Background: Extended-spectrum β-lactamase (ESBL)-producing Escherichia coli is among the most important multidrug-resistant pathogens causing bloodstream infections (BSIs).Cefotaximase (CTX-M) enzymes are the most common and highly diverse ESBL family in E.coli. CTX-M-15 in group CTX-M-1 and CTX-M-14 in group CTX-M-9 are the most extensively disseminated enzymes. Multidrug-resistant E. coli strains complicate empirical therapy and increase healthcare burden globally and in Korea. We investigated the molecular epidemiology, sequence types (STs), and ESBL genotypes of E. coli bloodstream isolates in Korea and identified clinical risk factors for cefotaxime resistance. Methods: We collected all non-duplicated isolates of E. coli and related clinical information from patients with BSIs at eight sentinel hospitals in the Korean Global Antimicrobial Resistance Surveillance System (Kor-GLASS) collection network during 2017–2021. Duplicate isolates were removed to ensure representativeness of the data. Antimicrobial susceptibility was tested using disk diffusion tests, and multilocus sequence typing and betalactamase genotyping were performed. Results: Among 9,232 E. coli blood isolates, resistance rates to cefotaxime and ceftazidime were 36.4% and 11.4%, respectively. Among the clinical factors, age > 65 yrs (adjusted odds ratio [aOR], 1.36), hospital-origin infection (aOR, 2.55), and admission type (intensive care unit [ICU] vs. general ward; aOR, 1.34) were significant cefotaxime resistance risk factors. ST131 was the most prevalent among cefotaxime-resistant E. coli (64.8%, 2,180/3,363), followed by ST1193 (5.3%, N = 177), and ST69 (5.1%, N = 170).ST131, ST648, ST405, and ST410 cefotaxime-resistant E. coli isolates frequently harbored blaCTX-M-15, whereas ST1193 and ST68 showed a high proportion of blaCTX-M-27 carriers, and most ST457 and ST5150 isolates carried blaCTX-M-55. Conclusions Continuous monitoring of ESBL-producing E. coli is required to prevent further dissemination, guide empirical therapy, inform infection control policies, and ensure early detection of multidrug-resistant clones with the potential for widespread transmission.

A phytochemical study of the root extract of Hemerocallis fulva var. kwanso Regel resulted in the isolation and structural characterization of four lignans (1‒4), three flavanones (5, 6, and 8), one chalcone (9), and two monoterpenes (7 and 10). Enzyme inhibition assays revealed that two flavanone glucosides (5 and 6) showed significant inhibitory effect against protein tyrosine phosphatase 1B (PTP1B), with IC50 values of 31.38 µM and 51.46 µM, respectively. Further enzyme kinetic studies demonstrated that these two compounds acted as noncompetitive PTP1B inhibitors, with Ki values of 30.88 µM and 50.38 µM, respectively.

Phytochemical investigation of the water extract and alkaloid fraction of Areca catechu L. led to theisolation of one new methoxyflavonoid rutinoside (1), together with eleven known compounds (2−12), five of which (8−12) belong to the pyridine alkaloid class. The structure of the new compound was elucidated through extensive spectroscopic analyses, including 1D and 2D NMR experiments and high-resolution mass spectrometry.Notably, rhamnazin-3-O-rutinoside (2) is reported here for the first time from this species. The isolated compounds were evaluated for their inhibitory activity against protein tyrosine phosphatase 1B (PTP1B) using a p-nitrophenyl phosphate assay. Flavonoids (3 and 4) and stilbene (5) exhibited notable inhibitory activity, with IC50 values of 13.30 ± 0.71, 13.44 ± 0.84, and 8.68 ± 0.12 μM, respectively. In contrast, methoxyflavonoid rutinosides (1 and 2) and pyridine alkaloids (8−12) did not show significant inhibitory activity against PTP1B.These findings provide additional chemical insights into A. catechu and its constituents in relation to PTP1B inhibition.

Background: The effects of propofol, a commonly used intravenous anesthetic, on the breast cancer tumor microenvironment are not well understood. This study examined the influence of propofol on natural killer group 2, member D (NKG2D) ligand expression, matrix metalloproteinase (MMP)-mediated immune evasion, and natural killer (NK) cell-mediated cytotoxicity in breast cancer cells. Methods: We studied three human breast cancer cell lines representing distinct receptor subtypes: MCF-7 (estrogen receptor - and progesterone receptor-positive), MDA-MB-453 (human epidermal growth factor receptor 2-positive), and HCC-70 (triple-negative). Cells were treated with propofol at concentrations of 0 μg/ml (control; C), 4 μg/ml (P4), or 8 μg/ml (P8). Assessments included mRNA and protein expression of NKG2D ligands, NK cell cytotoxicity, protein levels of MMP-1 and MMP-2, and concentrations of soluble NKG2D ligands. Results: In MCF-7 and HCC-70 cell lines, propofol upregulated the mRNA and protein expression of NKG2D ligands in a dose-dependent manner, enhancing NK cell-mediated lysis. In contrast, in MDA-MB-453 cell lines, propofol downregulated the mRNA and protein expression of NKG2D ligands, resulting in diminished NK cell-mediated lysis. Across all receptor subtypes, propofol did not affect the expression of MMP-1 or MMP-2 or the concentration of soluble NKG2D ligands. Conclusions Our results demonstrate that propofol exerts receptor subtype-dependent effects on NK cell-mediated immunosurveillance in breast cancer cell lines, potentially mediated by changes in the transcription of NKG2D ligands rather than by alterations in MMP expression or their proteolytic activity.

Background: Left bundle branch block (LBBB) significantly increases the risk of left ventricular systolic dysfunction (LVSD) due to cardiac dyssynchrony. Although artificial intelligence–enabled electrocardiography (AI-ECG) mod‑ els show promise in detecting LVSD, their performance in LBBB patients remains underexplored. We hypothesized that an AI-ECG model clinically validated for detecting LVSD would accurately detect LVSD and predict future clinical outcomes in LBBB patients. Methods: In this retrospective multicenter study, 5,689 expert-validated LBBB ECGs collected from 2,813 patients between 2016 and 2024 were analyzed using a previously developed and validated AI-ECG model. LVSD was defined as an ejection fraction of ≤ 40%. Model performance was assessed using the area under the receiver operating char‑ acteristic curve (AUROC), the area under the precision-recall curve (AUPRC), sensitivity, and specificity. Patients were stratified into high- and low-risk groups based on a threshold that achieved 90% sensitivity. A Kaplan–Meier analysis was used to compare clinical outcomes. Results: Among the 2,813 LBBB patients (mean age, 70.7 years; male sex, 43.7%), hypertension and a history of heart failure were common. The AiTiALVSD model showed strong diagnostic performance for LVSD (AUROC, 0.930 [95% CI, 0.924–0.937]; AUPRC, 0.913 [95% CI, 0.902–0.923]; sensitivity, 0.979; specificity, 0.473). During the mean follow-up of 4.1 years, high-risk patients had significantly higher hazards than low-risk patients for all-cause mortality (adjusted hazard ratio [HR], 1.87; 95% CI, 1.53–2.28), implantable cardioverter defibrillator/cardiac resynchronization therapy implantation (adjusted HR, 15.2; 95% CI, 7.51–30.77), and cardiovascular hospitalization (adjusted HR, 1.11; 95% CI, 0.96–1.28). Conclusions AiTiALVSD effectively detects LVSD and stratifies long-term cardiovascular risk in LBBB patients, support‑ ing its clinical utility for early detection and patient management.

Purpose: To identify US findings suggestive of malignancy in thyroid nodules with follicular lesions of undetermined significance (FLUS) or follicular neoplasm (FN) on fine-needle aspiration cytology (FNAC) and evaluate the diagnostic performance. Materials and Methods: Seventy FLUS (n = 57) or FN (n = 13) nodules on FNAC that underwent surgical excision between February 2018 and November 2020 were selected. US findings were retrospectively reviewed. Orientation, margin, echogenicity, calcification, additional findings of the rim, echogenicity, heterogeneity of the solid portion, and the ratio of anterior posterior diameter to lateral diameter (criteria) were assessed. The diagnostic performances of US findings, criteria, and the Korean Society of Thyroid Radiology Thyroid Imaging Reporting and Data System (K-TIRADS) were evaluated using logistic regression analysis. Results: Microcalcification, homogeneous solid echotexture, and thickened rims were suggestive of malignancy. Our criteria showed a highest area under the ROC curve (AUC) value of 0.771, sensitivity of 97.14%, accuracy of 77.14%, positive predictive value of 93.33%, negative predictive value of 95.24%, and specificity of 97.14%. The criteria showed a significantly higher AUC value than K-TIRADS. Conclusion US findings of homogenous solid portions, thick rims, and microcalcifications suggested malignancy in nodules with FLUS or FN on FNAC. These additional US findings could improve the diagnostic performance of K-TIRADS.

Purpose: Cancer poses a significant global health challenge, demanding precise genomic testing for individualized treatment strategies. Targeted-panel sequencing (TPS) has improved personalized oncology but often lacks comprehensive coverage of crucial cancer alterations. Whole-genome sequencing (WGS) addresses this gap, offering extensive genomic testing. This study demonstrates the medical potential of WGS. Materials and Methods: This study evaluates target-enhanced WGS (TE-WGS), a clinical-grade WGS method sequencing both cancer and matched normal tissues. Forty-nine patients with various solid cancer types underwent both TE-WGS and TruSight Oncology 500 (TSO500), one of the mainstream TPS approaches. Results: TE-WGS detected all variants reported by TSO500 (100%, 498/498). A high correlation in variant allele fractions was observed between TE-WGS and TSO500 (r=0.978). Notably, 223 variants (44.8%) within the common set were discerned exclusively by TE-WGS in peripheral blood, suggesting their germline origin. Conversely, the remaining subset of 275 variants (55.2%) were not detected in peripheral blood using the TE-WGS, signifying them as bona fide somatic variants. Further, TE-WGS provided accurate copy number profiles, fusion genes, microsatellite instability, and homologous recombination deficiency scores, which were essential for clinical decision-making. Conclusion TE-WGS is a comprehensive approach in personalized oncology, matching TSO500’s key biomarker detection capabilities. It uniquely identifies germline variants and genomic instability markers, offering additional clinical actions. Its adaptability and cost-effectiveness underscore its clinical utility, making TE-WGS a valuable tool in personalized cancer treatment.

The common data model (CDM) has found widespread application in healthcare studies, but its utilization in cancer research has been limited. This article describes the development and implementation strategy for Cancer Clinical Library Databases (CCLDs), which are standardized cancer-specific databases established under the Korea-Clinical Data Utilization Network for Research Excellence (K-CURE) project by the Korean Ministry of Health and Welfare. Fifteen leading hospitals and fourteen academic associations in Korea are engaged in constructing CCLDs for 10 primary cancer types. For each cancer type-specific CCLD, cancer data experts determine key clinical data items essential for cancer research, standardize these items across cancer types, and create a standardized schema. Comprehensive clinical records covering diagnosis, treatment, and outcomes, with annual updates, are collected for each cancer patient in the target population, and quality control is based on six-sigma standards. To protect patient privacy, CCLDs follow stringent data security guidelines by pseudonymizing personal identification information and operating within a closed analysis environment. Researchers can apply for access to CCLD data through the K-CURE portal, which is subject to Institutional Review Board and Data Review Board approval. The CCLD is considered a pioneering standardized cancer-specific database, significantly representing Korea’s cancer data. It is expected to overcome limitations of previous CDMs and provide a valuable resource for multicenter cancer research in Korea.