3%-76.8%), 56.7% (95% CI, 53.4%-60.2%), and 28.7% (95% CI, 27.0%-30.4%) for stage I, II, III, and IV, respectively. In period II, 3-year survival rates of patients with AD were 95.1% (95% CI, 94.4%-95.9%), 82.5% (95% CI, 79.1%-86.1%), 65.1% (95% CI, 61.8%-68.6%), and 42.4% (95% CI, 40.3%-44.7%) for each stage, respectively. In patients without AD, 3-year survival rates were 72.0% (95% CI, 68.8%-75.3%), 60.0% (95% CI, 56.2%-64.1%), 38.9% (95% CI, 35.6%-42.5%), and 9.7% (95% CI, 7.9%-12.1%) for each stage in period I. In period II, the 3-year survival rates of patients without AD were 79.3% (95% CI, 76.3%-82.4%), 67.3% (95% CI, 62.8%-72.1%), 48.2% (95% CI, 44.5%-52.3%), and 18.1% (95% CI, 15.1%-21.6%) for each stage., Conclusions and Relevance: In this cohort study of 10 years of clinical data, survival outcomes were improved across all stages, with larger increases in patients with stage III to IV disease. The incidence of never-smokers and the use of molecular testing increased.

Purpose: Evidence in favor of adding docetaxel in treatment of metastatic hormone-sensitive prostate cancer (mHSPC) has led to docetaxel in conjunction with androgen deprivation therapy (ADT) as standard therapy. The aim of this study was to examine the effectiveness of docetaxel with ADT for Korean patients with mHSPC in real-world practice., Materials and Methods: A retrospective cohort study was performed at six Korean hospitals for patients with mHSPC treated with docetaxel plus ADT. Patients were treated every 3 weeks for up to six cycles with 75 mg/m² of docetaxel. The primary endpoint was time to castration resistant prostate cancer (CRPC)., Results: This study included 46 eligible patients from June 2016 to February 2021. Median age was 68.5 years (range, 52-84) and all patients present with de novo M1 with high-volume disease. The median prostate-specific antigen (PSA) level at ADT initiation was 205.4 (7.7-1933) ng/mL, and time from ADT to docetaxel was 2.4 months (0-5.3). All six planned cycles of docetaxel were delivered in 36 patients (78%), 7 patients (15%) discontinued treatment due to adverse events, and 3 patients (7%) discontinued due to progression. At the time of the analysis, CRPC had developed in 34 patients (74%), and the median time to CRPC was 18.0 (95% confidence interval, 14.1-21.9) months. PSA <0.2 ng/mL was achieved in 11 patients (24%) after 6 months of ADT and in 10 patients (22%) after 12 months. At last follow-up, 35 patients (76%) were alive; the median overall survival was not reached., Conclusion: The effect of docetaxel combined with ADT for Korean patients with mHSPC is comparable with prior results in Western studies., Competing Interests: The authors have no potential conflicts of interest to disclose., (© Copyright: Yonsei University College of Medicine 2023.)

Objectives: We compared the viral cycle threshold (Ct) values of infected patients to better understand viral kinetics by vaccination status during different periods of variant predominance in Gyeonggi Province, Korea., Methods: We obtained case-specific data from the coronavirus disease 2019 (COVID-19) surveillance system, Gyeonggi in-depth epidemiological report system, and Health Insurance Review & Assessment Service from January 2020 to January 2022. We defined periods of variant predominance and explored Ct values by analyzing viral sequencing test results. Using a generalized additive model, we performed a nonlinear regression analysis to determine viral kinetics over time., Results: Cases in the Delta variant's period of predominance had higher viral shedding patterns than cases in other periods. The temporal change of viral shedding did not vary by vaccination status in the Omicron-predominant period, but viral shedding decreased in patients who had completed their third vaccination in the Delta-predominant period. During the Delta-predominant and Omicron-predominant periods, the time from symptom onset to peak viral shedding based on the E gene was approximately 2.4 days (95% confidence interval [CI], 2.2 to 2.5) and 2.1 days (95% CI, 2.0 to 2.1), respectively., Conclusions: In one-time tests conducted to diagnose COVID-19 in a large population, although no adjustment for individual characteristics was conducted, it was confirmed that viral shedding differed by the predominant strain and vaccination history. These results show the value of utilizing hundreds of thousands of test data produced at COVID-19 screening test centers.

Cardiometabolic (CM) risk differs in morbidity and disease progression depending on lifestyle and individual characteristics. This cross-sectional study aimed to analyze the association between CM risk and lifestyle and examine whether this association varies based on Sasang constitution (SC), a Korean medicine classification. Data were analyzed from 1996 individuals participating in the Korean Medicine Daejeon Citizen Cohort study. Individuals with CM risk had two to five CM risk factors. Lifestyle factors included physical activity, sleep duration, and eating index. SC types were Taeeum-in (TE) and non-TE. We estimated the odds ratio (OR) and 95% confidence interval for CM risk based on SC and lifestyle factors. Among the participants, 33.9% had a CM risk, and the TE and non-TE groups were 26.2% and 7.7%, respectively. In the TE group, CM risk was associated with low physical activity (OR, 1.63) and moderate eating index (OR, 1.41). In the non-TE group, CM risk was associated with ≥8 h of sleep (OR, 1.87) and marginally associated with ≤6 h of sleep. In the TE group alone, CM risk was significantly associated with lifestyle patterns that combined the three lifestyle factors and was approximately two-fold higher in patterns involving less physical activity. The effects of lifestyle on CM risk differed across SC types. To decrease the burden of cardiovascular diseases in middle-aged adults, we recommend an individualized management strategy of healthy lifestyle interventions for cardiovascular risks.

We hypothesized that a well-balanced intake of total essential amino acids (EAAs) may be associated with lower prevalence of metabolic syndrome among Korean adults. This population-based cross-sectional study included 25,787 participants aged ≥30 years from the 2008-2019 Korea National Health and Nutrition Examination Survey. Dietary information was obtained from 24 h recall data. Demographic and lifestyle factors were assessed using self-administered questionnaires, and metabolic biomarkers were obtained from a health examination. Total essential amino acid score (EAAS) was calculated to determine whether essential amino acid (EAA) intake meets the recommended nutrient intake (RNI). Multivariable-adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using logistic regression models. After adjusting for multiple confounding factors, participants with higher EAAS had a significantly lower prevalence of high blood pressure (OR: 0.86, 95% CI: 0.75-0.98), hypertriglyceridemia (OR: 0.86, 95% CI: 0.76-0.98), and Metabolic syndrome (MetS) (OR: 0.86, 95% CI: 0.74-0.996). Spline regression analysis confirmed linearity of the association between total EAAS and MetS. EAA intake and MetS are associated with an inverse dose-response relationship in which metabolic disease may be prevented when the overall EAA intake meets the RNI.

Background/objectives: Although previous in vivo and in vitro studies have reported the beneficial effects of phytochemical-rich food on cardiovascular health, limited information is available regarding its' health effect on the community-dwelling population. This is especially true in Korea. Here, we examined the cross-sectional association between phytochemical levels and hypertension in Korean adults., Subjects/methods: We analyzed data from 38,198 Koreans aged ≥30 years who participated in the Korea National Health and Nutrition Examination Survey (2008-2019) and met the study's inclusion criteria. The Korean version of the Phytochemical Index (PI) was computed based on 24 h recall data. Hypertension was defined based on the American College of Cardiology/American Heart Association definition in 2017. Multivariate logistic regression analysis was used to examine the association between PI and hypertension., Results: In the multivariable adjusted model, participants in the highest PI quintile had a significantly low prevalence of hypertension (Odd ratio, 0.86; 95% confidence interval, 0.79-0.95). A dose-response analysis confirmed the inverse linearity between PI and hypertension (p for nonlinearity = 0.2634)., Conclusions: Consumption of phytochemical-rich foods may lower the prevalence of hypertension. A large-scale, prospective cohort study is required to validate these findings., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: Occupational studies on N-N-dimethylformamide (DMF) exposure among migrant workers in Korea are scarce. We determined the urine concentration of N-methylformamide (NMF) among migrant workers with DMF exposure and compared the data with those of native workers., Methods: Data were collected from Workers' Special Health Examination and Work Environment Monitoring databases during 2014-2019. Workers aged ≥20 years were eligible to participate in the special health examination for DMF exposure. Urine concentrations of NMF were determined and compared between migrant and native workers. We also evaluated the factors affecting the difference in the urine concentration of NMF between the migrant and native workers. Multiple logistic regression was performed by adding confounders step by step., Results: Among 9259 subjects, 504 (5.2%) were migrant workers. The mean urinary concentration of NMF was 6.73 mg/L in migrant workers, which was significantly higher than that in native workers (2.06 mg/L, p < 0.001). The odds of a urine concentration of NMF > 30 mg/L were significantly higher in migrant workers than in native workers after adjusting for sex and age (odds ratio [OR] = 7.31, 95% confidence interval [CI] = 4.66-11.45). However, the odds between the native and migrant workers were not significantly different when fully adjusted for confounders (OR = 1.12, 95% CI = 0.65-1.94)., Conclusions: The excessive exposure to DMF among migrant workers was attributed not to differences in biological characteristics but to their work environment. Workers must have awareness of the use of protective equipment and knowledge of hazardous chemicals that they may be exposed to, especially at the workplace.

Background/aims: The early detection and prevention of non-alcoholic fatty liver disease (NAFLD) has been emphasized considering the burden of this disease. Both hepatic and peripheral insulin resistances are strongly associated with NAFLD. We aimed to compare the predictive powers of a hepatic insulin resistance index, the homeostatic model assessment for insulin resistance (HOMA-IR), and a novel peripheral insulin resistance index, the metabolic score for insulin resistance (METS-IR), for the prediction of prevalent and incident NAFLD., Methods: Data from 8,360 adults aged 40-69 years at baseline and 5,438 adults without NAFLD who were followed-up at least once after the baseline survey in the Korean Genome and Epidemiology Study were analyzed. The survey was performed biennially, up to the eighth follow-up., Results: The predictive powers of the METS-IR and HOMA-IR for prevalent NAFLD were not significantly different (area under the receiver operating characteristic [ROC] curve [95% confidence interval]: METS-IR, 0.824 [0.814-0.834]; HOMAIR, 0.831 [0.821-0.842]; P=0.276). The area under the time-dependent ROC curve (Heagerty's integrated area under the curve) of the METS-IR for incident NAFLD was 0.683 (0.671-0.695), significantly higher than that of the HOMA-IR (0.551 [0.539-0.563], P<0.001)., Conclusion: The METS-IR is superior to the HOMA-IR for the prediction of incident NAFLD and is not inferior to the HOMA-IR for the prediction of prevalent NAFLD. This suggests that the METS-IR can be a more useful insulin resistance index than the HOMA-IR for the early detection and prevention of NAFLD in Korean population.

Background: Whole-genome sequencing plays a critical role in the genomic epidemiology intended to improve understanding the spread of emerging viruses. Dabie bandavirus, causing severe fever with thrombocytopenia syndrome (SFTS), is a zoonotic tick-borne virus that poses a significant public health threat. We aimed to evaluate a novel amplicon-based nanopore sequencing tool to obtain whole-genome sequences of Dabie bandavirus, also known as SFTS virus (SFTSV), and investigate the molecular prevalence in wild ticks, Republic of Korea (ROK)., Principal Findings: A total of 6,593 ticks were collected from Gyeonggi and Gangwon Provinces, ROK in 2019 and 2020. Quantitative polymerase chain reaction revealed the presence of SFSTV RNA in three Haemaphysalis longicornis ticks. Two SFTSV strains were isolated from H. longicornis captured from Pocheon and Cheorwon. Multiplex polymerase chain reaction-based nanopore sequencing provided nearly full-length tripartite genome sequences of SFTSV within one hour running. Phylogenetic and reassortment analyses were performed to infer evolutionary relationships among SFTSVs. Phylogenetic analysis grouped SFTSV Hl19-31-4 and Hl19-31-13 from Pocheon with sub-genotype B-1 in all segments. SFTSV Hl20-8 was found to be a genomic organization compatible with B-1 (for L segment) and B-2 (for M and S segments) sub-genotypes, indicating a natural reassortment between sub-genotypes., Conclusion/significance: Amplicon-based next-generation sequencing is a robust tool for whole-genome sequencing of SFTSV using the nanopore platform. The molecular prevalence and geographical distribution of SFTSV enhanced the phylogeographic map at high resolution for sophisticated prevention of emerging SFTS in endemic areas. Our findings provide important insights into the rapid whole-genome sequencing and genetic diversity for the genome-based diagnosis of SFTSV in the endemic outbreak., Competing Interests: The authors have declared that no competing interests exist.

Background: Correctional institution inmates have reduced access to dental care; however, a quantitative assessment of their oral health condition has not yet been performed in South Korea. Therefore, this study aimed to assess dental caries and compare the prevalence of dental caries and associated factors between inmates and the general South Korean population., Methods: The dental records of two detention centers in South Korea were retrospectively analyzed to assess the clinical oral health condition of inmates using the Decayed, Missing, and Filled Teeth (DMFT) index and self-reported questionnaire. These data were compared with similar data obtained from the Korea National Health and Nutrition Examination Survey (KNHANES) for the general South Korean population., Results: In total, 642 inmates were analyzed and compared with 13,345 KNHANES participants in the KNHANES. The inmate and KNHANES groups demonstrated significant intergroup differences, with a higher prevalence of untreated caries, DMFT, decayed teeth (DT), and missing teeth (MT) values among the inmates. The prevalence of untreated caries decreased according to the history of dental pain in the inmate group but increased in the KNHANES group. The decrease in DMFT with a history of dental pain was significant only in the inmate group. Furthermore, self-rated oral health was significantly associated with prevalence of untreated caries, DMFT, DT, MT, and filled teeth (FT) in the inmate group but with prevalence of untreated caries, DMFT, DT, and MT in the KNHANES group. It was found that this is because there is an interaction effect by the group., Conclusions: The oral health of the inmate group was significantly poorer than that of the general group. Since DMFT, DT, MT, and FT values and prevalence of untreated caries in the inmate group were significantly related to their self-rated oral health, suggesting that self-rated oral health should be incorporated into the dental health screenings of correctional institution inmates., (© 2022. The Author(s).)

Purpose: In 2018, the Act to Improve Training Conditions and the Status of Medical Residents (AITR) was fully implemented in South Korea. This study aimed to investigate the effects of AITR implementation on the clinical outcomes of patients who underwent emergency abdominal surgery., Materials and Methods: A total of 2571 patients who underwent emergency abdominal surgery after visiting the emergency room (ER) between 2015 and 2019 was included. Electronic medical records were retrospectively reviewed. In addition, a comparative analysis was performed for patient groups treated before and after AITR implementation., Results: The median patient age was 48.0 years, and 49.2% of them were male. Appendicitis was the most common diagnosis (82.6%), followed by major abdominal emergencies (9.9%) and cholecystitis (7.5%). The median time from arrival to surgery was 439 min, and 52 (2.0%) patients died. A comparison of patients who underwent surgery before (pre-AITR; 1453, 56.5%) and after (post-AITR; 1118, 43.5%) AITR implementation revealed a significant difference in age, number of residents on a 24-h shift, and diagnosis. The time from ER arrival to surgery was not significantly longer after AITR implementation than before AITR implementation (434 min vs. 443 min, p =0.230). AITR was not a significant risk factor for mortality ( p =0.225)., Conclusion: The time from ER arrival to emergency surgery did not increase significantly after AITR implementation, and there was no difference in the patients' clinical outcomes., Competing Interests: The authors have no potential conflicts of interest to disclose., (© Copyright: Yonsei University College of Medicine 2022.)

The plasma atherogenic index (AIP) has been suggested as a useful independent predictor of cardiovascular diseases (CVDs) in high CV risk patients. We investigated the association between AIP and arterial stiffness measured by brachial-ankle pulse wave velocity (baPWV) in healthy adults. A total of 3468 healthy subjects without any metabolic or CV diseases were enrolled. Anthropometric and CV risk factors were measured. The AIP was defined as the base 10 logarithm of the ratio of the concentration of triglycerides to high-density lipoprotein-cholesterol. Subjects were classified into AIP quartiles. There were gradual deteriorations in metabolic parameters and increase in baPWV across the increasing AIP quartiles. In a fully adjusted analysis, compared with Q1 (lowest quartile) group, the odds ratio (95% confidence interval) for increased baPWV was higher in Q2 1.51, Q3 1.64, and Q4 (highest quartile) 2.77 among men, and Q2 1.09, Q3 1.55, and Q4 1.83 among women (all P trend  <0 .05). There was a strong association between AIP and baPWV, and a higher AIP was an independent predictor of increased arterial stiffness in healthy Korean men and women. The AIP may be a simple screening tool for subclinical atherosclerosis.

Background: To determine the validity and reliability of the Korean version of the Modified Fatigue Impact Scale (MFIS-K) questionnaire for patients with multiple sclerosis (MS)., Methods: We prospectively enrolled 52 patients with MS and 102 healthy controls. Subjects were asked to complete the Korean version of Fatigue Severity Scale (FSS) and MFIS-K. To evaluate sleep quality, depression, pain, and quality of life, patients completed the Pittsburgh Sleep Quality Index (PSQI), the Beck Depression Scale II (BDI), the Brief Pain Inventory (BPI), and the Short Form 36 Health Survey (SF-36)., Results: It was demonstrated that MFIS-K has appropriate construct validity with distinctive 3 factors (cognitive, physical, and psychosocial). The criterion validity was also confirmed with the total score and the factor scores of the patients with MS, which were all significantly higher than those of healthy controls. Convergent validity of the MFIS-K was verified with the correlations with Fatigue Severity Scale (FSS) and other concurrent measures of sleep disturbances, depression, pain, and limitations in activities due to health problems. Furthermore, the internal consistency, temporal stability, and score consistency of the MFIS-K turned out acceptable., Discussion: Our results indicate that the Korean version of MFIS is a valid and reliable scale to assess fatigue in the Korean MS population., (Copyright © 2022. Published by Elsevier B.V.)

Objective: To identify genetic variations which is associated with gastric cancer (GC) risk according to Helicobacter pylori infection., Methods: This study incorporated 527 GC patients and 441 controls from a cohort at Seoul National University Bundang Hospital. The associations between GC risk and single nucleotide polymorphisms were calculated, stratified by H. pylori status, adjusting for age, sex, and smoking. mRNA expression from non-cancerous gastric mucosae was evaluated using reverse transcription quantitative polymerase chain reaction., Results: In the entire cohort, genome-wide association study showed no significant variants reached the genome-wide significance level. In the H. pylori-positive group, rs2671655 (chr17:47,468,020;hg19, GH17J049387 enhancer region) was identified at a genome-wide significance level, which was more pronounced in diffuse type GC. There was no significant variant in the H. pylori-negative group, indicating the effect modification of rs2671655 by H. pylori. Among the target genes of GH17J049387 enhancer (PHB1, ZNF652 and SPOP), PHB1 mRNA was expressed more in cases than in controls, who were not affected by H. pylori. By contrast, an increase in ZNF652 and SPOP in GC was observed only in the H. pylori-negative group (P < 0.05). Mediation analysis showed that PHB1 (P = 0.0238) and SPOP (P = 0.0328) mediated the effect of rs2671655 on GC risk. The polygenic risk score was associated with the number of rs2671655 risk alleles only in the H. pylori-positive group (P = 0.0112)., Conclusion: After H. pylori infection, rs2671655 may increase GC risk, especially in diffuse-type GC, by regulating the expression of several genes that consequently modify susceptibility to GC., (© 2022. The Author(s) under exclusive licence to The International Gastric Cancer Association and The Japanese Gastric Cancer Association.)

Background/aims: Drugs with anticholinergic properties (DAPs) are associated with adverse health outcomes in older patients. The objective of this study was to evaluate the factors that determine the prescribing of more DAPs in long-term care hospitals (LTCHs) in Korea. In addition, the current patterns of DAP prescription were explored using a novel platform, which can collect data from LTCHs., Methods: This was a Health-RESPECT (integrated caRE Systems for elderly PatiEnts using iCT) sub-study, which is a pragmatic, cluster-randomized, controlled trial. The Health-RESPECT platform was used to collect prescribed medication data of 466 patients (aged ≥ 65 years) from seven LTCHs. DAPs were identified using the Korean Anticholinergic Burden Scale (KABS). Physical frailty, cognitive function, functional status, and quality of life were evaluated., Results: Among 466 LTCH patients, 88.8% (n = 414) were prescribed DAPs, and the prevalence of high KABS (≥ 3) was 70.4% (n = 328). The drugs that contributed most to the total KABS were quetiapine (20.7%), chlorpheniramine (19.5%), tramadol (9.8%), cimetidine (5.8%), and furosemide (3.6%). Polypharmacy, higher body mass index, less dependence, better communication and cognitive functions, and poorer quality of life were associated with high KABS., Conclusion: Although the patients with a high burden of DAPs were less dependent and had better cognitive and communication functions, they had poorer quality of life. DAP use in LTCH patients should be monitored carefully, and the risk/ benefit relationship for their use should be considered.