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The use of statins in nonalcoholic fatty liver disease (NAFLD) may reduce cardiovascular morbidity, although their effect on NAFLD itself is not well known. We aimed to investigate the role of statins on the development of de novo NAFLD and progression of significant liver fibrosis. This study included 11,593,409 subjects from the National Health Information Database of the Republic of Korea entered in 2010 and followed up until 2016. NAFLD was diagnosed by calculating fatty liver index (FLI), and significant liver fibrosis was evaluated using the BARD score. Controls were randomly selected at a ratio of 1:5 from individuals who were at risk of becoming the case subjects at the time of selection. Among 5,339,901 subjects that had a FLI < 30 and included in the non-NAFLD cohort, 164,856 subjects eventually had NAFLD developed. The use of statin was associated with a reduced risk of NAFLD development (adjusted odds ratio [AOR] 0.66; 95% confidence interval [CI] 0.65-0.67) and was independent of associated diabetes mellitus (DM) (with DM: AOR 0.44; 95% CI 0.41-0.46, without DM: AOR 0.71; 95% CI 0.69-0.72). From 712,262 subjects with a FLI > 60 and selected in the NAFLD cohort, 111,257 subjects showed a BARD score ≥ 2 and were defined as liver fibrosis cases. The use of statins reduced the risk of significant liver fibrosis (AOR 0.43; 95% CI 0.42-0.44), independent of DM (with DM: AOR 0.31; 95% CI 0.31-0.32, without DM: AOR 0.52; 95% CI 0.51-0.52). In this large population-based study, statin use decreased the risk of NAFLD occurrence and the risk of liver fibrosis once NAFLD developed.

This study investigated the relationships among exposure to risky online content, moral disengagement, media literacy, and cyberaggression in adolescents (aged 13–15 years). Data were obtained from the 2021 Cyber Violence Survey ( N  = 3,002) conducted by a national agency in the Republic of Korea using systematic stratified sampling. The survey assessed eight aggressive online behaviors as indicators of cyberaggression: verbal violence, defamation, stalking, sending provocative content, personal information leakage, bullying, extortion, and coercion. Additionally, media literacy was assessed using two components relevant to the online environment: trust testing and privacy management, and intimacy sharing with strangers. The findings revealed a positive association between exposure to risky online content and moral disengagement among adolescents, which was mitigated by higher levels of media literacy, particularly regarding intimacy sharing (e.g., disagreeing with exchanging photos or information with strangers or sharing passwords with friends). Moral disengagement related to cyberaggression increased the likelihood of aggressive behavior online. Furthermore, media literacy (trust testing and privacy management, intimacy sharing) reduced both cyberaggression and moral disengagement. Our findings imply that providing media literacy along with tackling moral disengagement would counter cyberaggression effectively. Future research could consider the longitudinal impact of media literacy on cyberaggression.

Low serum bilirubin levels have been associated with increased risk of cardiovascular disease (CVD) and metabolic syndrome. Testosterone deficiency could also contribute to increased risk of CVD and metabolic syndrome. Therefore, this study aimed to examine the relationship between serum bilirubin level and testosterone deficiency in 1284 Korean men aged 45 to 70 years. Serum bilirubin level was categorized into quartiles: Q1 ≤ 0.7, Q2 0.8–0.9, Q3 1.0–1.1, and Q4 ≥ 1.2 mg/dL. Testosterone deficiency was defined as level less than 8.0 nmol/L, as suggested by the position statement of International Society of Andrology. The overall prevalence of testosterone deficiency was 5.8% and significantly decreased with the quartiles from Q1 to Q4. Compared with the referent fourth quartile (serum bilirubin ≥ 1.2 mg/dL), the ORs (95% CIs) for testosterone deficiency was 2.29 (1.04–4.94) for the first quartile after adjusting for age, fasting glucose, triglyceride, HDL-cholesterol, leukocyte count, hemoglobin, smoking status, and alcohol intake. We found inversely graded associations of serum bilirubin level with testosterone deficiency. These findings suggest that low bilirubin level may be interpreted as a state of testosterone deficiency in middle-aged and older men.

The quality of recovery (QoR) of remimazolam-based and propofol-based total intravenous anesthesia was compared as measured by QoR-15 scores. A prospective, double-blind, randomized controlled, non-inferiority trial. An operating room, a post-anesthesia care unit (PACU), and a hospital ward. Female patients (n = 140; 20–65 years) scheduled for open thyroidectomy were enrolled and randomly assigned to the remimazolam or propofol group. The remimazolam group received continuous remimazolam infusions and effect-site target-controlled remifentanil infusions. The propofol group received effect-site target-controlled infusions of propofol and remifentanil. The primary outcome was QoR-15 on postoperative day 1 (POD1). The mean difference between the groups was compared against a non-inferiority margin of −8. Secondary outcomes were QoR-15 on POD2, hemodynamic data, time to lose and recover consciousness, sedation score upon PACU admission, pain, and postoperative nausea and vomiting profiles at the PACU and ward. Group-time interaction effects in hemodynamic data and QoR-15 were analyzed using a linear mixed model. The total QoR-15 score on POD1 in the remimazolam group was non-inferior to that in the propofol group (mean [SD] 111.2 [18.8] vs. 109.1 [18.9]; mean difference [95% CI] 2.1 [−4.2, 8.5]; p = 0.002 for non-inferiority). The QoR-15 score on POD2 was comparable between the groups, and no group-time interaction was observed. At the end of anesthesia, after extubation, and upon arrival at the PACU, mean arterial pressure was significantly higher in the remimazolam group. Remimazolam group was more sedated at the time of admission to PACU. Pain intensity and the requirement for analgesics were lower in the remimazolam group than in the propofol group. Remimazolam-based total intravenous anesthesia provided a similar QoR to propofol. Remimazolam and propofol can be used interchangeably for general anesthesia in female patients undergoing thyroid surgery. •Evidence regarding quality of recovery after remimazolam-based total intravenous anesthesia has been limited.•Remimazolam-based total intravenous anesthesia was explored in female patients undergoing open thyroidectomy.•Remimazolam-based total intravenous anesthesia demonstrated similar quality of recovery to propofol.•Hypotensive incidence at cessation of anesthetics was lower in patients administered with remimazolam compared to propofol.•Remimazolam-based total intravenous anesthesia was associated with reduced pain intensity and analgesic requirement.

Background It has been recognized that alternate day calorie restriction (ADCR) or exercise has positive effects on cardio-metabolic risk factors. It is unclear whether the combined effect of ADCR and exercise (aerobic + resistance training) influences risk. We investigated effects of an 8-week ADCR and exercise program (aerobic + resistance training) on cardio-metabolic risk factors in overweight and obese adults. Methods This study randomized 45 overweight or obese but healthy adults (F = 26, M = 19; aged about 32 to 40 years) into 4 groups: ADCR ( n  = 13), exercise ( n  = 10), exercise plus ADCR ( n  = 12), and control (n = 10) for 8 weeks. Body composition, blood lipids profile, and insulin resistance were measured. The intention to treat (ITT) method was used to analyze all participants that were randomized. Results A total of 35 participants completed the trial (78%). Body weight, body mass index, waist circumference, fat mass and percent body fat were reduced in the exercise plus ADCR group (− 3.3 ± 2.4 kg, p  < 0.01; − 1.3 ± 1.0 kg/m 2 , p  < 0.01; − 4.1 ± 3.9 cm, p  < 0.01; − 2.7 ± 2.0 kg, p  < 0.01; − 2. 5 ± 2.2%, p  < 0.01). Insulin, glucose, homeostasis model assessment insulin resistance and triglyceride (− 2.9 ± 4.1 μIU/ml, p  < 0.05; − 10.9 ± 16.9 mg/dl, p  < 0.05; − 0.9 ± 1.3, p  < 0.05; − 43.8 ± 41.9 mg/dl, p  < 0.01) decreased in the exercise plus ADCR group only. Conclusions ADCR and exercise both proved to be beneficial, but the combined intervention was most effective at inducing beneficial changes in body weight, body composition, glucose, insulin, insulin resistance and triglyceride in overweight and obese adults. Trial registration ClinicalTrials.gov: NCT03652532 , Registered August 28, 2018, ‘retrospectively registered’.

Background The intrinsic immuno-ge7nomic characteristics of colorectal cancer cells that affect tumor biology and shape the tumor immune microenvironment (TIM) are unclear. Methods We developed a patient-derived colorectal cancer organoid (CCO) model and performed pairwise analysis of 87 CCOs and their matched primary tumors. The TIM type of the primary tumor was classified as immuno-active, immuno-exhausted, or immuno-desert. Results The gene expression profiles, signaling pathways, major oncogenic mutations, and histology of the CCOs recapitulated those of the primary tumors, but not the TIM of primary tumors. Two distinct intrinsic molecular subgroups of highly proliferative and mesenchymal phenotypes with clinical significance were identified in CCOs with various cancer signaling pathways. CCOs showed variable expression of cancer-specific immune-related genes such as those encoding HLA-I and HLA-II, and molecules involved in immune checkpoint activation/inhibition. Among these genes, the expression of HLA-II in CCOs was associated with favorable patient survival. K-means clustering analysis based on HLA-II expression in CCOs revealed a subgroup of patients, in whom cancer cells exhibited Intrinsically Immunogenic Properties (Ca-IIP), and were characterized by high expression of signatures associated with HLA-I, HLA-II, antigen presentation, and immune stimulation. Patients with the Ca-IIP phenotype had an excellent prognosis, irrespective of age, disease stage, intrinsic molecular type, or TIM status. Ca-IIP was negatively correlated with intrinsic E2F/MYC signaling. Analysis of the correlation between CCO immuno-genotype and TIM phenotype revealed that the TIM phenotype was associated with microsatellite instability, Wnt/β-catenin signaling, APC/KRAS mutations, and the unfolded protein response pathway linked to the FBXW7 mutation in cancer cells. However, Ca-IIP was not associated with the TIM phenotype. Conclusions We identified a Ca-IIP phenotype from a large set of CCOs. Our findings may provide an unprecedented opportunity to develop new strategies for optimal patient stratification in this era of immunotherapy.

The visceral adiposity index (VAI), an indirect marker of visceral adipose tissue, serves as a model associated with cardiometabolic risk, but has limitations regarding the Asian population. We sought to develop a new VAI (NVAI) for the Korean population and compare it to VAI for prediction of atherosclerotic cardiovascular disease (ASCVD) risk and development of major cardiovascular diseases (CVD) and stroke. Patients (969) who underwent visceral fat area measurement were analyzed. After exclusion, 539 patients (142 men, 397 women) were randomly divided into internal (n = 374) and external validation (n = 165) data set. The NVAI was developed using univariate and multivariate logistic regression with backward selection of predictors. Receiver operating characteristic (ROC) curve analysis and comparison of the area under the curve (AUC) verified the better predictor of ASCVD risk score. Additionally, nationwide population-based cross-sectional survey data (Korean National Health and Nutrition Examination Survey [KNHANES] 2008-2010, n = 29,235) was used to validate the NVAI's ability to predict ASCVD risk and major CVD and stroke. The NVAI better reflected visceral fat area in internal and external data sets, with AUCs of 0.911 (95% confidence interval [CI]: 0.882-0.940) and 0.879 (95% CI: 0.828-0.931), respectively. NVAI better discriminated for ASCVD risk (AUC = 0.892, 95% CI: 0.846-0.938) compared to VAI (0.559, 95% CI: 0.439-0.679). The NVAI also better predicted MI or angina, and stroke with AUCs of 0.771 (95% CI: 0.752-0.789), and 0.812 (95% CI: 0.794-0.830), respectively, compared with waist circumference (WC), body mass index (BMI), TG to HDL ratio, and VAI via KNHANES, in a statistically significant manner. The NVAI has advantages as a predictor of visceral obesity and is significantly associated with ASCVD risks and development of major CVD and stroke in the Korean population. The NVAI could be a screening tool for improved risk estimation related to visceral obesity.

Low-density-lipoprotein cholesterol (LDL-C) is the main target in atherosclerotic cardiovascular disease (ASCVD). We aimed to validate and compare a new LDL-C estimation equation with other well-known equations. 177,111 samples were analysed from two contemporary population-based cohorts comprising asymptomatic Korean adults who underwent medical examinations. Performances of the Friedewald (FLDL), Martin (MLDL), and Sampson (SLDL) equations in estimating direct LDL-C by homogenous assay were assessed by measures of concordance (R 2 , RMSE, and mean absolute difference). Analyses were performed according to various triglyceride (TG) and/or LDL-C strata. Secondary analyses were conducted within dyslipidaemia populations of each database. MLDL was superior or at least similar to other equations regardless of TG/LDL-C, in both the general and dyslipidaemia populations (RMSE = 11.45/9.20 mg/dL; R 2  = 0.88/0.91; vs FLDL: RMSE = 13.66/10.42 mg/dL; R 2  = 0.82/0.89; vs SLDL: RMSE = 12.36/9.39 mg/dL; R 2  = 0.85/0.91, per Gangnam Severance Hospital Check-up/Korea Initiatives on Coronary Artery Calcification data). MLDL had a slight advantage over SLDL with the lowest MADs across the full spectrum of TG levels, whether divided into severe hyper/non-hyper to moderate hypertriglyceridaemia samples or stratified by 100-mg/dL TG intervals, even up to TG values of 500–600 mg/dL. MLDL may be a readily adoptable and cost-effective alternative to direct LDL-C measurement, irrespective of dyslipidaemia status. In populations with relatively high prevalence of mild-to-moderate hypertriglyceridaemia, Martin’s equation may be optimal for LDL-C and ASCVD risk estimation.

Although previous studies have established that dietary fiber (DF) intake reduces the total cardiovascular disease (CVD) mortality in general populations, limited studies have been conducted in individuals with pre-existing chronic conditions, especially in Asian countries. We aimed to investigate the association of DF intake with all-cause and CVD mortality in the general population and in the subpopulation with hypertension, diabetes, and dyslipidemia. We examined the relationship between DF intake and all-cause and CVD mortality using the Korean genome and epidemiology study. Diet was assessed using a food-frequency questionnaire at baseline. Cox proportional hazard models were used to estimate the hazard ratio (HR) and 95% confidence intervals (CIs) after adjusting for confounders. During the mean 10.1 years of follow-up, higher DF intake was significantly associated with a lower risk of all-cause mortality after adjusting for confounders (HR and 95% CIs for Q5 vs. Q1: 0.84 (0.76–0.93); p < 0.001). DF intake was inversely associated with a lower risk of CVD mortality after adjusting for the same confounders (HR and 95% CIs for Q5 vs. Q1: 0.61 (0.47–0.78); p < 0.001). Total DF intake was inversely associated with all-cause and CVD mortality in middle-aged and older adults.

ObjectiveSusceptibility-weighted imaging (SWI) can be used to evaluate deep medullary veins (DMVs). This study aimed to apply texture analysis on SWI to evaluate developmental and ischemic changes of DMV in infants.MethodsA total of 38 infants with normal brain MRI (preterm [n = 12], term-equivalent age [TEA] [n = 18], and term [n = 8]) and seven infants with ischemic injury (preterm [n = 2], TEA [n = 1], and term [n = 4]) were included. Regions of interests were manually drawn to include DMVs. First-order texture parameters including entropy, skewness, and kurtosis were derived from SWI. The parameters were compared between groups according to age and presence of ischemic injury. A regression analysis was performed to correlate postmenstrual age (PMA) and parameters. A ROC analysis was performed to differentiate ischemic infants from normal infants.ResultsAmong parameters, entropy showed a significant difference between the age groups (preterm vs. TEA vs. term; 5.395 vs. 4.885 vs. 4.883, p = 0.001). There was a significant positive relationship between PMA and entropy (R square = 0.402, p < 0.001). Skewness was significantly higher in the ischemic group compared with that in the normal group (1.37 vs. 0.70, p = 0.001). The ROC on skewness resulted in an AUC of 0.87 (accuracy, 83.2%) for differentiating infants with ischemic injury.ConclusionA texture analysis of DMVs on SWI showed differences according to age and presence of ischemic injury. The texture parameters can potentially be used as quantitative markers for differentiating infants with ischemic injury through DMV changes.Key Points• The DMV structure of the infant brain could be quantified on SWI with texture analysis.• Entropy from texture analysis on SWI increased as infants got older.• Normal and ischemic injured infants could be differentiated with a cutoff value of 1.025 for skewness.