Alzheimer’s disease (AD) is characterized by progressive cognitive deterioration and significant depression. However, the mechanisms linking depression to AD pathology remain unclear. Here, we investigated whether Notch2 signaling mediates depressionlike behaviors in presenilin-2 (PS2) N141I mutant mice, an early-onset AD model. PS2 wild-type (WT) and mutant (MT) mice aged 12-15 months were subjected to unpredictable chronic mild stress (UCMS) for 4 weeks, followed by sucrose preference, tail-hanging, and forced swimming tests. Behavioral assessments showed that UCMS exacerbated anhedonia and immobility only in PS2 MT mice. Molecular analysis revealed concomitant increases in plasma corticosterone, hippocampal γ-secretase activity, and Notch2 expression, and elevated total and phosphorylated glucocorticoid receptor levels in PS2 MT-UCMS mice. Gene expression profiling of human hippocampal datasets confirmed upregulation of NOTCH2 in Alzheimer’s disease and depression.Pharmacological inhibition of γ-secretase and Notch signaling with DAPT normalizes depressive behavior, reduces corticosterone release, attenuates GR phosphorylation, and inhibits Notch2 signaling in PS2 MT mice. These findings identify Notch2 as a pivotal mediator linking chronic stress to molecular changes associated with depression and AD, and suggest that targeting Notch2 signaling may provide therapeutic benefits for comorbid mood and neurodegenerative disorders.

This study examined sleep-related characteristics among university students and the associations between sleep quality, dietary habits, and diet quality.Three hundred and ninety-three university students (206 men and 187 women) enrolled at universities in the Chungcheong region of Korea participated in this study between November and December 2023. Data on the general characteristics, dietary habits, sleep status, and the Nutrition Quotient (NQ) for adults were collected using a structured questionnaire. The sleep quality was assessed using the Pittsburgh Sleep Quality Index– Korean version (PSQI-K). The participants were classified into a good sleeper group (PSQI-K≤5) and a poor sleeper group (PSQI-K≥6). The dietary habits and NQ scores were compared according to the sleep quality. Compared with good sleepers, poor sleepers had a significantly higher prevalence of eating alone at least once per day (P<0.01) and higher scores for unhealthy dietary behaviors, including overeating, eating quickly, a preference for salty food, skipping meals, and irregular meal timing (P<0.05). Although the total NQ scores and balance and practice domain scores did not differ according to sleep quality, the moderation domain scores were significantly lower among poor sleepers, particularly in men (P<0.05). In conclusion, poor sleep quality among university students was associated with unhealthy dietary habits and lower diet quality related to dietary restraint. These findings highlight the importance of improving sleep quality as a part of health education and dietary intervention programs for university students.

Objective: To provide a decade-long molecular and phenotypic characterization of APP isolates from Korean pig farms, focusing on the serovar distribution, apx-based toxingene profiles, and antimicrobial susceptibility. Methods: Between 2015 and 2025, 1,215 pneumonic lung samples from 965 pig farms yielded 132 APP isolates. The species identity was confirmed by 16S rRNA sequencing. The serovars were determined using capsule polysaccharide (CPS) gene-based multiplex polymerase chain reaction (PCR). Toxin genes (apxIA–apxIVA) were profiled, and the antimicrobial susceptibility to 29 agents was assessed by broth microdilution according to the Clinical and Laboratory Standards Institute guidelines. Results: Serovar 1 was predominant (66.7%), followed by serovars 5 (17.4%) and 2 (6.8%).CPS multiplex PCR identified three isolates (2.3%) as serovar 15, which displayed heterogeneous toxin gene profiles, including apxIICA-deficient profiles. Most isolates exhibited classical repeats-in-toxin operon arrangements, suggesting ongoing diversification of toxin gene profiles. High resistance rates were observed for oxytetracycline (90.9%) and florfenicol (50.8%), and recurrent multidrug-resistant combinations were frequently detected. Conclusions and Relevance: Serovar 1 is dominant in Korea, but the emergence of atypical toxin gene profiles in serovar 15 may carry immunological implications. Persistent resistance to older drug classes underscores the necessity for long-term molecular surveillance, evaluation of vaccine coverage against evolving strains, and enhanced antimicrobial stewardship to strengthen the control efforts for porcine pleuropneumonia in Korea.

Background/Aims: Cardiovascular disease remains a major cause of mortality in patients with metabolic dysfunction-associated steatotic liver disease (MASLD). This study evaluated the association between subclinical carotid atherosclerosis (SCA) and MASLD or MASLD and increased alcohol intake (MetALD) in asymptomatic individuals. Methods: This cross-sectional study included 56,889 adults undergoing health check-ups in South Korea. Hepatic steatosis was diagnosed by ultrasound, and SCA was defined by carotid plaques or increased intima-media thickness. Liver fibrosis was evaluated using the fibrosis-4 index and elastography. Results: SCA was identified in 13.5%. MASLD and MetALD were significantly associated with SCA in models adjusted for demographic and lifestyle factors (adjusted odds ratio [aOR], 1.26;95% confidence interval [CI], 1.19 to 1.33; aOR, 1.43; 95% CI, 1.30 to 1.58; respectively, p<0.001for both). However, these associations attenuated and lost statistical significance when metabolic risk factors were further adjusted. The risk of SCA increased with greater hepatic steatosis and liver fibrosis severity. In patients with MASLD, aORs were 1.70 (hepatic steatosis index >36),1.23 (fibrosis-4 index ≥1.3), and 1.78 (liver stiffness measurement ≥5.6 kPa), compared to indi-viduals without MASLD. Similar trends were observed in the MetALD group. Additionally, hyper-tension and clustering of ≥3 cardiometabolic risk factors were significantly associated with SCA inthe MASLD group, supporting the role of metabolic burden in SCA development. Conclusions MASLD and MetALD were associated with increased SCA risk, particularly in individuals with hepatic steatosis and fibrosis. These findings suggest that metabolic burden and liver disease severity jointly contribute to subclinical atherosclerosis risk.

Objective: Patients with panic disorder (PD) are approximately four times more likely than the general population to exhibit suicidal ideation (SI) and suicide attempts. Although prolonged duration of untreated illness (DUI) is a known risk factor for adverse outcomes in mood disorders, its impact on suicidality among patients with PD has not been well established. This study investigated whether prolonged DUI is associated with heightened SI among patients with PD, considering sociodemographic and clinical factors. Methods: A total of 804 patients with PD were recruited. DUI was defined as the time between symptom onset and the initiation of psychiatric treatment. Clinical assessments included the Scale for Suicide Ideation (SSI), Beck Depression Inventory-II (BDI-II), and Panic Disorder Severity Scale. Sociodemographic and clinical predictors of SI were examined using independent t-tests, Pearson’s correlations, and multiple regression analysis. Results: In patients with PD, the mean DUI was 41.56 months. Longer DUI was positively correlated with higher SSI total scores, along with greater depression severity. Gender women, unmarried status, and elevated BDI-II scores were significantly predicted higher SSI total scores. In the multiple regression model, prolonged DUI remained an independent predictor of SSI (B=0.116, p=0.012) after adjusting for other variables. Conclusion These findings indicate that delayed treatment contributes to increased suicidality in PD, beyond demographic and depressive risk factors. Therefore, early detection and timely intervention using treatment strategies that enhance awareness, improve the accessibility of psychiatric services, and provide social support may reduce DUI and mitigate suicide risk among patients with PD.

Background: The Korean National Cancer Screening Program (NCSP) for gastric cancer requires economic evaluation due to the low sensitivity of upper gastrointestinal series (UGIs) and the associated low cancer survival rate. This study aimed to ascertain the most cost-effective strategy for the NCSP. Methods: The hypothetical target population of this study was aged 40 years or older, and no actual participants were involved. Markov simulation models were constructed for 25 strategies, combinations of 1) screening methods (UGIs or endoscopy vs. endoscopy-only), 2) screening intervals (one, two, or three-year), and 3) upper age limit of screening (69, 74, 79 years old, or “no limit”). Costs, utility, and other input parameters were extracted from various databases and previous studies. Cost-utility, sensitivity, and scenario analyses were conducted. Results: The endoscopy-only strategy with a three-year interval with an upper age limit of 69 was the most cost-effective strategy with an incremental cost-utility ratio of KRW 13,354,106 per quality-adjusted life years. According to the probabilistic sensitivity analysis, the uncertainty of the result was significantly small. Scenario analysis is showed that as the screening rate increased, the endoscopy-only strategy saved more costs compared to the current NCSP. Therefore, it is important to maintain a high screening rate when altering the NCSP strategy. Conclusion Endoscopy-only screening was more cost-effective method than UGIs for the NCSP. Furthermore, a three-year interval with an upper-age limit of 69 years was the most cost-effective strategy. Efforts to improve cost-effective screening guidelines will support the efficient use of medical resources. Additionally, maintaining a higher screening rate may maximize the impact of the modification in strategy on cost-effectiveness.

Echinochrome A (Ech A) isolated from marine organisms is a therapeutic effector for various cardiovascular diseases, but its precise mechanisms are unclear.This study identified the role and mechanisms mediating the effects of Ech A on the migration of vascular smooth muscle cells (VSMCs) induced by high-mobility group box 1 (HMGB1). Compared to the control cells, the migration of VSMCs stimulated with HMGB1 (100 ng/ml) was markedly increased, which was significantly attenuated in cells pretreated with MPIIIB10 (100 ng/ml), a neutralizing monoclonal antibody for osteopontin (OPN). In VSMCs stimulated with HMGB1, the increased expression of OPN mRNA and protein was accompanied by an increased OPN promoter activity. In reporter gene assays using OPN promoter-luciferase constructs, the promoter region 538-234 bp of the transcription start site containing the binding sites for activator protein 1 (AP-1) was shown to be responsible for the increased transcriptional activity by HMGB1. In addition, the binding activity of AP-1 was increased in HMGB1-stimulated cells, highlighting the pivotal role of AP-1 on OPN expression in HMGB1-stimulated VSMCs. An examination of the vascular effects of Ech A showed that the increased AP-1 binding/promoter activities and OPN expression induced by HMGB1 were attenuated in cells pretreated with Ech A (3 or 10 μM). Similarly, Ech A inhibited HMGB1-induced VSMC migration in a concentration-dependent manner. These findings suggest that Ech A inhibits VSMC migration by suppressing OPN expression.Hence, Ech A is suggested as a potential therapeutic strategy for vascular remodeling in the injured vasculatures.

Purpose: Recent treatments for pediatric acute lymphoblastic leukemia (ALL) are founded on risk stratification. We examined the survival rates and prognostic factors of patients over a 20-year period at a single institution. Materials and Methods: This study analyzed patients diagnosed with ALL and treated at the Pediatric Department of Samsung Medical Center (SMC). Patients were categorized into standard-risk (SR), high-risk (HR), and very high-risk (VHR) groups. The SMC protocol for the HR group underwent two changes during the study period: a modified Children’s Cancer Group (CCG)-1882 protocol was used from 2000 to 2005, the Korean multicenter HR ALL-0601 protocol from 2006 to 2014, and the Korean multicenter HR ALL-1501 protocol from 2015 to 2019. Results: Of the 460 patients, complete remission was achieved in 436 patients (94.8%). The 10-year overall survival rate (OS) was 83.8±1.9% for all patients. OS according to the SMC risk group was as follows: 95.9%±1.4% in the SR group, 83.8%±3.6% in the HR group, and 66.2%±6.9% in the VHR group. The 5-year OS within the HR group varied according to the treatment protocol: 73.9%±7.5%, in the modified CCG-1882 protocol, 83.0%±3.9%, in the 0601 protocol, and 96.2%±2.6%, in the 1501 protocol. For those aged 15 years and older, the OS was only 56.5%±13.1%. Relapse occurred in 71 patients (15.4%), and the OS after relapse was 37.7%±6.0%. Conclusion The treatment outcomes of patients with ALL improved markedly. However, there is a need to further characterize adolescents and young adult patients, as well as those who have experienced relapses.

Purpose: Hematopoietic stem cell transplantation (HSCT) has been an important method of treatment in the advance of pediatric acute lymphoblastic leukemia (ALL). The indications for HSCT are evolving and require updated establishment. In this study, we aimed to investigate the efficacy of HSCT on the treatment outcome of pediatric ALL, considering the indications for HSCT and subgroups. Materials and Methods: A retrospective analysis was conducted on ALL patients diagnosed and treated at a single center. Risk groups were categorized based on age at diagnosis, initial white blood cell count, disease lineage (B/T), and cytogenetic study results. Data on the patients’ disease status at HSCT and indications of HSCT were collected. Indications for HSCT were categorized as upfront HSCT at 1st complete remission, relapse, and refractory disease. Results: Among the 549 screened patients, a total of 418 patients were included in the study; B-cell ALL (n=379) and T-cell ALL (T-ALL) (n=39). HSCT was conducted on a total of 106 patients (25.4%), with a higher frequency as upfront HSCT in higher-risk groups and specific cytogenetics. The overall survival (OS) was significantly better when done upfront than in relapsed or refractory state in T-ALL patients (p=0.002). The KMT2A-rearranged ALL patients showed superior event-free survival (p=0.002) and OS (p=0.022) when HSCT was done as upfront treatment. Conclusion HSCT had a substantial positive effect in a specific subset of pediatric ALL. In particular, frontline HSCT for T-ALL and KMT2A-rearranged ALL offered a better prognosis than when HSCT was conducted in a relapsed or refractory setting.