This study analyzed 22 criminal cases involving obstetricians and gynecologists to identify legal trends and propose measures to reduce the legal burden on medical professionals while maintaining stable healthcare services. The cases were retrieved from the Supreme Court of Korea Judicial Information Disclosure Portal using keywords such as “obstetrics,” “gynecology,” “expectant mother,” “fetus,” “neonate,” “delivery,” “uterus,” and “placenta.” The cases were classified into two categories:medical malpractice (16 cases, 72.7%) and abortion and bioethics (6 cases, 27.3%). Guilty verdicts were issued in 8 cases (36.4%), whereas 14 cases (63.6%) resulted in acquittal. The qualitative analysis showed that courts consistently protected physicians’ clinical discretion in unpredictable and unavoidable situations, such as amniotic fluid embolism and uterine atony, provided that standard medical protocols were followed. Procedural appropriateness, rather than the perfection of clinical outcomes, appeared to be the primary basis for judicial protection. Although the judiciary acknowledges the inherent limitations of medical practice and tends to protect physicians when established guidelines are followed, the high frequency of criminal prosecution remains a substantial burden on healthcare providers and may threaten the sustainability of obstetric care.

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: Current guidelines recommend vaccination at least 2 weeks before chemotherapy initiation to optimize the immune response despite limited evidence. Our previous study indicated no differences in short-term immune response for the 13-valent pneumococcal conjugate vaccine (PCV13) according to the vaccination timing. This study aims to investigate the long-term efficacy of PCV13 and clinical factors associated with the respective antibody response. Materials and Methods: Patients with gastric or colorectal cancer who received adjuvant chemotherapy were enrolled and divided into two groups: vaccinated 2 weeks before chemotherapy (arm A) and vaccinated concurrently with chemotherapy (arm B). Serum samples were collected before vaccination and in one month, 3 years, and 5 years. Immune responses were measured using enzyme-linked immunosorbent assay and multiplex opsonophagocytosis assay. Results: Including 63 patients, both groups showed an initial increase in the geometric mean titers of opsonophagocytic activity and the geometric mean concentrations of serotype-specific IgG levels after one month, followed by a decline at 3 and 5 years, particularly for serotypes 1, 14, 18C, and 19A. Despite the decline, global protection was maintained for 5 years, although global response decreased. The two arms did not show significant differences in immunogenicity nor in factors such as vaccination timing, age, cancer type, or chemotherapy regimen. Conclusion Vaccination timing is not a significant factor for the immunogenicity of PCV13 in cancer patients undergoing adjuvant chemotherapy. Global protection against pneumococcal infection was sustained for > 5 years, and global response remained in over half of patients.

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.

Purpose: To develop and validate an artificial intelligence (AI)-based personalized outcome prediction model for upper-urinary tract urothelial carcinoma patients undergoing radical nephroureterectomy. Materials and Methods: Data from patients who underwent radical nephroureterectomy between 2010 and 2020 across three hospitals were retrospectively analyzed. A model was developed using one tertiary center’s data and externally validated with data from two other hospitals. An AI model using XGBoost as risk estimator and bootstrapped Weibull Accelerated Failure Time model for 10-year survival probability was employed. Hyperparameter tuning used Optuna method. Model efficacy was assessed using concordance index, average Brier score, D-calibration, and six-month interval time-dependent area under the curve (AUC). Results: Of 1,039 patients, 627 qualified after excluding 50 with neoadjuvant chemotherapy. Model development used 564 patients (507 training, 57 test) with 9:1 stratified random split, plus 63 for internal validation and 362 for external validation. Significant parameters included preoperative glomerular filtration rate (p<0.001), hydroureteronephrosis (p=0.013), pathological N stage (p<0.001), concurrent carcinoma in situ (p<0.001), disease progression (p<0.001), and survival rate (p<0.001). Disease-free survival (DFS) model’s concordance index: internal validation 0.789, external validations 0.734 and 0.771. Overall survival (OS) model’s concordance index: internal validation 0.819, external validations 0.780 and 0.771. Mean time-dependent AUC was 0.66–0.77 for DFS and 0.67–0.80 for OS during 10-year periods. Conclusions AI-based model effectively predicts disease-free and OS outcomes for upper-urinary tract urothelial carcinoma patients with post-radical nephroureterectomy, showcasing robust performance across multicenter settings.

Background: Research on the relationship between the progression of interstitial lung abnormalities (ILA) and serum biomarkers, including white blood cell differential counts and Krebs von den Lungen-6 (KL-6), is limited. This study aimed to examine the clinical characteristics of patients with ILA and evaluate the association between disease progression and serum biomarkers. Methods: This retrospective cohort study analyzed data from 159 patients (63 with ILA and 74 with interstitial lung diseases) between October 2021 and September 2022. Data collected included clinical characteristics, pulmonary function tests, chest computed tomography (CT), complete blood cell counts, and KL-6 levels. In 52 of these patients who had previously undergone chest CT, the utility of serum biomarkers in reflecting radiologic progression was assessed using receiver operating characteristic curve analysis. Results: Patients with ILA exhibited clinical characteristics similar to those with idiopathic pulmonary fibrosis. Serum KL-6 levels did not correlate with forced vital capacity or diffusing capacity of the lung for carbon monoxide in patients with ILA. Among the 52 patients with ILA, 13 demonstrated radiologic progression. Serum KL-6 displayed moderate predictive performance, with area under the curves ranging from 0.57 to 0.89 (p=0.014) for radiologic progression. Levels of KL-6 greater than 400 U/mL were more frequently observed in patients with radiologic progression (61.5% vs. 20.5%, p=0.006). In multivariate analysis, age and KL-6 were independently associated with radiologic progression in patients with ILA. Conclusion Serum KL-6 levels may serve as a potential indicator of ILA progression in asymptomatic patients. Those with KL-6 levels exceeding 400 U/mL should be closely monitored for radiologic progression.

Objective: This study aims to investigate may moesin deficiency resulted in neurodevelopmental abnormalities caused by negative impact on synaptic signaling ultimately leading to synaptic structure and plasticity. Methods: Behavioral assessments measured neurodevelopment (surface righting, negative geotaxis, cliff avoidance), anxiety (open field test, elevated plus maze test), and memory (passive avoidance test, Y-maze test) in moesin-knockout mice (KO) compared to wild-type mice (WT). Whole exome sequencing (WES) of brain (KO vs. WT) and analysis of synaptic proteins were performed to determine the disruption of signal pathways downstream of moesin. Risperidone, a therapeutic agent, was utilized to reverse the neurodevelopmental aberrance in moesin KO. Results: Moesin-KO pups exhibited decrease in the surface righting ability on postnatal day 7 (p<0.05) and increase in time spent in the closed arms (p<0.01), showing increased anxiety-like behavior. WES revealed mutations in pathway aberration in neuron projection, actin filament-based processes, and neuronal migration in KO. Decreased cell viability (p<0.001) and expression of soluble NSF adapter protein 25 (SNAP25) (p<0.001) and postsynaptic density protein 95 (PSD95) (p<0.01) was observed in days in vitro 7 neurons. Downregulation of synaptic proteins, and altered phosphorylation levels of Synapsin I, mammalian uncoordinated 18 (MUNC18), extracellular signal-regulated kinase (ERK), and cAMP response element-binding protein (CREB) was observed in KO cortex and hippocampus. Risperidone reversed the memory impairment in the passive avoidance test and the spontaneous alternation percentage in the Y maze test. Risperidone also restored the reduced expression of PSD95 (p<0.01) and the phosphorylation of Synapsin at Ser605 (p<0.05) and Ser549 (p<0.001) in the cortex of moesin-KO. Conclusion Moesin deficiency leads to neurodevelopmental delay and memory decline, which may be caused through altered regulation in synaptic proteins and function.

To investigate the relationship between depression and AD, water avoidance stress (WAS) was induced for 10 days in both Tg2576 mice and wild-type (WT) mice. After WAS, memory function and depressive-like behavior were investigated in Tg2576 mice. Tg2576 WAS mice exhibited more depressive-like behaviors than WT WAS and Tg2576 control (CON) mice. Strikingly, Tg2576 CON mice showed more depressive-like behaviors than WT mice. Moreover, corticosterone and phospho-glucocorticoid receptor (p-GR) levels were also higher in Tg2576 WAS mice in comparison to Tg2576 CON mice. Spinster homologue 2 (SPNS2) is a member of non-ATP-dependent transporter. The role of SPNS2 was widely known as a sphingosine-1-phosphate (S1P) transporter, which export intracellular S1P from cells. Using GEO database to analyze SPNS2 gene expression changes in patients with AD and depression, we show that SPNS2 gene expression correlates with AD and depression. Interestingly, Tg2576 WAS mice displayed significantly increased levels of SPNS2 w1hen compared to Tg2576 CON counterparts. SPNS2 levels were also higher in Tg2576 CON mice in comparison with WT CON mice. Remarkably, we found a decrease in S1P brain levels and an increase in S1P serum levels of Tg2576 WAS mice in comparison with Tg2576 CON mice. Accordingly, WAS induced group further decreased S1P levels in the brains. However, the level in the serum further increased in comparison with non-induced group. Therefore, these results suggest that AD and depression could be associated, and that Tg2576 transgenic mice are more susceptible to stress-induced depression through the release of S1P by SPNS2 up-regulation.