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: The triggering receptor expressed on myeloid cells 2 (TREM2) creates an immunosuppressive environment, but the effects of anticancer treatment on TREM2 and the tumor microenvironment (TME) are not well established. This study investigates the impact of chemotherapy on TREM2-expressing macrophages within the lung adenocarcinoma TME. Materials and Methods: Using single-cell RNA sequencing datasets of paired normal-appearing lung tissue (NL) and tumor (Tu), human and mouse lung cancer tissue, and THP-1 cells, we observed the effects of anticancer drugs on them. Results: Myeloid cells (MY) were the second-most abundant non-epithelial component in the Tu, though less prevalent than in NL. Specific MY subclusters abundant in Tu showed overexpression of TREM2. In lung cancer-induced Kras-G12D mice, M2 proportion increased in Tu compared to NL; cisplatin increased TREM2+ M2 proportion in Tu. TREM2+ cells in Tu showed interactions with cell clusters showing characteristics of interstitial macrophage such as mo-lineage, mono-Mc, and CD163/LGMN cells via FN:CD44 and MIF:CD74+CXCR4, suggesting that they influence the recruitment of those cells to Tu and TME reshape. In M0-state THP-1 cells, cisplatin and osimertinib treatments induced polarization towards M1 and M2 states and increased TREM2 expression. Cisplatin promoted uptake of phosphatidylserine-coated latex beads by M0 cells, whereas osimertinib reduced uptake by polarized macrophages. These findings suggest anticancer treatments impact the lung immune microenvironment by altering the TREM2+ cells. Conclusion Given TREM2’s central inhibitory role in the tumor immune environment, effects of chemotherapeutic agents should be considered in developing TREM2-targeting therapies.

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.

Janus kinase (JAK) inhibitors are an important treatment option for ulcerative colitis, providing rapid onset of action, oral administration, and efficacy even after biologic failure. The 3 approved agents—tofacitinib, filgotinib, and upadacitinib—differ in JAK isoform selectivity, leading to clinically meaningful differences in efficacy and safety. Evidence from network meta-analyses, clinical trials, and real-world studies consistently shows that upadacitinib provides the highest efficacy for induction and maintenance of remission, whereas filgotinib demonstrates the most favorable safety profile. The strong efficacy of upadacitinib and tofacitinib is particularly relevant in patients with severe disease, including acute severe ulcerative colitis, and upadacitinib maintains high efficacy regardless of prior advanced therapy exposure. JAK inhibitors also benefit extraintestinal manifestations. Although risks such as herpes zoster, serious infection, thromboembolism, and major cardiovascular events differ among agents, long-term data suggest generally acceptable safety when used appropriately. Intraclass JAK-to-JAK cycling is feasible, with about half of patients achieving steroid-free clinical remission in retrospective cohorts. Based on mechanistic, clinical, and real-world evidence, filgotinib may be a first-line option for patients with lower disease activity or when safety is a priority, whereas upadacitinib or tofacitinib may be preferred in higher disease activity. Strategically selecting agents may improve durability and outcomes.

Although aspartate aminotransferase (AST) is a serum marker of hepatocellular damage in chronic hepatitis, it is difficult to interpret very high AST levels with concurrent low alanine aminotransferase (ALT) levels. Macro-AST is an immunoglobulin-AST complex that can present as aberrant high enzymatic activity without significant inflammation in the liver. Two patients with chronic hepatitis B presented with disproportionate AST elevations. Their plasma samples were precipitated with polyethylene glycol (PEG) and stored at 4°C for macro-AST determinations. In Case 1, PEG precipitation showed 100% removal of AST activity, and refrigerated storage resulted in a ~70% decline over seven days, confirming macro-AST. In Case 2, both tests showed minimal changes, suggesting that macro-AST was unlikely. The AST levels normalized after antiviral therapy, suggesting immune-active hepatitis as the probable cause, but the other contributing factors could not be completely excluded. The abrupt decrease in AST activity after PEG precipitation and during refrigeration storage suggests that relatively high AST values compared to ALT might be attributed to the presence of macro-AST.These non-invasive methods for detecting macroenzymes might help the patient avoid unnecessary further work-ups.

Objective: Posterior interosseous nerve (PIN) syndrome (PINS) is a compressive neuropathy of the deep branch of the radial nerve that primarily presents with motor weakness of finger and thumb extension. Although some patients respond to conservative management, others develop persistent motor deficits requiring surgical decompression. This study aimed to evaluate the clinical outcomes of external neurolysis in patients with PINS presenting with refractory motor weakness. Methods: Seven patients with clinically diagnosed PINS who exhibited persistent motor weakness despite conservative treatment and subsequently underwent surgical decompression were retrospectively reviewed. Clinical characteristics, magnetic resonance imaging (MRI) findings, intraoperative compression sites, and postoperative motor recovery were analyzed. Motor strength was evaluated using the Medical Research Council grading system. Preoperative and postoperative motor strength grades were compared using the Wilcoxon signed-rank test. Results: The patients presented with progressive weakness of finger extension, resulting in impaired hand opening. MRI demonstrated denervation-related signal changes and atrophy in the affected muscles innervated by the PIN. Surgical exploration revealed compressive structures within the radial tunnel, most commonly at the arcade of Frohse. Significant improvement in motor strength was observed within 2 months postoperatively (thumb extension, p = 0.018; second digit extension, p = 0.011; third to fifth digit extension, p = 0.009). One patient experienced symptom recurrence approximately 6 months after the initial surgery and subsequently underwent revision decompression. Conclusion External neurolysis provides meaningful recovery of finger extension in patients with PINS presenting with refractory motor weakness. MRI may support the diagnosis by demonstrating denervation-related morphological changes in the affected muscles. Recurrence of PINS may occur even after initial recovery, highlighting the importance of careful postoperative follow-up.

Purpose: To propose improvements for promoting eyeball donation and managing donated corneas, this study analyzed the current system in Korea and reviewed relevant Korean laws, international standards, and foreign practices. Methods: To understand the current situation in Korea, annual reports published by the Korean Network for Organ Sharing and existing Korean laws were examined. For the international context, references were made to the National Organ Transplant Act, 21 CFR Part 1271 (Code of Federal Regulations Title 21 Part 1271), Current Good Tissue Practice guidelines of the Food and Drug Administration, and the Medical Standards of the Eye Bank Association of America in the United States. Opinions on promoting eyeball donation, improving the monitoring system for donated corneas and revising laws related to cornea management were gathered. The perspectives of 31 experts affiliated with the Korea Cornea Society were collected through a survey. Results: Currently, there are no laws or regulations that can be appropriately applied to the cornea which has properties of both organs and tissue. Additionally, there is no law regulating imported corneas. Therefore, there is a need to legislate or revise the current law; all experts who conducted the survey agreed on this. Furthermore, the current system faces limitations in the efficient procurement, stable supply, and management of donor corneas, as well as in donation promotion. To address these issues, the establishment of independent legislation for managing donated corneas and a National Central Eye Bank was proposed. This central body would oversee continuous personnel training, education, and monitoring, along with ensuring stable procurement, processing, and supply of corneas within a structured management system. Sixty-eight percent of the surveyed experts agreed with this proposal. Conclusions To establish a safe and efficient Korean corneal supply and demand system, it is imperative to enact cornea-specific laws, including the establishment of a National Central Eye Bank.

Medial opening wedge supramalleolar osteotomy (SMO) is a representative joint-preserving surgical procedure for varus ankle osteoarthritis, based on the principle of load redistribution, with favorable radiologic and clinical outcomes. This procedure is indicated for patients with Takakura stage 2 or 3A arthritis, whereas severe vascular or neurological impairment and osteomyelitis are considered absolute contraindications. Although SMO is generally limited to patients younger than 70 years because of the risk of delayed or nonunion in elderly individuals, few reports on the outcomes in elderly patients have been published. This paper reports two cases of varus ankle osteoarthritis in patients over 75 years of age who underwent SMO after failed conservative treatment, with a follow-up exceeding 2 years, along with a review of the relevant literature. Both cases achieved successful bone union without delayed healing. At the final follow-up, the foot and ankle ability measure (FAAM)–activities of daily living and FAAM-sport scores showed marked improvement compared with the preoperative values. In conclusion, SMO may be a viable joint-preserving treatment option, even in elderly patients, provided that their general health is favorable.

Multiple myeloma (MM), a hematological malignancy, is characterized by malignant plasma cell proliferation in the bone marrow. Recent treatment advances have significantly improved patient outcomes associated with MM.In this study, we aimed to develop comprehensive, evidence-based guidelines for the diagnosis, prognosis, and treat‑ ment of MM. We identified 12 key clinical questions essential for MM management, guiding the extensive literature review and meta-analysis of the study. Our guidelines provide evidence-based recommendations by integrating patient preferences with survey data. These recommendations include current and emerging diagnostic tools, thera‑ peutic agents, and treatment strategies. By prioritizing a patient-centered approach and rigorous data analysis, these guidelines were developed to enhance MM management, both in Korea and globally.

With a rapidly aging population and increasing use of antiresorptive agents, medication-related osteonecrosis of the jaw (MRONJ) represents a growing clinical challenge worldwide. To address the need for tailored clinical guidance, a multidisciplinary task force was convened. Five Korean academic societies—the Korean Society for Bone and Mineral Research, the Korean Association of Oral and Maxillofacial Surgeons, the Korean Association of Maxillofacial Plastic and Reconstructive Surgeons, the Korean Society of Osteoporosis, and the Korean Endocrine Society—collaborated to develop this position statement. The consensus was formulated through comprehensive reviews of literature, combined with three rounds of formal surveys to consolidate expert opinion on controversial topics. This position paper provides evidence-based clinical guidelines for the prevention, diagnosis, and management of MRONJ tailored to the Korean healthcare environment. The diagnostic criteria affirm the standard definition but add a provision for diagnosis based on clinical or radiographic evidence of necrotic bone, even if the traditional 8-week timeframe has not been met. The committee advocates for retaining Stage 0 in the staging system to emphasize early detection and preventive intervention. Key recommendations include prescriptive, drug-specific guidelines for prophylactic drug holidays (e.g., a 2-month pause for oral bisphosphonates; timing surgery 3-4 months after the last denosumab injection) to minimize MRONJ risk from dental procedures. This statement also provides a clear framework for therapeutic drug holidays in established MRONJ, carefully balancing the need for jaw healing against systemic fracture risk. For treatment, this statement advocates for early and active surgical intervention across all MRONJ stages, supported by evidence of superior long-term outcomes compared to conservative management.This position statement offers a unique, evidence-based Korean clinical practice guideline for managing MRONJ. It is intended to standardize care, reduce clinical confusion, and ultimately improve patient outcomes by providing a clear framework for decision-making.