1.Study Protocol of Expanded Multicenter Prospective Cohort Study of Active Surveillance on Papillary Thyroid Microcarcinoma (MAeSTro-EXP)
Jae Hoon MOON ; Eun Kyung LEE ; Wonjae CHA ; Young Jun CHAI ; Sun Wook CHO ; June Young CHOI ; Sung Yong CHOI ; A Jung CHU ; Eun-Jae CHUNG ; Yul HWANGBO ; Woo-Jin JEONG ; Yuh-Seog JUNG ; Kyungsik KIM ; Min Joo KIM ; Su-jin KIM ; Woochul KIM ; Yoo Hyung KIM ; Chang Yoon LEE ; Ji Ye LEE ; Kyu Eun LEE ; Young Ki LEE ; Hunjong LIM ; Do Joon PARK ; Sue K. PARK ; Chang Hwan RYU ; Junsun RYU ; Jungirl SEOK ; Young Shin SONG ; Ka Hee YI ; Hyeong Won YU ; Eleanor WHITE ; Katerina MASTROCOSTAS ; Roderick J. CLIFTON-BLIGH ; Anthony GLOVER ; Matti L. GILD ; Ji-hoon KIM ; Young Joo PARK
Endocrinology and Metabolism 2025;40(2):236-246
Background:
Active surveillance (AS) has emerged as a viable management strategy for low-risk papillary thyroid microcarcinoma (PTMC), following pioneering trials at Kuma Hospital and the Cancer Institute Hospital in Japan. Numerous prospective cohort studies have since validated AS as a management option for low-risk PTMC, leading to its inclusion in thyroid cancer guidelines across various countries. From 2016 to 2020, the Multicenter Prospective Cohort Study of Active Surveillance on Papillary Thyroid Microcarcinoma (MAeSTro) enrolled 1,177 patients, providing comprehensive data on PTMC progression, sonographic predictors of progression, quality of life, surgical outcomes, and cost-effectiveness when comparing AS to immediate surgery. The second phase of MAeSTro (MAeSTro-EXP) expands AS to low-risk papillary thyroid carcinoma (PTC) tumors larger than 1 cm, driven by the hypothesis that overall risk assessment outweighs absolute tumor size in surgical decision-making.
Methods:
This protocol aims to address whether limiting AS to tumors smaller than 1 cm may result in unnecessary surgeries for low-risk PTCs detected during their rapid initial growth phase. By expanding the AS criteria to include tumors up to 1.5 cm, while simultaneously refining and standardizing the criteria for risk assessment and disease progression, we aim to minimize overtreatment and maintain rigorous monitoring to improve patient outcomes.
Conclusion
This study will contribute to optimizing AS guidelines and enhance our understanding of the natural course and appropriate management of low-risk PTCs. Additionally, MAeSTro-EXP involves a multinational collaboration between South Korea and Australia. This cross-country study aims to identify cultural and racial differences in the management of low-risk PTC, thereby enriching the global understanding of AS practices and their applicability across diverse populations.
2.Artificial Intelligence Models May Aid in Predicting Lymph Node Metastasis in Patients with T1 Colorectal Cancer
Ji Eun BAEK ; Hahn YI ; Seung Wook HONG ; Subin SONG ; Ji Young LEE ; Sung Wook HWANG ; Sang Hyoung PARK ; Dong-Hoon YANG ; Byong Duk YE ; Seung-Jae MYUNG ; Suk-Kyun YANG ; Namkug KIM ; Jeong-Sik BYEON
Gut and Liver 2025;19(1):69-76
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.
3.Zinc Finger Protein 639 Expression Is a Novel Prognostic Determinant in Breast Cancer
Fang LEE ; Shih-Ping CHENG ; Ming-Jen CHEN ; Wen-Chien HUANG ; Yi-Min LIU ; Shao-Chiang CHANG ; Yuan-Ching CHANG
Journal of Breast Cancer 2025;28(2):86-98
Purpose:
Zinc finger protein 639 (ZNF639) is often found within the overlapping amplicon of PIK3CA, and previous studies suggest its involvement in the pathogenesis of esophageal and oral squamous cell carcinomas. However, its expression and significance in breast cancer remain uncharacterized.
Methods:
Immunohistochemical analysis of ZNF639 was performed using tissue microarrays.Functional studies, including colony formation, Transwell cell migration, and in vivo metastasis, were conducted on breast tumor cells with ZNF639 knockdown via small interfering RNA transfection.
Results:
Reduced ZNF639 immunoreactivity was observed in 82% of the breast cancer samples, independent of hormone receptor and human epidermal growth factor receptor 2 status. In multivariate Cox regression analyses, ZNF639 expression was associated with favorable survival outcomes, including recurrence-free survival (hazard ratio, 0.35; 95% confidence interval [CI], 0.14–0.89) and overall survival (hazard ratio, 0.41; 95% CI, 0.16– 1.05). ZNF639 knockdown increased clonogenicity, cell motility, and lung metastasis in NOD/ SCID mice. Following the ZNF639 knockdown, the expression of Snail1, vimentin, and C-C chemokine ligand 20 (CCL20) was upregulated, and the changes in cell phenotype mediated by ZNF639 were reversed by the subsequent knockdown of CCL20.
Conclusion
Low ZNF639 expression is a novel prognostic factor for recurrence-free survival in patients with breast cancer.
4.Safety and Tolerability of Wharton’s Jelly-Derived Mesenchymal Stem Cells for Patients With Duchenne Muscular Dystrophy: A Phase 1 Clinical Study
Jiwon LEE ; Sang Eon PARK ; Mira KIM ; Hyeongseop KIM ; Jeong-Yi KWON ; Hong Bae JEON ; Jong Wook CHANG ; Jeehun LEE
Journal of Clinical Neurology 2025;21(1):40-52
Background:
and Purpose This study was an open-label, dose-escalation, phase 1 clinical trial to determine the safety and dose of EN001 for patients with Duchenne muscular dystrophy (DMD). EN001, developed by ENCell, are allogeneic early-passage Wharton’s jelly-derived mesenchymal stem cells that originate at the umbilical cord, with preclinical studies demonstrating their high therapeutic efficacy for DMD.
Methods:
This phase 1 clinical trial explored the safety and tolerability of EN001 as a potential treatment option for patients with DMD. Six pediatric participants with DMD were divided into two subgroups of equal size: low-dose EN001 (5.0×105 cells/kg) and high-dose EN001 (2.5×106 cells/kg). All participants were monitored for 12 weeks after EN001 administration to assess its safety. Dose-limiting toxicity (DLT) was evaluated across 2 weeks post administration. Exploratory efficacy was evaluated by measuring serum creatine kinase levels, and functional evaluations—including spirometry, myometry, the North Star Ambulatory Assessment, and the 6-minute walk test—were conducted at week 12 and compared with the baseline values.
Results:
No participants experienced serious adverse events related to EN001 injection during the 12-week follow-up period. Mild adverse events included injection-related local erythema, edema, parosmia, and headache, but DLT was not observed. Functional evaluations at week 12 revealed no significant changes from baseline.
Conclusions
These results demonstrated that EN001 are safe and well tolerated for patients with DMD, and did not cause serious adverse events. The efficacy of EN001 could be confirmed through larger-scale future studies that incorporate repeated dosing and have a randomized controlled trial design.
5.Physician–Scientist Training System and Development Strategies in Korea
Gwang Hyeon EOM ; Jungmin KIM ; Jong-Il KIM ; Hyo Yi CHOI ; Dong Hyeon LEE
Journal of Korean Medical Science 2025;40(15):e140-
Physician–scientists play a pivotal role in bridging clinical practice and biomedical research, advancing medical science, and tackling complex healthcare challenges. In South Korea, the declining number of medical doctors engaging in basic medical sciences has prompted the implementation of various training initiatives since the 2000s. Notable initiatives, such as the Integrated Physician–Scientist Training Program (2019) and the Global Physician–Scientist Training Program (2024), aim to cultivate multidisciplinary physician–scientists capable of addressing unmet medical needs. This study offers a comprehensive overview of the current training systems, funding mechanisms, and strategic approaches for physician–scientists in South Korea, compares them with international best practices, and proposes actionable policy recommendations to enhance their effectiveness and long-term sustainability.
6.A Study on the Healthcare Workforce and Care for Acute Stroke: Results From the Survey of Hospitals Included in the National Acute Stroke Quality Assessment Program
Jong Young LEE ; Jun Kyeong KO ; Hak Cheol KO ; Hae-Won KOO ; Hyon-Jo KWON ; Dae-Won KIM ; Kangmin KIM ; Myeong Jin KIM ; Hoon KIM ; Keun Young PARK ; Kuhyun YANG ; Jae Sang OH ; Won Ki YOON ; Dong Hoon LEE ; Ho Jun YI ; Heui Seung LEE ; Jong-Kook RHIM ; Dong-Kyu JANG ; Youngjin JUNG ; Sang Woo HA ; Seung Hun SHEEN
Journal of Korean Medical Science 2025;40(16):e44-
Background:
With growing elderly populations, management of patients with acute stroke is increasingly important. In South Korea, the Acute Stroke Quality Assessment Program (ASQAP) has contributed to improving the quality of stroke care and practice behavior in healthcare institutions. While the mortality of hemorrhagic stroke remains high, there are only a few assessment indices associated with hemorrhagic stroke. Considering the need to develop assessment indices to improve the actual quality of care in the field of acute stroke treatment, this study aims to investigate the current status of human resources and practices related to the treatment of patients with acute stroke through a nationwide survey.
Methods:
For the healthcare institutions included in the Ninth ASQAP of the Health Insurance Review and Assessment Service (HIRA), data from January 2022 to December 2022 were collected through a survey on the current status and practice of healthcare providers related to the treatment of patients with acute stroke. The questionnaire consisted of 19 items, including six items on healthcare providers involved in stroke care and 10 items on the care of patients with acute stroke.
Results:
In the treatment of patients with hemorrhagic stroke among patients with acute stroke, neurosurgeons were the most common providers. The contribution of neurosurgeons in the treatment of ischemic stroke has also been found to be equivalent to that of neurologists. However, a number of institutions were found to be devoid of healthcare providers who perform definitive treatments, such as intra-arterial thrombectomy for patients with ischemic stroke or cerebral aneurysm clipping for subarachnoid hemorrhage. The intensity of the workload of healthcare providers involved in the care of patients with acute stroke, especially those involved in definitive treatment, was also found to be quite high.
Conclusion
Currently, there are almost no assessment indices specific to hemorrhagic stroke in the ASQAP for acute stroke. Furthermore, it does not reflect the reality of the healthcare providers and practices that provide definitive treatment for acute stroke. The findings of this study suggest the need for the development of appropriate assessment indices that reflect the realities of acute stroke care.
7.Second Allogeneic Hematopoietic Cell Transplantation Following Graft Failure in Children
Eun Sang YI ; Hee Young JU ; Ji Won LEE ; Ki Woong SUNG ; Jin HUR ; Keon Hee YOO
Journal of Korean Medical Science 2025;40(10):e48-
Background:
Graft failure (GF) is a major complication of allogeneic hematopoietic cell transplantation (allo-HCT). Secondary transplantation has been recognized as a potential curative intervention.
Methods:
This study aimed to investigate the characteristics and outcomes of salvage transplantation by analyzing the patients who underwent a second HCT for GF following the initial allo-HCT between 1998 and 2020.
Results:
Overall, 23 recipients were identified, including 14 and 9 individuals with primary and secondary GF, respectively. Nine recipients underwent a second transplant from the same donor. Familial mismatched donors predominated in the second HCT (86.9%), with reduced-intensity conditioning as the prevailing approach (60.9%). Neutrophil engraftment occurred in 17 patients (73.9%) following the second HCT at a median of 17 days (range: 9–58 days) post-transplantation. However, secondary GF subsequently occurred in 5 patients, and successful engraftment following salvage transplantation was achieved in 12 (52.2%) patients. In the entire study population, the estimated 5-year probability of overall survival (OS) and treatment-related mortality (TRM) were 30.4% and 58.5%, respectively. Among patients who achieved successful engraftment following a second transplantation, the OS and TRM rates were 41.7% and 33.3%, respectively, indicating a trend toward better OS and significantly lower TRM compared to those with GF. Notably, 17 patients died, with infection being the most common cause (n = 12), irrespective of the engraftment status.
Conclusion
A successful engraftment following a second allo-HCT reduced the TRM; however, the OS remained suboptimal. The effective control of infectious diseases remains crucial for patients with GF, regardless of the engraftment status following salvage transplantation.
8.Natural History of Hypertrophic Cardiomyopathy in Korea:A Nationwide Population-Based Retrospective Cohort Study
Shin Yi JANG ; Wook Sung KIM ; Sang-Chol LEE
Journal of Korean Medical Science 2025;40(17):e61-
Background:
There are few long-term large-scale epidemiologic studies on hypertrophic cardiomyopathy (HCM; 10th revision of the International Statistical Classification of Diseases and Related Health Problems codes: I42.1, I42.2). This analysis used the Korean National Health Insurance Service (KNHIS) data between 2006 and 2017 to evaluate the natural history of HCM over a decade.
Methods:
KNHIS data and death statistics were evaluated according to age, sex, socioeconomic position, and comorbidities. Survival rates (SRs) and adjusted hazard ratio (HR) were compared with death data of the Korean population from 2006 through 2018.
Results:
The mean age was 47.3 ± 14.9 years in males and 57.5 ± 15.4 years in females (P < 0.001).The male proportion was 58.9%. The most common cause of death was diseases of the circulatory system. The 10-year SR of HCM was higher in males (75.9% vs. 62.5%, P < 0.001).The adjusted HR for different age groups was significantly high in most age group: 3.67 (95% confidence interval [CI], 2.65–5.10) for 0–9 years, and it gradually increased from the 30s to the 80s group (1.39 [95% CI, 1.05–1.83] for 30–39 years and 48.2 [95% CI, 37.0–62.7] for those older than 80 years). The adjusted HR was 1.12 (95% CI, 1.07–1.17) for males, 1.40 (95% CI, 1.33–1.48) for the lower income level, and 1.18 (95% CI, 1.12–1.25) for the medium income level. In patients with comorbidities, the adjusted HRs were 1.23 (95% CI, 1.16–1.30) for diabetes, 1.45 (95% CI, 1.30–1.62) for myocardial infarction, 1.63 (95% CI, 1.52–1.76) for atrial fibrillation, 1.83 (95% CI, 1.68–1.99) for ischemic stroke, 1.66 (95% CI, 1.31–2.10) for hemorrhagic stroke, 2.42 (95% CI, 2.16–2.70) for chronic kidney disease, and 3.18 (95% CI, 2.87–3.52) for malignant neoplasm.
Conclusion
HCM in Korea showed a higher prevalence and incidence in males. The 10-year SR of HCM was approximately 70% and lower in females than that in males. The risk of death from HCM increased with age and was significantly higher in males, individuals with low income levels, and patients with various comorbidities. These findings should be considered for the long-term management and allocation of healthcare resources for patients with HCM.
10.Subjective market food freshness as a moderator of healthy eating intentions: based on the theory of planned behavior
Yi JIANG ; Seungwoo LEE ; Ji-Yun HWANG
Journal of Nutrition and Health 2025;58(2):227-237
Purpose:
Food freshness may influence the healthy eating choices of consumers. This study aimed to examine whether self-reported market food freshness moderates the relationships between the three major constructs of the theory of planned behavior (TPB) and the intention for healthy eating among Chinese adults.
Methods:
A cross-sectional online survey was conducted in 2019 among 408 Chinese adults aged 18–64 years residing in Shanghai and parts of the Anhui Province, using a previously validated questionnaire. Structural equation modeling was applied to examine the moderating effects of market food freshness.
Results:
Based on a single subjective measure, 42.9% of the participants perceived market food freshness as low, and 57.1% perceived it as high. In the unconstrained model, perceived behavioral control (PBC) showed positive relationships with both short-term and long-term intentions for healthy eating (p < 0.001). Among participants reporting lower market food freshness, the relationship between PBC and short-term intention remained significant (p < 0.001), and the relationship between short-term and long-term intentions became significant (p = 0.042). However, among participants reporting higher market food freshness, PBC maintained significant relationships with short-term (p < 0.001) and longterm (p = 0.028) intentions, and the relationship between subjective norms and short-term intention became significant (p = 0.013). The moderating effect of market food freshness was significant (p < 0.001).
Conclusion
Market food freshness may moderate the relationships between the TPB constructs and the intentions for healthy eating in Chinese adults. These findings highlight the importance of developing tailored, region-specific strategies to enhance healthy eating behaviors among the Chinese population, accounting for disparities in resource availability and contextual differences. Further research should examine the underlying mechanisms driving regional variations in these associations.

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