This study examined the inhibitory effects of pluviatolide, a lignan derived from Podophyllum hexandrum, on mast cell activation and IgE-mediated type I hypersensitivity, focusing on FcεRI-dependent and calcium-mediated pathways. Using bone marrowderived mast cells (BMMCs) and rat basophilic leukemia (RBL)-2H3 cells, we found that pluviatolide significantly decreased β-hexosaminidase release and suppressed the expression and secretion of TNF-α and IL-6 in a concentration-dependent manner, without causing cytotoxicity. While we initially hypothesized that it would selectively modulate antigen-specific FcεRI signaling, pluviatolide also inhibited degranulation induced by calcium ionophore and thapsigargin, indicating its effects extend to receptorindependent, Ca2+-dependent activation mechanisms. Immunoblot analyses revealed decreased phosphorylation of proximal kinases (Lyn, Syk), adaptor proteins (LAT, PLCγ1), MAPKs (ERK1/2, JNK, p38), and NF-κB p65. In a passive cutaneous anaphylaxis (PCA) mouse model, oral administration of pluviatolide significantly reduced Evans blue extravasation and mast cell degranulation in ear tissues. These findings demonstrate that pluviatolide suppresses both early and late-phase mast cell responses through multi-nodal inhibition of activation pathways, highlighting its potential as a therapeutic candidate for both IgE-mediated and non-IgE-mediated allergic disorders.

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.

Synthetic data, generated using advanced artificial intelligence (AI) techniques, replicates the statistical properties of real-world datasets while excluding identifiable information.Although synthetic data does not consist of actual data points, it is derived from original datasets, thereby enabling analyses that yield results comparable to those obtained with real data. Synthetic datasets are evaluated based on their utility—a measure of how effectively they mirror real data for analytical purposes. This paper presents the generation of synthetic datasets through the Healthcare Big Data Showcase Project (2019–2023). The original dataset comprises comprehensive multi-omics data from 400 individuals, including cancer survivors, chronic disease patients, and healthy participants. Synthetic data facilitates efficient access and robust analyses, serving as a practical tool for research and education. It addresses privacy concerns, supports AI research, and provides a foundation for innovative applications across diverse fields, such as public health and precision medicine.

Human rhinovirus (HRV) causes the common cold and exacerbates chronic respiratory diseases, such as asthma and chronic obstructive pulmonary disease. Despite its significant impact on public health, there are currently no approved vaccines or antiviral treatments for HRV infection. Apoptosis is the process through which cells eliminate themselves through the systematic activation of intrinsic death pathways in response to various stimuli. It plays an important role in viral infections and serves as a key immune defense mechanism in the interactions between viruses and the host. In the present study, we investigated the antiviral effects of quercetin-3-methyl ether, a flavonoid isolated from Serratula coronata, on human rhinovirus 1B (HRV1B). Quercetin-3-methyl ether significantly inhibited HRV1B replication in HeLa cells in a concentration-dependent manner, thereby reducing cytopathic effects and viral RNA levels. Time-course and time-of-addition analyses confirmed that quercetin-3-methyl ether exhibited antiviral activity during the early stages of viral infection, potentially targeting the replication and translation phases. Gene expression analysis using microarrays revealed that pro-apoptotic genes were upregulated in quercetin-3-methyl ether-treated cells, suggesting that quercetin-3-methyl ether enhances early apoptosis to counteract HRV1B-induced immune evasion. In vivo administration of quercetin-3-methyl ether to HRV1B-infected mice significantly reduced viral RNA levels and inflammatory cytokine production in the lung tissues. Our findings demonstrated the potential of quercetin-3-methyl ether as a novel antiviral agent against HRV1B, thereby providing a promising therapeutic strategy for the management of HRV1B infections and related complications.

Background: and Purpose: This clinical practice guideline provides evidence-based recommendations for treatment of dementia, focusing on cholinesterase inhibitors and N-methyl-D-aspartate (NMDA) receptor antagonists for Alzheimer’s disease (AD) and other types of dementia. Methods: Using the Population, Intervention, Comparison, Outcomes (PICO) framework, we developed key clinical questions and conducted systematic literature reviews. A multidisciplinary panel of experts, organized by the Korean Dementia Association, evaluated randomized controlled trials and observational studies. Recommendations were graded for evidence quality and strength using Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology. Results: Three main recommendations are presented: (1) For AD, cholinesterase inhibitors (donepezil, rivastigmine, galantamine) are strongly recommended for improving cognition and daily function based on moderate evidence; (2) Cholinesterase inhibitors are conditionally recommended for vascular dementia and Parkinson’s disease dementia, with a strong recommendation for Lewy body dementia; (3) For moderate to severe AD, NMDA receptor antagonist (memantine) is strongly recommended, demonstrating significant cognitive and functional improvements. Both drug classes showed favorable safety profiles with manageable side effects. Conclusions This guideline offers standardized, evidence-based pharmacologic recommendations for dementia management, with specific guidance on cholinesterase inhibitors and NMDA receptor antagonists. It aims to support clinical decision-making and improve patient outcomes in dementia care. Further updates will address emerging treatments, including amyloid-targeting therapies, to reflect advances in dementia management.

Background: and Purpose To determine whether the RNF213 p.R4810K mutation modifies the number of moyamoya disease manifestations and recurrent strokes in isolated intracranial arterial steno-occlusive disease (ICAD). Methods: This retrospective case–control study analyzed patients who visited the Asan Medical Center with steno-occlusive lesions in the M1 segment of the middle cerebral artery and terminal internal carotid artery, and underwent RNF213 genetic testing for screening moyamoya disease between January 2010 and November 2022. Patients with supportive findings of moyamoya disease or moderate-to-severe stenosis in the extracranial arteries were excluded.After matching antiplatelet drugs, the presentation of moyamoya disease and stroke recurrence were analyzed using chi-squared analysis and Kaplan–Meier survival curve analysis. Results: The 1,567 patients who underwent evaluations of RNF213 polymorphisms included 753 with ICAD, among whom females predominated (n=452, 60.0%) and 289 (38.4%) had an RNF213 mutation. The follow-up period was 2.47±3.51 years (mean±standard deviation; median=1.00 year, interquartile range=0–4 years). The risk of progression to moyamoya disease was higher in the RNF213-related-vasculopathy group than the RNF213-negative stenosis group (n=27 [9.3%] versus n=6 [1.3%], p<0.01), as were the risks of ischemic stroke (n=13 [4.5%] versus n=7 [1.5%], p=0.01) and hemorrhagic stroke (n=5 [1.7%] versus n=1 [0.2%], p=0.02, respectively). Furthermore, the presence of an RNF213 mutation was significantly associated with the risk of stroke recurrence (odds ratio=2.34, 95% confidence interval=1.44–3.80, p< 0.01). Conclusions Evaluations of RNF213 polymorphisms may help to identify patients with isolated ICAD at a high risk of progression to moyamoya disease and stroke.

Background: and Purpose We aimed to determine the proportion of Korean patients with early Alzheimer’s disease (AD) who are eligible to receive lecanemab based on the United States Appropriate Use Recommendations (US AUR), and also identify the barriers to this treatment. Methods: We retrospectively enrolled 6,132 patients with amnestic mild cognitive impairment or mild amnestic dementia at 13 hospitals from June 2023 to May 2024. Among them, 2,058 patients underwent amyloid positron emission tomography (PET) and 1,199 (58.3%) of these patients were amyloid-positive on PET. We excluded 732 patients who did not undergo brain magnetic resonance imaging between June 2023 and May 2024. Finally, 467 patients were included in the present study. Results: When applying the criteria of the US AUR, approximately 50% of patients with early AD were eligible to receive lecanemab treatment. Among the 467 included patients, 36.8% did not meet the inclusion criterion of a Mini-Mental State Examination (MMSE) score of ≥22. Conclusions Eligibility for lecanemab treatment was not restricted to Korean patients with early AD except for those with an MMSE score of ≥22. The MMSE criteria should therefore be reconsidered in areas with a higher proportion of older people, who tend to have lower levels of education.

Objective: It has been 1 year since the start of the worldwide coronavirus disease-19 (COVID-19) pandemic. This study analyzed the indirect effects of COVID-19 on treating patients with non-infectious diseases by comparing the incidence of complicated appendicitis before and after the pandemic. Methods: The target group included patients aged at least 16 years diagnosed with acute appendicitis between February 23 and July 31, 2020. Patients diagnosed during the same period in 2019 were selected as the control group. The differences in the incidence of complicated appendicitis before and after COVID-19 were investigated, and the association with various variables was analyzed using the odds ratios and 95% confidence intervals (CIs). Results: The study included 120 subjects in 2019 (pre-COVID group) and 119 cases in 2020 (post-COVID group). The pre-COVID group included 25 cases (20.8%) of complicated appendicitis, while the post-COVID group included 48 cases (40.3%). The median time from symptom onset to visit (pre-hospital time) increased from 15 to 22 hours, and the median time from the visit to surgery (in-hospital time) increased from 7 to 11 hours. Multivariate regression analysis of the three variables revealed odds ratios (95% CIs) of pre-hospital time, erythrocyte sedimentation rate, and inclusion in the post-COVID group of 1.02 (1.01-1.02), 2.07 (1.11-3.86), and 2.15 (1.12-4.11), respectively. Conclusion The incidence of complicated appendicitis increased after the COVID-19 pandemic. Therefore, a healthcare system that can minimize the delay in treating non-infectious emergency patients is needed.

Synthetic data, generated using advanced artificial intelligence (AI) techniques, replicates the statistical properties of real-world datasets while excluding identifiable information.Although synthetic data does not consist of actual data points, it is derived from original datasets, thereby enabling analyses that yield results comparable to those obtained with real data. Synthetic datasets are evaluated based on their utility—a measure of how effectively they mirror real data for analytical purposes. This paper presents the generation of synthetic datasets through the Healthcare Big Data Showcase Project (2019–2023). The original dataset comprises comprehensive multi-omics data from 400 individuals, including cancer survivors, chronic disease patients, and healthy participants. Synthetic data facilitates efficient access and robust analyses, serving as a practical tool for research and education. It addresses privacy concerns, supports AI research, and provides a foundation for innovative applications across diverse fields, such as public health and precision medicine.

Synthetic data, generated using advanced artificial intelligence (AI) techniques, replicates the statistical properties of real-world datasets while excluding identifiable information.Although synthetic data does not consist of actual data points, it is derived from original datasets, thereby enabling analyses that yield results comparable to those obtained with real data. Synthetic datasets are evaluated based on their utility—a measure of how effectively they mirror real data for analytical purposes. This paper presents the generation of synthetic datasets through the Healthcare Big Data Showcase Project (2019–2023). The original dataset comprises comprehensive multi-omics data from 400 individuals, including cancer survivors, chronic disease patients, and healthy participants. Synthetic data facilitates efficient access and robust analyses, serving as a practical tool for research and education. It addresses privacy concerns, supports AI research, and provides a foundation for innovative applications across diverse fields, such as public health and precision medicine.