Adipose-derived mesenchymal stem cells (Ad-MSCs) have been widely studied for their regenerative potential in skin wound healing due to their ability to modulate inflammation, regulate immune responses, promote angiogenesis, and facilitate extracellular matrix (ECM) remodeling. However, the therapeutic efficacy of single-cell transplantation is often limited by low engraftment efficiency and transient effects, restricting its long-term regenerative impact. To overcome these challenges, we developed a spheroid-like structure, Microblock (MiB), designed to enhance the expression of key regenerative proteins compared to conventional single-cell Ad-MSCs. To evaluate its therapeutic potential, we conducted a wound healing assay in a rat model and performed proteomic analysis to investigate its underlying molecular mechanisms. Additionally, a comprehensive non-clinical safety evaluation, including toxicity, tumorigenicity, biodistribution, and persistence studies, was conducted to assess its feasibility for clinical application. Our findings demonstrated that MiB significantly enhanced skin regeneration and tissue remodeling, as evidenced by the upregulation of ECM-related proteins such as Collagen Type I and fibronectin and the activation of TGF-β1 signaling. Furthermore, key TGF-β target proteins associated with VEGFA signaling were identified, and MiB treatment resulted in a substantial increase in collagen deposition. These results suggest that MiB effectively promotes skin regeneration by reinforcing ECM remodeling and activating essential signaling pathways. Compared to single-cell Ad-MSC transplantation, MiB exhibited superior regenerative potential, highlighting its promise as a novel cell-based therapeutic for skin repair and laying the groundwork for future clinical applications.

Background: The burden of severe pediatric obesity is increasing globally, including in South Korea, and associated with metabolic and cardiovascular complications. However, longitudinal data of Korean children with severe obesity are limited.Purpose: This study evaluated the changes in body mass index (BMI) and associated metabolic syndrome components in children and adolescents with severe obesity managed without pharmacological or surgical treatment.Methods: We retrospectively reviewed participants diagnosed with severe obesity (BMI ≥120% of the 95th percentile) before the age of 18 years at 3 medical centers in 2017–2024. Participants with more than 1 year of follow-up were included. Management consisted exclusively of lifestyle modifications, including nutritional counseling and physician-led education on physical activity, screen time, and sleep. Patients with chronic illnesses, with psychiatric disorders, or who were taking medications that affect weight were excluded. The primary outcome was the change in BMI z score from baseline to the last visit. Predictors of a change in the BMI z score were analyzed using multivariable linear regression with adjustment for age, sex, pubertal stage, baseline BMI z score, and follow-up duration and frequency.Results: Among 124 participants (mean age, 9.69±3.39 years; 61.3% boys) followed for a mean duration of 2.64±1.51 years, BMI z scores significantly decreased (from 3.68±0.75 to a mean change of -0.27±0.79, P<0.001). Younger age and male sex were associated with greater reductions in BMI z scores. However, most participants remained severely obese. Except for modest improvements in liver transaminase levels, no substantial differences were observed in other metabolic syndrome components.Conclusion: Lifestyle modification resulted in a modest BMI z score reduction; however, most participants remained severely obese with no significant improvements in most metabolic syndrome components. These findings underscore the need for early and intensive interventions for pediatric obesity.

Validation of immune-related analyses using spatial transcriptomics demonstrated distinct gene expression patterns and correlations in thymoma samples, highlighting differences between GTF2I-type and CN-type tumors

Mapping thymic epithelial tumors onto developmental trajectories from normal TECs involves analyzing RNA velocity to visualize their dynamic progression, characterizing cell types and gene expression patterns, and comparing tumor subgroups across cohorts using various indices and gene selection criteria

Background Acute decompensated heart failure (ADHF) is a state of systemic congestion which frequently requires hospitalization. Early and noninvasive detection of decompensation remains challenging. This study evaluated whether voice characteristics differ between patients hospitalized with ADHF and after recovery to examine the potential of voice as a non-invasive biomarker for ADHF. Methods Patients requiring hospital admission for ADHF were prospectively enrolled. Patients with respiratory infection, sepsis, lung or vocal cord disease, acute coronary syndrome, or serum creatinine>3.0mg/dL were excluded. Voice was recorded at two time points: at admission for ADHF and at discharge after recovery. Low-level audio features were extracted, and Mel-spectrograms derived from the voice waveforms were used as the input feature for deep learning-based classification models. Model performance was primarily evaluated at the patient-state level using area under the receiver operating characteristic curve (AUC) with 95% confidence intervals estimated by patient-level bootstrap resampling. Results A total of 100 patients were included (mean age 70.5 years; 47% women) and randomly divided into a training group (N=88) and a test group (N=12). In the analysis with low-level audio features, harmonics-to-noise ratio and Shimmer demonstrated discriminative potential between decompensated and recovered states. In patient-state-level analysis, the best-performing model, ConvNeXt-large, achieved a mean AUC of 0.83 (95% CI 0.70-0.95). Segment-level analysis demonstrated higher discriminative performance (AUC up to 0.87), suggesting the presence of discriminative acoustic features. Conclusions Voice characteristics differed between admission and discharge states in patients hospitalized for ADHF, and voice analysis using deep learning models was able to distinguish acute decompensated and recovered states in patients with ADHF. Our results suggest that voice analysis may provide a novel and non-invasive approach for detection of ADHF.

Immune profiles of thymic epithelial tumors, highlighting the correlation between non-tumor cell proportions and thymopoiesis scores, with significant contributions from thymopoiesis and TET subgroups, and demonstrates differences in immune and B cell scores across tumor types and clinical histories

Abstract The influence of microbiota residing within tumors on patient response to immunotherapies for gastric cancer (GC) is not yet fully understood. We aim to define the characteristics and functional role of tumor-resident microbiota in the context of immune checkpoint inhibitor (ICI) efficacy in GC. A comprehensive multi-omics analysis was performed on samples from 137 GC patients, all of whom were treatment-naïve regarding chemo- or antibiotics. This extensive dataset included both metagenomes and host transcriptomes, with single-cell RNA sequencing data. To achieve accurate quantification, we developed a novel tumor-resident microbial index (TM index) that compared taxon-level load between tumor tissue and matched normal tissue. Treatment responses were subsequently validated using syngeneic mouse models with a cancer-bacteria co-culture platform. Abundance analyses consistently highlighted Helicobacter pylori as the only species significantly decreased in tumor tissue compared to paired normal tissue. Metagenome-assembled genomes showed patient-specific H. pylori strains, maintaining over 99% genomic identity across the paired samples. The TMHP index indicated that high levels of H. pylori were predominantly found in the genomically stable (GS) subtype, characterized by a partially preserved normal physiology. Single-cell RNA sequencing data showed that H. pylori-infected cells exhibit a signature of elevated T cell stress, correlating with the overexpression of HSPA1A. Critically, H. pylori significantly compromised the therapeutic effectiveness of anti-PD-L1 by reducing the infiltration of T cells in mouse models. However, a negative effect was not observed with standard 5-fluorouracil or oxaliplatin treatments. Our findings implicate H. pylori as a mediator of immunotherapy resistance and a therapeutically actionable target for overcoming ICI resistance in GC. Citation Format: Donghyeok Seol, Jieun Lee, Junwoo Jo, Chanmi Bang, Hyeon Jeong Oh, Sejoon Lee, Mira Yoo, Duyeong Hwang, So Hyun Kang, Young Suk Park, Sang-Hoon Ahn, Masami Yamamoto, Tetsuya Tsukamoto, Sachiyo Nomura, Qi Su, Seong-Ho Kong, Do Joong Park, Hyuk-Joon Lee, Hyung-Ho Kim, Charles Lee, Han-Kwang Yang, Sunjae Lee, Yun-Suhk Suh. Helicobacter pylori-driven T cell stress in tumors as a mediator of resistance to immune checkpoint blockade in gastric cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 4895.

Tumor cell fractions across histologic types, the correlation between point mutations and tumor cell fraction, detection of GTF2I mutations through VAFs from WES and RNA-seq, and presents a case of rescued GTF2I L404H mutation with read alignment examples

Background : Reduced handgrip strength (HGS) is associated with adverse cardiometabolic outcomes. This study aimed to determine reference values for HGS among Korean youth and young adults and to evaluate their relationships with metabolic syndrome (MS). Methods : We analyzed data from 9,024 individuals aged 10 to 29 years in the Korea National Health and Nutrition Examination Survey (2014-2019). The adjusted combined handgrip strength (aCHGS; the average of maximum values from both hands divided by body weight) was used as the primary outcome variable. Percentile curves for aCHGS were generated using the lambda-mu-sigma (LMS) method and locally estimated scatterplot smoothing regression analysis, excluding outliers. Associations between aCHGS z-scores and MS were assessed. Results : Percentile curves for aCHGS plateaued after 20 years of age in both sexes. At age 10, aCHGS was comparable between males and females. Males showed a marked rise in aCHGS after early adolescence, maintaining higher levels thereafter. The adjusted odds ratio for MS was 0.313 (95% confidence interval [CI], 0.276 to 0.354) using International Diabetes Federation (IDF) criteria and 0.348 (95% CI, 0.310 to 0.390) using modified National Cholesterol Education Program-Adult Treatment Panel III (NCEP-ATP III) criteria. aCHGS z-scores demonstrated strong predictive power for MS (area under the curve, 0.802 for IDF and 0.776 for modified NCEP-ATP III criteria). The optimal aCHGS z-score cutoff values for predicting MS were -0.508 (IDF) and -0.519 (modified NCEP-ATP III). Conclusion : We established age- and sex-specific aCHGS reference values among Korean youth and young adults, demonstrating effectiveness in predicting MS risk. These standards may serve as a practical clinical tool to identify individuals at increased risk of MS early in development.

Results of gene set enrichment analysis comparing GTF2I-type and CN-type thymomas

Background:Data on the familial occurrence of type 1 diabetes mellitus (T1DM) in Korean pediatric populations are limited. This study evaluated the clinical characteristics of children with T1DM according to family history and estimated the T1DM prevalence among relatives. Methods:We conducted a multicenter retrospective cohort study including patients aged ≤18 years newly diagnosed with T1DM at 18 university-affiliated hospitals in Korea between 2010 and 2024. The index child was defined as the first sibling diagnosed with T1DM and categorized according to the presence of affected parents or siblings. Familial T1DM prevalence was calculated for siblings, first-degree relatives, and twin pairs. Results:Among 936 index children, 32 (3.4%) exhibited a T1DM family history. Compared with index children, subsequent-affected children presented with lower plasma glucose (300.0 mg/dL vs. 412.0 mg/dL, P=0.009) and glycosylated hemoglobin levels (10.4% vs. 12.6%, P<0.001), and a lower frequency of diabetic ketoacidosis (13.8% vs. 49.7%, P<0.001). Venous pH and serum bicarbonate levels were higher (7.4 vs. 7.3, P=0.005; 22.0 mmol/L vs. 17.0 mmol/L, P=0.004, respectively), whereas urine ketone levels were significantly lower (P<0.001). Sibling, first-degree relative, and twin-pair prevalence rates were 3.0% (23/779), 1.3% (34/2,651), and 42.9% (3/7), respectively. Conclusion:In this multicenter Korean cohort, familial T1DM accounted for 3.4% of pediatric cases, which was lower than in Western populations. Subsequent-affected children exhibited milder metabolic decompensation at diagnosis than did index children, likely reflecting earlier recognition through family awareness and screening. These findings underscore the importance of early education and monitoring of at-risk relatives within affected families.

Background Acute increases in blood pressure (BP) after electronic cigarette (e-cigarette) use have been reported, but its long-term association with hypertension is unclear. Objectives The purpose of this study was to assess whether e-cigarette use is associated with prevalent and incident hypertension. Methods We analyzed visit 2 (2014-2017) and visit 3 (2020-2024) data from the HCHS/SOL (Hispanic Community Health Study/Study of Latinos), a population-based cohort study including 11,623 individuals aged 18 to 74 years across 4 U.S. communities. The primary exposure was ever e-cigarette use at visit 2. We also explored current use and dual use with combustible cigarette use. Hypertension was defined as measured BP ≥ 140/90 mm Hg or self-reported antihypertensive medication use. Multivariable Poisson and Cox regression were used for prevalent and incident hypertension, respectively. Longitudinal BP change from visit 2 to 3 was assessed using mixed-effects models. All analyses accounted for the complex survey design. Results Of 11,593 participants with e-cigarette data (mean age 47 years; 52.2% female), 937 reported ever use (136 current users). Ever vs never e-cigarette use was not associated with prevalent hypertension. Over a median follow-up of 6.0 years, 1,409 participants developed hypertension. Ever vs never e-cigarette use was associated with incident hypertension (HR: 1.49; 95% CI: 1.14-1.95), as were current use (HR: 1.89; 95% CI: 1.12-3.18), former use (HR: 1.43; 95% CI: 1.07-1.93), and dual ever use (HR: 1.85; 95% CI: 1.37-2.49), compared to never use. Longitudinal BP change did not differ by e-cigarette use. Conclusions Ever e-cigarette use was associated with increased risk of incident hypertension, suggesting potential long-term cardiovascular harm.

Abstract Gastric cancer (GC) is the fifth most prevalent cancer and the fourth leading cause of cancer mortality. However, clinical strategies targeting these amplifications in GC have been unsuccessful, often leading to treatment resistance and poor prognosis. Extrachromosomal DNA (ecDNA) has emerged as a major mechanism associated with oncogene focal amplification and adverse outcomes. In this study, we performed whole genome sequencing (WGS) and whole transcriptome sequencing (WTS) on paired tumor-normal samples from 76 Korean GC patients collected through Seoul National University Bundang Hospital to understand the prevalence of ecDNAs and their clinical relevance in GC patients. Focal amplification regions amplicons were identified and classified using AmpliconArchitect (AA) and Amplicon Classifier into ecDNA (circular amplification) and non-ecDNA (Chromosomal Amplicons, ChAmps). Focal amplifications were highly frequent and showed a strong association with the chromosomal instability (CIN) subtype (P = 2.37e-09). Of the 76 patients, 17 (22.4%) were classified as "ecDNA positive patients". Notably, 75% of CIN subtype patients carried one or more ecDNA amplicons. Genomic analysis revealed that ecDNA amplicons were significantly larger (P = 0.00056) and more structurally complex than ChAmps, exhibiting a higher frequency of structural variants. ecDNA amplicons also harbored significantly more canonical cancer genes (P = 3.90e-03) and displayed significantly higher copy numbers of these genes compared to ChAmps (P = 6.50e-04). Furthermore, ecDNA regions were significantly enriched with putative transcriptional regulatory elements (P = 1.20e-04) and GC-specific accessible chromatin regions. In WTS data, genes within ecDNA exhibited significantly higher expression compared to in ChAmp (P = 3.59e-05). Gene Set Enrichment Analysis (GSEA) revealed that ecDNA cohorts displayed a significantly more pronounced immunosuppressive phenotype—characterized by downregulation of immune response gene sets—compared to ChAmp patients in both SNUBH and TCGA cohorts. Clinically, the presence of ecDNA conferred a significantly worse Overall Survival (OS) rate compared to ChAmp cohorts (Log-rank test, P = 0.012). Multivariate Cox proportional hazards analysis confirmed that ecDNA status acts as an independent risk factor for OS (HR = 14.4, P = 0.001)Our findings demonstrate that ecDNA amplification is frequent in GC, particularly within the CIN subtype, and is associated with distinct genomic complexity, higher oncogene burden, unique transcriptional consequences (immune suppression), and poor patient prognosis. The presence of ecDNA amplification may serve as a critical prognostic factor in GC, highlighting the need for personalized treatment, including the development of ecDNA-targeted therapies to improve treatment outcomes. Citation Format: Jieun Lee, Donghyeok Seol, Seunghyun Kang, Chanmi Bang, Mira Yoo, Soyeon Kim, Hyeongjin Cho, So Hyun Kang, Young Suk Park, Sang-Hoon Ahn, Hyung-Ho Kim, Eunhee YI, Sanghyun Kim, Hoon Kim, Yun-Suhk Suh. Extrachromosomal DNA amplification defines a high-risk subgroup and unique molecular features in gastric cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 1411.

Gastric cancer peritoneal metastasis (GCPM) is a distinct clinical entity with a poor prognosis, characterized by aggressive features and limited treatment options. Understanding its molecular biology is critical for developing effective therapies. We performed whole genome and transcriptome sequencing on GCPM samples and partially paired primary gastric cancer (GC) tissues from 14 and 26 patients, respectively. Our analysis reveals substantial intra-patient heterogeneity between GCPM and primary tumors at both genetic and functional levels. Inter-patient variability is observed in mutational overlaps, with some signatures unique to either GCPM or primary tumors. Tumor evolution analysis suggests divergent clonal evolution, with distinct clones specific to GCPM or primary tumors in most patients. Transcriptomic profile reveals a high heterogeneity in the primary tumors, with five tumors presenting GCPM characteristics. The tumor microenvironment (TME) is poorly conserved between primary GC and GCPM, with desert-type primary tumors often transitioning to immune-enriched TMEs in metastases. These findings suggest that immunotherapy resistance in GCPM may arise from factors beyond intrinsic TME characteristics, such as limited drug delivery due to the peritoneal-plasma barrier. Collectively, our results highlight significant molecular and TME heterogeneity between GCPM and primary tumors, emphasizing the need for GCPM-specific stratification and innovative treatment strategies to improve outcomes.

Validation of immune scores in thymic epithelial tumors involved correlation analysis with established immune signatures, comparison with single-cell RNA-seq data, and assessment of B cell and T cell scores, including samples with tertiary lymphoid structures

PURPOSE:Brain magnetic resonance imaging (MRI) is used to assess anatomical abnormalities in children with idiopathic growth hormone deficiency (IGHD), but its prognostic relevance remains uncertain. We investigated whether structural abnormalities on brain MRI are associated with 1-year growth response to recombinant human growth hormone (rhGH) therapy in Korean children with IGHD. METHODS:This multicenter retrospective study included 457 IGHD patients from the LG Growth Study registry who had baseline brain MRI and received rhGH therapy for ≥1 year. MRI findings were categorized as normal or as showing pituitary or extrapituitary abnormalities. Growth outcomes-change in height SDS (ΔHeight SDS) and height velocity-were compared across groups. Multivariable regression was performed to adjust for clinical variables. RESULTS:Among 457 patients, 122 (26.7%) had structural abnormalities on brain MRI, while 335 (73.3%) had normal findings. In unadjusted analysis, those with abnormalities showed slightly lower ΔHeight SDS than those with normal brain MRI (p=0.028). However, subgroup differences were not significant when analyzed categorically. In multivariable regression, younger age at treatment (β=-0.050, p=0.004), higher baseline body mass index SDS (β=0.055, p=0.002), and greater rhGH dose (β=0.806, p=0.039) were significantly associated with greater ΔHeight SDS, while brain MRI abnormalities were not predictive of response. CONCLUSION:While brain MRI is an important diagnostic tool in IGHD for identifying anatomical abnormalities, our findings suggest that such abnormalities, particularly when mild or isolated, have limited utility in predicting short-term growth response to rhGH therapy.

BACKGROUND:Hearing loss is an emerging public health concern, with women typically experiencing deterioration during menopause; however, longitudinal studies across this transition are limited. This study examined hearing changes across the menopausal transition in order to identify distinct patterns of hearing decline from 11 years before to 9 years after the final menstrual period, with the goal of informing strategies for early detection and intervention. MATERIALS AND METHODS:We followed 4448 women aged 42-52 years who underwent regular health exams at the Kangbuk Samsung Hospital Total Healthcare Centers (2014-2018) through 2023. Hearing changes were analyzed using linear mixed-effects models across the menopausal transition. Group-based trajectory modeling was applied to assess heterogeneity in hearing deterioration relative to the final menstrual period. RESULTS:A significant change in average bilateral hearing thresholds was observed across menopausal transition. Hearing change during the menopausal transition varied by obesity, with minimal change in those with obesity and slight improvement in those without during early transition. Group-based trajectory modeling identified two patterns: Group 1 (71.7 %) had stable hearing until the final menstrual period, then declined; Group 2 (28.3 %) showed poorer baseline hearing with a steeper, persistent decline. At baseline, Group 2 exhibited a significantly higher prevalence of overweight/obesity and hyperglycemia than Group 1. CONCLUSIONS:Postmenopausal stages were associated with significant hearing decline in middle-aged women. Furthermore, subgroups with metabolically unhealthy profiles exhibited poorer baseline hearing and a steeper decline in hearing, highlighting the need for appropriate screening and management during the menopausal transition.