Background: As nationwide government-led whole-genome sequencing (WGS) projects progress, optimizing the clinical integration of large-scale WGS results is crucial. We explored how the initial analysis from Korea’s First WGS Pilot Study for Rare Diseases was applied in clinical practice, and then we reanalyzed the data comprehensively at Samsung Medical Center (SMC) Seoul, Korea. Methods: A prospective cohort study designed to collect WGS data under a Korean national initiative was conducted from August 2020 to December 2021. We focused on patients with rare diseases recruited from 16 university hospitals. The participants included 5,000 individuals (2,200 probands and 2,800 family members). The initial WGS data and diagnostic reference reports (from 682 probands and 484 family members), generated based on the First Korean WGS Pilot Study for Rare Diseases, were subsequently reanalyzed by SMC. Results: The initial analysis of the First Korean WGS Pilot Study data revealed a diagnostic rate of 17%. Upon receiving these results, the SMC conducted two rounds of reanalysis, increasing the diagnostic rate from 15% in the first analysis, to 18% in the second, and finally to 24% in the third (P = 1.6 × 10 −5 ). Key factors in improving the genetic diagnosis included increased detection of novel (likely) pathogenic variants (P = 1.0 × 10 −4 ), improved diagnostic rates with larger family recruitment (P = 0.004), and refined clinical information for more precise genotype–phenotype correlation analysis (40%). Conclusions Although national WGS projects lay a foundation for rare disease diagnosis, hospital-level reanalysis and multidisciplinary collaborations are crucial for optimizing diagnostic outcomes.

The Pheochromocytoma of the Adrenal Gland Scaled Score (PASS) is widely used for risk stratification in pheochromocytoma and paraganglioma (PPGL), but its clinical utility is limited by inter-observer variability of its parameters and inconsistent predictive performance. Methods: We conducted a multicenter retrospective study of 1,518 patients with PPGL from five tertiary referral centers in Korea. Prognostic utility of PASS system was assessed using logistic regression, Kaplan-Meier analysis, and receiver operating characteristic (ROC) curve analysis. Inter-observer variability was inferred by comparing area under the ROC curve (AUCs) across institutions. Simplified PASS systems were developed based on multivariable analysis of key histopathological parameters. Results: The PASS system was a significant predictor of adverse events and recurrence-free survival. Although the PASS system demonstrated only modest discriminative ability (AUC, 0.673), it showed a high negative predictive value (NPV, 0.885), supporting its usefulness as a screening tool for benign behavior. However, there was significant inter-institutional variability in PASS performance (AUC; range, 0.513 to 0.727; p < .05). The 3-factor Simple PASS, which incorporates necrosis, spindling, and mitotic figures, exhibited less inter-observer variation. The 4-factor Simple PASS, which adds vascular invasion to the 3-factor model, also showed reduced inter-observer variability and improved AUC and NPV compared to the original PASS system. Conclusions: In this multicenter cohort, the PASS system demonstrated high NPV and screening potential, but significant inter-observer variability remains a challenge. Simplification of the PASS system and enhanced pathologist training may improve reproducibility and clinical utility in PPGL risk stratification.

This study aimed to determine the prevalence of human epidermal growth factor receptor 2 (HER2)–ultralow breast cancer among cases initially classified as HER2 immunohistochemistry (IHC) 0 and assess interobserver variability in interpreting low-level HER2 expression. Methods: In this multicenter retrospective study, all invasive breast cancer cases diagnosed between January and December 2022 across 10 Korean institutions were retrieved. Institutional pathologists reexamined HER2 IHC slides originally reported as IHC 0 according to the 2018 American Society of Clinical Oncology/College of American Pathologists guidelines and reclassified them as HER2-null (0), HER2-ultralow (0+), or HER2-low (1+). Slides from 10% of HER2-null and HER2-ultralow cases were digitized for central review and independently assessed by two pathologists, with discrepancies resolved by consensus. Results: Among 8,026 cases, 2,836 cases (35.5%) were initially reported as IHC 0. Upon re-review, 1,673 (59.0%), 1,139 (40.2%), and 24 (0.8%) cases were reclassified as HER2-null, HER2-ultralow, and HER2-low, respectively. The prevalence of HER2-ultralow breast cancer varied considerably across institutions (23.7%–78.1%). Central review of 268 digitized cases showed concordance in 193 cases (72.0%). Among the 75 discordant cases, 54 tumors (72.0%) were upgraded from HER2-null to HER2-ultralow, and 18 (24.0%) tumors were upgraded from HER2-ultralow to HER2-low. Furthermore, two tumors (2.7%) were downgraded from HER2-ultralow to HER2-null. Conclusions: Approximately 40% of cases initially categorized as IHC 0 were reclassified as HER2-ultralow. The substantial inter-institutional variability observed in interpreting low-level HER2 expression highlights the need for standardized training and quality assurance to ensure accurate identification of patients eligible for HER2-targeted antibody–drug conjugates.

Purpose: This study aimed to identify the academic stress experienced by medical students in basic medical science courses and analyze its underlying factors. Methods: A survey was conducted among 228 students from a medical school in Seoul, South Korea, of whom 204 who had completed at least one basic science course were included in the final analysis. A modified stress scale for medical students and a newly developed subject-specific academic stress scale, validated through literature review, student feedback, and expert review, were employed. Data were analyzed using IBM SPSS ver. 25.0 with descriptive statistics, t-tests, chi-square tests, and one-way analysis of variance. Results: The overall academic stress among students was relatively high. The highest stress levels were observed in cell biology (mean=7.15), followed by bioinformatics (mean=5.97), molecular biology (mean=5.47), and organic chemistry (mean=5.20). Key stress factors included a lack of connectivity with clinical subjects, excessive learning volume, and inappropriate difficulty levels. Conclusion Academic stress varied significantly across courses, underscoring the need for curriculum improvements in basic medical science education. Faculty should consider adjusting course difficulty, enhancing clinical integration, motivating students, and managing workloads to reduce stress and support learning outcomes.

Myopia, particularly high myopia, is a significant risk factor for several ocular pathologies including cataract, glaucoma, and retinal detachment. Excessive axial elongation associated with high myopia can induce biomechanical stretching, increasing the risk of serious complications like posterior staphyloma and myopic maculopathy. Global meta-analyses estimate that approximately 10 million people were visually impaired due to myopic maculopathy in 2015, with 3 million being blind. Recent nationwide surveys in South Korea revealed a prevalence of 65.4% for myopia and 6.9% for high myopia in children and adolescents, highlighting the urgent need for effective management. Delaying the onset and slowing the progression of myopia during childhood and adolescence is crucial for reducing the potential lifetime risk of these complications. This consensus statement, prepared by the Korean Myopia Society for the Korean Association for Pediatric Ophthalmology and Strabismus (KAPOS), reviews the current evidence for myopia control interventions and provides management strategies applicable to the South Korean clinical setting. Key interventions covered include lifestyle modifications (outdoor time, near work adjustment), optical methods (myopia-control spectacle lenses, dual-focus soft contact lenses, orthokeratology), and pharmacologic treatment (low-concentration atropine), as well as combination therapies. The statement also addresses patient selection, treatment outcome evaluation using spherical equivalent and axial length changes, and the crucial aspects related to treatment cessation and the rebound effect.

Objective: Although most gallbladder polyps are benign, some neoplastic polyps may be malignant or may serve as precursors to malignancy. Distinguishing neoplastic and non-neoplastic polyps using imaging examinations remains a major challenge.This meta-analysis aimed to identify the ultrasound (US) features that are significantly associated with neoplastic polyps. Materials and Methods: The MEDLINE, EMBASE, Cochrane, and KoreaMed databases were searched for articles published up to August 31, 2025. Bivariate random-effects models were used to calculate the meta-analytic pooled diagnostic odds ratios (DORs), sensitivities, and specificities, along with their 95% confidence intervals (CIs), for each US imaging feature in the diagnosis of neoplastic polyps. Results: Thirty studies evaluating 8,953 patients, including 1,216 (13.6%) patients with neoplastic polyps, were included.Among the nine evaluated US imaging features, namely, size ≥10 mm, sessile morphology, single polyp, coexisting gallstones, hypoechogenicity, heterogeneous echogenicity, gallbladder wall thickening (GBWT), absence of hyperechoic spot, and vascularity, eight were significantly associated with neoplastic polyps: size ≥10 mm (DOR: 6.23 [95% CI: 1.86– 20.90]), sessile morphology (DOR: 3.54 [1.93–5.97]), single polyp (DOR: 2.21 [1.76–2.74]), coexisting gallstones (DOR:1.86 [1.29–2.60]), hypoechogenicity (DOR: 3.55 [1.47–7.30]), GBWT (DOR: 9.38 [1.47–32.20]), absence of hyperechoic spots (DOR: 4.23 [2.46–6.83]), and vascularity (DOR: 9.72 [5.81–15.30]). Of these, size ≥10 mm demonstrated the highest pooled sensitivity (0.79 [95% CI: 0.68–0.87]), whereas hypoechogenicity showed the highest pooled specificity (0.93 [95% CI: 0.82–0.98]). Conclusion Eight US imaging features (size ≥10 mm, sessile morphology, single polyp, coexisting gallstones, hypoechogenicity, GBWT, absence of hyperechoic spots, and vascularity) were significantly associated with the presence of neoplastic polyps.These features may facilitate the management of gallbladder polyps.

Objectives: This pilot study examined the preliminary findings associated with a cognitive-load-controlled structured psychodrama program on affect, fear of negative evaluation, and general psychopathology in long-term psychiatric inpatients, most of whom had schizophrenia spectrum disorders. Methods: A single-group pre-post design was used. A total of 125 stabilized long-term psychiatric inpatients participated in a 25-session structured psychodrama program. To enhance measurement validity in consideration of participants’ cognitive characteristics, self-report measures were administered in small-group sessions with individualized explanation. Primary outcomes (Positive and Negative Affect Schedule [PANAS], Affect Balance Scale [ABS], and Brief Fear of Negative Evaluation [BFNE]) were assessed in 125 participants, and the secondary outcome (Brief Psychiatric Rating Scale [BPRS]) was assessed in a randomly selected subgroup of 53 participants. Results: After the intervention, positive affect significantly increased, whereas negative affect significantly decreased on both the PANAS and ABS (all p＜0.001). BFNE scores significantly decreased from 43.14 to 28.94 (p＜0.001). Total BPRS scores also significantly decreased from 47.49 to 34.76 (p＜0.001), with notable improvements in depressive mood, anxiety, tension, somatic concern, and emotional withdrawal. Conclusion A structured psychodrama program may be a feasible and potentially beneficial psychosocial intervention for long-term psychiatric inpatients. However, given the single-group pre-post design and other methodological limitations, the magnitude of the observed changes should be interpreted cautiously. These findings may serve as preliminary data for future controlled trials.

Peripheral nerve injury and oxidative stress can severely impair Schwann cell function by disrupting the expression of key myelin proteins, promoting intracellular lipid accumulation, and damaging mitochondrial integrity. These pathological changes are central to various neurodegenerative disorders and chemotherapy-induced peripheral neuropathy, yet effective therapeutic approaches remain limited. Clemastine, an FDA-approved antihistamine with known remyelination-enhancing effects in the central nervous system, has not been thoroughly explored for its protective role in peripheral myelinating cells under oxidative stress. In this study, we investigated the time-dependent protective effects of Clemastine in S16 Schwann cells exposed to hydrogen peroxide (H2O2) as a model of oxidative injury. Treatment with Clemastine significantly increased the expression of myelin-related proteins such as myelin protein zero (MPZ), alongside in increase in AMPK phosphorylation at Thr172. However, co-treatment with H2O2 ensued oxidative damage, leading to reduced pAMPK(T172) and MPZ expression, elevated ROS levels, and increased lipid accumulation. These results suggest that oxidative stress can attenuate Clemastine’s effects in association with disrupted redox balance and energy metabolism. Subsequent treatment with Metformin (Met), a pharmacological activator of AMPK, was associated with partial recovery from H2O2-induced oxidative damage. Overall, our findings support the potential of a combinatorial approach using Clemastine and Met to promote myelin-related protein expression and lipid metabolic balance in Schwann cells under oxidative stress, rather than establishing a definitive synergistic or causal mechanism.

Purpose: Chronic myeloid leukemia (CML) in children, adolescents, and young adults is rare and differs from older adults. This study evaluated the outcomes of allogeneic hematopoietic stem cell transplantation (HSCT) in young Korean CML patients during the tyrosine kinase inhibitor (TKI) era. Materials and Methods: A retrospective analysis of 35 CML patients aged < 40 years who underwent allogeneic HSCT from 2009 to 2019 was conducted using Korean Blood and Marrow Transplantation Registry data. Patients were grouped by age < 20 years at HSCT (group 1, n=15) and 20-40 years at HSCT (group 2, n=20). Survival outcomes including overall survival (OS), relapse-free survival (RFS), and event-free survival (EFS) were analyzed using the Kaplan-Meier method. Results: The median time between diagnosis and HSCT was 8.9 months. All the patients achieved engraftment but platelet recovery was significantly slower in group 1 (p=0.034). Acute and chronic graft-versus-host disease occurred in 54.3% and 34.3%, respectively. Five-year OS, RFS, and EFS rates of total patients were 66.8%, 50.8%, and 47.6%, with better OS was observed in group 1 by multivariable analysis (p=0.048). Disease status at HSCT was a significant predictor of OS (p=0.028), RFS (p=0.003), and EFS (p=0.004). Disease progression occurred in 13 out of 35 patients (37.1%); treatment-related mortality accounted for 63.6% of deaths (7 out of 11). Conclusion When performed at a younger age, allogeneic HSCT result in superior outcome in CML. Achieving remission before HSCT is critical for improved outcomes, highlighting the importance of pretransplant remission via optimal TKI strategies and minimal residual disease monitoring.