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: Accumulating evidence has clarified that gut dysbiosis is involved in lung cancer development and progression. Although the relationship between tumors and gut microbiota has been extensively studied using clinical samples, no studies have examined the association between mutant epidermal growth factor receptor (EGFR)–induced lung carcinogenesis and dysbiosis in gut microbiota. Therefore, we investigated the gut microbiota profiles in stool samples from human lung-specific conditional EGFR-mutant transgenic mice during lung tumor carcinogenesis. Materials and Methods: Stool samples were collected before tamoxifen treatment (V1) and at each time point following mutant EGFR expression in lung tissue (V2) and lung tumor appearance (V3). Fecal 16S rRNA taxonomy was analyzed to assess microbial diversity, composition, and dynamic changes at each time point. Results: We found that microbiota richness and diversity were significantly elevated when tumors developed and grew in the lung. Phylogenetic analysis of the microbial community revealed that Lachnospiraceae, Ruminococcaceae, Porphyromonadaceae, Rhodospirillaceae, Odoribacteraceae, and Desulfovibrionaceae showed a significant increase at the V3 stage compared to the V1 stage at the family level. In contrast, Lactobacillaceae, Bacteroidaceae, Muribaculaceae, Coriobacteriaceae, and Rikenellaceae significantly decreased at the V3 stage compared to the V1 stage. Furthermore, Lactobacillus species, also known as short chain fatty acid-producing bacteria, were relatively abundant at the V1 stage but were depleted with the occurrence of lung tumors at the V3 stage. Conclusion Changes in gut microbiota, such as Lactobacillus species, may be a predictive factor for the emergence and progression of tumors in an animal model of lung adenocarcinoma induced by mutant EGFR.

Purpose: The male predominance in the incidence of gastric cancer (GC) is established; however, sex differences in the prognosis of GC remain controversial. As such, this study analyzed the prognosis of patients with GC based on age and sex. Materials and Methods: Data from 14,739 patients diagnosed with GC at Seoul National University Bundang Hospital between 2003 and 2023 were analyzed. Baseline characteristics, histological types of GC, overall and GC-specific survival rates (age and stage stratification), and associated risk factors were analyzed. Results: Females were significantly younger (p < 0.001) and exhibited more gastric body cancers (p < 0.001) and tumors with diffuse-type or poorly differentiated histology (p < 0.001) than males. Females exhibited an advantage over males in terms of overall survival (p=0.004), but not in GC-specific survival. However, age stratification revealed significant sex differences, that females < 50 years of age exhibited survival disadvantages (p < 0.001); however, this trend was reversed with age, and females > 60 years exhibited survival advantages (p < 0.001) for both overall and GC-specific survival. This may be explained by the lower ratio of diffuse-type GC as females age. Furthermore, in the analysis according to stage, females with stage IV disease exhibited significant survival disadvantages, with significantly younger age and a higher proportion of diffuse-type GC which exhibits aggressive features, resulting in poorer survival than in males. Conclusion Age and stage stratification revealed significant differences in survival between the sexes, which can be helpful for public health strategies.

Background: Long working hours have been associated with adverse physical and mental health outcomes; however, evidence regarding their relationship with satisfaction with work environment remains limited, particularly when long working hours are defined using a specific daily threshold. This study examined the association between working ≥10 hours per day and satisfaction with work environment among Korean wage workers, focusing on the cumulative number of such workdays per month. Methods: This cross-sectional study analyzed data from the 7th Korean Working Conditions Survey. A total of 24,269 wage workers aged ≥18 years were included after excluding self-employed workers, unpaid family workers, shift workers, and respondents with missing data. Working ≥10 hours per day was categorized as 0, 1–9, and ≥10 days per month. Satisfaction with work environment was categorized as satisfied or dissatisfied. Multiple logistic regression analyses were conducted to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for dissatisfaction with work environment according to the number of long working days, adjusting for demographic and occupational characteristics. Results: Compared with workers who did not work ≥10 hours per day, those who worked 1–9 days and ≥10 days per month showed progressively higher levels of dissatisfaction with work environment. After adjustment for demographic and occupational factors, the odds of dissatisfaction with work environment were significantly higher among workers who worked ≥10 hours per day for 1–9 days per month (OR: 1.380; 95% CI: 1.145–1.665) and ≥10 days per month (OR: 2.106; 95% CI: 1.627–2.725), demonstrating a dose–response relationship. Conclusions Among the analytic sample of Korean wage workers included in this study, working ≥10 hours per day was associated with greater dissatisfaction with work environment, with a dose–response pattern according to the number of long working days per month.

Objective: To classify life stages for companion dogs and cats by identifying clusters in age-specific disease proportions derived from medical records, providing a data-driven foundation for health examination programs. Methods: We collected 505,667 medical records from 82 veterinary facilities in South Korea between 2020 and 2023. Diagnoses were standardized using GPT-4o and S-BioBERT. Following preprocessing, data from 27 facilities yielded 222,706 canine and 39,910 feline records for the final analysis. Principal component analysis and K-means clustering (K = 4) were applied to age-specific disease proportions to identify life stages.The 10 most highest-proportion diagnoses diseases were determined for each cluster. Results: Canine life stages were classified as ≤ 1 year, 2–5 years, 6–10 years, and 11–15+ years.Feline life stages were 1–2 years, 3–8 years, 9–12 years, and 13–15+ years. In dogs, developmental diseases were common in the youngest age group, while chronic diseases were more prevalent in older groups. In cats, oral and urinary diseases were high-ranking, conjunctivitis was most common in the early stage, and chronic diseases increased with age. Conclusions and Relevance: Age-specific diagnosis patterns support four practical life stages for dogs and cats in South Korea. These boundaries can inform evidence-based preventive examination schedules, animal health policy, and pet insurance product design.

The brain-derived neurotrophic factor (BDNF) plays a crucial role in neuroprotection, and we have previously demonstrated BDNF-mediated neuroprotective effects in mesenchymal stromal cells (MSCs). The present study aimed to investigate whether BDNF-overexpressing MSCs enhance the therapeutic efficacy of naïve MSCs in a preclinical model of severe neonatal intraventricular hemorrhage (IVH). We exposed primary rat neuronal cells to 40 U of thrombin overnight in vitro. Subsequently, the neuronal cells were co-cultured with either naïve MSCs or BDNF-overexpressing MSCs (1×105 cells in 1 mL media) for 24 hours. Next, 300 μL of maternal blood was injected into bilateral ventricles on postnatal day (P)4 to induce severe IVH in newborn Sprague-Dawley male rats. At P6, either naïve MSCs or BDNF-overexpressing MSCs (1×105 cells in 10 μL saline) were transplanted intraventricularly. Behavioral function tests, including passive avoidance, followed by endpoint analyses of brain tissue and cerebrospinal fluid were performed at P35. BDNF-overexpressing MSCs enhanced the effects of naïve MSCs against cell death, cytotoxicity, and oxidative stress in vitro. Notably, naïve and BDNF-overexpressing MSCs did not attenuate post-hemorrhagic ventricular dilatation, neuronal cell death, or gliosis. However, BDNF-overexpressing MSCs attenuated microglial activation.Furthermore, inflammatory cytokine (interleukin [IL]-1α, IL-1β, IL-6, and tumor necrosis factor-α) levels and memory function assessed using a passive avoidance test significantly improved in the BDNF-overexpressing MSC transplanted group compared with the naïve MSC transplanted group. Our data suggest that BDNF-overexpressing MSCs may offer superior protective effects to naïve MSCs in a neonatal IVH model.

Purpose: Since 1995, the Korean Gastric Cancer Association (KGCA) has been periodically conducting nationwide surveys on patients with surgically treated gastric cancer. This study details the results of the survey conducted in 2023. Materials and Methods: The survey was conducted from March to December 2024 using a standardized case report form. Data were collected on 86 items, including patient demographics, tumor characteristics, surgical procedures, and surgical outcomes. The results of the 2023 survey were compared with those of previous surveys. Results: Data from 12,751 cases were collected from 66 institutions. The mean patient age was 64.6 years, and the proportion of patients aged ≥71 years increased from 9.1% in 1995 to 31.7% in 2023. The proportion of upper-third tumors slightly decreased to 16.8% compared to 20.9% in 2019. Early gastric cancer accounted for 63.1% of cases in 2023.Regarding operative procedures, a totally laparoscopic approach was most frequently applied (63.2%) in 2023, while robotic gastrectomy steadily increased to 9.5% from 2.1% in 2014.The most common anastomotic method was the Billroth II procedure (48.8%) after distal gastrectomy and double-tract reconstruction (51.9%) after proximal gastrectomy in 2023.However, the proportion of esophago-gastrostomy with anti-reflux procedures increased to 30.9%. The rates of post-operative mortality and overall complications were 1.0% and 15.3%, respectively. Conclusions The results of the 2023 nationwide survey demonstrate the current status of gastric cancer treatment in Korea. This information will provide a basis for future gastric cancer research.

This review summarized the results of clinical trials in 2024 that were believed to have a significant impact on clinical practice in the field of gynecologic oncology. The SHAPE trial, INTERLACE and KEYNOTE-A18 trials, and BEATcc and COMPASSION-16 trials were included in early-stage, locally advanced, and recurrent/metastatic cervical cancer, respectively. For uterine corpus cancer, updated survival data of the four trials (NRG-GY018, RUBY, AtTEnd, DUO-E) for endometrial cancer and the first survival data of LMS-04 trial for leiomyosarcoma were described. For ovarian cancer, the final overall survival results of PRIMA study were followed by DUO-O, ATHENA-combo, and FIRST-ENGOT-OV44 trial in different disease conditions. Finally, the results of DESTINY-PanTumor02, a basket trial of trastuzumab deruxtecan, were briefly addressed.

We updated the Korean Society of Gynecologic Oncology (KSGO) practice guideline for the management of ovarian cancer as version 5.1. The ovarian cancer guideline team of the KSGO published announced the fifth version (version 5.0) of its clinical practice guidelines for the management of ovarian cancer in December 2023. In version 5.0, the selection of the key questions and the systematic reviews were based on the data available up to December 2022.Therefore, we updated the guidelines version 5.0 with newly accumulated clinical data and added 5 new key questions reflecting the latest insights in the field of ovarian cancer between 2023 and 2024. For each question, recommendation was provided together with corresponding level of evidence and grade of recommendation, all established through expert consensus.