Background: As nationwide government-led whole-genome sequencing (WGS) projects progress, optimizing the clinical integration of large-scale WGS results is crucial. We explored how the initial analysis from Korea’s First WGS Pilot Study for Rare Diseases was applied in clinical practice, and then we reanalyzed the data comprehensively at Samsung Medical Center (SMC) Seoul, Korea. Methods: A prospective cohort study designed to collect WGS data under a Korean national initiative was conducted from August 2020 to December 2021. We focused on patients with rare diseases recruited from 16 university hospitals. The participants included 5,000 individuals (2,200 probands and 2,800 family members). The initial WGS data and diagnostic reference reports (from 682 probands and 484 family members), generated based on the First Korean WGS Pilot Study for Rare Diseases, were subsequently reanalyzed by SMC. Results: The initial analysis of the First Korean WGS Pilot Study data revealed a diagnostic rate of 17%. Upon receiving these results, the SMC conducted two rounds of reanalysis, increasing the diagnostic rate from 15% in the first analysis, to 18% in the second, and finally to 24% in the third (P = 1.6 × 10 −5 ). Key factors in improving the genetic diagnosis included increased detection of novel (likely) pathogenic variants (P = 1.0 × 10 −4 ), improved diagnostic rates with larger family recruitment (P = 0.004), and refined clinical information for more precise genotype–phenotype correlation analysis (40%). Conclusions Although national WGS projects lay a foundation for rare disease diagnosis, hospital-level reanalysis and multidisciplinary collaborations are crucial for optimizing diagnostic outcomes.

Objective: Although most gallbladder polyps are benign, some neoplastic polyps may be malignant or may serve as precursors to malignancy. Distinguishing neoplastic and non-neoplastic polyps using imaging examinations remains a major challenge.This meta-analysis aimed to identify the ultrasound (US) features that are significantly associated with neoplastic polyps. Materials and Methods: The MEDLINE, EMBASE, Cochrane, and KoreaMed databases were searched for articles published up to August 31, 2025. Bivariate random-effects models were used to calculate the meta-analytic pooled diagnostic odds ratios (DORs), sensitivities, and specificities, along with their 95% confidence intervals (CIs), for each US imaging feature in the diagnosis of neoplastic polyps. Results: Thirty studies evaluating 8,953 patients, including 1,216 (13.6%) patients with neoplastic polyps, were included.Among the nine evaluated US imaging features, namely, size ≥10 mm, sessile morphology, single polyp, coexisting gallstones, hypoechogenicity, heterogeneous echogenicity, gallbladder wall thickening (GBWT), absence of hyperechoic spot, and vascularity, eight were significantly associated with neoplastic polyps: size ≥10 mm (DOR: 6.23 [95% CI: 1.86– 20.90]), sessile morphology (DOR: 3.54 [1.93–5.97]), single polyp (DOR: 2.21 [1.76–2.74]), coexisting gallstones (DOR:1.86 [1.29–2.60]), hypoechogenicity (DOR: 3.55 [1.47–7.30]), GBWT (DOR: 9.38 [1.47–32.20]), absence of hyperechoic spots (DOR: 4.23 [2.46–6.83]), and vascularity (DOR: 9.72 [5.81–15.30]). Of these, size ≥10 mm demonstrated the highest pooled sensitivity (0.79 [95% CI: 0.68–0.87]), whereas hypoechogenicity showed the highest pooled specificity (0.93 [95% CI: 0.82–0.98]). Conclusion Eight US imaging features (size ≥10 mm, sessile morphology, single polyp, coexisting gallstones, hypoechogenicity, GBWT, absence of hyperechoic spots, and vascularity) were significantly associated with the presence of neoplastic polyps.These features may facilitate the management of gallbladder polyps.

Objective: To evaluate the diagnostic performance of the “probable hepatocellular carcinoma (HCC)” category in the Korean Liver Cancer Association-National Cancer Center (KLCA-NCC) v2022 guidelines. Materials and Methods: This multicenter retrospective study included patients at risk of HCC who underwent gadoxetic acid-enhanced MRI between January 2015 and June 2018; a subgroup of these patients also underwent liver CT. Eligible patients had at least one non-cystic lesion (≥10 mm) with a reference standard. Four radiologists interpreted the images independently and the results were pooled. The performance of “definite HCC” and “probable HCC” together and “probable HCC” alone were compared between v2018 and v2022. Results: A total of 2,237 patients (1,666 men; mean age, 59 ± 11 years) with 2,445 lesions were included. In v2022, 1.5% (143/9,780) of the lesions were additionally categorized as “probable HCC” by four reviewers on MRI; among these, 104 lesions were not HCCs. Focal nodular hyperplasia (FNH) or FNH-like nodules constituted 90.4% (94/104) of the false positives. When “definite HCC” and “probable HCC” were combined, v2022 showed higher sensitivity (83.7% [5,670/6,776] vs. 83.1% [5,631/6,776]) but lower specificity (77.1% [2,316/3,004] vs. 80.6% [2,420/3,004]) than v2018 (P < 0.001). For “probable HCC” alone, v2022 showed a lower positive predictive value (PPV) than v2018 (64.1% [373/582] vs. 76.1% [334/439], P < 0.001). In v2022, lesions with non-rim arterial-phase hyperenhancement (APHE) showed a lower PPV than those without APHE (42.3% [91/215] vs. 76.8% [282/367], P < 0.001). In the CT subgroup (n = 1,590), 1.6% (99/6,360) of the lesions were reassessed as “probable HCC,” and its PPV was 83.8% (83/99) in v2022 whereas no lesions were classified as “probable HCC” under v2018. Conclusion The revised “probable HCC” category in the KLCA-NCC v2022 aligns with updates in the diagnostic flow, demonstrating acceptable performance on MRI and CT. Notably, FNH or FNH-like nodules can be misclassified as “probable HCC” when MRI is used.

Purpose: Due to its rarity, treatment guidelines for appendiceal cancer have traditionally followed those established for colorectal cancer, despite showing distinct histologic and clinical features. This study aimed to compare the clinicopathologic characteristics and long-term oncologic outcomes of appendiceal cancer with those of right-sided colon cancers. Methods: We retrospectively reviewed the records of patients with stage I–III appendiceal, cecal, or ascending colon cancer who underwent curative resection between 2010 and 2020 at our center. A 1:3:3 exact matching for age, sex, TNM stage, and adjuvant chemotherapy was performed. Survival outcomes were analyzed using the Kaplan-Meier and Cox regression methods. Results: Overall, 245 patients with appendiceal cancer (n = 35), ascending colon cancer (n = 105), and cecal cancer (n = 105) were analyzed. Appendiceal cancer exhibited a higher proportion of T4 tumors and fewer harvested lymph nodes compared with ascending or cecal cancers. The mean follow-up duration was 9.5 years. The 5- and 10-year overall survival rates were lower in appendiceal cancer (66.2% and 52.9%) than in ascending (91.2% and 78.4%) or cecal cancer (88.5% and 78.3%). Similarly, the 10-year disease-free survival rate was lower in appendiceal cancer (59.2%) compared with ascending (83.1%) and cecal cancers (78.4%). Cox regression analysis identified age (≥65 years), perforation, nodal metastasis, and lymphovascular invasion as independent predictors of poor prognosis. Conclusion Appendiceal cancer exhibited significantly worse long-term survival compared to cecal or ascending colon cancer. Tumor perforation, nodal metastasis, and lymphovascular invasion were adverse prognostic factors for overall and disease-free survival.

Chrysoeriol, a flavonoid naturally found in several plants, including Danggui Susan, a traditional herbal medicine, exhibits promising anti-inflammatory and antioxidant properties. Its potential to prevent cardiovascular diseases, primarily through inhibiting platelet activation and aggregation, has attracted significant interest. This study aimed to investigate the molecular mechanisms underlying the antiplatelet effects of chrysoeriol. The compound effectively suppressed collagen-induced platelet aggregation without inducing cytotoxicity. Chrysoeriol elevated intracellular levels of cyclic AMP (cAMP) and cyclic GMP (cGMP), enhanced inositol 1,4,5-trisphosphate receptor (IP 3R) phosphorylation, and reduced cytosolic calcium (Ca2+ ) mobilization, all of which contributed to its antiplatelet action. Furthermore, chrysoeriol inhibited the phosphorylation of PI3K, Akt, JNK, and p38 MAPK, pathways involved in the activation of cytosolic phospholipase A2 (cPLA 2) and thromboxane A2 (TXA2) production. These effects were accompanied by reduced TXA2 production and secretion of dense granules (ATP and serotonin). Chrysoeriol also impaired thrombin-induced clot retraction, further suggesting its capacity to regulate platelet responses and cytoskeletal rearrangements. These findings highlight chrysoeriol’s multi-target mechanisms, including modulation of cyclic nucleotides, kinase pathways, and platelet function, offering potential as a therapeutic agent to prevent thrombotic cardiovascular events.

Arterial thrombosis remains a leading cause of cardiovascular morbidity and mortality despite widespread use of dual antiplatelet therapy (DAPT) with aspirin and P2Y12 inhibitors. Although these agents reduce ischemic events, their efficacy is counterbalanced by dose-dependent bleeding and their inability to distinguish pathological platelet activation from physiological hemostasis.Recent advances in platelet biology have shifted therapeutic development toward hemostasis-sparing antiplatelet strategies— approaches designed to selectively inhibit thrombosis while preserving baseline hemostatic function. These strategies target upstream adhesion receptors (GPVI, GPIb–vWF, CLEC-2) and receptor-proximal intracellular signaling nodes (SYK, BTK, PI3Kβ, PLCγ2, NADPH oxidases) that are preferentially engaged under high-shear or strongly prothrombotic conditions. Early-phase clinical and translational studies of such agents demonstrate antithrombotic efficacy with minimal impact on bleeding time, supporting their mechanistic selectivity. In parallel, contemporary clinical practice increasingly utilizes individualized risk assessment, platelet function testing, and genetic profiling to tailor treatment intensity. This integration of mechanism-selective agents with patient-specific risk evaluation forms the basis of precision-based thrombosis prevention, a framework aimed at aligning the duration and depth of platelet inhibition with the dynamic balance between ischemic and bleeding risk. Together, these developments mark a paradigm shift from broad platelet suppression toward rational, context-adaptive, and safer antiplatelet therapy.

Autophagy is a conserved catabolic process that degrades proteins and damaged organelles to maintain cellular homeostasis, and its role in cancer depends on stage and context. Farnesyl-diphosphate farnesyltransferase 1 (FDFT1) is an essential enzyme in the sterol branch of the mevalonate pathway, but its functions in hepatocellular carcinoma (HCC) and in the regulation of autophagy remain poorly understood. In this study, we show that FDFT1 acts as a negative regulator of autophagy in HCC cells. Loss of FDFT1 led to increased autophagosome formation and fusion with lysosomes, whereas its overexpression suppressed both basal and induced autophagy. These changes were associated with AMPK–ULK1 signaling, suggesting that FDFT1 influences a central pathway controlling autophagy. Our findings connect cholesterol metabolism with autophagy regulation and tumor growth, highlighting FDFT1 as a potential prognostic marker and therapeutic target in liver cancer.

Purpose: The triggering receptor expressed on myeloid cells 2 (TREM2) creates an immunosuppressive environment, but the effects of anticancer treatment on TREM2 and the tumor microenvironment (TME) are not well established. This study investigates the impact of chemotherapy on TREM2-expressing macrophages within the lung adenocarcinoma TME. Materials and Methods: Using single-cell RNA sequencing datasets of paired normal-appearing lung tissue (NL) and tumor (Tu), human and mouse lung cancer tissue, and THP-1 cells, we observed the effects of anticancer drugs on them. Results: Myeloid cells (MY) were the second-most abundant non-epithelial component in the Tu, though less prevalent than in NL. Specific MY subclusters abundant in Tu showed overexpression of TREM2. In lung cancer-induced Kras-G12D mice, M2 proportion increased in Tu compared to NL; cisplatin increased TREM2+ M2 proportion in Tu. TREM2+ cells in Tu showed interactions with cell clusters showing characteristics of interstitial macrophage such as mo-lineage, mono-Mc, and CD163/LGMN cells via FN:CD44 and MIF:CD74+CXCR4, suggesting that they influence the recruitment of those cells to Tu and TME reshape. In M0-state THP-1 cells, cisplatin and osimertinib treatments induced polarization towards M1 and M2 states and increased TREM2 expression. Cisplatin promoted uptake of phosphatidylserine-coated latex beads by M0 cells, whereas osimertinib reduced uptake by polarized macrophages. These findings suggest anticancer treatments impact the lung immune microenvironment by altering the TREM2+ cells. Conclusion Given TREM2’s central inhibitory role in the tumor immune environment, effects of chemotherapeutic agents should be considered in developing TREM2-targeting therapies.

Objective: To classify life stages for companion dogs and cats by identifying clusters in age-specific disease proportions derived from medical records, providing a data-driven foundation for health examination programs. Methods: We collected 505,667 medical records from 82 veterinary facilities in South Korea between 2020 and 2023. Diagnoses were standardized using GPT-4o and S-BioBERT. Following preprocessing, data from 27 facilities yielded 222,706 canine and 39,910 feline records for the final analysis. Principal component analysis and K-means clustering (K = 4) were applied to age-specific disease proportions to identify life stages.The 10 most highest-proportion diagnoses diseases were determined for each cluster. Results: Canine life stages were classified as ≤ 1 year, 2–5 years, 6–10 years, and 11–15+ years.Feline life stages were 1–2 years, 3–8 years, 9–12 years, and 13–15+ years. In dogs, developmental diseases were common in the youngest age group, while chronic diseases were more prevalent in older groups. In cats, oral and urinary diseases were high-ranking, conjunctivitis was most common in the early stage, and chronic diseases increased with age. Conclusions and Relevance: Age-specific diagnosis patterns support four practical life stages for dogs and cats in South Korea. These boundaries can inform evidence-based preventive examination schedules, animal health policy, and pet insurance product design.