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: Limited treatment options exist for patients with metastatic castration-resistant prostate cancer (mCRPC) after the failure of taxane-based chemotherapy and novel hormonal therapy. Here, we report the safety and efficacy of ifosfamide and mesna in patients with mCRPC after the failure of taxane-based chemotherapy and novel hormonal therapy (NCT06236789). Materials and Methods: Patients with histologically confirmed prostate cancer who had failed taxane-based chemotherapy and novel hormonal therapy received ifosfamide 2,500 mg/m2 and mesna 1,500 mg/m2 on days 1–3, repeated every 21 days. Safety, objective response rate, disease control rate, reduction in serum prostate-specific antigen (PSA) concentration by >50% (PSA50) or >90% (PSA90), radiographic progression-free survival (rPFS), and overall survival (OS) were analyzed. Results: A total of 47 patients with mCRPC were included in the study. The median number of lines of treatment was 5 (range, 3 to 7). All patients were previously administered docetaxel and novel hormonal therapies including abiraterone (51.1%) and/or enzalutamide (61.7%). Thirty-eight patients (80.9%) were administered cabazitaxel. The objective response and disease control rates were 21.3% and 80.9%, respectively. PSA50 and PSA90 were achieved in 31.9% and 10.6%, respectively. During a median follow-up duration of 54.3 months, rPFS and OS were 5.0 and 9.0 months, respectively. All the patients experienced treatment-related adverse events of any grades; however, no new safety signs were detected. Genomic biomarker analysis revealed that alterations in the TP53 pathway were associated with inferior rPFS and OS. Conclusion Ifosfamide and mesna showed appreciable efficacy and manageable safety profiles in heavily treated patients with mCRPC.

Objective: To explain process of developing basic veterinary clinical performance guidelines, based on frequently observable clinical manifestations, thereby supporting competencybased veterinary education in Korea. Methods: A structured review of learning outcomes established by Korean Association of Veterinary Medical Colleges (KAVMC) was conducted by a planning committee including veterinary educators, practitioners, and advisory members. Owner-oriented descriptions were used to frame each performance task, and each was mapped to corresponding learning outcomes. These tasks were aligned with learning outcomes recommended by the KAVMC to support the development of communication, clinical reasoning, and performance-related competencies among veterinary students, thereby enhancing day-one clinical readiness. Results: In total, 63 clinical manifestations for a guidebook format that can be used for clinical education were identified and categorized by organ systems that are described in language understandable to animal owners. Conclusions and Relevance: The basic veterinary clinical performance guidelines based on common clinical manifestations would serve as a vital component in veterinary education to reinforce core graduation competencies.

Background: Adequate tissue oxygenation is a key determinant of diabetic foot ulcer (DFU) outcomes. Though transcutaneous oxygen pressure (TcPO2) is the gold standard for evaluating tissue oxygenation, its limited availability restricts routine clinical use. Consequently, toe pressure is frequently utilized as a practical surrogate; however, the direct correlation between these two modalities has yet to be rigorously investigated. This study aimed to assess the correlation and agreement between TcPO2 and toe pressure in patients with DFUs. Methods: A retrospective review was conducted on 837 DFU patients who received simultaneous TcPO2 and toe pressure assessments. The correlation between the two tests was analyzed using the Pearson correlation coefficient, and agreement was evaluated using Bland–Altman analysis. To aid interpretation, a scatterplot and Bland–Altman plot were generated. Results: TcPO2 and toe pressure demonstrated a strong correlation (R=0.66; 95% confidence interval, 0.62 to 0.70; P<0.001). Bland–Altman analysis showed a mean bias of 26.9 mmHg (standard deviation of differences, 28.8 mmHg; 95% limits of agreement, −28.9 to 82.6 mmHg) between toe pressure and TcPO2, reflecting limited agreement and increased variability at higher perfusion levels. Conclusion TcPO2 and toe pressure are strongly correlated. However, they are not interchangeable, particularly in DFU patients with high tissue perfusion.

Background: The clinical manifestations of metastatic brachial plexopathy include pain, sensory loss, paresthesia, weakness, and reduced range of motion. These symptoms closely resemble those of shoulder disorders and peripheral nerve entrapment, which are commonly diagnosed in pain clinics, increasing the risk of misdiagnosis or delayed diagnosis, particularly in patients with a history of malignancy.Case: A 51-year-old woman with a history of breast cancer in complete remission for 19 years presented with shoulder pain, arm weakness, and tingling in the fingers. Initial treatments for suspected cervical radiculopathy, shoulder disorders, and nerve entrapment were ineffective. Electromyography and nerve conduction studies revealed electrophysiological abnormalities consistent with left brachial plexopathy. Magnetic resonance imaging of the brachial plexus confirmed metastatic involvement. The patient is currently undergoing chemotherapy. Conclusions Clinicians must be vigilant of the possibility of malignancy in patients with a history of cancer and should pursue comprehensive diagnostic evaluations to exclude cancer recurrence.

Purpose: This multicenter, open-label, phase II trial evaluated the efficacy and safety of bortezomib combined with dexamethasone for the treatment of relapsed/refractory cutaneous T-cell lymphoma (CTCL) in previously treated patients across 14 institutions in South Korea. Materials and Methods: Between September 2017 and July 2020, 29 patients with histologically confirmed CTCL received treatment, consisting of eight 4-week cycles of induction therapy followed by maintenance therapy, contingent upon response, for up to one year. The primary endpoint was the proportion of patients achieving an objective global response. Results: Thirteen of the 29 patients (44.8%) achieved an objective global response, including two complete responses. The median progression-free survival (PFS) was 5.8 months, with responders showing a median PFS of 14.0 months. Treatment-emergent adverse events were generally mild, with a low incidence of peripheral neuropathy and hematologic toxicities. Despite the trend toward shorter PFS in patients with higher mutation burdens, genomic profiling before and after treatment showed no significant emergence of new mutations indicative of disease progression. Conclusion This study supports the use of bortezomib and dexamethasone as a viable and safe treatment option for previously treated CTCL, demonstrating substantial efficacy and manageability in adverse effects. Further research with a larger cohort is suggested to validate these findings and explore the prognostic value of mutation profiles.

Background/Aims: Inaccurate prediction of lymph node metastasis (LNM) may lead to unnecessary surgery following endoscopic resection of T1 colorectal cancer (CRC). We aimed to validate the usefulness of artificial intelligence (AI) models for predicting LNM in patients with T1 CRC. Methods: We analyzed the clinical data, laboratory results, pathological reports, and endoscopic findings of patients who underwent radical surgery for T1 CRC. We developed AI models to predict LNM using four algorithms: regularized logistic regression classifier (RLRC), random forest classifier (RFC), CatBoost classifier (CBC), and the voting classifier (VC). Four histological factors and four endoscopic findings were included to develop AI models. Areas under the receiver operating characteristics curves (AUROCs) were measured to distinguish AI model performance in accordance with the Japanese Society for Cancer of the Colon and Rectum guidelines. Results: Among 1,386 patients with T1 CRC, 173 patients (12.5%) had LNM. The AUROC values of the RLRC, RFC, CBC, and VC models for LNM prediction were significantly higher (0.673, 0.640, 0.679, and 0.677, respectively) than the 0.525 suggested in accordance with the Japanese Society for Cancer of the Colon and Rectum guidelines (vs RLRC, p<0.001; vs RFC, p=0.001; vs CBC, p<0.001; vs VC, p<0.001). The AUROC value was similar between T1 colon versus T1 rectal cancers (0.718 vs 0.615, p=0.700). The AUROC value was also similar between the initial endoscopic resection and initial surgery groups (0.581 vs 0.746, p=0.845). Conclusions AI models trained on the basis of endoscopic findings and pathological features performed well in predicting LNM in patients with T1 CRC regardless of tumor location and initial treatment method.

Background/Aims: The study investigated the incidence, risk factors, and clinical outcomes of chronic antibiotic-refractory pouchitis (CARP) in Korean patients with ulcerative colitis (UC). Methods: This single-center retrospective study included patients with UC who underwent total proctocolectomy with ileal pouch-anal anastomosis at the Asan Medical Center in Korea between January 1987 and December 2022. The primary outcomes were endoscopic remission and pouch failure. The Cox’s proportional hazard model was used to identify the risk factors for CARP. Results: The clinical data of 232 patients were analyzed. The most common cause of surgery was steroid refractoriness (50.9%), followed by dysplasia/colorectal cancer (26.7%). Among 74 patients (31.9%) with chronic pouchitis (CP), 31 (13.4%) had CARP, and 43 (18.5%) had chronic antibiotic-dependent pouchitis (CADP). The most frequent endoscopic phenotype was focal inflammation of the pouch (CP, 47.3%; CARP, 35.5%; CADP, 55.8%). Patients with CARP were less likely to use concomitant probiotics than patients with CADP (29.0% vs 72.1%, p<0.01). The endoscopic remission rate of CP, CARP, and CADP was 14.9%, 9.7%, and 18.6%, respectively.The pouch failure rate associated with CP, CARP, and CADP was 13.5%, 16.1%, and 11.6%, respectively. Current smoking status (adjusted hazard ratio [aHR], 2.96; 95% confidence interval [CI], 1.27 to 6.90; p=0.01) and previous use of biologics/small molecules (aHR, 2.40; 95% CI, 1.05 to 5.53; p=0.04) were significantly associated with CARP development. Conclusions UC patients who were current smokers and previously used biologics/small molecules had a higher risk of developing CARP. Concomitant use of probiotics was less likely to be associated with CARP development.