1.Molecular and Phenotypic Characterization of Fluid-Derived Patient-Derived Cell and Organoid Models in Advanced Gastric Cancer
Ye Jin MOON ; Woo Sun KWON ; Chan Hee PARK ; Jinsoo JANG ; Juin PARK ; Byeong Gyu YOON ; Han Byeol MUN ; Namju KIM ; Choong-kun LEE ; Hei Cheul JEUNG ; Su-Jin SHIN ; Tae Soo KIM ; Sun Young RHA
Journal of Gastric Cancer 2026;26(2):260-278
Purpose:
Patient-derived cells (PDCs) and patient-derived organoids (PDOs) are complementary preclinical models widely used in translational cancer research. However, their molecular and functional differences have not been systematically characterized. This study established and analyzed paired PDC and PDO models derived from the same gastric cancer ascites to delineate platform-dependent molecular and functional profiles.
Materials and Methods:
Malignant ascites or pleural fluid obtained from 6 patients with advanced gastric cancer were used to establish paired PDC and PDO models. All pairs underwent comprehensive multi-omics profiling, integrating genomic, transcriptomic, and proteomic data. Phenotypic characterization included morphological, histological, proliferative, and cell cycle analyses. Drug sensitivity assays were performed using 4 chemotherapeutic agents commonly used to treat gastric cancer.
Results:
The 6 paired PDC and PDO models exhibited distinct morphological characteristics.Whole-genome analyses demonstrated high concordance among primary tumors, PDCs, and PDOs, confirming tumor representation across platforms. Multi-omics profiling identified platform-dependent molecular signatures; PDOs were enriched for extracellular matrix remodeling and stemness, whereas PDCs displayed proliferation- and immune-related signatures. Clinically relevant biomarkers, including HER2 and MET alterations, were concordant with primary tumors. Notably, drug responses differed between platforms and patients, indicating platform-dependent and patient-specific chemosensitivity.
Conclusions
Paired PDC and PDO models derived from the same patients preserved core patient-specific tumor characteristics while exhibiting distinct molecular and functional profiles. These findings underscore the culture platform as a critical determinant of experimental outcomes and therapeutic responses. Therefore, careful selection of an appropriate preclinical model is essential to accurately address biological questions and optimize precision oncology strategies.
2.3-Dimensional reconstruction reveals frequent intraluminal growth of submucosal veins in surgically resected pT1 colorectal cancers
Jihyun PARK ; Mi-Ju KIM ; Yeon Wook KIM ; Byong-Wook LEE ; Junyoung SHIN ; Jinho SHIN ; Chan-Gi PACK ; Dong-Hoon YANG ; Jihun KIM ; In Ja PARK ; Ralph H. HRUBAN ; Seung-Mo HONG
Journal of Pathology and Translational Medicine 2026;60(2):246-262
Although venous invasion (VI) is associated with distant metastasis and observed in >50% of pT2–4 colorectal cancers (CRCs), the role of VI in pT1 CRCs is not well-defined. Methods: Thirty-four surgically resected pT1 CRCs were reevaluated for 2-dimensional (2D) VI using hematoxylin and eosin (H&E)–stained slides with additional elastic and desmin immunohistochemical staining (cohort A). Additionally, 27 pT1 CRCs without knowing VI status were selected for 3-dimensional (3D) VI evaluation only (cohort B). All 61 cases (cohorts A and B) were studied in 3D using tissue clearing. Results: VI was detected more commonly in 3D (17/34, 50.0%) than in 2D H&E slide evaluation (9/34, 26.5%, p = .047). When VI was identified in 3D (27/61, 44.3%), the most common phase was that of intraluminal growth (22/27, 81.5%), followed by intravasation (7/27, 25.9%) and extravasation (5/27, 18.5%). E-cadherin expression was characterized in 3D in foci of VI and varied in each phase of invasion. Conclusions: All three phases were observed in VI of pT1 CRCs. The extravasation of neoplastic cells from foci of VI in pT1 CRC suggests that VI could be a route of intratumoral spreading in a subset of pT1 CRCs.
3.Multicenter evaluation of the PASS score as a negative predictive tool and the impact of inter-observer variability in pheochromocytoma and paraganglioma risk stratification
Sungyeon JUNG ; Hye-Ri SHIN ; Su-Jin SHIN ; Hee Young NA ; Soon-Won HONG ; So Yeon PARK ; Chan Kwon JUNG ; Kyeong Cheon JUNG ; Young Lyun OH ; Jae-Kyung WON
Journal of Pathology and Translational Medicine 2026;60(2):202-213
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.
4.Prosthetic rehabilitation of traumatized maxillary anterior teeth using a digital workflow: a case report
Jong-Hyun SHIN ; Sang-Ah LEE ; Lee-Ra CHO ; Chan-Jin PARK ; Kyung-Ho KO ; Yoon-Hyuk HUH
The Journal of Korean Academy of Prosthodontics 2026;64(1):84-94
The maxillary anterior region is critical for esthetics and function, requiring precise analysis and restoration when damaged by trauma. This case report presents the restorative process using a digital workflow for a patient with anterior trauma. A 22-year-old female exhibited fractures and extrusive luxation of maxillary central incisors, diagnosed with pulp necrosis. After endodontic treatment, intraoral and facial scans were performed, and provisional and definitive restorations were digitally designed. Various shade-matching techniques were employed to achieve natural esthetics. The definitive prosthesis improved harmony between the incisal edge and lower lip, as well as tooth axis, length, and zenith position, fulfilling the patient’s esthetic demands. This case suggests that combining digital technology and gingivectomy with a minimally invasive approach enables esthetic and functional restoration of the maxillary anterior region.
5.Acute Heart Failure Across the Ejection Fraction Spectrum: Phenotypes, Management, and Outcomes From Nationwide KorHF III Registry
Huijin LEE ; Eung Ju KIM ; Seong Woo HAN ; Seong-Mi PARK ; Hyung-Seop KIM ; Myung-Chan CHO ; Hyo-Suk AHN ; Mi-Seung SHIN ; Seok-Jae HWANG ; Jin-Ok JEONG ; Dong Heon YANG ; Junho HYUN ; Jin Oh CHOI ; Hae-Young LEE ; Byung-Su YOO ; Seok-Min KANG ; Dong-Ju CHOI ; Hyun-Jai CHO ;
International Journal of Heart Failure 2026;8(1):43-55
Background and Objectives:
Clinical characteristics and outcomes in acute heart failure (AHF) vary by phenotype. We assessed phenotype-specific features, treatment patterns, and outcomes in a nationwide Korean cohort.
Methods:
The Korean Heart Failure III registry prospectively enrolled 7,351 AHF admissions at 47 hospitals. Among 6,777 patients with available left ventricular ejection fraction (EF), phenotypes were defined as heart failure with reduced EF (HFrEF, ≤40%), mildly reduced EF (HFmrEF,41–49%), or preserved EF (HFpEF, ≥50%). The primary endpoint was a 12-month composite of all-cause death or heart transplantation, evaluated from index admission and, among hospital survivors, from discharge. We used inverse probability weighting (multinomial generalized boosted models with stabilized, trimmed weights) and weighted Cox proportional-hazards models to estimate hazard ratios (HRs).
Results:
Phenotype distribution was 58.9% HFrEF, 13.6% HFmrEF, and 27.5% HFpEF. Crude 12-month composite rates from index admission were 13.4% (HFrEF), 12.7% (HFmrEF), and 16.8% (HFpEF). After weighting, from index admission, HFmrEF (HR, 0.892; 95% confidence interval [CI], 0.731–1.088) and HFpEF (HR, 1.101; 95% CI, 0.939–1.291) did not differ from HFrEF; from discharge, HFpEF had modestly higher risk (HR, 1.207; 95% CI, 1.008–1.445) whereas HFmrEF did not (HR, 1.039; 95% CI, 0.844–1.279). Hyponatremia and chronic kidney disease were consistent adverse markers, while angiotensin-converting enzyme inhibitor/ angiotensin II receptor blocker use at discharge was protective.
Conclusions
Across the EF spectrum, phenotypes showed distinct profiles and risk. Postdischarge risk was modestly higher in HFpEF, supporting phenotype-tailored care and systematic discharge optimization in Korean patients with AHF.
6.Psychometric Properties of the Mixed State Severity Index for Patients With Mood Disorder
Woojae MYUNG ; Hyeona YU ; Hyo Shin KANG ; Daseul LEE ; Junwoo JANG ; Jakyung LEE ; Joohyun YOON ; Yun Seong PARK ; Hyun A RYOO ; Ye Rim KIM ; Kwang Ho PARK ; Chan Woo LEE ; Yoonjeong JANG ; Kimyoung KIM ; Nara LEE ; Sanghoon HONG ; Hong-Hee WON ; Tae Hyon HA ; Jungkyu PARK
Psychiatry Investigation 2026;23(1):106-117
Objective:
This study aimed to develop a reliable and valid Mixed State Severity Index (MSSI) to assess mood instability in patients with mood disorders and determine cutoff scores.
Methods:
Twenty-one items were selected based on Koukopoulos’ criteria for mixed depressive episode, historically referred to as agitated depression, and Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, Text Revision mixed features criteria. The MSSI was administered to 242 patients (major depressive disorder [n=92], bipolar disorder [BD] I [n=78], and BD II [n=72]) and 726 controls.
Results:
The MSSI demonstrated high internal consistency (α=0.78–0.90). Exploratory factor analysis revealed a stable four-factor structure. Based on receiver operating characteristic analysis, optimal cutoff scores were identified to distinguish mood disorder groups from controls, ranging from 19.5 to 27.5 depending on diagnosis.
Conclusion
The MSSI is a reliable and valid instrument for assessing the severity of mixed features in patients with mood disorders. The established cutoff scores enhance its clinical utility, providing robust diagnosis and treatment planning support.
7.Implant–supported fixed prosthesis for orthognathic surgery in ectodermal dysplasia: a case report
Yeon-Ah SHIN ; Ji-Eun MOON ; Se-Ha KANG ; Chan-Ik PARK ; Yoon-Joo BAE ; Min-Seok OH ; Woo-Jin JEON ; Na-Ra KANG ; Min-Jung BAEK
The Journal of Korean Academy of Prosthodontics 2025;63(1):20-30
Patients with ectodermal dysplasia often have atrophied alveolar bone and an inadequate maxillomandibular relationship owing to congenital edentulism.Accurate implant placement that can overcomes anatomical limitations and orthognathic surgery to improve the maxillomandibular relationship is necessary for creating implant-supported prosthesis for these patients. Implant placement and provisional prosthesis fabrication before orthognathic surgery can provide critical fixed reference points and ensure accuracy during orthognathic surgery.In our patient, a digital system was used to design a surgical guide that considered the predictable position of the definitive prosthesis, allowing the placement of implants to overcome anatomical limitations and the creation of fixed reference points via the delivery of a provisional prosthesis for effective orthognathic surgery. The lack of compensation during orthognathic surgery was considered in the definitive prosthesis. As a result, a prosthesis with a minimal anterior cantilever was fabricated. This study aimed to determine the appropriate sequence of multidisciplinary collaborations that would, result in the best functional and aesthetic outcomes.
8.Toxicity and efficacy study of a combination of two retinoic acids in an ApoE knockout mouse model of atherosclerosis
Da Som JEONG ; Ji-Young LEE ; Hyo-Jeong HAN ; Soo Min KO ; Dong Hyun LEE ; Yerin LEE ; Young-Sik PARK ; Byong-Cheol SHIN ; Woo-Chan SON
The Korean Journal of Physiology and Pharmacology 2025;29(2):179-189
Atherosclerosis is a major contributor to cardiovascular disease, characterized by inflammation and lipid accumulation in arterial walls, leading to plaque formation. Elevated low-density lipoprotein cholesterol is a primary risk factor for atherosclerosis. All-trans retinoic acid (ATRA), a metabolite of vitamin A, has demonstrated anti-inflammatory effects and potential in regulating vascular injury. 9-cisretinoic acid (9cRA) is an active metabolite of vitamin A and activates the retinoid X receptor. This study investigates whether potassium retinoate (PA9RA), a synthetic combination of ATRA and 9cRA, offers superior efficacy in treating atherosclerosis compared to established treatments such as clopidogrel and atorvastatin. Male ApoE -/- mice were fed a Western-type diet and treated with PA9RA, clopidogrel, or atorvastatin for 10 weeks. The body weight, organ weight, serum biochemistry, and histopathology, including atherosclerotic lesion area and liver steatosis were assessed. PA9RA treatment led to a significant reduction in body weight and inguinal fat, with the 45 mg/kg/day dose showing marked efficacy in decreasing atherosclerotic lesion size and ameliorating liver steatosis. Histopathological evaluation revealed decreased foam cell formation and improved liver histology in PA9RA-treated groups compared to controls. Notable side effects included epidermal hyperplasia and gastric hyperplasia at high doses of PA9RA. PA9RA exhibits superior efficacy over clopidogrel and atorvastatin in ameliorating atherosclerosis and fatty liver in ApoE –/–mice. This study highlights PA9RA's potential as a promising therapeutic agent for atherosclerosis. Further research is needed to elucidate its mechanisms of action and assess long-term safety and efficacy.
9.Validation of Devices for the Five Times Sit To Stand Test:Comparing Plantar Pressure and Head Motion Analysis with Manual Measurement
Sanghyun JEE ; Chan Woong JANG ; Kyoungmin PARK ; Sanghoon SHIN ; Min-Chul PAEK ; Jung Hyun PARK
Yonsei Medical Journal 2025;66(1):51-57
Purpose:
This study aims to evaluate a new method for the five times sit to stand test (FTSST), crucial for addressing frailty in an aging population. It utilizes a smart insole for plantar pressure analysis and a marker-less motion capture device for head height analysis.
Materials and Methods:
Thirty-five participants aged 50 years or older underwent FTSST assessment using three methods: manual measurement with a stopwatch (FTSST-M), plantar pressure analysis with smart insoles (FTSST-P), and head height analysis with a marker-less motion capture device (FTSST-H). Simultaneous measurements using three methods were done. Correlation between results of these methods were analyzed using intraclass correlation coefficient (ICC) and κ coefficient. Comprehensive clinical examinations were conducted with ethical approval.
Results:
Participants’ mean scores for FTSST-M, FTSST-P, and FTSST-H were 2.43±1.20, 2.43±1.29, and 2.37±1.31, respectively. Correlations of the times and corresponding scores between FTSST-P and FTSST-M, as well as FTSST-H and FTSST-M, exceeded 0.9 (ICC and κ coefficients, p<0.001). Using an FTSST score of 3 or less to indicate vulnerability, the κ value for vulnerability classification between two measurements was 0.886 (p<0.001).
Conclusion
This study showed strong correlation between FTSST results using smart insoles and marker-less motion capture, compared to conventional methods. These findings highlight the potential of these technologies for precise FTSST measurements, offering convenience and cost-effectiveness. Simultaneous use of these devices enables diverse analyses, enhancing our understanding of frailty.
10.Implant–supported fixed prosthesis for orthognathic surgery in ectodermal dysplasia: a case report
Yeon-Ah SHIN ; Ji-Eun MOON ; Se-Ha KANG ; Chan-Ik PARK ; Yoon-Joo BAE ; Min-Seok OH ; Woo-Jin JEON ; Na-Ra KANG ; Min-Jung BAEK
The Journal of Korean Academy of Prosthodontics 2025;63(1):20-30
Patients with ectodermal dysplasia often have atrophied alveolar bone and an inadequate maxillomandibular relationship owing to congenital edentulism.Accurate implant placement that can overcomes anatomical limitations and orthognathic surgery to improve the maxillomandibular relationship is necessary for creating implant-supported prosthesis for these patients. Implant placement and provisional prosthesis fabrication before orthognathic surgery can provide critical fixed reference points and ensure accuracy during orthognathic surgery.In our patient, a digital system was used to design a surgical guide that considered the predictable position of the definitive prosthesis, allowing the placement of implants to overcome anatomical limitations and the creation of fixed reference points via the delivery of a provisional prosthesis for effective orthognathic surgery. The lack of compensation during orthognathic surgery was considered in the definitive prosthesis. As a result, a prosthesis with a minimal anterior cantilever was fabricated. This study aimed to determine the appropriate sequence of multidisciplinary collaborations that would, result in the best functional and aesthetic outcomes.

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