Background: Vascular smooth muscle cells (VSMCs) play a crucial role in the development of occlusive vascular diseases through abnormal proliferation and migration. This pathological behavior is closely associated with mitochondrial reactive oxygen species (ROS)-mediated mitochondrial DNA (mtDNA) damage. The mitochondrial carrier protein solute carrier family 25 member 33 (SLC25A33), essential for nucleoside transport, is integral to mtDNA production. This study aimed to investigate the effects of SLC25A33 inhibition on the proliferation and migration of VSMCs, as well as its impact on neointima formation. Methods: VSMCs were isolated from the thoracic aorta of 4-week-old Sprague-Dawley rats. The effects of small interfering RNAinduced silencing of SLC25A33 mRNA on platelet-derived growth factor (PDGF)-induced proliferation and migration of VSMCs were analyzed. The in vivo effects of targeting the SLC25A33 gene on neointima formation were evaluated using a murine carotid artery ligation model by perivascularly applying Lenti-shSLC25A33 with Pluronic F-127 gel. Results: First, we observed an upregulation of the SLC25A33 protein in the carotid artery ligation-induced neointima in mice. Silencing of SLC25A33 suppressed the PDGF-stimulated proliferation and migration of VSMCs and cell cycle progression. Knockdown of SLC25A33 inhibited PDGF-induced production of mtDNA and ROS, consequently inactivating the cyclic GMP-AMP synthesis (cGAS)-stimulator of interferon genes (STING)-TANK-binding kinase 1 (TBK1)-nuclear factor kappa B (NF-κB) pathway. Furthermore, the downregulation of SLC25A33 reduced carotid artery ligation-induced neointima in mice. Conclusion This study suggests that targeting SLC25A33 in VSMCs could be a novel therapeutic strategy to prevent occlusive vascular diseases.

Background: Precision oncology is advancing, increasing the demand for comprehensive, non-invasive genomic profiling tools. Liquid biopsy using circulating tumor DNA (ctDNA) enables real-time molecular profiling, treatment monitoring, and early detection of resistance variants. We developed the PAN100 panel (Dxome), a hybridization capture panel targeting 101 genes, as a pan-cancer genotyping assay to detect clinically actionable variants across various cancer types. This study presents the first comprehensive validation of the PAN100 panel including both analytical and clinical performance across eight cancer types using reference materials and matched tissue samples. Methods: For analytical validation, we assessed accuracy, limit of detection (LoD), and precision using Seraseq ctDNA v2 Reference Materials (SeraCare, Milford, MA, USA). Clinical validation was performed using plasma samples from 27 patients with eight types of cancer and 17 matched tumor samples. Positive percent agreement (PPA) between ctDNA and tissue next-generation sequencing (NGS) results was assessed using TruSight Oncology 500 and TruSight Tumor 170 assays. The limit of blank (LoB) was evaluated in 34 healthy individuals. Results: The PAN100 panel demonstrated high precision and linearity (LoD, 0.3%; 95.0% confidence interval, 0.29–0.35) variant allele frequency. The PPA between ctDNA and tissue NGS was 73.1% for single-nucleotide variants, 80.0% for insertions/deletions, and 74.2% overall. The LoB was 0.00001%. Conclusions The PAN100 panel is a robust tool for detecting clinically significant variants with high concordance with tissue NGS. Its sensitivity for low-frequency variants enables real-time treatment adaptation, supporting precision oncology. Its comprehensive design is particularly valuable for challenging diagnoses and clonal evolution monitoring.

Purpose: The effect of behavior changes in alcohol drinking on gastric cancer (GC) development, and the sex differences in those effects have not yet been fully elucidated. This study investigated the effect of behavior changes in alcohol drinking on the GC risk by sex. Materials and Methods: The cohort consisted of 310,192 Koreans (≥ 40 years) from the National Health Insurance Service–Health Screening Cohort with a median follow-up period of 12 years. Subjects were classified according to alcohol consumption behavior changes (non-drinker, quitter, reducer, sustainer, and increaser). The independent effect of changes in alcohol drinking patterns or concurrent effect of alcohol on GC risk were evaluated using the Cox proportional hazard regression. Results: In males, non-drinkers showed a lower risk of developing GC (hazard ratio [HR], 0.91; 95% confidence interval [CI], 0.84 to 0.98), whereas increasers showed a higher risk of GC than sustainers (HR, 1.11; 95% CI, 1.02 to 1.20). Starting to drink alcohol, even at a mild level, was associated with an increased GC risk, while a decreased GC risk was induced when alcohol consumption dose decreases to a mild from a moderate level among males. However, in females, only substantial change of alcohol consumption dose from non- to heavy-drinking was associated with increased GC risk (HR, 1.97; 95% CI, 0.98 to 3.96). Conclusion These results suggest that alcohol abstinence can reduce the risk of developing GC, particularly among males.

Background: Chronic pain significantly affects daily activities, mental health, and the interpersonal relationships of patients. Consequently, physicians use various treatments to manage pain. This study investigated the perceptions of treatment, accompanying symptoms, and other problems in patients with chronic pain. Methods: The authors enrolled patients with chronic pain from 19 university hospitals in South Korea. Data was collected on age, gender, diagnosis, disease duration, severity of pain, perception of pain treatment, and accompanying symptoms or problems using an anonymous survey comprising 19 questions. Results: In total, 833 patients with chronic pain completed the survey, and 257 (31.0%) and 537 (64.5%) patientsexpressed concerns about the potential adverse effects of medication and opioid addiction, respectively. Personalitychanges such as irritability or anger were the most frequent accompanying symptoms in 507 (63.8%) patients, followed by depression and sleep disturbance in 462 (58.1%) and 450 (54.5%) patients, respectively. Depression (P = 0.001) and anxiety (P = 0.029) were more common among women, whereas divorce (P = 0.016), family conflict (P < 0.001), unemployment (P < 0.001), suicide attempts (P < 0.001), and restrictions on economic activity (P < 0.001) were more common among men. The frequency of accompanying symptoms, except for suicidal ideation,was higher in the younger patients aged ≤ 40 years than in the older patients aged > 40 years. Conclusions Many patients with chronic pain had concerns about adverse effects or medication tolerance and experienced anxiety, depression, or sleep disturbances. The prevalence of accompanying problems varies according to age and gender.

Background: and Purpose To determine the clinical phenotypes, relapse timing, treatment responses, and outcomes of children with relapsing myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD). Methods: We collected the demographic, clinical, laboratory, and radiological data of patients aged <18 years who had been diagnosed with MOGAD at Seoul National University Children’s Hospital between January 2010 and January 2022; 100 were identified as positive for MOG antibodies, 43 of whom experienced relapse. Results: The median age at onset was 7 years (range 2–16 years). The median number of relapses was 2 (range 1–8), and patients were followed up for a median of 65 months (range 5–214 months). The first relapse was experienced before 3 months from onset by 15 patients (34.9%). The most-common initial phenotypes were acute disseminated encephalomyelitis (n=17, 39.5%) and optic neuritis (ON; n=11, 25.6%). The most-common relapse phenotypes were neuromyelitis optica spectrum disorder (n=9, 20.9%), relapsing ON (n=6, 14.0%), and multiphasic disseminated encephalomyelitis (n=6, 14.0%). Many of the patients (n=18, 41.9%) were not specifically categorized. A high proportion of these patients had non-acute disseminated encephalomyelitis encephalitis. Atypical phenotypes such as prolonged fever or hemiplegic migraine-like episodes were also noted. Mycophenolate mofetil and cyclic immunoglobulin treatment significantly reduced the annual relapse rates. Conclusions Our 43 pediatric patients with relapsing MOGAD showed a tendency toward early relapse and various relapse phenotypes. The overall prognoses of these patients were good regardless of phenotype or response to second-line immunosuppressant treatment.

Purpose: Physical activity (PA) is considered a potentially effective factor in the primary prevention of gastric cancer (GC). As body mass index (BMI) and waist circumference (WC) differ by sex, particularly with age, this study aimed to investigate the impact of PA on GC development, considering BMI and WC variations by sex. Materials and Methods: We analyzed the impact of PA on GC development using Cox proportional hazard regression in a cohort of 314,525 Korean individuals from the National Health Insurance Service–Health Screening database, using data from 2009–2019.Additionally, subgroup analyses were conducted based on BMI and WC. The models were adjusted for age, sex, smoking status, alcohol consumption, BMI, and comorbidities. Results: The effect of PA on the prevention of GC development was relatively evident in males. The high PA group (metabolic equivalents of task, METs/week of 500–999) showed a lower risk of GC compared to the group with METs/week of 0 (hazard ratio [HR], 0.88; 95% confidence interval [CI], 0.79–0.98). Especially in males with WC <90 cm and BMI <23 kg/m2 , a lower risk of GC was observed in the group with METs/week of 1–499 compared to the group with METs/week of 0 (HR, 0.80; 95% CI, 0.67–0.96). In contrast, no consistent association was observed between PA levels and risk of GC in females. Conclusions Moderate PA had a preventive effect on GC development in males, particularly in those with low BMI and WC. However, this effect was not observed in females.

Background: Chronic pain significantly affects daily activities, mental health, and the interpersonal relationships of patients. Consequently, physicians use various treatments to manage pain. This study investigated the perceptions of treatment, accompanying symptoms, and other problems in patients with chronic pain. Methods: The authors enrolled patients with chronic pain from 19 university hospitals in South Korea. Data was collected on age, gender, diagnosis, disease duration, severity of pain, perception of pain treatment, and accompanying symptoms or problems using an anonymous survey comprising 19 questions. Results: In total, 833 patients with chronic pain completed the survey, and 257 (31.0%) and 537 (64.5%) patientsexpressed concerns about the potential adverse effects of medication and opioid addiction, respectively. Personalitychanges such as irritability or anger were the most frequent accompanying symptoms in 507 (63.8%) patients, followed by depression and sleep disturbance in 462 (58.1%) and 450 (54.5%) patients, respectively. Depression (P = 0.001) and anxiety (P = 0.029) were more common among women, whereas divorce (P = 0.016), family conflict (P < 0.001), unemployment (P < 0.001), suicide attempts (P < 0.001), and restrictions on economic activity (P < 0.001) were more common among men. The frequency of accompanying symptoms, except for suicidal ideation,was higher in the younger patients aged ≤ 40 years than in the older patients aged > 40 years. Conclusions Many patients with chronic pain had concerns about adverse effects or medication tolerance and experienced anxiety, depression, or sleep disturbances. The prevalence of accompanying problems varies according to age and gender.

Background: and Purpose To determine the clinical phenotypes, relapse timing, treatment responses, and outcomes of children with relapsing myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD). Methods: We collected the demographic, clinical, laboratory, and radiological data of patients aged <18 years who had been diagnosed with MOGAD at Seoul National University Children’s Hospital between January 2010 and January 2022; 100 were identified as positive for MOG antibodies, 43 of whom experienced relapse. Results: The median age at onset was 7 years (range 2–16 years). The median number of relapses was 2 (range 1–8), and patients were followed up for a median of 65 months (range 5–214 months). The first relapse was experienced before 3 months from onset by 15 patients (34.9%). The most-common initial phenotypes were acute disseminated encephalomyelitis (n=17, 39.5%) and optic neuritis (ON; n=11, 25.6%). The most-common relapse phenotypes were neuromyelitis optica spectrum disorder (n=9, 20.9%), relapsing ON (n=6, 14.0%), and multiphasic disseminated encephalomyelitis (n=6, 14.0%). Many of the patients (n=18, 41.9%) were not specifically categorized. A high proportion of these patients had non-acute disseminated encephalomyelitis encephalitis. Atypical phenotypes such as prolonged fever or hemiplegic migraine-like episodes were also noted. Mycophenolate mofetil and cyclic immunoglobulin treatment significantly reduced the annual relapse rates. Conclusions Our 43 pediatric patients with relapsing MOGAD showed a tendency toward early relapse and various relapse phenotypes. The overall prognoses of these patients were good regardless of phenotype or response to second-line immunosuppressant treatment.

Purpose: Physical activity (PA) is considered a potentially effective factor in the primary prevention of gastric cancer (GC). As body mass index (BMI) and waist circumference (WC) differ by sex, particularly with age, this study aimed to investigate the impact of PA on GC development, considering BMI and WC variations by sex. Materials and Methods: We analyzed the impact of PA on GC development using Cox proportional hazard regression in a cohort of 314,525 Korean individuals from the National Health Insurance Service–Health Screening database, using data from 2009–2019.Additionally, subgroup analyses were conducted based on BMI and WC. The models were adjusted for age, sex, smoking status, alcohol consumption, BMI, and comorbidities. Results: The effect of PA on the prevention of GC development was relatively evident in males. The high PA group (metabolic equivalents of task, METs/week of 500–999) showed a lower risk of GC compared to the group with METs/week of 0 (hazard ratio [HR], 0.88; 95% confidence interval [CI], 0.79–0.98). Especially in males with WC <90 cm and BMI <23 kg/m2 , a lower risk of GC was observed in the group with METs/week of 1–499 compared to the group with METs/week of 0 (HR, 0.80; 95% CI, 0.67–0.96). In contrast, no consistent association was observed between PA levels and risk of GC in females. Conclusions Moderate PA had a preventive effect on GC development in males, particularly in those with low BMI and WC. However, this effect was not observed in females.