1.Comparative Evaluation of Pre-Test Probability Models for Coronary Artery Disease with Assessment of a New Machine Learning-Based Model
Kyung-A KIM ; Min Soo KANG ; Byoung Geol CHOI ; Ji Hun AHN ; Wonho KIM ; Myung-Ae CHUNG
Yonsei Medical Journal 2025;66(4):211-217
Purpose:
This study aimed to validate pivotal pre-test probability (PTP)-coronary artery disease (CAD) models (CAD consortium model and IJC-CAD model).
Materials and Methods:
Traditional PTP models-CAD consortium models: two traditional PTP models were used under the CAD consortium framework, namely CAD1 and CAD2. Machine learning (ML)-based PTP models: two ML-based PTP models were derived from CAD1 and CAD2, and used to enhance predictive capabilities [ML-CAD2 and ML-IJC (IJC-CAD)]. The primary endpoint was obstructive CAD. The performance evaluation of these PTP models was conducted using receiver-operating characteristic analysis.
Results:
The study included 238 participants, among whom 157 individuals (65.9% of the total sample) had CAD. The IJC-CAD model demonstrated the highest performance with an area under the curve (AUC) of 0.860 [95% confidence interval (CI): 0.812– 0.909]. Following this, the ML-CAD2 model exhibited an AUC of 0.814 (95% CI: 0.758–0.870), CAD1 showed an AUC of 0.767 (95% CI: 0.705–0.830), and CAD2 had an AUC of 0.785 (95% CI: 0.726–0.845). Each of the PTP models was adjusted to have a CAD score cutoff that classified cases with a sensitivity of over 95%. The respective cutoff values were as follows: CAD1 and CAD2 >12, MLCAD2 >0.380, and IJC-CAD >0.367. All PTP models achieved a CAD sensitivity of over 95%. Similar to the AUC performance, the accuracy of the PTP models was highest for IJC-CAD, reaching 80.3%. The accuracy of ML-CAD2 was 77.7%, while that for CAD1 and CAD2 was 74.8% and 75.2%, respectively.
Conclusion
ML-CAD2 and IJC-CAD showed superior performance compared to traditional existing models (CAD1 and CAD2)
2.Synergistic effects of L-arginine and argininosuccinate synthetase 1 in inducing apoptosis in hepatocellular carcinoma
Jin Sun KIM ; Won-Mook CHOI ; Ha-Il KIM ; Sung Won CHUNG ; Jonggi CHOI ; Danbi LEE ; Kang Mo KIM
Journal of Liver Cancer 2025;25(1):79-90
Background:
s/Aims: Hepatocellular carcinoma (HCC) is a malignant cancer with an increasing incidence worldwide. Although numerous efforts have been made to identify effective therapies for HCC, current strategies have limitations. We present a new approach for targeting L-arginine and argininosuccinate synthetase 1 (ASS1).
Methods:
ASS1 expression in HCC cell lines and primary hepatocytes was detected using polymerase chain reaction and western blotting. Proliferation, migration, signaling pathways, and nitric oxide production in HCC cell lines were measured using MTS, colony formation, wound healing, Western blot, and Griess assays.
Results:
ASS1 expression varied among the HCC cell lines, and cisplatin cytotoxicity was ASS1-dependent. L-arginine alone induced apoptosis in HCC cell lines, regardless of ASS1 expression; however, its effect was enhanced in ASS1-expressing HCC cell lines. Cisplatin cytotoxicity also increased, suggesting that L-arginine acts as a sensitizer to cisplatin in HCC cell lines. ASS1 and L-arginine produced nitric oxide and inhibited key proliferation- and survival-related signaling pathways such as PI3K/Akt and MAPK. Additionally, ASS1 and L-arginine reduced the expression of PKM1 and PKM2 in the glycolysis pathway.
Conclusions
Our study revealed that ASS1 and L-arginine exhibited anticancer effects in HCC and sensitized cisplatin-resistant HCC cells to chemotherapy. The combination of ASS1 and L-arginine significantly enhanced the anticancer effects, even in HCC cell lines with low or absent ASS1 expression. These findings highlight the critical roles of arginine and ASS1 in HCC and suggest that increasing arginine availability could be a promising therapeutic strategy.
3.The Emerging Threat of Micro- and Nanoplastics on the Maturation and Activity of Immune Cells
Kang-Bin DAN ; Ji Yoon YOO ; Hyeyoung MIN
Biomolecules & Therapeutics 2025;33(1):95-105
With the increasing use of plastics worldwide, the amount of plastic waste being discarded has also risen. This plastic waste undergoes physical and chemical processes, breaking down into smaller particles known as microplastics (MPs) or nanoplastics (NPs). Advances in technology have enhanced our ability to detect these smaller particles, and it has been confirmed that plastics can be found in marine organisms as well as within the human body. However, research on the effects of MPs or NPs on living organisms has only recently been started, and our understanding remains limited. Studies on the immunological impacts are still ongoing, revealing that MPs and NPs can differentially affect various immune cells based on the material, size, and shape of the plastic particles. In this review, we aim to provide a comprehensive understanding of the effects of MPs and NPs on the immune system. We will also explore the methods for plastic removal through physicochemical, microbial, or biological means.
4.Hyperlipidemia and Rotator Cuff Tears: Exploring Mechanisms and Effective Treatment
Kang-San LEE ; Sung-Jin PARK ; Dong-Hyun KIM ; Seok Won CHUNG ; Jun-Young KIM ; Chul-Hyun CHO ; Jong Pil YOON
Clinics in Orthopedic Surgery 2025;17(2):187-193
The detrimental effects of hyperlipidemia on the healing of rotator cuff tears are well documented. The proposed underlying mechanisms for these effects include alterations in the extracellular matrix, inflammation, and oxidative stress, which hamper the reparative processes in the affected tendon tissues. Recent therapeutic strategies target these pathways, reflecting a growing body of research dedicated to mitigating these effects and promoting healing. This literature review aims to provide a comprehensive understanding of the pathophysiology underlying rotator cuff tears, examine the interplay between hyperlipidemia and rotator cuff tear healing, synthesize current knowledge on contributing biological mechanisms, and outline potential therapeutic interventions to optimize clinical management and treatment outcomes for patients.
5.A Comparative Study on the Effects of Repeated Subacromial Injections of Parecoxib and Triamcinolone in a Rat Model of Normal Rotator Cuff
Jong Pil YOON ; Dong Hyun KIM ; Sung-Jin PARK ; Yoon Seong CHOI ; Hyun Joo LEE ; Seok Won CHUNG ; Kang-San LEE ; Jeoung Wook LEE
Clinics in Orthopedic Surgery 2025;17(2):291-299
Background:
This study aimed to investigate changes after repeated subacromial drug injections in a rat model of normal rotator cuff.
Methods:
Thirty-nine male Sprague-Dawley rats were divided into groups 1 (no injection, n = 3), 2 (parecoxib, n = 18; 6 subgroups, n = 3 each; 0.5 mg/kg), and 3 (triamcinolone, n = 18; 6 subgroups, n = 3 each; 0.3 mg/kg). Groups 2 and 3 received subacromial injections 1–6 times once weekly for 6 weeks. The supraspinatus and infraspinatus tendons and muscles were used for biomechanical and histological evaluation. The subacromial bursa was used to analyze the prostaglandin E2 (PEG2) level.
Results:
In the biomechanical test, load-to-failure and ultimate stress decreased in groups 2 and 3 with repeated injections and the values were significantly lower in group 3 than in group 1 only at the sixth injection (p = 0.007 and p = 0.008, respectively). On the Bonar score, the cellularity, ground substance, and total score were significantly different among the 3 groups at the fifth and sixth injections (cellularity: p = 0.028 and p = 0.033, ground substance: p = 0.018 and p = 0.006, and total score: p = 0.029 and p = 0.027, respectively). The myocyte cross-sectional area of the infraspinatus muscle showed a significant difference among the 3 groups at the third and fourth injections (p = 0.031 and p = 0.020, respectively). The PEG2 level in the subacromial bursa was significantly different among the 3 groups at the third, fifth, and sixth injections (p = 0.019, p = 0.004, and p = 0.004, respectively).
Conclusions
In the rat model of normal rotator cuff, repeated local injections of the cyclooxygenase-2 inhibitor showed fewer negative effects on the biomechanical and histological properties of the normal tendon than triamcinolone.
6.Percutaneous Transpedicular Intravertebral Cage Augmentation with Short-Segment Fixation Using Specially Designed Cannulated Cage Trials for Advanced Kümmell Disease: A Preliminary Study Comparing with Vertebroplasty with Short-Segment Fixation
Sung Cheol PARK ; Gene CHEH ; Yongjung KIM ; Hoon-Jae CHUNG ; Min-Seok KANG ; Ji-Hye CHOI
Clinics in Orthopedic Surgery 2025;17(1):29-38
Background:
The treatment of Kümmell disease (KD) is controversial. Corpectomy and reconstruction or osteotomy with long-level fusion was traditionally performed for the advanced KD. However, these procedures can be disadvantageous for elderly patients.Several alternative surgical procedures including transpedicular intravertebral cage augmentation (TPICA) or vertebroplasty (VP) combined with short-segment fixation (SSF) have been suggested to minimize the surgical burden. This study aimed to compare the outcomes of percutaneous TPICA plus SSF with VP plus SSF for advanced thoracolumbar (T11–L2) KD and to introduce our novel percutaneous TPICA technique using specially designed cannulated cage trials.
Methods:
We devised specially designed cannulated cage trials to make the TPICA procedure safer and more reproducible, minimizing the risk of the pedicle medial wall violation. All consecutive patients who underwent percutaneous TPICA or VP combined with SSF for advanced thoracolumbar KD, from January 2021 to June 2022, with ≥ 1-year follow-up at a single institution, were included. Perioperative details, clinical outcomes (visual analog scale and Oswestry Disability Index), and radiological outcomes (anterior vertebral body compression percentage and vertebral kyphotic angle [VKA] of the fractured vertebra, and local Cobb angle [LCA]) were collected and compared between the groups.
Results:
A total of 42 patients were enrolled, with 21 patients in each group. There were no patients with pedicle medial wall fracture in the TPICA group. Both procedures provided significantly favorable radiological outcomes compared to those preoperatively. No significant differences were observed in the changes over time in all radiological parameters between the groups. Loss of correction during the follow-up period was significantly smaller in patients with TPICA than in those with VP in VKA (median [interquartile range], 2.15 [0.30–2.80] vs. 2.90 [0.90–6.53]; p = 0.030) and LCA (2.70 ± 2.90 vs. 5.17 ± 4.40, p = 0.037).
Conclusions
Both procedures are minimally invasive and useful options for advanced KD, especially for elderly patients with high comorbidity. Our novel percutaneous TPICA technique using cannulated cage trials, being safer and more reproducible, may allow spine surgeons to easily perform TPICA.
7.Effects of Pancreatitis and Type 2 Diabetes Mellitus on the Development of Pancreatic Cancer: A Nationwide Nested Case-Control Study
Young-eun KIM ; Min Heui YU ; Chung Mo NAM ; Eun Seok KANG
Diabetes & Metabolism Journal 2025;49(2):252-263
Background:
Despite diabetes mellitus (DM) and pancreatitis being known risk factors for pancreatic cancer, patients with these conditions are not included in pancreatic cancer screening due to the low incidence of pancreatic cancer in these populations. This study aimed to determine the high-risk subgroup of patients with diabetes and pancreatitis that would benefit from pancreatic cancer screening.
Methods:
A nested case-control study was conducted using data from the National Health Information Database of the Korean National Health Insurance Service. Patients were categorized into the following groups: type 2 diabetes mellitus only (T2DM-only), pancreatitis-only (PAN-only), T2DM followed by pancreatitis (T2DM-PAN), post-pancreatitis diabetes mellitus (PPDM), and no diabetes and no pancreatitis (NDNP). Conditional logistic regression was used to determine significant associations of each group with pancreatic cancer development risk.
Results:
The risk of pancreatic cancer was significantly higher in the T2DM-PAN (adjusted odds ratio [AOR], 4.96; 95% confidence interval [CI], 4.48 to 5.49) and PPDM (AOR, 4.71; 95% CI, 4.12 to 5.37) groups than in the NDNP group. Compared to patients in the NDNP group, those with PPDM using insulin had a 17-fold increased risk (AOR, 16.72; 95% CI, 9.50 to 29.43), and individuals with PPDM who had diabetes for less than 3 years had a more than 8-fold increased risk of pancreatic cancer (AOR, 8.83; 95% CI, 5.99 to 13.01).
Conclusion
In patients with post-pancreatitis diabetes, insulin use or shorter duration of diabetes was associated with a higher risk of pancreatic cancer, suggesting that patients in these subgroups may require close monitoring for pancreatic cancer development.
9.Diagnosis of Pneumocystis jirovecii Pneumonia in Non-HIV Immunocompromised Patient in Korea: A Review and Algorithm Proposed by Expert Consensus Group
Raeseok LEE ; Kyungmin HUH ; Chang Kyung KANG ; Yong Chan KIM ; Jung Ho KIM ; Hyungjin KIM ; Jeong Su PARK ; Ji Young PARK ; Heungsup SUNG ; Jongtak JUNG ; Chung-Jong KIM ; Kyoung-Ho SONG
Infection and Chemotherapy 2025;57(1):45-62
Pneumocystis jirovecii pneumonia (PJP) is a life-threatening infection commonly observed in immunocompromised patients, necessitating prompt diagnosis and treatment. This review evaluates the diagnostic performance of various tests used for PJP diagnosis through a comprehensive literature review. Additionally, we propose a diagnostic algorithm tailored to non-human immunodeficiency virus immunocompromised patients, considering the specific characteristics of current medical resources in Korea.
10.Probiotic-Derived P8 Protein: Promoting Proliferation and Migration in Stem Cells and Keratinocytes
Soo Bin JANG ; Yoojung KIM ; Han Cheol YEO ; Geun-Ho KANG ; Byung Chull AN ; Yongku RYU ; Myung-Jun CHUNG ; Ssang-Goo CHO
International Journal of Stem Cells 2025;18(1):87-98
Probiotics exert various effects on the body and provide different health benefits. Previous reports have demonstrated that the P8 protein (P8), isolated from Lactobacillus rhamnosus, has anticancer properties. However, its efficacy in stem cells and normal cells has not been reported. In this study, the effect of P8 on cell proliferation and wound healing was evaluated, investigating its underlying mechanism. Based on scratch assay results, we demonstrated that P8 treatment significantly increases wound healing by activating the cell cycle and promoting stem cell stemness.Cellular mechanisms were further investigated by culturing stem cells in a medium containing Lactobacillus-derived P8 protein, revealing its promotion of cell proliferation and migration. Also, it is found that P8 enhances the expression of stemness markers, such as OCT4 and SOX2, along with activation of the mitogen-activated protein kinase (MAPK) signaling and Hippo pathways. These results indicate that P8 can promote cell growth by increasing stem cell proliferation, migration, and stemness in a manner associated with MAPK and Hippo signaling, which could contribute to the increased wound healing after P8 treatment. Furthermore, P8 could promote wound healing in keratinocytes by activating the MAPK signaling pathways. These results suggest that P8 might be a promising candidate to enhance stem cell culture efficiency by activating cell proliferation, and enhance therapeutic effects in skin diseases.

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