Background/Aims: Metabolic dysfunction-associated steatotic liver disease (MASLD) is characterized by fat accumulation in the liver. MASLD encompasses both steatosis and MASH. Since MASH can lead to cirrhosis and liver cancer, steatosis and MASH must be distinguished during patient treatment. Here, we investigate the genomes, epigenomes, and transcriptomes of MASLD patients to identify signature gene set for more accurate tracking of MASLD progression. Methods: Biopsy-tissue and blood samples from patients with 134 MASLD, comprising 60 steatosis and 74 MASH patients were performed omics analysis. SVM learning algorithm were used to calculate most predictive features. Linear regression was applied to find signature gene set that distinguish the stage of MASLD and to validate their application into independent cohort of MASLD. Results: After performing WGS, WES, WGBS, and total RNA-seq on 134 biopsy samples from confirmed MASLD patients, we provided 1,955 MASLD-associated features, out of 3,176 somatic variant callings, 58 DMRs, and 1,393 DEGs that track MASLD progression. Then, we used a SVM learning algorithm to analyze the data and select the most predictive features. Using linear regression, we identified a signature gene set capable of differentiating the various stages of MASLD and verified it in different independent cohorts of MASLD and a liver cancer cohort. Conclusions We identified a signature gene set (i.e., CAPG, HYAL3, WIPI1, TREM2, SPP1, and RNASE6) with strong potential as a panel of diagnostic genes of MASLD-associated disease.

Background: and Purpose: The SoUth Korea study to PrEvent cognitive impaiRment and protect BRAIN health through lifestyle intervention (SUPERBRAIN) proved the feasibility of multidomain intervention for elderly people. One-quarter of the Korean population over 65 years of age has mild cognitive impairment (MCI). Digital health interventions may be costeffective and have fewer spatial constraints. We aim to examine the efficacy of a multidomain intervention through both face-to-face interactions and video communication platforms using a tablet personal computer (PC) application in MCI. Methods: Three hundred participants aged 60–85 years, with MCI and at least one modifiable dementia risk factor, will be recruited from 17 centers and randomly assigned in a 1:1 ratio to the multidomain intervention and the waiting-list control groups. Participants will receive the 24-week intervention through the tablet PC SUPERBRAIN application, which encompasses the following five elements: managing metabolic and vascular risk factors, cognitive training,physical exercise, nutritional guidance, and boosting motivation. Participants will attend the interventions at a facility every 1–2 weeks. They will also engage in one or two self-administered cognitive training sessions utilizing the tablet PC application at home each week. They will participate in twice or thrice weekly online exercise sessions at home via the ZOOM platform. The primary outcome will be the change in the total scale index score of the Repeatable Battery for the Assessment of Neuropsychological Status from baseline to study end. Conclusions This study will inform the effectiveness of a comprehensive multidomain intervention utilizing digital technologies in MCI.

Background: Wilson’s disease (WD) is an autosomal recessive disorder in which copper (Cu) accumulates in organs, particularly in the liver and central nervous system. This study aimed to investigate the prevalence, incidence, and treatment patterns of WD patients in Korea. Methods: National Health Insurance System (NHIS) claims data from 2010 to 2020 were analyzed. patients with WD as a primary or additional diagnosis at least once were identified using the International Classification of Diseases (ICD)-10 disease code E83.0 and a record for a registration program for rare intractable diseases in Korea. Results: The average age- and sex-adjusted prevalence and incidence of WD between 2010 and 2020 were 3.06/100,000 and 0.11/100,000, respectively. The mean age of the patients with newly diagnosed WD was 21.0 ± 15.9 years. Among the 622 WD incident cases during the study period, 19.3% of the patients had liver cirrhosis and 9.2% had received liver transplantation. Psychological and neurological diseases were present in 40.7% and 48.1% of the patients, respectively. Regarding the diagnosis of WD, liver biopsy was performed in only 51.6% of new cases. D-penicillamine, trientine, or zinc were prescribed in 81.5% of the incident cases, and the treatment uptake rates decreased with increasing age. Conclusion The prevalence of WD in Korea is 3.06/100,000 and approximately 1,800 patients use medical services annually. A significant proportion of patients are diagnosed at the cirrhotic stage and not treated with Cu-chelating therapeutics, suggesting the need for early diagnosis and adequate treatment to improve prognosis.

Purpose: This study aimed to investigate the presence of autoantigens in the gastric juices of children. Methods: Gastric juice and serum samples were obtained from 53 children <15 years of age who underwent gastric endoscopy. Among these, 8, 22, and 23 participants were in the age groups 0–5, 6–10, and 11–15 years, respectively. These samples were analyzed using two-dimensional electrophoresis (2-DE), immunoblot analysis, and matrix-assisted laser desorption ionization-time of-flight mass spectrometry. Furthermore, we reviewed the histopathological findings and urease test results and compared them with the results of 2-DE and immunoblot analysis. Results: There were no statistically significant differences in urease test positivity, grades of chronic gastritis, active gastritis, or Helicobacter pylori infiltration of the antrum and body among the three age groups. Three distinct patterns of gastric juice were observed on 2-DE. Pattern I was the most common, and pattern III was not observed below the age of 5 years.Histopathological findings were significantly different among active gastritis (p=0.037) and H. pylori infiltration (p=0.060) in the gastric body. The immunoblots showed large spots at an approximate pH of 3–4 and molecular weights of 31–45 kDa. These distinct, large positive spots were identified as gastric lipase and pepsin A and C. Conclusion Three enzymes, which are normally secreted under acidic conditions were identified as autoantigens. Further investigation of the pathophysiology and function of autoantigens in the stomach is required.

Amyloid precursor protein (APP) plays an important role in the pathogenesis of Alzheimer’s disease (AD), but the normal function of APP at synapses is poorly understood. We and others have found that APP interacts with Reelin and that each protein is individually important for dendritic spine formation, which is associated with learning and memory, in vitro. However, whether Reelin acts through APP to modulate dendritic spine formation or synaptic function remains unknown. In the present study, we found that Reelin treatment significantly increased dendritic spine density and PSD-95 puncta number in primary hippocampal neurons. An examination of the molecular mechanisms by which Reelin regulates dendritic spinogenesis revealed that Reelin enhanced hippocampal dendritic spine formation in a Ras/ERK/CREB signaling-dependent manner. Interestingly, Reelin did not increase dendritic spine number in primary hippocampal neurons when APP expression was reduced or in vivo in APP knockout (KO) mice. Taken together, our data are the first to demonstrate that Reelin acts cooperatively with APP to modulate dendritic spine formation and suggest that normal APP function is critical for Reelin-mediated dendritic spinogenesis at synapses.

Purpose: The starting time for probiotic supplementation in preterm infants after birth varies widely. This study aimed to investigate the optimal time for initiating probiotics to reduce adverse outcomes in preterm or very low birth weight (VLBW) infants. Methods: Medical records of preterm infants born at a gestational age (GA) of <32 weeks or VLBW infants in 2011–2020 were reviewed respectively. The infants who received Saccharomyces boulardii probiotics within 7 days of birth were grouped into an early introduction (EI) group, and those who received supplemented probiotics after 7 days of birth were part of the late introduction (LI) group. Clinical characteristics were compared between the two groups and analyzed statistically. Results: A total of 370 infants were included. The mean GA (29.1 weeks vs. 31.2 weeks, p<0.001) and birth weight (1,235.9 g vs. 1491.4 g, p<0.001) were lower in the LI group (n=223) than in the EI group. The multivariate analysis indicated that factors affecting the LI of probiotics were GA at birth (odds ratio [OR], 1.52; p<0.001) and the enteral nutrition start day (OR, 1.47; p<0.001). The late probiotic introduction was associated with a risk of late-onset sepsis (OR, 2.85; p=0.020), delayed full enteral nutrition (OR, 5.44; p<0.001), and extrauterine growth restriction (OR, 1.67; p=0.033) on multivariate analyses after adjusting for GA. Conclusion Early supplementation of probiotics within a week after birth may reduce adverse outcomes among preterm or VLBW infants.

Despite the availability of direct-acting antivirals (DAAs) for chronic hepatitis C virus (HCV) infection in Korea, need remains for pangenotypic regimens that can be used in the presence of hepatic impairment, comorbidities, or prior treatment failure. We investigated the efficacy and safety of sofosbuvir–velpatasvir and sofosbuvir–velpatasvir–voxilaprevir for 12 weeks in HCV-infected Korean adults. Methods: This Phase 3b, multicenter, open-label study included 2 cohorts. In Cohort 1, participants with HCV genotype 1 or 2 and who were treatment-naive or treatment-experienced with interferon-based treatments, received sofosbuvir–velpatasvir 400/100 mg/day. In Cohort 2, HCV genotype 1 infected individuals who previously received an NS5A inhibitor-containing regimen ≥ 4 weeks received sofosbuvir–velpatasvir–voxilaprevir 400/100/100 mg/day. Decompensated cirrhosis was an exclusion criterion. The primary endpoint was SVR12, defined as HCV RNA < 15 IU/mL 12 weeks following treatment. Results: Of 53 participants receiving sofosbuvir–velpatasvir, 52 (98.1%) achieved SVR12. The single participant who did not achieve SVR12 experienced an asymptomatic Grade 3 ASL/ALT elevation on day 15 and discontinued treatment. The event resolved without intervention. All 33 participants (100%) treated with sofosbuvir–velpatasvir–voxilaprevir achieved SVR 12. Overall, sofosbuvir–velpatasvir and sofosbuvir–velpatasvir–voxilaprevir were safe and well tolerated. Three participants (5.6%) in Cohort 1 and 1 participant (3.0%) in Cohort 2 had serious adverse events, but none were considered treatment-related. No deaths or grade 4 laboratory abnormalities were reported. Conclusions: Treatment with sofosbuvir–velpatasvir or sofosbuvir–velpatasvir–voxilaprevir was safe and resulted in high SVR12 rates in Korean HCV patients.

Purpose: This study evaluated whether combination therapy is more effective than monotherapy in elderly patients with metastatic or recurrent gastric cancer (MRGC) as first-line chemotherapy. Materials and Methods: Elderly (≥ 70 years) chemo-naïve patients with MRGC were allocated to receive either combination therapy (group A: 5-fluorouracil [5-FU]/oxaliplatin, capecitabine/oxaliplatin, capecitabine/cisplatin, or S-1/cisplatin) or monotherapy (group B: 5-FU, capecitabine, or S-1). In group A, starting doses were 80% of standard doses, and they could be escalated to 100% at the discretion of the investigator. Primary endpoint was to confirm superior overall survival (OS) of combination therapy vs. monotherapy. Results: After 111 of the planned 238 patients were randomized, enrollment was terminated due to poor accrual. In the full-analysis population (group A [n=53] and group B [n=51]), median OS of combination therapy vs. monotherapy was 11.5 vs. 7.5 months (hazard ratio [HR], 0.86; 95% confidence interval [CI], 0.56 to 1.30; p=0.231). Median progression-free survival (PFS) was 5.6 vs. 3.7 months (HR, 0.53; 95% CI, 0.34 to 0.83; p=0.005). In subgroup analyses, patients aged 70-74 years tended to have superior OS with combination therapy (15.9 vs. 7.2 months, p=0.056). Treatment-related adverse events (TRAEs) occurred more frequently in group A vs. group B. However, among severe TRAEs (≥ grade 3), there were no TRAEs with a frequency difference of > 5%. Conclusion Combination therapy was associated with numerically improved OS, although statistically insignificant, and a significant PFS benefit compared with monotherapy. Although combination therapy showed more frequent TRAEs, there was no difference in the frequency of severe TRAEs.

Objectives: . Particulate matter (PM) is a risk factor for various diseases. Recent studies have established an association between otitis media (OM) and PM exposure. To confirm this relationship, we developed a novel exposure model designed to control the concentration of PM, and we observed the effects of PM exposure on the Eustachian tube (ET) and middle ear mucosa of rats. Methods: . Forty healthy, 10-week-old, male Sprague-Dawley rats were divided into 3-day, 7-day, 14-day exposure, and control groups (each, n=10). The rats were exposed to incense smoke as the PM source for 3 hours per day. After exposure, bilateral ETs and mastoid bullae were harvested, and histopathological findings were compared using microscopy and transmission electron microscopy (TEM). The expression levels of interleukin (IL)-1β, IL-6, tumor necrosis factor-α, and vascular endothelial growth factor (VEGF) in the middle ear mucosa of each group were compared using real-time reverse transcription polymerase chain reaction (RT-PCR). Results: . In the ET mucosa of the exposure group, the goblet cell count significantly increased after PM exposure (P=0.032). In the middle ear mucosa, subepithelial space thickening, increased angio-capillary tissue, and inflammatory cell infiltration were observed. Moreover, the thickness of the middle ear mucosa in the exposure groups increased compared to the control group (P<0.01). The TEM findings showed PM particles on the surface of the ET and middle ear mucosa, and RT-PCR revealed that messenger RNA (mRNA) expression of IL-1β significantly increased in the 3-day and 7-day exposure groups compared to the control group (P=0.035). VEGF expression significantly increased in the 7-day exposure group compared to the control and 3-day exposure groups (P<0.01). Conclusion . The ET and middle ear mucosa of rats showed histopathologic changes after acute exposure to PM that directly reached the ET and middle ear mucosa. Therefore, acute exposure to PM may play a role in the development of OM.

Purpose: To evaluate the reliability and validity of the Cataract-related Visual Function Questionnaire (CVFQ). Methods: A prospective cross-sectional study of 141 cataract patients was conducted from March 2022 to June 2022. The questionnaire was created based on a literature review and advice from an expert panel. This study determined its construct validity, criterion validity, internal consistency, and test-retest reliability. Results: The CVFQ consists of 15 items distributed among five categories: overall visual quality, overall visual function, distance vision, near vision, and glare. In the exploratory factor analysis of validity, the first three principal components explained 77.8% of the variance. The p-values in the Spearman correlation test comparing the pre- and postoperative total CVFQ score and best-corrected visual acuity (BCVA) were 0.006 and 0.004, respectively. In the reliability analysis, Cronbach’s alpha was > 0.9 for internal consistency and the p-values of each subcategory were all significant in the analysis of test-retest reliability. Conclusions Our results indicate that the CVFQ is useful for measuring the visual quality and visual function of cataract patients in Korea.