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: Neuro-oncological ventral antigen 1 (NOVA1), a neuron-specific pre-mRNA splicing factor, is involved in neuronal development and oncogenesis. NOVA1 overexpression is associated with favorable prognosis in head and neck squamous cell carcinoma (HNSCC) and gastric adenocarcinoma, whereas its downregulation correlates with poor outcomes. High NOVA1 levels in these cancers correlate with increased CD3+ and CD8+ T lymphocyte densities, suggesting involvement in tumor immune-inflammatory signals. This study explores NOVA1's role in regulating the immune-inflammatory cGAS-STING pathway in HNSCC cells and clinical tissues. Materials and Methods: HNSCC cell lines (FaDu, YD-10B, SNU-1066, and SNU-1076) were transfected with NOVA1 and poly(dA:dT). Quantitative real-time polymerase chain reaction and Western blot analysis were used to assess gene/protein expression. Enzymelinked immunosorbent assay quantified cytokine levels, and immunoprecipitation assessed protein interactions. Clinical tissue samples from 234 HNSCC patients were analyzed using immunohistochemistry to correlate NOVA1 and STING pathway markers with immune cell infiltration. Results: NOVA1 overexpression in HNSCC cells increased phosphorylation of STING (p-STING) without altering cGAS or TBK1. Immunoprecipitation showed an interaction between NOVA1 and p-STING. Overexpression of NOVA1, particularly with poly(dA:dT) treatment, tended to elevate CCL5 and CXCL10 expression. In clinical samples, NOVA1 expression strongly correlated with p-STING levels (r=0.749, p<0.001). Higher NOVA1 and p-STING expressions were linked to increased infiltration of CD3+ T cells, CD8+ T cells, and FOXP3+ regulatory T cells. Conclusion NOVA1 modulates the cGAS-STING pathway through STING phosphorylation and associated immune responses in HNSCC, providing a potential therapeutic target for enhancing anti-tumor immunity.

Background: s/Aims: The patatin-like phospholipase domain-containing protein 3 (PNPLA3) I148M variant has been implicated in metabolic dysfunction-associated steatotic liver disease (MASLD), but its role in hepatocellular carcinoma (HCC) development is unclear. This study examines the association between the PNPLA3 I148M variant and HCC occurrence. Methods: A total of 562 MASLD patients, with and without HCC, were prospectively and consecutively enrolled at two universityaffiliated hospital between June 2024 and June 2025. Genomic DNA was extracted from buccal swabs or liver biopsy samples, and single nucleotide polymorphism genotyping was performed to determine the rs738409 genotype at codon 148 of PNPLA3. The histological grade of HCC was assessed using the Edmondson-Steiner (ES) grading system in patients who underwent core-needle liver biopsy. Results: Among 474 non-HCC patients, the GG genotype was found in 39.9%, GC in 37.1%, and CC in 23.0%. In 88 HCC patients, these frequencies were 45.5%, 36.4%, and 18.2%, respectively. No significant differences in GG genotype distribution were observed between HCC and non-HCC groups (P=0.509), nor in subgroups by sex, age, obesity status, cirrhosis status, fibrosis-4 index, or liver stiffness measurement. However, among HCC patients with histological grading, the GG genotype was significantly associated with higher ES grades (P=0.0076). Conclusions The PNPLA3 I148M GG genotype was not significantly associated with increased HCC occurrence in Korean MASLD patients within the present cohort. Although the GG genotype is known to play a role in development and progression of MASLD, further studies are warranted to clarify its contribution to tumor initiation and dedifferentiation.

Background: Posterior reversible encephalopathy syndrome (PRES) is a rare complication of lung transplantation with poorly understood risk factors and clinical characteristics. This study aimed to examine the occurrence, risk factors, and clinical data of patients who developed PRES following lung transplantation. Methods: A retrospective analysis was conducted on 147 patients who underwent lung transplantation between February 2013 and December 2023. The patients were diagnosed with PRES based on the clinical symptoms and radiological findings. We compared the baseline characteristics and clinical information, including primary lung diseases and immunosuppressive therapy related to lung transplantation operations, between the PRES and non-PRES groups. Results: PRES manifested in 7.5% (n=11) of the patients who underwent lung transplantation, with a median onset of 15 days after operation. Seizures were identified as the predominant clinical manifestation (81.8%, n=9) in the group diagnosed with PRES. All patients diagnosed with PRES recovered fully. Patients with PRES were significantly associated with connective tissue disease-associated interstitial lung disease (45.5% vs. 18.4%, P=0.019, odds ratio=9.808; 95% CI, 1.064–90.386; P=0.044). Nonetheless, no significant variance was observed in the type of immunotherapy, such as the use of calcineurin inhibitors, blood pressure, or acute renal failure subsequent to lung transplantation. Conclusions PRES typically manifests shortly after lung transplantation, with seizures being the predominant initial symptom. The presence of preexisting connective tissue disease as the primary lung disease represents a significant risk factor for PRES following lung transplantation.

Background: and Purpose Previous research on patients with acute ischemic stroke (AIS) has shown a 0.5% incidence of major gastrointestinal bleeding (GIB) requiring blood transfusion during hospitalization. The existing literature has insufficiently explored the long-term incidence in this population despite the decremental impact of GIB on stroke outcomes. Methods: We analyzed the data from a cohort of patients with AIS admitted to 14 hospitals as part of a nationwide multicenter prospective stroke registry between 2011 and 2013. These patients were followed up for up to 6 years. The occurrence of major GIB events, defined as GIB necessitating at least two units of blood transfusion, was tracked using the National Health Insurance Service claims data. Results: Among 10,818 patients with AIS (male, 59%; mean age, 68±13 years), 947 (8.8%) experienced 1,224 episodes of major GIB over a median follow-up duration of 3.1 years. Remarkably, 20% of 947 patients experienced multiple episodes of major GIB. The incidence peaked in the first month after AIS, reaching 19.2 per 100 person-years, and gradually decreased to approximately one-sixth of this rate by the 2nd year with subsequent stabilization. Multivariable analysis identified the following predictors of major GIB: anemia, estimated glomerular filtration rate <60 mL/min/1.73 m2 , and a 3-month modified Rankin Scale score of ≥4. Conclusion Patients with AIS are susceptible to major GIB, particularly in the first month after the onset of AIS, with the risk decreasing thereafter. Implementing preventive strategies may be important, especially for patients with anemia and impaired renal function at stroke onset and those with a disabling stroke.

Background: and Purpose Previous research on patients with acute ischemic stroke (AIS) has shown a 0.5% incidence of major gastrointestinal bleeding (GIB) requiring blood transfusion during hospitalization. The existing literature has insufficiently explored the long-term incidence in this population despite the decremental impact of GIB on stroke outcomes. Methods: We analyzed the data from a cohort of patients with AIS admitted to 14 hospitals as part of a nationwide multicenter prospective stroke registry between 2011 and 2013. These patients were followed up for up to 6 years. The occurrence of major GIB events, defined as GIB necessitating at least two units of blood transfusion, was tracked using the National Health Insurance Service claims data. Results: Among 10,818 patients with AIS (male, 59%; mean age, 68±13 years), 947 (8.8%) experienced 1,224 episodes of major GIB over a median follow-up duration of 3.1 years. Remarkably, 20% of 947 patients experienced multiple episodes of major GIB. The incidence peaked in the first month after AIS, reaching 19.2 per 100 person-years, and gradually decreased to approximately one-sixth of this rate by the 2nd year with subsequent stabilization. Multivariable analysis identified the following predictors of major GIB: anemia, estimated glomerular filtration rate <60 mL/min/1.73 m2 , and a 3-month modified Rankin Scale score of ≥4. Conclusion Patients with AIS are susceptible to major GIB, particularly in the first month after the onset of AIS, with the risk decreasing thereafter. Implementing preventive strategies may be important, especially for patients with anemia and impaired renal function at stroke onset and those with a disabling stroke.

Background: and Purpose Previous research on patients with acute ischemic stroke (AIS) has shown a 0.5% incidence of major gastrointestinal bleeding (GIB) requiring blood transfusion during hospitalization. The existing literature has insufficiently explored the long-term incidence in this population despite the decremental impact of GIB on stroke outcomes. Methods: We analyzed the data from a cohort of patients with AIS admitted to 14 hospitals as part of a nationwide multicenter prospective stroke registry between 2011 and 2013. These patients were followed up for up to 6 years. The occurrence of major GIB events, defined as GIB necessitating at least two units of blood transfusion, was tracked using the National Health Insurance Service claims data. Results: Among 10,818 patients with AIS (male, 59%; mean age, 68±13 years), 947 (8.8%) experienced 1,224 episodes of major GIB over a median follow-up duration of 3.1 years. Remarkably, 20% of 947 patients experienced multiple episodes of major GIB. The incidence peaked in the first month after AIS, reaching 19.2 per 100 person-years, and gradually decreased to approximately one-sixth of this rate by the 2nd year with subsequent stabilization. Multivariable analysis identified the following predictors of major GIB: anemia, estimated glomerular filtration rate <60 mL/min/1.73 m2 , and a 3-month modified Rankin Scale score of ≥4. Conclusion Patients with AIS are susceptible to major GIB, particularly in the first month after the onset of AIS, with the risk decreasing thereafter. Implementing preventive strategies may be important, especially for patients with anemia and impaired renal function at stroke onset and those with a disabling stroke.

Informed consent is a fundamental aspect of surgical care, designed to reinforce patient autonomy, promote shared decision-making, and potentially mitigate legal conflicts by ensuring the provision of comprehensive and consistent information in clinical practice. The Korean Society of Gynecologic Oncology (KSGO) previously published detailed informed consent documents for cervical, endometrial, and ovarian cancer surgery. However, standardized consent forms remain relatively lacking for laparoscopic-robotic hysterectomy performed for non-malignant indications, as well as for vulvar cancer surgery. Hence, the KSGO subcommittee collected, reviewed, and discussed consent forms from domestic medical institutions and subsequently developed informed consent for laparoscopic-robotic hysterectomy and vulvar cancer surgery, aiming to build patient trust and understanding.

Background: This study aimed to assess the Geriatric Oral Health Assessment Index (GOHAI) based on oral health-relatedbehaviors and oral health status among older adults in Gangneung-si. Methods: A total of 77 adults aged 65 years or older in Gangneung-si who voluntarily participated in an oral health care programwere included. GOHAI was administered as a self-reported questionnaire to evaluate oral health-related quality of life (OHRQoL).GOHAI consists of 12 items rated on a six-point Likert scale, with higher scores indicating better oral health and higher QoL.Assessment items included general characteristics, systemic disease, oral health-related behaviors, and tooth and periodontal status. The Shapiro–Wilk test was used to assess normality prior to comparing GOHAI scores across independent variables.Depending on normality results, differences in mean scores were analyzed using the independent samples t-test, one-way analysis of variance, or the Mann–Whitney U test. Results: The highest-scoring item was “Did your teeth or dentures bother you when you wanted to speak?”, whereas the lowest-scoring item was “Were you pleased or happy looking at your teeth, gums, or dentures?” A significant difference was observed according to the number of remaining teeth; participants with 20 or more teeth had higher GOHAI scores (41.86±5.22) than those with 19 or fewer teeth (38.33±3.83; p=0.046). Conclusion Significant differences in GOHAI scores were found in relation to systemic disease and the number of remaining teeth.These findings can support the development of strategies and policies to improve OHRQoL in older adults in Gangneung-si.

Purpose: Smoking is causally related to alcohol use disorder. Although polycyclic aromatic hydrocarbons (PAHs) are major neurotoxic pollutants in tobacco smoke, evidence is lacking on the role of PAHs in the relationship between smoking and alcohol use disorder. This study investigated the types of PAHs associated with smoking and whether exposure to those PAHs mediated the effect of smoking on alcohol use disorder. Materials and Methods: A total of 968 male firefighters were analyzed. Smoking history and cumulative pack-years were obtained using self-reported questionnaires. Alcohol use disorder was defined using the Alcohol Use Disorder Identification Test.PAH exposure was assessed by urinary metabolites. Regression analyses were performed between exposure (smoking), outcome (alcohol use disorder), and mediator (PAH metabolites) variables. A mediation analysis was performed to test the indirect effect of PAH metabolites on the association between smoking and alcohol use disorder. All analyses were repeated for 770 participants who were followed up after 2 years, while alcohol use disorder was redefined from follow-up data ensuring the temporal sequence of the variables. Results: Both 2-naphthol [β=0.78, 95% confidence interval (CI): 0.59–0.98] and 2-hydroxyfluorene (β=0.69, 95% CI: 0.56–0.82) were associated with smoking history. Furthermore, 2-naphthol and 2-hydroxyfluorene mediated the associations of smoking history (proportion mediated: 14.2%, 23.6% respectively) or cumulative pack-years (proportion mediated: 14.4%, 25.4% respectively) with alcohol use disorder. The results were consistent in longitudinal settings. Conclusion Exposure to PAHs mediated the association between tobacco smoking and alcohol use disorder. PAH exposure from tobacco may increase the risk of addictive disorders.