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.

Angiogram-negative subarachnoid hemorrhage (SAH) represents a diagnostic challenge because rebleeding risk persists despite negative initial angiography. We report a rare case of a 65-year-old man presenting with diffuse SAH on initial CT but with negative CTA and transfemoral cerebral angiography (TFCA). Serial follow-up CT scans demonstrated gradual resolution of subarachnoid blood except for persistent prepontine cisternal hemorrhage. On hospital day 7, repeat TFCA revealed a bilobulated pseudoaneurysm arising from a midbasilar perforator artery. The lesion was treated using a modified stent-assisted coiling technique involving partial coil deployment, achieving complete angiographic obliteration with parent artery preservation. Post-procedural diffusion-weighted MRI demonstrated a left pontine infarction, but the patient achieved meaningful functional recovery and returned to work at the 3-month follow-up. This case underscores the necessity of repeat angiography in diffuse angiogram-negative SAH and highlights tailored endovascular strategies for fragile basilar perforator pseudoaneurysm.

Streptococcus gordonii is an oral commensal viridans streptococcus that rarely causes invasive infections such as lung abscess or intracranial empyema. The sequential presentation of concomitant pulmonary and cranial abscesses by this organism is extremely uncommon. A 70-year-old man presented with progressive dyspnea and fever. Chest CT demonstrated a 14.4 × 6.8cm mass like lung lesion consistent with a lung abscess. Percutaneous drainage yielded Streptococcus gordoniii. On hospital day 5 following drainage, patient presented with scalp swelling and headache. Brain MRI revealed a subgaleal abscess with an epidural empyema. Emergent craniectomy and debridement were performed, and cultures again grew Streptococcus gordonii. This case is a rare but clinically significant pattern of sequential presentation of concomitant pulmonary and cranial abscesses caused by Streptococcus gordonii, emphasizing the need for dental evaluation, meticulous inpatient monitoring, and early neuroimaging when viridans streptococci are revealed from deep infections.

Objective: The escalating global mental health crisis necessitates innovative solutions to address traditional service limitations such as high costs and professional shortages. This review examines the emerging role of artificial intelligence (AI) chatbots in digital psychiatry, analyzing their clinical efficacy, ethical challenges, and future directions. Methods: This narrative review synthesizes evidence from recent randomized controlled trials, meta-analyses, and scholarly publications on AI chatbots for mental health. It also discusses the ethical and social implications, including data privacy, algorithmic bias, and cognitive effects, and provides a forward-looking roadmap for regulation and development. Results: Chatbots grounded in evidence-based principles like cognitive-behavioral therapy demonstrate clinical effectiveness in reducing symptoms of depression and anxiety, with some studies reporting a strong “therapeutic alliance” comparable to that with human therapists. AI models also show promise in diagnostic and predictive roles by analyzing selfreport questionnaires and physiological data. However, critical risks include inappropriate responses in crisis situations, potential for AI psychosis, and the erosion of cognitive abilities due to over-reliance. Conclusion The future of digital psychiatry lies in a blended care model that combines the accessibility of AI with the indispensable empathy and professional judgment of human clinicians. A collaborative roadmap is essential, mandating safety protocols, strengthened data governance, expert involvement, and ethical design to ensure AI acts as a transformative and responsible tool.

Purpose: Exon 20 insertion mutations (E20ins) in epidermal growth factor receptor (EGFR) or human epidermal growth factor receptor 2 (HER2) in non–small cell lung cancer (NSCLC) patients has become more important with emergence of novel agents targeting E20ins. Materials and Methods: Advanced/Metastatic NSCLC patients with E20ins were included. EGFR E20ins was identified by two methods, next-generation sequencing (NGS) or real-time polymerase chain reaction (PCR), while HER2 E20ins was done by NGS only. Results: Between December 2013 and July 2021, E20ins were identified in 107 patients at Asan Medical Center; 67 EGFR E20ins and 40 HER2 E20ins. Out of 32 patients with EGFR E20ins who had tested both PCR and NGS, 17 were identified only through NGS and the other 15 through both tests, giving a discordance rate of 53.1%. There was no clinically significant difference in clinicopathologic features between EGFR and HER2 E20ins; both were observed more frequently in adenocarcinoma, female and never-smokers. Brain metastases were evident at diagnosis in 31.8% of EGFR E20ins and 27.5% of HER2 E20ins, respectively. Platinum-based doublets demonstrated objective response rates (ORR) of 13.3% with a median progression-free survival (PFS) of 4.2 months for EGFR E20ins and 35.3% with 4.7 months for HER2 E20ins, respectively. In contrast, novel EGFR E20ins-targeted agents exhibited an ORR of 46.2% with a median PFS of 5.4 months, while HER2-targeted agents showed an ORR of 50% with that of 7.0 months. Conclusion Identification of EGFR and HER2 E20ins is more important as their targeted therapies improved outcomes. Upfront NGS test as a comprehensive molecular approach is strongly warranted.

Background: and Purpose: This study aimed to evaluate the brain magnetic resonance imaging (MRI) of patients with acute transient global amnesia (TGA) using volumetric analysis to verify whether the brains of TGA patients have pre-existing structural abnormalities. Methods: We evaluated the brain MRI data from 87 TGA patients and 20 age- and sexmatched control subjects. We included brain MRIs obtained from TGA patients within 72 hours of symptom onset to verify the pre-existence of structural change. For voxel-based morphometric analyses, statistical parametric mapping was employed to analyze the structural differences between patients with TGA and control subjects. Results: TGA patients exhibited significant volume reductions in the bilateral ventral anterior cingulate cortices (corrected p<0.05). Conclusions TGA patients might have pre-existing structural changes in bilateral ventral anterior cingulate cortices prior to TGA attacks.

Viral load and the duration of viral shedding of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are important determinants of the transmission of coronavirus disease 2019.In this study, we examined the effects of viral doses on the lung and spleen of K18-hACE2 transgenic mice by temporal histological and transcriptional analyses. Approximately, 1×105 plaque-forming units (PFU) of SARS-CoV-2 induced strong host responses in the lungs from 2 days post inoculation (dpi) which did not recover until the mice died, whereas responses to the virus were obvious at 5 days, recovering to the basal state by 14 dpi at 1×102 PFU. Further, flow cytometry showed that number of CD8+ T cells continuously increased in 1×102 PFU-virusinfected lungs from 2 dpi, but not in 1×105 PFU-virus-infected lungs. In spleens, responses to the virus were prominent from 2 dpi, and number of B cells was significantly decreased at 1×105PFU; however, 1×102 PFU of virus induced very weak responses from 2 dpi which recovered by 10 dpi. Although the defense responses returned to normal and the mice survived, lung histology showed evidence of fibrosis, suggesting sequelae of SARS-CoV-2 infection. Our findings indicate that specific effectors of the immune response in the lung and spleen were either increased or depleted in response to doses of SARS-CoV-2. This study demonstrated that the response of local and systemic immune effectors to a viral infection varies with viral dose, which either exacerbates the severity of the infection or accelerates its elimination.

Background: Achieving a definitive genetic diagnosis of unexplained multiple congenital anomalies (MCAs) in neonatal intensive care units (NICUs) infants is challenging because of the limited diagnostic capabilities of conventional genetic tests. Although the implementation of whole genome sequencing (WGS) has commenced for diagnosing MCAs, due to constraints in resources and faculty, many NICUs continue to utilize chromosomal microarray (CMA) and/or karyotyping as the initial diagnostic approach. We aimed to evaluate the diagnostic efficacy of WGS in infants with MCAs who have received negative results from karyotyping and/or CMA. Methods: In this prospective study, we enrolled 80 infants with MCAs who were admitted to a NICU at a single center and had received negative results from CMA and/or karyotyping.The phenotypic characteristics were classified according to the International Classification of Diseases and the Human Phenotype Ontology. We assessed the diagnostic yield of trioWGS in infants with normal chromosomal result and explored the process of diagnosing by analyzing both phenotype and genotype. Also, we compared the phenotype and clinical outcomes between the groups diagnosed with WGS and the undiagnosed group. Results: The diagnostic yield of WGS was 26% (21/80), of which 76% were novel variants.There was a higher diagnostic yield in cases of craniofacial abnormalities, including those of the eye and ear, and a lower diagnostic yield in cases of gastrointestinal and genitourinary abnormalities. In addition, higher rates of rehabilitation therapy and gastrostomy were observed in WGS-diagnosed infants than in undiagnosed infants. Conclusion This prospective cohort study assessed the usefulness of trio-WGS following chromosomal analysis for diagnosing MCAs in the NICU and revealed improvements in the diagnostic yield and clinical utility of WGS.

Background/Aims: This study evaluated the long-term cardiovascular complications among Korean patients with hypertension and compared them with that of controls without hypertension. Methods: The Korean Hypertension Cohort (KHC) enrolled 11,043 patients with hypertension and followed them for more than 10 years. Age- and sex-matched controls without hypertension were enrolled at a 1:10 ratio. We compared the incidence of cardiovascular events and death among patients and controls without hypertension. Results: The mean age was 59 years, and 34.8% and 16.5% of the patients belonged to the high and moderate cardiovascular risk groups, respectively. During the 10-year follow-up, 1,591 cardiovascular events (14.4%) with 588 deaths (5.3%) occurred among patients with hypertension and 7,635 cardiovascular events (6.9%) with 4,826 deaths (4.4%) occurred among controls. Even the low-risk population with hypertension showed a higher cardiovascular event rate than the population without hypertension. Although blood pressure measurements in the clinic showed remarkable inaccuracy compared with those measured in the national health examinations, systolic blood pressure (SBP) ≥ 150 mmHg was significantly associated with a higher risk of cardiovascular events. Conclusions This long-term follow-up study confirmed the cardiovascular event rates among Korean hypertensive patients were substantial, reaching 15% in 10 years. SBP levels ≥ 150 mmHg were highly associated with occurrence of cardiovascular event rates.

Purpose: The purpose of this study is to share our outcomes and experiences on allogeneic hematopoietic stem cell transplantation (HSCT) in elderly patients aged 60 years and older with myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) in South Korea, and to compare them with other studies. Materials and Methods: We analyzed the clinical outcomes of 116 patients with AML or MDS aged 60 years and older who underwent allogeneic HSCT. We also analyzed which pretreatment factors affect the overall survival (OS) after allogeneic HSCT. Results: Neutrophil and platelet engraftment were achieved at median day +11 [interquartile range (IQR) 10–15] and +14 (IQR 11–19), respectively. A complete donor chimerism was confirmed in 65 (56.0%) patients at 3 weeks and in 63 (54.3%) patients at 3 months after HSCT. The estimated incidence of grade II–IV acute graft-versus-host disease (GVHD) at day 100 was 13.7%. The estimated incidence of chronic GVHD at 2 years was 38.8%. Within a median follow-up of 14 months after HSCT, OS was 64% at 1 year and 55% at 2 years, and non-relapse mortality (NRM) was 20% at 1 year and 28% at 2 years. Multivariate analysis revealed that male sex and Hematopoietic Cell Transplantation-Specific Comorbidity Index ≥3 were associated with poor OS. Conclusion This study showed that allogeneic HSCT in elderly adults aged 60 and older can be performed with successful engraftment and acceptable NRM and OS are expected given the generally known survival of patients with higher risk MDS and poor risk AML.