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.

Purpose: Molecular characteristics of synchronous colorectal cancers (SCRCs) remain incompletely elucidated, despite their importance in targeted therapy selection. We compared the molecular characteristics and somatic mutations between SCRCs. Materials and Methods: This retrospective study (2012-2014) included 98 consecutive patients with surgically resected SCRCs. Molecular characteristics, including microsatellite instability (MSI) and tumor-infiltrating lymphocytes (TILs), were analyzed for all cancer lesions. The intertumoral heterogeneity of SCRCs was evaluated using whole-exome sequencing (WES) for 18 cancers from nine patients with at least one MSI-high (MSI-H) tumor. Results: Twelve patients had at least one MSI-H tumor; five showed discordant MSI status. Mucinous adenocarcinoma frequency and TIL density were higher in patients with at least one MSI-H tumor than in those with only microsatellite-stable tumors. WES revealed that, except one patient (6.5%), most synchronous cancers shared few variants in each patient (0.09%-0.36%). The concordance rates for BRAF, KRAS, NRAS, and PIK3CA, in synchronous cancers from each patient were 66.7%, 66.7%, 66.7%, and 55.6%, respectively. Conclusion Although synchronous cancers shared a mutated gene, the mutation subtypes differed. SCRCs exhibited 5.1% MSI status discordance rate and a high discordance rate in somatic mutational variants. As intertumoral heterogeneity may affect the targeted therapy response, molecular analysis of all tumors is recommended for patients with SCRCs.

Background: and Purpose To compare the epidemiological and clinical features of the rare patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) with age- and sex-matched controls in a nationwide cohort from South Korea. Methods: This observational cohort study analyzed newly diagnosed CADASIL patients aged at least 20 years and matched controls using data from the National Health Information Database for 2004–2022. The cumulative incidence of CADASIL was assessed by age and sex, and compared between regions. Neurologic and systemic diseases were compared between the CADASIL and control groups. Results: The study analyzed 816 CADASIL patients and 816 age- and sex-matched controls aged 56.8±15.2 years (mean±standard deviation), among whom 48.3% were male. The cumulative incidence of CADASIL was 1.86 per 100,000 people (95% confidence interval [CI]=1.85– 1.87 per 100,000), and peaked at 60–69 years of age. In terms of regional distribution, the incidence was highest for Jeju, at 39.67 per 100,000 (95% CI 37.84–41.49 per 100,000). Neurologic diseases were more frequent in CADASIL patients, including Alzheimer’s disease (33.1% vs.20.0%), vascular dementia (84.9% vs. 5.0%), epilepsy (34.6% vs. 15.9%), stroke (70.7% vs. 27.6%), parkinsonism (18.9% vs. 11.0%), and depression (60.8% vs. 44.9%). Systemic diseases such as diabetes mellitus (78.9% vs. 68.9%) were also more common in CADASIL patients, while cancer (27.9% vs. 38.7%) and myocardial infarction (10.0% vs. 13.6%) were less common than in controls. The onset ages of all diseases were lower in CADASIL patients. Conclusions This study has provided a precise nationwide estimate of the CADASIL incidence and its regional distribution in South Korea. CADASIL patients showed higher incidence rates and earlier onsets of diverse clinical manifestations.

Heart failure (HF) prevalence and associated socio-economic costs have risen rapidly in Korea, creating urgent demand for a national, standardized prospective registry to support quality monitoring, outcome comparison, and real-world evidence. Standardized data definitions are essential for valid comparisons across studies and healthcare settings. We created a unified national HF cohort by integrating the two largest Korean registries, KorAHF (2011–2014;n=5,625) and KorHF III (2018–2023; n=7,351), yielding 12,976 hospitalized HF patients. Because heterogeneous variable definitions impeded direct comparisons, we implemented a harmonization pipeline across demographic, clinical, imaging, biomarker, therapeutic, and outcome domains, aligned with international standards and reinforced by systematic data quality checks.A multidisciplinary panel then conducted a structured decision process to produce the Korean HF Standard Dataset, a tiered and interoperable variable set spanning six domains: demographics, presentation at admission, in-hospital events and comorbidities, discharge status, outpatient follow-up, and readmission events. This integrated platform and standardized variables enable precise identification of HF patient phenotypes and prognostic factors, establishing an evidence-based foundation for disease management. This supports an analysis of temporal changes in treatment patterns and outcomes, generates data to inform future clinical practice guidelines, and provides a practical basis for planning large, continuous, prospective HF registries. Furthermore, it also facilitates pragmatic, registry-based randomized clinical trials and unmet-needs assessments that can guide national health policy. Establishing a foundation for future linkage with national health databases, this platform will allow for enhanced accuracy, comparability, and representativeness, powering quality improvement initiatives and population-level monitoring of Korea’s growing HF burden.

Purpose: This study aimed to develop a digital multimedia-based educational intervention for hematopoietic stem cell (HSC) donors and to evaluate its effects on anxiety, knowledge, attitudes toward hematopoietic stem cell donation, and educational satisfaction. Methods: This quasi-experimental study employed a nonequivalent control group non-synchronized pretest-posttest design. Participants were 60 HSC donors admitted to a general hospital in Seoul, Republic of Korea, between April and December 2024. The participants were assigned to an experimental group (n=30) and a control group (n=30). The experimental group received a digital multimediabased educational intervention in addition to the usual education using a standardized handout, whereas the control group received the usual education only. The intervention was provided in three sessions: on the day of admission (20 minutes), on the day of stem cell collection (10 minutes), and on the day of discharge (10 minutes). Data were collected at admission and discharge using structured questionnaires. Anxiety was analyzed using generalized estimating equations (GEE), knowledge and attitudes using mixed ANOVA, and educational satisfaction using an independent t-test. Results: The experimental group showed significantly lower anxiety (p=.048) and higher knowledge levels (p=.005) than the control group. No significant differences were found between the groups in attitudes toward donation or educational satisfaction. Conclusion The digital multimedia-based educational intervention was effective in reducing anxiety and improving knowledge among HSC donors. This intervention may enhance donors’ understanding of the donation process and support a more positive donation experience. Further multicenter studies with larger samples and longitudinal follow-up measurements are needed to verify the long-term effects and generalizability of the intervention.

19 cinnamamide/ester-triazole compounds were designed, synthesized and evaluated for their anti-Alzheimer's disease (AD) activity. Among them, compound 4f displayed excellent anti-β-amyloid protein (Aβ)-mediated cytotoxicity (EC₅₀ = 2.03 ± 2.45 μmol·L^-1) in APPswe cells and acetylcholinesterase inhibiton (IC₅₀ = 4.88 ± 4.70 μmol·L^-1). Further study indicated that, at dosages of (1, 5 and 25 mg·kg^-1), compound 4f was effective in improving spatial learning and memory deficits in Aβ_1-42-impaired mice, which was achieved by promoting the nonamyloidogenic signaling and inhibiting the amyloidogenic pathway, along with the suppression of Aβ-induced Tau phosphorylation. All animal experiments in this study were approved by the Experimental Animal Care and Use Committee of the Institute of Medicinal Biotechnology (IMB-20220908D701). In conclusion, compound 4f holds promise as a lead candidate for AD treatment, and the present study lays the foundation for its subsequent development.

Purpose: Cancer poses a significant global health challenge, demanding precise genomic testing for individualized treatment strategies. Targeted-panel sequencing (TPS) has improved personalized oncology but often lacks comprehensive coverage of crucial cancer alterations. Whole-genome sequencing (WGS) addresses this gap, offering extensive genomic testing. This study demonstrates the medical potential of WGS. Materials and Methods: This study evaluates target-enhanced WGS (TE-WGS), a clinical-grade WGS method sequencing both cancer and matched normal tissues. Forty-nine patients with various solid cancer types underwent both TE-WGS and TruSight Oncology 500 (TSO500), one of the mainstream TPS approaches. Results: TE-WGS detected all variants reported by TSO500 (100%, 498/498). A high correlation in variant allele fractions was observed between TE-WGS and TSO500 (r=0.978). Notably, 223 variants (44.8%) within the common set were discerned exclusively by TE-WGS in peripheral blood, suggesting their germline origin. Conversely, the remaining subset of 275 variants (55.2%) were not detected in peripheral blood using the TE-WGS, signifying them as bona fide somatic variants. Further, TE-WGS provided accurate copy number profiles, fusion genes, microsatellite instability, and homologous recombination deficiency scores, which were essential for clinical decision-making. Conclusion TE-WGS is a comprehensive approach in personalized oncology, matching TSO500’s key biomarker detection capabilities. It uniquely identifies germline variants and genomic instability markers, offering additional clinical actions. Its adaptability and cost-effectiveness underscore its clinical utility, making TE-WGS a valuable tool in personalized cancer treatment.

Background: We investigated whether nutritional intake is associated with physical activity (PA) and handgrip strength (HGS) in individuals with airflow limitation. Methods: This study analyzed data from the 2014 and 2016 Korean National Health and Nutrition Examination Survey. We assessed total protein intake (g/day), caloric intake (kcal/day), and other nutritional intakes, using a 24-hour dietary recall questionnaire. HGS was measured three times for each hand using a digital grip strength dynamometer, and PA was assessed as health-enhancing PA. Airflow limitation was defined as a forced expiratory volume/forced vital capacity ratio of 0.7 in individuals over 40 years of age. Participants were categorized into groups based on their PA levels and HGS measurements: active aerobic PA vs. non-active aerobic PA, and normal HGS vs. low HGS. Results: Among the 622 individuals with airflow limitation, those involved in active aerobic PA and those with higher HGS had notably higher total food, calorie, water, protein, and lipid intake. The correlations between protein and caloric intake with HGS were strong (correlation coefficients=0.344 and 0.346, respectively). The forest plots show that higher intakes of food, water, calories, protein, and lipids are positively associated with active aerobic PA, while higher intakes of these nutrients are inversely associated with low HGS. However, in the multivariate logistic regression analysis, no significant associations were observed between nutritional intake and active aerobic PA or HGS. Conclusion Nutritional intake was found to not be an independent factor associated with PA and HGS. However, the observed correlations suggest potential indirect effects that warrant further investigation.