Idiopathic pulmonary fibrosis (IPF) is characterized by maladaptive epithelial–mesenchymal crosstalk and progressive extracellular matrix accumulation, whereas currently available antifibrotic agents merely decelerate functional decline.This study investigated whether exosomes derived from human mesenchymal stem cells derived from embryonic stem cells (ESC-MSCs) restore epithelial stress responses and attenuate fibrotic remodeling. Human IPF lung transcriptomes were integrated with a bleomycin-induced murine model analyzed by RNA sequencing and protein signaling, together with cigarette smoke extract-induced injury in A549 epithelial cells. ESC-MSCs-derived exosomes exhibited typical morphology and size distribution, enrichment of tetraspanins, and absence of endoplasmic reticulum contamination, consistent with high-purity preparations. Across human IPF and bleomycin-injured lungs, transcriptomic profiling revealed prominent enrichment of extracellular matrix and cytoskeletal gene programs, whereas mitogen-activated protein kinase (MAPK) and Smad families displayed only modest alterations at the mRNA level. In vivo administration of exosomes during the fibrotic remodeling phase, via either intravenous or intratracheal delivery, resulted in improved body weight, reduced lung weight-to-body weight ratios, and decreased collagen deposition and Ashcroft scores. These structural and functional improvements were accompanied by suppression of profibrotic and mesenchymal markers and selective attenuation of activator protein-1 (AP-1) activity. In epithelial injury models, ESC-MSCs-derived exosomes enhanced cell viability, restored redox homeostasis, and constrained stress-induced mesenchymal gene expression and MAPK phosphorylation in both co-treatment and post-treatment settings. Collectively, these data support an epithelial-centered mechanism in which ESC-MSCs-derived exosomes re-establish oxidative balance and selectively restrict AP-1-driven stress signaling, thereby secondarily limiting extracellular matrix accumulation and fibrotic remodeling.

The brain-derived neurotrophic factor (BDNF) plays a crucial role in neuroprotection, and we have previously demonstrated BDNF-mediated neuroprotective effects in mesenchymal stromal cells (MSCs). The present study aimed to investigate whether BDNF-overexpressing MSCs enhance the therapeutic efficacy of naïve MSCs in a preclinical model of severe neonatal intraventricular hemorrhage (IVH). We exposed primary rat neuronal cells to 40 U of thrombin overnight in vitro. Subsequently, the neuronal cells were co-cultured with either naïve MSCs or BDNF-overexpressing MSCs (1×105 cells in 1 mL media) for 24 hours. Next, 300 μL of maternal blood was injected into bilateral ventricles on postnatal day (P)4 to induce severe IVH in newborn Sprague-Dawley male rats. At P6, either naïve MSCs or BDNF-overexpressing MSCs (1×105 cells in 10 μL saline) were transplanted intraventricularly. Behavioral function tests, including passive avoidance, followed by endpoint analyses of brain tissue and cerebrospinal fluid were performed at P35. BDNF-overexpressing MSCs enhanced the effects of naïve MSCs against cell death, cytotoxicity, and oxidative stress in vitro. Notably, naïve and BDNF-overexpressing MSCs did not attenuate post-hemorrhagic ventricular dilatation, neuronal cell death, or gliosis. However, BDNF-overexpressing MSCs attenuated microglial activation.Furthermore, inflammatory cytokine (interleukin [IL]-1α, IL-1β, IL-6, and tumor necrosis factor-α) levels and memory function assessed using a passive avoidance test significantly improved in the BDNF-overexpressing MSC transplanted group compared with the naïve MSC transplanted group. Our data suggest that BDNF-overexpressing MSCs may offer superior protective effects to naïve MSCs in a neonatal IVH model.

Purpose: The accurate localization of bifurcation points in the brain near the circle of Willis is essential for labeling cerebral arteries and detecting potential aneurysms. Studies on the development of segmentation-based landmark localization methods for cerebral angiography are lacking. This study aimed to develop and validate a method for localizing anatomical landmarks using a three-dimensional (3D) encoder-decoder deep convolutional neural network architecture. Materials and Methods: Time-of-flight magnetic resonance angiography (MRA) images of 224 subjects obtained from publicly available datasets were used. Ten anatomical landmark points were annotated, and four different landmark subset configurations were trained and validated. For each configuration, 3D U-Net-based models were developed using the MRA images and their corresponding annotated landmarks. The deep learning prediction results were evaluated in terms of landmark localization errors. Results: Among the four configurations, the configuration with five landmark subsets produced the smallest landmark localization errors in the test dataset. Post-processing of the U-Net-predicted segmentation masks further reduced the mean localization errors across all landmark points for the configuration with five subsets. Conclusion The proposed landmark localization method effectively identified major anatomical landmarks around the circle of Willis and showed the potential to automate segmental analyses of intracranial arterial tortuosity.

Purpose: While the benefit of neoadjuvant chemotherapy (NAC) has been established in human epidermal growth factor receptor 2 (HER2)-positive and triple-negative breast cancers, its effectiveness in achieving pathological complete response (pCR) and optimal patient selection in estrogen receptor (ER)-positive, HER2-negative breast cancers remain less clearly defined. This study aimed to identify immunohistochemistry (IHC)-based predictors of pCR and to develop a scoring model for ER-strong positive/HER2-negative breast cancer. Methods: Data from a prospective cohort were retrospectively analyzed. We included 522 patients with ER-strong positive/HER2-negative tumors who received NAC and surgery between 2008 and 2021. IHC markers including progesterone receptor (PR), Ki-67, epidermal growth factor receptor (EGFR), cytokeratin 5/6 (CK5/6), and p53 were evaluated to identify predictors of pCR. Independent predictors of pCR from multivariate logistic regression were used to develop a weighted 4-point model. Model performance was assessed using receiver operating characteristic analysis. The prognostic impact of pCR was evaluated using KaplanMeier and Cox regression analyses. Results: Independent predictors of pCR included PR-negative status, positivity for basallike markers (EGFR or CK5/6), and Ki-67 ≥ 50%. The scoring model demonstrated good discrimination for pCR (area under the curve = 0.754). pCR rates increased stepwise, with scores of 4.9% (low), 10.7% (intermediate), and 36.2% (high). In the high-score group, pCR was significantly associated with improved disease-free survival (hazard ratio [HR], 0.09; p = 0.023) and distant metastasis-free survival (HR, 0.11; p = 0.035), whereas no significant survival differences according to pCR status were observed in the low and intermediate score groups. Conclusion This IHC-based model predicts pCR and helps identify subgroups in which pCR is associated with meaningful survival benefit following NAC in ER-positive/HER2-negative breast cancers. High-scoring patients may benefit from NAC, while patients with low- or intermediatescores may be better managed with surgery and endocrine therapy. This model may support personalized treatment decisions regarding NAC.

Purpose: Lobular carcinoma In Situ (LCIS) is a noninvasive lesion associated with an increased risk of invasive cancer. Since its removal from the tumor, node, metastasis classification in the 8th edition of the American Joint Committee on Cancer (AJCC) guidelines, the clinical management of LCIS has shifted from surgery to surveillance. However, studies focusing on the risk and associated factors for invasive cancer development in pure LCIS without ductal carcinoma In Situ (DCIS) or invasive cancer remain limited. Methods: We retrospectively analyzed 106 patients diagnosed with pure LCIS between 2008 and 2018. This study evaluated the effect of tamoxifen use and histologic type on the development of invasive cancer. Results: All 106 patients underwent surgery, and nine (8.5%) developed invasive cancer over a median follow-up of 67.5 months. The incidence of invasive cancer was lower in the tamoxifen group (6.3%, n = 4) than in the non-tamoxifen group (11.9%, n = 5), although this difference was not statistically significant (p = 0.266). Pleomorphic LCIS had a significantly higher incidence of invasive cancer (30.0%, n = 3) than classic LCIS (6.3%, n = 6) (p = 0.045).Multivariable Cox regression analysis showed no significant difference in the risk of invasive cancer according to tamoxifen use (hazard ratio [HR], 2.031; 95% confidence interval [CI], 0.544–7.579; p = 0.292). However, pleomorphic LCIS showed a trend toward an increased risk of invasive cancer compared to classic LCIS (HR, 3.856; 95% CI, 0.922–16.126; p = 0.064). Conclusion Postoperative tamoxifen did not significantly lower invasive cancer development in patients with pure LCIS. Pleomorphic LCIS may carry a higher risk than classic LCIS. These findings require tailored follow-up and treatment strategies based on the histologic subtype of LCIS.

Objective: This study compared clinical and cosmetic outcomes of cranioplasty using customized three-dimensional (3-D) printed implants versus autologous bone in patients with aneurysmal subarachnoid hemorrhage (aSAH) after decompressive craniectomy (DC). Methods: We retrospectively reviewed 50 patients who underwent cranioplasty after DC for aSAH between July 2018 and December 2023. Patients were divided into the three-dimensional cranioplasty(3-DC, n=26) and autologous bone cranioplasty (AC, n=24) groups. Demographics, aneurysm characteristics, surgical parameters, morphometric analysis of defect coverage, complications, and functional outcomes assessed by the modified Rankin Scale (mRS) were compared. Results: A total of 54 hemispheres underwent cranioplasty. Compared with AC, the 3-DC group had larger defects but achieved higher coverage (96.7% vs. 93.4%, p=0.044) and smaller residual defects (338.7±274.2 mm² vs. 528.5±331.3 mm², p=0.049). Complication rates were lower in 3-DC (9 cases) than AC (15 cases, p=0.0994). Wound dehiscence and fluid collection were more frequent with 3-DC, while bone flap resorption and epidural abscess occurred only with AC. Revision surgery was required in six patients, five initially treated with autologous bone. Neurological outcomes (mRS) were maintained or improved in both groups. Conclusions In aSAH patients undergoing cranioplasty after DC, customized 3-D printed implants achieved significantly better anatomical restoration and showed a numerical trend toward fewer complications compared with autologous bone. While AC remains feasible, its risks of resorption and infection often necessitate revision. 3-D printed implants may be considered a reasonable alternative, particularly in aSAH patients at higher risk of complications.

Objectives: Endoscopic submucosal dissection (ESD) has become a standard minimally invasive treatment for selected patients with early gastric cancer (EGC). This study presents the first nationwide survey of patients with EGC treated with ESD in 2023, conducted by the Korean College of Helicobacter and Upper Gastrointestinal Research. Methods: Data were retrospectively collected from participating referral centers across Korea using a standardized case report form covering patient characteristics, tumor features, procedural details, histopathological findings, and clinical outcomes. Descriptive and comparative analyses were conducted to summarize nationwide ESD practice patterns and outcomes. Results: Data from 5460 ESD cases from 5250 patients across 27 institutions were analyzed. The mean age was 67.4 years, with 74.1% males. Multiple synchronous lesions were identified in 3.7%. Most lesions were located in the lower third of the stomach (64.0%), and differentiated-type adenocarcinomas accounted for 87.8%. The en bloc and complete resection rates were 99.2% and 91.4%, respectively. Curative resection was achieved in 80.5%, whereas local non-curative resection (L-NCR) and surgical non-curative resection (S-NCR) were identified in 2.8% and 16.7%, respectively. Additional surgery was performed more frequently in patients with S-NCR than in those with L-NCR (59.3% vs. 24.7%). The bleeding and perforation rates were 3.6% and 0.9%, respectively, and were mostly managed conservatively or endoscopically. The median length of hospitalization was 4.0 days. Conclusions This first nationwide survey provides a comprehensive overview of the current practice of EGC treatment using ESD in Korea, demonstrating high technical success and safety, and establishing a baseline dataset for future longitudinal research.

Objectives: In May 2025, clusters of salmonellosis were identified in 7 cities in the Republic of Korea, all associated with consumption of identical bakery products. This investigation aimed to characterize the outbreak, identify potential contributing factors, and inform strategies for preventing similar multi-facility foodborne outbreaks. Methods: A case series study was conducted among individuals who consumed Manufacturer H’s Product I and Product II on May 15–16, 2025 at 7 facilities (n = 1,235). Clinical specimens from symptomatic individuals, retained food samples, and environmental samples were collected and tested. Food-exposure histories were assessed, and active case finding was implemented across all supplied facilities. Traceback investigations were conducted at the manufacturer, distributor, and egg farms. Human and food isolates underwent pulsed-field gel electrophoresis (PFGE) and whole-genome sequencing (WGS). Results: A total of 323 cases met the outbreak case definition (attack rate, 26.2%), of which 48 were laboratory-confirmed. Salmonella Enteritidis was isolated from both clinical specimens and retained bakery products. PFGE patterns were indistinguishable between human and food isolates, and WGS demonstrated high genetic relatedness. These findings confirmed a common-source outbreak linked to the implicated bakery products. Conclusion This outbreak underscores the value of integrating epidemiological investigation, active case finding, and molecular typing to identify common food vehicles in outbreaks involving widely distributed manufactured foods. Coordinated collaboration between public health and food safety authorities is essential for the effective detection, response, and prevention of multi-facility foodborne outbreaks.

Background/Aims: This study investigated the clinical efficacy of low-dose mepolizumab (100 mg) in controlling severe eosinophilic asthma, aiming to induce eosinophilic granulomatosis with polyangiitis (EGPA) remission and reduce systemic steroid usage. Additionally, we constructed a basic frame for our longitudinal EGPA cohort by collecting serial blood samples before, during, and after mepolizumab treatment in EGPA patients. Methods: We conducted a 2-year prospective observational cohort study in patients with uncontrolled severe eosinophilic asthma and refractory EGPA who used systemic steroids (≥ 7.5 mg/day of prednisolone) or other immunosuppressant drugs for at least 6 months. All patients were treated with 100 mg of mepolizumab every 4 weeks for 1 year to control severe eosinophilic asthma and then were followed for an additional 1 year to monitor their disease course. We analyzed total systemic steroid use and EGPA remission/relapse during the study period. Results: Three EGPA patients were included in this study and completed 16 study visits over a 2-year period. After 1 year of treatment with mepolizumab (100 mg monthly), all 3 patients were able to reduce their maintenance dose of systemic steroids, with 2 patients completely discontinuing use. These 2 patients achieved EGPA remission during mepolizumab treatment, and their remission status remained stable for 1 year after they stopped receiving the medication. Conclusions Low-dose mepolizumab treatment demonstrated clinical efficacy in reducing the maintenance dose of systemic steroids required for severe refractory EGPA. While not all patients achieved EGPA remission with low-dose mepolizumab, some did, and their remission persisted even after treatment discontinuation.

Purpose: The chromodomain helicase DNA-binding (CHD) protein family comprises adenosine triphosphate-dependent chromatin remodelers that regulate chromatin structure and gene expression. Pathogenic CHD2 variants are associated with neurodevelopmental phenotypes, but these genotype–phenotype correlations remain unclear. This study aimed to delineate the clinical and genetic features of patients with CHD2-related disorders and to explore the associated genotype–phenotype relationships. Methods: Among 22 patients with pathogenic or likely pathogenic CHD2 variants identified using a customized 172-gene neurodevelopmental and epilepsy panel, 19 with sufficient clinical data were included. Demographic, clinical, neuroimaging, electroencephalographic, and genetic data were retrospectively reviewed. Results: Eighteen pathogenic or likely pathogenic variants were identified, including eight novel variants: nine nonsense (50.0%), five splice-site (27.8%), two missense (11.1%), and two exon deletions (11.1%). All patients had epilepsy, with a median age of seizure onset of 2.33 years. Comorbidities included global developmental delay (89.5%), intellectual disability (82.0%), and neuropsychiatric symptoms (47.4%). Seizure types were heterogeneous, with a predominance of generalized-onset seizures, and 13 patients (68.4%) achieved seizure freedom. Marked phenotypic variability was observed: two unrelated patients with the same truncating variant had different developmental and seizure-related profiles, a symptomatic child with an inherited exon 5 deletion contrasted with her asymptomatic father, and a patient with an exon 17–29 deletion exhibited relatively mild features. Conclusion Epilepsy was a consistent manifestation in this study and was accompanied by diverse developmental and neurobehavioral features, with substantial genotype–phenotype discordance. Further research on genotype–phenotype correlation is warranted.