Purpose: This developmental study explored the conceptual feasibility and applicability of a metaverse-based clinical assessment platform as a complementary tool to conventional objective structured clinical examinations in undergraduate medical education. Methods: A targeted literature review and expert consensus process were conducted to identify domains of clinical competence in which metaverse technologies could provide added value. Based on these findings, prototype virtual patient simulations were developed within a metaverse environment. Large language models (LLMs) were integrated to support dynamic, interactive history-taking simulations, and pilot modules for physical examination were also created. Results: Integration of LLMs into virtual patient scenarios enabled realistic, context-sensitive medical interviews, facilitating interactive dialogue between examinees and simulated patients. In contrast, physical examination modules faced technical limitations, particularly in replicating procedures requiring tactile or haptic feedback, such as palpation and percussion. Nevertheless, the metaverse environment enabled delivery of consistent and reproducible scenarios, supporting objective assessment of communication and diagnostic reasoning skills. Conclusion Metaverse-based simulations augmented by LLMs offer a promising approach to scalable and standardized clinical assessment, particularly within cognitive and interpersonal competency domains. Although current technological constraints limit the fidelity of physical examination simulations, rapid advancements in immersive and haptic technologies may help overcome these barriers in the near future. Further research is needed to evaluate the educational efficacy, validity, and feasibility of deploying such platforms in summative, high-stakes assessment contexts.

Purpose: Colorectal cancer (CRC) remains a leading cause of cancer-related mortality, necessitating the identification of novel therapeutic targets. The E3 ubiquitin ligase WW domain-containing E3 ubiquitin protein ligase 2 (WWP2) has been implicated in various cancers, yet its specific role and underlying molecular mechanisms in CRC are poorly understood. This study aimed to investigate the functional role of WWP2 in CRC progression and to elucidate its regulatory mechanisms. Methods: WWP2 expression was evaluated in CRC patient tissues and cell lines using immunohistochemistry, quantitative real-time polymerase chain reaction, and western blotting. The biological functions of WWP2 were assessed using in vitro assays for cell proliferation, migration, and invasion following adenovirus-mediated overexpression. The molecular mechanism was investigated by analyzing the protein expression levels of p53 and its downstream target, p21, via western blot. An in vivo xenograft mouse model was used to confirm the oncogenic role of WWP2. Results: WWP2 expression was significantly upregulated in CRC tissues. Overexpression of WWP2 promoted CRC cell proliferation, migration, and invasion. Mechanistically, increased WWP2 expression led to a marked reduction in the protein levels of the tumor suppressor p53. Consequently, the expression of the p53 downstream target, the cell cycle inhibitor p21, was also suppressed. In the xenograft model, WWP2 overexpression significantly enhanced tumor growth. Conclusion Our findings demonstrate that WWP2 functions as an oncogene in CRC. It promotes cancer progression by destabilizing the tumor suppressor p53 and downregulating p21. This study highlights the WWP2-p53-p21 axis as a potential novel therapeutic target for CRC.

Background: Catecholamines play a crucial role in muscle biogenesis, but their persistent elevation is linked to muscle wasting, which is poorly understood. This study aimed to investigate the association between catecholamine levels and age-related muscle loss. Methods: This retrospective study evaluated the plasma levels of two catecholamines, metanephrine and normetanephrine, and the clinical characteristics of 830 patients with adrenal incidentaloma on computed tomography (CT). Cross-sectional CT data at the L3 lumbar vertebrae were used to measure muscle areas. In vitro studies on C2C12 myotubes were conducted to examine β-adrenergic receptor signaling pathways and their role in myogenesis. Results: Men had significantly higher mean metanephrine levels of 0.17 nmol/L and normetanephrine levels of 0.63 nmol/L than women (P<0.05). Total abdominal muscle area was negatively correlated with catecholamine levels in both men and women, with the strongest negative correlation between normetanephrine levels and total abdominal muscle area in men (r=–0.31, P<0.001). Similarly, the strongest negative correlation between visceral fat area and metanephrine was observed in men (r=–0.25, P=0.004). Clenbuterol, a β-adrenergic receptor agonist, inhibited myogenesis, including myotube formation by extracellular signal-regulated kinase (ERK) suppression in C2C12 myoblasts. Conversely, β-blockers increased myogenesis via increasing ERK phosphorylation in C2C12 cells. These findings suggest that β-adrenergic modulation influences skeletal muscle differentiation, with ERK phosphorylation. Conclusion Catecholamine levels are associated with age, sex, muscle mass, and fat mass. Monitoring catecholamine levels, particularly in older men and in individuals with reduced muscle mass, may help manage age-related muscle loss and lead to individualized treatment strategies.

Purpose: This study aimed to develop and implement an antimicrobial stewardship education program for physician assistant nurses and to evaluate its effects on their knowledge and clinical performance. Methods: A quasi-experimental, single-group pre-post design was conducted with 50 physician assistant nurses at a university hospital in Seoul, Republic of Korea. The antimicrobial stewardship education program, developed using the ADDIE model, consisted of 12 sessions including lectures and case-based learning (CBL)-based discussions.Knowledge was measured before and immediately after the intervention, while performance was assessed pre-intervention and four weeks post-program. Data were analyzed using paired t-tests, Wilcoxon signed-rank tests, and analysis of covariance (ANCOVA). Results: Knowledge scores significantly improved from 44.65±7.45 to 58.50±10.11 (p<.001), and all subdomains showed significant increases (p<.001). Performance scores increased from 3.68±0.77 to 4.28±0.68 (p<.001). Knowledge gain did not differ significantly between the medical and surgical departments (p=.710). Likewise, after adjusting for pre-test scores, no significant difference in performance improvement was observed between the two departments (ANCOVA, p=.170). These results indicate that the program was effective across both departments regardless of their characteristics. Conclusion The antimicrobial stewardship education program improved both knowledge and performance among physician assistant nurses. This program may contribute to the standardization of antimicrobial stewardship education and to appropriate antimicrobial use and the reduction of antimicrobial resistance.

Background: and Purpose Treatments for neuromyelitis optica spectrum disorder (NMOSD) such as eculizumab, ravulizumab, satralizumab, and inebilizumab have significantly advanced relapse prevention, but they remain expensive. Rituximab is an off-label yet popular alternative that offers a cost-effective solution, but its real-world efficacy needs better quantification for guiding the application of newer approved NMOSD treatments (ANTs). This study aimed to determine real-world rituximab failure rates to anticipate the demand for ANTs and aid in resource allocation. Methods: We conducted a nationwide retrospective study involving 605 aquaporin-4-antibody-positive NMOSD patients from 22 centers in South Korea that assessed the efficacy and safety of rituximab over a median follow-up of 47 months. Results: The 605 patients treated with rituximab included 525 (87%) who received continuous therapy throughout the follow-up period (median=47 months, interquartile range=15–87 months). During this period, 117 patients (19%) experienced at least 1 relapse. Notably, 68 of these patients (11% of the total cohort) experienced multiple relapses or at least 1 severe relapse.Additionally, 2% of the patients discontinued rituximab due to adverse events, which included severe infusion reactions, neutropenia, and infections. Conclusions This study has confirmed the efficacy of rituximab in treating NMOSD, as evidenced by an 87% continuation rate among patients over a 4-year follow-up period. Nevertheless, the occurrence of at least one relapse in 19% of the cohort, including 11% who experienced multiple or severe relapses, and a 2% discontinuation rate due to adverse events highlight the urgent need for alternative therapeutic options.

Purpose: Cancer poses a significant global health challenge, demanding precise genomic testing for individualized treatment strategies. Targeted-panel sequencing (TPS) has improved personalized oncology but often lacks comprehensive coverage of crucial cancer alterations. Whole-genome sequencing (WGS) addresses this gap, offering extensive genomic testing. This study demonstrates the medical potential of WGS. Materials and Methods: This study evaluates target-enhanced WGS (TE-WGS), a clinical-grade WGS method sequencing both cancer and matched normal tissues. Forty-nine patients with various solid cancer types underwent both TE-WGS and TruSight Oncology 500 (TSO500), one of the mainstream TPS approaches. Results: TE-WGS detected all variants reported by TSO500 (100%, 498/498). A high correlation in variant allele fractions was observed between TE-WGS and TSO500 (r=0.978). Notably, 223 variants (44.8%) within the common set were discerned exclusively by TE-WGS in peripheral blood, suggesting their germline origin. Conversely, the remaining subset of 275 variants (55.2%) were not detected in peripheral blood using the TE-WGS, signifying them as bona fide somatic variants. Further, TE-WGS provided accurate copy number profiles, fusion genes, microsatellite instability, and homologous recombination deficiency scores, which were essential for clinical decision-making. Conclusion TE-WGS is a comprehensive approach in personalized oncology, matching TSO500’s key biomarker detection capabilities. It uniquely identifies germline variants and genomic instability markers, offering additional clinical actions. Its adaptability and cost-effectiveness underscore its clinical utility, making TE-WGS a valuable tool in personalized cancer treatment.

Background: and Purpose Treatments for neuromyelitis optica spectrum disorder (NMOSD) such as eculizumab, ravulizumab, satralizumab, and inebilizumab have significantly advanced relapse prevention, but they remain expensive. Rituximab is an off-label yet popular alternative that offers a cost-effective solution, but its real-world efficacy needs better quantification for guiding the application of newer approved NMOSD treatments (ANTs). This study aimed to determine real-world rituximab failure rates to anticipate the demand for ANTs and aid in resource allocation. Methods: We conducted a nationwide retrospective study involving 605 aquaporin-4-antibody-positive NMOSD patients from 22 centers in South Korea that assessed the efficacy and safety of rituximab over a median follow-up of 47 months. Results: The 605 patients treated with rituximab included 525 (87%) who received continuous therapy throughout the follow-up period (median=47 months, interquartile range=15–87 months). During this period, 117 patients (19%) experienced at least 1 relapse. Notably, 68 of these patients (11% of the total cohort) experienced multiple relapses or at least 1 severe relapse.Additionally, 2% of the patients discontinued rituximab due to adverse events, which included severe infusion reactions, neutropenia, and infections. Conclusions This study has confirmed the efficacy of rituximab in treating NMOSD, as evidenced by an 87% continuation rate among patients over a 4-year follow-up period. Nevertheless, the occurrence of at least one relapse in 19% of the cohort, including 11% who experienced multiple or severe relapses, and a 2% discontinuation rate due to adverse events highlight the urgent need for alternative therapeutic options.

Background: s/Aims: Hepatocellular carcinoma (HCC) is the sixth most common cancer and second leading cause of cancer-related deaths in South Korea. This study evaluated the characteristics of Korean patients newly diagnosed with HCC in 2016-2018. Methods: Data from the Korean Primary Liver Cancer Registry (KPLCR), a representative database of patients newly diagnosed with HCC in South Korea, were analyzed. This study investigated 4,462 patients with HCC registered in the KPLCR in 2016-2018. Results: The median patient age was 63 years (interquartile range, 55-72). 79.7% of patients were male. Hepatitis B infection was the most common underlying liver disease (54.5%). The Barcelona Clinic Liver Cancer (BCLC) staging system classified patients as follows: stage 0 (14.9%), A (28.8%), B (7.5%), C (39.0%), and D (9.8%). The median overall survival was 3.72 years (95% confidence interval, 3.47-4.14), with 1-, 3-, and 5-year overall survival rates of 71.3%, 54.1%, and 44.3%, respectively. In 2016-2018, there was a significant shift toward BCLC stage 0-A and Child-Turcotte-Pugh liver function class A (P<0.05), although survival rates did not differ by diagnosis year. In the treatment group (n=4,389), the most common initial treatments were transarterial therapy (31.7%), surgical resection (24.9%), best supportive care (18.9%), and local ablation therapy (10.5%). Conclusions Between 2016 and 2018, HCC tended to be diagnosed at earlier stages, with better liver function in later years. However, since approximately half of the patients remained diagnosed at an advanced stage, more rigorous and optimized HCC screening strategies should be implemented.

Radiofrequency ablation (RFA) is a minimally invasive treatment modality used as an alternative to surgery in patients with benign thyroid nodules, recurrent thyroid cancers (RTCs), and primary thyroid microcarcinomas. The Korean Society of Thyroid Radiology (KSThR) initially developed recommendations for the optimal use of RFA for thyroid tumors in 2009 and revised them in 2012 and 2017. As new meaningful evidence has accumulated since 2017 and in response to a growing global interest in the use of RFA for treating malignant thyroid lesions, the task force committee members of the KSThR decided to update the guidelines on the use of RFA for the management of RTCs based on a comprehensive analysis of current literature and expert consensus.

Objective: To investigate the effects of methylphenidate and atomoxetine treatment on motor coordination in children with attention-deficit/hyperactivity disorder (ADHD). Methods: In this single-site, open-label, naturalistic follow-up study, 157 children (7.6±1.4 years; 139 males) with ADHD were recruited between March 2015 and May 2020 from the Department of Psychiatry, Asan Medical Center, and treated for 12 weeks with methylphenidate (n=48) or atomoxetine (n=109). Children completed the Advanced Test of Attention (ATA), and caregivers completed the ADHD Rating Scale (ARS) questionnaire and Developmental Coordination Disorder Questionnaire (DCDQ) at baseline and at 12 weeks. Paired t-tests, a mixed-effects model, and linear regression were used to compare treatment groups and assess factors influencing motor coordination changes. Results: Methylphenidate and atomoxetine resulted in significant improvement in DCDQ fine motor/handwriting, general coordination, and total scores over 12 weeks. Fine motor/handwriting had a significant main effect for time (F1=16.64, p<0.001, η2=0.097); however, the interaction effect between group and time was not significant (F1=0.24, p=0.625, η2=0.002). Changes in parent-reported ARS inattention scores (β=-0.174, p=0.029) and auditory commission errors of ATA (β=0.191, p=0.022) were significantly associated with changes in fine motor/handwriting. Additionally, changes in parent-reported ARS inattention scores (β=-0.177, p=0.034) and rater-reported ARS inattention scores (β=-0.198, p=0.017) were significant predictors of improvements in general coordination in separate models. Conclusion Methylphenidate and atomoxetine had a positive effect on motor coordination in children with ADHD. Improvement in motor coordination was associated with ADHD symptom improvement.