This study is a convergence study that empirically verifies the principles of the Hunminjeongeum Joongsung-Ja (中聲字, vowel) system, especially the principles of the pictorial patterns of the initial and re-involved characters, using magnetic resonance imaging (MRI). According to the principle stated in the Jejahae (制字解) of the Hunminjeongeum Haeryebon—that “the 28 characters of Jeongeum were each modeled after their shapes”—this study aimed to prove that all characters were devised to reflect the shape of the vocal tract when pronounced. Four participants, including both younger and older adults including both sexes were enrolled in this study, and real-time MRI scans and acoustic analysis were conducted. In the analysis of the Cho-Chul-Ja (初出字, /ㅗ, ㅏ, ㅜ, ㅓ/), clear differences were observed in the structure of the vocal tract and the shape of the resonance cavity according to the vowels, and the degree of lip opening and the length of the vocal tract showed a close relationship with the acoustic characteristics of each vowel. In the Jae-Chul-Ja (再出字, /ㅛ, ㅑ, ㅠ, ㅕ/), changes in the shape of the resonance cavity were observed along with changes in tongue movement and lip opening during diphthong utterances, and it was confirmed that this is directly related to acoustic characteristics. The results of this study confirmed that the principle of the Hunminjeongeum Joongsung-Ja (中聲字, vowel) is closely related to the form of resonance cavity in the actual articulation process. It was confirmed that it was created by the synthesis (Hapsung, 合成) of the three letters “Cheon-ji-in (天地人, /•, ㅡ, ㅣ/)”, and it was also confirmed that the pictorial principles of the first and second versions are based on the shape and movement of the resonance tube. It is significant in that it re-examines the scientific sophistication of the vowel system devised during the creation of Hunminjeongeum in the 15th century with modern technology. This shows that Hunminjeongeum is not just a philosophical symbol, but a writing system that reflects the anatomical structure and physiological movements of actual speech organs.

Background: With the aging population and advancements in medical care worldwide, the number of older patients with end-stage kidney disease continues to rise. This study aimed to identify factors associated with osteoporosis and osteopenia in older patients undergoing incident hemodialysis and assess their impact on mortality. Methods: We analyzed a large multicenter retrospective cohort of patients aged ≥70 years undergoing incident hemodialysis to identify factors associated with osteoporosis using logistic regression analysis and to assess the association of death with osteoporosis and osteopenia using Cox multivariable analysis. Results: Among 710 patients, 39.0% and 19.6% had osteoporosis and osteopenia, respectively. Osteoporosis was significantly associated with female sex, a history of fractures, and the absence of phosphate binder use. During a median follow-up of 36.8 months, 348 participants (58.8%) died. Mortality rates were the highest in the osteoporosis group (79.8%), followed by the osteopenia (77.2%) and normal bone mineral density (BMD) groups (35.2%). Cox regression analysis revealed that even after adjusting for covariates, the osteoporosis group was significantly associated with a higher mortality risk than the normal BMD group. Osteoporosis at the start of hemodialysis was significantly associated with higher mortality. Conclusion We should consider the importance of bone health in patients undergoing incident hemodialysis and pay attention to the use of phosphate binders and fracture prevention.

Background: Obesity is a well-known risk factor for chronic kidney disease and its progression. However, the impact of obesity on the renal function of the elderly population is uncertain. We investigated the association between obesity and renal outcomes in the elderly. Methods: We analyzed 130,504 participants from the Korean National Health Insurance Service-Senior cohort. Obesity was classified according to body mass index (BMI), sex-specific waist circumference (WC), and the presence of metabolic syndrome. The primary outcome was renal function decline, defined as a decline in the estimated glomerular filtration rate (eGFR) of at least 50% from baseline or new-onset end-stage renal disease. Results: During a follow-up period of 559,531.1 person-years (median, 4.3 years), 2,486 participants (19.0%; incidence rate of 4.44 per 1,000 person-years) showed renal function decline. A multivariate Cox proportional hazards model revealed that BMI/WC was not associated with renal function decline. However, the group with metabolic syndrome had a significantly increased risk of renal function decline compared to the group without metabolic syndrome (adjusted hazard ratio [HR], 1.24; 95% confidence interval [CI], 1.13–1.36). Compared with the non-metabolic syndrome group, the adjusted HRs (95% CI) for participants with one through five components were 0.96 (0.84–1.11), 1.10 (0.96–1.27), 1.24 (1.06–1.45), 1.37 (1.12–1.66), and 1.99 (1.42–2.79), respectively (p for trend < 0.001). Conclusion In elderly Korean adults, metabolic syndrome and the number of its components were associated with a higher risk of renal function decline, but BMI or WC was not significant.

Background: and Purpose: Given the irreversible nature of dementia, this study examined the effects of a 20-week exercise-based dementia prevention program in community-dwelling older adults, focusing on prior exercise experience and program adherence. Methods: In this exploratory, non-randomized trial, 55 older adults (65–79 years) were allocated to an intervention (n=26) or control (n=29) group, and blinding was not feasible.The intervention comprised supervised rhythmic aerobic exercise with cognitive-motor components performed three times per week. Cognition was the primary outcome, and secondary outcomes included physical fitness, blood pressure, and blood biomarkers.Subgroup analyses classified participants by prior exercise experience and intervention exposure: G1 and G2 comprised control subgroups with no intervention exposure, whereas G3 and G4 comprised intervention-exposed subgroups stratified by adherence. Results: No significant group-by-time interactions were observed for cognitive outcomes.Participants with prior exercise experience and low adherence (G2) showed significant improvement on the Korean Mini-Mental State Examination (β=1.66, p=0.024) despite declines in physical fitness, whereas higher adherence in G3–G4 was associated with stable or favorable physical performance, with G4 showing a positive trend in the 30-second sit-tostand test. Systolic blood pressure decreased significantly in G2–G4. Conclusions Although overall cognitive gains were modest and not group specific, prior exercise experience and sustained adherence were associated with favorable changes in physical fitness and vascular outcomes, suggesting that tailored multicomponent exercise programs and long-term engagement may help promote cognitive health in older adults.

Background: and Purpose: Tailored physical exercise interventions have the potential to promote cognitive health in older adults and offer significant advantages for those more vulnerable to decline. The specific relationship between physical fitness and cognition among the elderly has not been clearly established. The purpose of this investigation was to assess the relationship between physical fitness and cognitive function in older Korean adults. Methods: Eighty-four community-dwelling older adults (mean age: 70.7±5.3 years; 81.0% female) completed a standardized physical fitness battery assessing handgrip strength, sit-and-reach, 30-second sit-to-stand, 2-minute stationary march, 3-m sit-walk-and-return, figure-8-walk, and T-wall response time. Cognitive function was evaluated using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Descriptive statistics, partial correlation analyses, and stepwise multiple linear regression were conducted. Results: Slower T-wall response time was significantly correlated with lower RBANS total index, immediate memory, and delayed memory scores. In regression models, slower T-wall response time was independently associated with lower RBANS total index (β=−0.234, p=0.026) and delayed memory scores (β=−0.295, p=0.029). The regression model for immediate memory was not statistically significant overall; therefore, no predictive conclusion was drawn for this domain. Higher education showed a significant positive association with cognitive performance. Conclusions Coordination, as measured by T-wall response time, emerged as the only physical fitness component consistently associated with cognitive performance in older adults. Coordination-related fitness may be an important correlate of cognitive function in older adults and a promising target for future exercise interventions.

Background/Aims: Recent advances in computer-aided diagnosis (CADx) systems have demonstrated expert-level accuracy in the optical diagnosis of colorectal polyps. High-confidence (HC) diagnoses have been defined as those made within 3 seconds without hesitation, and these systems have been shown to improve diagnostic accuracy. We aimed to evaluate the performance of endoscopists with varying levels of experience in diagnosing colorectal polyps with the assistance of a new CADx system applying the 3-second rule and without artificial intelligence assistance. Methods: In this multicenter ex vivo study, 35 endoscopists assessed 100 polyps (51 adenomas, 39 hyperplastic polyps, 10 sessile serrated lesions) using narrow-band imaging video clips on an online platform. Assessments consisted of individual endoscopist diagnosis and CADx-assisted diagnosis. HC assignments followed the 3-second rule in both phases. Performance metrics included HC accuracy, HC rate, and adherence to the Preservation and Incorporation of Valuable Endoscopic Innovations (PIVI) and Simple Optical Diagnosis Accuracy (SODA) thresholds. Results: HC diagnostic accuracy improved from 78.3% (95% confidence interval [CI], 76.6% to 80.0%) to 89.8% (95% CI, 88.6% to 90.9%) with CADx assistance (p<0.001). The proportion of HC predictions increased from 64.2% to 75.4% (p<0.001). Novice endoscopists showed marked improvement with CADx (74.1% vs 88.8%; p<0.001). CADx-assisted diagnoses nearly met SODA and PIVI thresholds under the 3-second rule. Additional analysis demonstrated that CADx assistance significantly improved interobserver agreement and ground truth, particularly for novices (κ=0.37 to κ=0.65; p<0.001). Conclusions Integrating CADx with the 3-second rule significantly enhances the performance of endoscopists in the optical diagnosis of colorectal polyps, with the greatest benefit observed among novice endoscopists.

Janus kinase (JAK) inhibitors are an important treatment option for ulcerative colitis, providing rapid onset of action, oral administration, and efficacy even after biologic failure. The 3 approved agents—tofacitinib, filgotinib, and upadacitinib—differ in JAK isoform selectivity, leading to clinically meaningful differences in efficacy and safety. Evidence from network meta-analyses, clinical trials, and real-world studies consistently shows that upadacitinib provides the highest efficacy for induction and maintenance of remission, whereas filgotinib demonstrates the most favorable safety profile. The strong efficacy of upadacitinib and tofacitinib is particularly relevant in patients with severe disease, including acute severe ulcerative colitis, and upadacitinib maintains high efficacy regardless of prior advanced therapy exposure. JAK inhibitors also benefit extraintestinal manifestations. Although risks such as herpes zoster, serious infection, thromboembolism, and major cardiovascular events differ among agents, long-term data suggest generally acceptable safety when used appropriately. Intraclass JAK-to-JAK cycling is feasible, with about half of patients achieving steroid-free clinical remission in retrospective cohorts. Based on mechanistic, clinical, and real-world evidence, filgotinib may be a first-line option for patients with lower disease activity or when safety is a priority, whereas upadacitinib or tofacitinib may be preferred in higher disease activity. Strategically selecting agents may improve durability and outcomes.

Background: and Purpose Temporal dissociation between electrographic and clinical seizure onset in mesial temporal lobe epilepsy (MTLE) implies network heterogeneity. We hypothesized that MTLE consists of distinct electroclinical phenotypes defined by divergent seizure propagation dynamics. Methods: We retrospectively analyzed 167 seizures from 13 patients with drug-resistant MTLE who achieved Engel Class I surgical outcomes. Based on the predominant relationship between scalp electroencephalography (EEG) and clinical onset, patients were classified as EEG-first (n=7) or Clinical-first (n=6). Seizure onset patterns, propagation pathways, and temporal dynamics were assessed using scalp and stereoelectroencephalography (SEEG). Results: The cohort included 83 scalp and 84 SEEG seizures. By definition, onset order differed: in EEG-first seizures, scalp changes preceded clinical signs in 70.5%, whereas the reverse occurred in 65.8% of Clinical-first seizures (p<0.001). EEG-first seizures demonstrated longer SEEG-to-clinical latency (28.8±7.7 s vs. 13.0±7.7 s; p=0.004) and rhythmic theta onset on scalp EEG with focal SEEG low-voltage fast activity or preictal spikes. In contrast, Clinical-first seizures showed heterogeneous scalp patterns (theta, delta–theta, or delta slowing). Propagation tended to differ, with anterior pathways more common in EEG-first (69.6%) and posterior pathways in Clinical-first (26.3%), though with partial overlap (p=0.138). Conclusions MTLE comprises two pathophysiologically distinct phenotypes: EEG-first, reflecting a slowly propagating anterior mesial network, and Clinical-first, involving a rapidly spreading posterior network. This classification offers a mechanistic framework for understanding electroclinical dissociation and may refine presurgical evaluation.

Background: and Purpose Whole-exome sequencing (WES) is a valuable tool for identifying causative mutations in adult moyamoya disease (MMD), thereby advancing our understanding of the genetic mechanisms underlying this condition. Here, we conducted the first WESbased association study aimed at identifying genetic modifiers implicated in MMD. Methods: This WES study involved 160 patients with MMD and 189 controls from a multicenter hospital-based biobank, and evaluated combined annotation-dependent depletion (CADD) scores. Mutant-allele frequencies were compared in 369,121 individuals derived from the UK Biobank (UKB) WES. Mutant-allele risk scores (MARSs) were created based on WESidentified mutations. Gene-based association analyses and pooled analyses in East-Asian populations were further performed. Results: Fourteen mutations reached the genome-wide significance criterion (p<5×10-8 ), among which the p.R4810K mutation in the ring finger protein 213 gene (RNF213) showed the strongest significance (odds ratio=117.4, p=8.54×10-24 ). Notably, two mutations—p.G576S (alpha-glucosidase [GAA]) and p.D54N (charged multivesicular body protein 6 [CHMP6])— exhibited high CADD scores of 32 and 25, respectively, whereas the RNF213 p.R4810K mutation demonstrated a moderate deleteriousness score of 10.63. Fourteen mutations exhibited significant differences in allele frequencies between patients and UKB controlled data (p<1×10-8 ).The MARS9 model (incorporating nine missense mutations) showed better predictability for MMD (90.89%). The analysis of gene-based associations revealed four candidate genes: GAA, RNF213, CHMP6, and CARD14 (p=5×10-19 to 4×10-7 ). The subsequent pooled analyses validated four mutations in East Asian populations: p.V1195M, p.D1331G, p.S2334N, and p.R4810K (p<3×10-8 ). Conclusions This pioneering study has corroborated the significance of p.R4810K and identified several causative mutations predisposing patients to MMD, which helps to improve the understanding of its polygenetic nature.

Subarachnoid hemorrhage (SAH) is a stroke subtype with high mortality and poor functional outcomes. Prompt occlusion of a ruptured aneurysm at an early stage is crucial to prevent rebleeding, which can result in even higher mortality and more severe disabilities. The most critical initial decision in SAH management is the choice of treatment method with surgical clipping or endovascular coiling. We aimed to develop an evidence-based clinical guideline to select the optimal initial treatment in patients with SAH. We developed this guideline based on evidence from systematic reviews and meta-analyses via a de novo process. A systematic literature review was conducted across four databases (MEDLINE, Embase, Cochrane, and KoreaMed) to answer two population, intervention, comparison, outcome questions comparing clipping and coiling. The risk of bias was assessed using ROB 2.0 and the Newcastle-Ottawa Scale. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses flow diagrams and meta-analyses were generated for functional outcome and mortality. We included six randomized control trials (RCTs) and 58 observational studies. Meta-analysis of RCTs showed that coiling improved functional outcomes compared to clipping (odds ratio [OR], 0.91; 95% confidence interval [CI], 0.86–0.97). No significant mortality difference was observed in RCTs (OR, 1.38; 95% CI, 0.91–2.09), but non-RCTs favored clipping for reduced mortality (OR, 0.77; 95% CI, 0.69–0.86). However, it is difficult to generalize these findings to all clinical situations, as patients with SAH have a highly variable clinical course. Final treatment decision should be tailored to the individual patient’s status, including aneurysm location, morphology, and the expertise available at the treatment center. Such decisions are best made by specialists such as a board-certified physician and should be explained to the patient and their caregivers, along with the rationale for selecting the most appropriate treatment at the given hospital. Korea has many certified endovascular neurosurgeons, cerebrovascular surgeons, and certified cerebrovascular centers. Proper selection of the most suitable treatment method by certified physicians and centers would greatly benefit patient outcomes and healthcare professionals.