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.

Purpose: Atypical hyperplasia (AH) management remains controversial due to variable malignant disease progression rates. While Western studies report 10% to 25% upgrade rates, data from Asian populations, particularly from referral academic centers, are limited. We aimed to identify predictive factors for malignant upgrade in Korean women with AH at academic hospitals. Methods: This retrospective multi-institutional study analyzed 340 patients diagnosed with AH on initial biopsy who underwent subsequent excision at five Korean academic hospitals from 2000 to 2022. Malignant upgrade was defined as ductal carcinoma in situ or invasive cancer on the final pathology. Multivariate logistic regression was used to identify independent predictors of upgrades. Results: Among 340 patients (319 atypical ductal hyperplasia, 20 atypical lobular hyperplasia, and 1 mixed), 128 (37.6%) experienced a malignant upgrade, 98 (76.6%) to ductal carcinoma in situ, and 30 (23.4%) to invasive cancer. In multivariate analysis, multifocal atypia (odds ratio [OR], 25.61; 95% confidence interval [CI], 11.20–58.55; P<0.001) and Breast Imaging-Reporting and Data System 4c-5 lesions (OR, 11.02; 95% CI, 1.43–84.86; P=0.021) were significant predictors. Multifocal atypia showed an 84.4% upgrade rate. Core needle biopsy had higher upgrade rates than vacuum-assisted biopsy (45.2% vs. 20.0%; P<0.001). The upgrade rates decreased from 50% to 25% over the study period (P<0.05). Conclusion The 37.6% upgrade rate in this tertiary referral cohort exceeded that in Western reports, with multifocal atypia emerging as the strongest predictor. These findings support immediate excision for multifocal atypia while allowing individualized management for unifocal lesions with favorable imaging in Korean tertiary care settings.

Background: and Purpose: To assess the long-term effectiveness, safety, and economic viability of recently approved Alzheimer’s disease (AD) therapies, as well as to evaluate the real-world application of novel diagnostics among AD patients with diverse comorbidities, comprehensive real-world data (RWD) analysis is essential. The Korean JOint RegistrY for ALZheimer’s Treatment and Diagnostics (JOY-ALZ) endeavors to create a registry of RWD derived from clinical practice on new diagnostic methods and therapeutic agents for AD introduced in Korea since 2021. Methods: Participants must fulfill all the following: 1) be at least 19 years old; 2) be actively receiving, scheduled to initiate, or undergoing evaluation for any AD disease-modifying treatment; 3) have completed amyloid positron emission tomography or cerebrospinal fluid AD immunoassay (a positive result is not essential for participation); 4) have a clinical classification of cognitively unimpaired, mild cognitive impairment, or probable AD dementia. Data generated during routine care is segmented into a minimum dataset, extended dataset, and research-only dataset requiring extra consent. Assessments encompass clinical, cognitive, functional, neurobehavioral, neuroimaging, and biomarker evaluations, in addition to systematic monitoring of new AD treatments and their safety.Data are collected and monitored at baseline, at semiannual intervals during the initial 2 years, and then annually up to 2034. To date, 46 medical centers will participate in JOY-ALZ. Conclusions JOY-ALZ is expected to promote understanding of the long-term clinical outcomes, safety, and cost-effectiveness of recently introduced diagnostics and treatments for AD, thereby supporting the progress of precision medicine in AD care and diagnosis.

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.

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.

Cervical foraminal lipoma is a rare cause of cervical radiculopathy. We report the case of a 47-year-old woman who presented with a 1-year history of right arm pain and paresthesia that was refractory to conservative treatment. Magnetic resonance imaging demonstrated a well-defined mass within the right C5-6 neural foramen, causing compression of the exiting C6 nerve root. The patient underwent microsurgical excision via posterior cervical laminoforaminotomy. Intraoperatively, a lipomatous mass compressing the nerve root was identified and completely removed. Histopathological examination confirmed a benign lipoma. Postoperatively, the patient experienced marked symptomatic improvement, with no recurrence of symptoms at a 6-month follow-up. Although it is uncommon, cervical foraminal lipoma should be considered in patients with persistent radiculopathy and atypical imaging findings, and surgical excision can provide favorable clinical outcomes.

Background/Aims: Biliary tract cancer (BTC) is a rare malignancy with poor prognosis. We investigated genomic determinants of clinical benefit from gemcitabine, cisplatin, and nab-paclitaxel (GAP) versus gemcitabine and cisplatin (GC) in advanced BTC. Methods: Clinical and genomic data using TruSight Oncology 500 were analyzed from patients treated with GAP (N=198) or GC (N=89) as first-line therapy. Results: With a median follow-up of 33.0 months, GAP modestly improved progression-free survival (PFS) (hazard ratio [HR] 0.764; 95% confidence interval [CI] 0.591–0.989) without significant overall survival (OS) difference compared to GC. Genomic profiling revealed frequent alterations in TP53 (35.2%), KRAS (16.4%), SMAD4 (10.5%), and TNFRSF14 (10.5%), involving RTK/RAS (44.3%), TP53 (41.8%), and PI3K (20.2%) pathways. Single-gene mutations did not predict treatment benefit. However, pathway-level analysis identified PI3K pathway activation as significantly associated with inferior PFS (HR 2.148; 95% CI 1.478–3.124) and OS (HR 2.096; 95% CI 1.413–3.109) in patients receiving GAP, an effect not observed with GC. Importantly, GAP conferred clinical benefit only in patients without PI3K pathway activation, while no survival advantage was seen in those with such alterations (Pinteraction=0.023 for PFS, Pinteraction=0.003 for OS). Similar results were obtained in the independent validation cohort treated with GAP (N=103) or GC (N=64) for BTC. Conclusions Genomic profiling using next-generation sequencing identified PI3K pathway activation as key molecular determinant that differentiates patient outcomes between GAP and GC treatments in advanced BTC.

In patients with differentiated thyroid cancer (DTC), initial recurrence risk stratification based on clinical, histopathological, and perioperative data remains the key determinant for guiding management strategies during the first 1-2 years post-treatment. However, the adoption of ongoing risk stratification (ORS), which dynamically reassesses risk by integrating longitudinal clinical data and treatment response, enables more precise long-term prognostic assessment and facilitates highly individualized management. Building upon recent guidelines, the 2026 KTA guideline has been further refined by incorporating robust evidence from large-scale national cohorts and comprehensive systematic reviews. These updated recommendations outline contemporary concepts of ORS, risk-adapted TSH suppression targets, optimized surveillance modalities for recurrence detection, and disease-specific long-term follow-up strategies. Reflecting the paradigm shift toward de-escalated treatment, this revision integrates evolved perspectives on TSH suppression intensity, the clinical interpretation of thyroglobulin levels, and tailored follow-up intervals. These evidence-based recommendations aim to minimize unnecessary treatment and excessive surveillance in the large proportion of patients with excellent prognosis after initial therapy, while ensuring that each patient receives appropriately tailored and effective long-term management.

suggest that some reproductive factors associated with BC differ across ethnicities and time trends, perhaps due to the prevalence of reproductive factors and the baseline hazard of BC.

Abrupt vessel closure (AVC) is a complication of percutaneous coronary intervention (PCI) and is defined as the sudden cessation of forward coronary blood flow due to a variety of mechanisms. The incidence of AVC has markedly decreased from approximately 3.0% in the early era to about 0.3% today. Nevertheless, cardiovascular interventionists must remain prepared to manage AVC effectively, given its significant impact on clinical outcomes.AVC can arise from several mechanisms, including dissection, intramural hematoma, intracoronary thrombosis, air embolism, vasospasm, and no-reflow. The clinical impact of AVC varies depending on the extent of myocardium affected, ranging from asymptomatic events or transient ischemic chest pain to cardiogenic shock or cardiac arrest. Both a general approach for stabilizing hemodynamic consequences and an etiology-specific management strategy are essential. Hasty decision-making may worsen the situation, whereas a structured approach—focused on hemodynamic stabilization, logical diagnostic processes, and targeted interventions—can improve outcomes. In this narrative review, we describe the mechanisms underlying each etiology, outline mechanism-specific management strategies, and discuss general approaches to managing patients with AVC through logical diagnostic and treatment processes. We hope this review offers valuable insights into this uncommon but significant complication and enhances readers’ skills in managing AVC more effectively during PCI.