Background/Aims: Hepatocellular carcinoma (HCC) exhibits significant sex disparities in incidence, yet its molecular mechanisms remain unclear. We explored the role of telomerase reverse transcriptase (TERT) genetic alterations and hepatitis B virus (HBV) integration, both known major contributors to HCC, in sex-specific risk for HBV-related HCC. Methods: We examined 310 HBV-related HCC tissues to investigate sex-specific TERT promoter (TERT-pro) mutations and HBV integration profiles, stratified by sex and age, and validated with single-cell RNA sequencing (scRNA-seq) data. Results: Tumors predominantly exhibited TERT-pro mutations (26.0% vs. 0%) and HBV-TERT integration (37.0% vs. 3.0%) compared to non-tumorous tissues. While TERT-pro mutations increased with age in both sexes, younger males (≤60 years) showed marked predominance compared to younger females. Males had significantly more HBV integrations at younger ages, while females initially had fewer integrations that gradually increased with age. Younger males' integrations showed significantly greater enrichment in the TERT locus compared to younger females, alongside a preference for promoters, PreS/S regions, and CpG islands. Overall, TERT genetic alterations were significantly sex-differential in younger individuals (75.3% in males vs. 23.1% in females) but not in older individuals (76.9% vs. 83.3%, respectively). These alterations were associated with increased TERT expression. The skewed TERT abnormalities in younger males were further corroborated by independent scRNA-seq data. Conclusions Our findings highlight the critical role of TERT alterations and HBV integration patterns in the male predominance of HCC incidence among younger HBV carriers, offering insights for future exploration to optimize sex-specific patient care and HCC surveillance strategies.

Background: This study explores effective fixation methods for Pauwel type III femoral neck fractures by evaluating the biomechanical benefits of adding a screw to the Femoral Neck System (FNS). Methods: Computed tomography (CT) scans of an 82-year-old female patient with an intertrochanteric fracture were used to establish a finite element femur model with heterogeneous material properties. Finite element models of Pauwel type III fractures were created with and without an additional screw. The central and inferior trajectories of the FNS bolt were examined separately and combined with an additional screw for virtual fixation. Walking and stair-climbing loads were applied. Results: With the addition of a screw, both peak maximum and minimum principal strains consistently stayed comparable or decreased in models with both central and inferior bolt trajectories, while the volume of elements with principal strain exceeding 1% decreased by more than half. The peak von Mises stress observed in the implants ranged from 215.7 to 359.3 MPa, remaining below the titanium alloy's yield strength of 800 MPa. For normal walking, the addition of a screw to the central bolt trajectory model decreased the fracture gap by 50.6% and reduced sliding distance by 8.6%. For the inferior bolt trajectory, the gap was reduced by 57.9% and sliding distance by 25.0%.Under stair-climbing conditions, these improvements were also evident; the central trajectory model saw a halved fracture gap and a 7.9% decrease in sliding distance, while the inferior trajectory model experienced a 55.7% gap reduction and a 27.2% decrease in sliding distance. The additional screw increased the area ratio of the fracture site experiencing interfragmentary compression 34%–39%, while the additional screw alleviated peak interfragmentary compression by 12%–18% under both normal walking and stair-climbing conditions. Conclusions The addition of a screw reduced the fracture gap, sliding distance, and peak interfragmentary compression, while increasing the area ratio of interfragmentary compression under both walking and stair-climbing loads, regardless of the FNS bolt trajectory, suggesting a better mechanical environment for fracture healing.

Background: Meniscal scaffold implantation has been introduced as a treatment for meniscal injuries, but there is still no clear consensus on its clinical impact, including its chondroprotective effect. This review aimed to assess the chondroprotective effects, clinical outcomes, and survivorship of meniscal scaffold implantation compared to meniscectomy, as well as among different types of scaffolds. Methods: A comprehensive search strategy was performed on the databases of PubMed, Embase, Cochrane Library, and Google Scholar, encompassing articles published until June 1, 2024. Randomized controlled trials (RCT) and comparative studies published in English that reported results using collagen meniscal implant (CMI) and polyurethane meniscal scaffold for meniscal tear were included. Results: A total of 421 studies were initially identified across databases, and a systematic review was conducted on 8 studies involving 596 patients. Among the 5 studies that addressed the chondroprotective effect, none found that meniscal scaffolds had a higher chondroprotective effect compared to meniscectomy. In studies comparing CMI and meniscectomy, the Lysholm score results showed a mean difference (MD) range between –5.90 and –4.40. In the case of visual analog scale score, the MD ranged from –1.0 to 1.0. In studies comparing polyurethane meniscal scaffolds and CMI, the Tegner score results showed an MD range of –2.0 to 0.4. Conclusions There was no superiority in chondroprotective effects for both CMI and polyurethane meniscal scaffolds compared to meniscectomy. Although meniscal scaffolds may provide improvements in clinical outcomes, no clinically relevant differences were observed in comparison to meniscectomy. There are no discernible differences between the 2 types of scaffolds.

Background: Patients with diabetes are known to be at high risk for end-stage kidney disease (ESKD), but the accurate annual risk data for new-onset ESKD is still limited. In South Korea, the prevalence and incidence of ESKD are increasing more rapidly compared to the global average. This study aimed to determine the incidence rate (IR) of ESKD by diabetes status from 2012 to 2022. Methods: Using data from the Korean National Health Insurance Service, we calculated the IR and hazard ratio (HR) for newonset ESKD in the general population. Individuals were categorized based on diabetes status into nondiabetes, impaired fasting glucose (IFG), diabetes duration <5 and ≥5 years. Results: Among the participants, 67.6% were nondiabetic, 22.3% had IFG, and 10% had diabetes. In Korea, the IRs of ESKD were 139 per million population (pmp) for nondiabetes, 188 pmp for IFG, 632 pmp for diabetes <5 years, and 3,403 pmp for diabetes ≥5 years. An advanced estimated glomerular filtration rate (eGFR) category was the strongest risk factor for ESKD development. However, even in patients with normal renal function, those with long-standing diabetes had a 14-fold higher risk of ESKD compared to nondiabetic individuals. The risk of ESKD associated with diabetes increased exponentially with declining renal function. Notably, IFG showed an increasing tendency for ESKD in younger patients (<65 years) with early-stage chronic kidney disease (CKD; eGFR ≥60 mL/min/1.73 m²). Conclusion Longer diabetes duration amplifies ESKD risk, particularly as renal function declines. Even in patients with normal renal function, long-standing diabetes significantly increases ESKD risk, while IFG is associated with elevated risk only in younger individuals with early-stage CKD.

Background: Sarcopenia, a multifactorial disorder involving metabolic disturbance, suggests potential for metabolite biomarkers. Carnitine (CN), essential for skeletal muscle energy metabolism, may be a candidate biomarker. We investigated whether CN metabolites are biomarkers for sarcopenia. Methods: Associations between the CN metabolites identified from an animal model of sarcopenia and muscle cells and sarcopenia status were evaluated in men from an age-matched discovery (72 cases, 72 controls) and a validation (21 cases, 47 controls) cohort. Results: An association between CN metabolites and sarcopenia showed in mouse and cell studies. In the discovery cohort, plasma C5-CN levels were lower in sarcopenic men (P=0.005). C5-CN levels in men tended to be associated with handgrip strength (HGS) (P=0.098) and were significantly associated with skeletal muscle mass (P=0.003). Each standard deviation increase in C5-CN levels reduced the odds of low muscle mass (odd ratio, 0.61; 95% confidence interval [CI], 0.42 to 0.89). The area under the receiver operating characteristic curve (AUROC) of CN score using a regression equation of C5-CN levels, for sarcopenia was 0.635 (95% CI, 0.544 to 0.726). In the discovery cohort, addition of CN score to HGS significantly improved AUROC from 0.646 (95% CI, 0.575 to 0.717; HGS only) to 0.727 (95% CI, 0.643 to 0.810; P=0.006; HGS+CN score). The improvement was confirmed in the validation cohort (AUROC=0.563; 95% CI, 0.470 to 0.656 for HGS; and AUROC=0.712; 95% CI, 0.569 to 0.855 for HGS+CN score; P=0.027). Conclusion C5-CN, indicative of low muscle mass, is a potential circulating biomarker for sarcopenia in men. Further studies are required to confirm these results and explore sarcopenia-related metabolomic changes.

Background: The positive relationship between triiodothyronine (T3) and steatotic liver disease (SLD) demonstrated only in crosssectional study. We aimed to evaluated whether total T3 (TT3) is associated with the development/resolution of SLD in longitudinal design. Methods: This retrospective, longitudinal, population-based cohort study included 1,665 South Korean euthyroid adults with ≥4 thyroid function test. We explored the impact of mean TT3 during follow-up on development/resolution of either SLD (diagnosed by ultrasound) or modified metabolic dysfunction-associated steatotic liver disease (MASLD) using Cox proportional hazards regression models. Results: During about median 5 years follow-up, 807/1,216 (66.3%) participants among participants without SLD at baseline developed SLD, and 253/318 (79.5%) participants among participants with SLD at baseline SLD resolved fatty liver. Mean TT3 rather than thyroid stimulating hormone or mean free thyroxine was significantly related with development (adjusted hazard ratio [HR], 1.01; 95% confidence interval [CI], 1.00 to 1.02; P=0.002) and resolution (adjusted HR, 0.97; 95% CI, 0.96 to 0.99; P=0.005) of SLD. Compared with low mean TT3 group, high mean TT3 group was positively associated with development of SLD (adjusted HR, 1.20; 95% CI, 1.05 to 1.38; P=0.008) and inversely associated with resolution of SLD (adjusted HR, 0.66; 95% CI, 0.51 to 0.85; P=0.001). The statistical significance remained for development (adjusted HR, 1.29; 95% CI, 1.10 to 1.51; P=0.001) and resolution (adjusted HR, 0.71; 95% CI, 0.54 to 0.94; P=0.018) of modified MASLD. Conclusion In Korean euthyroid adults, TT3 level was associated with development and resolution of either SLD or modified MASLD.

Background/Aims: This study aimed to evaluate the performance of the Model for End-Stage Liver Disease (MELD) 3.0 for predicting mortality and liver-related complications compared with the Child-Pugh classification, albumin-bilirubin (ALBI) grade, the MELD, and the MELD sodium (MELDNa) score. Methods: We evaluated a multicenter retrospective cohort of incorporated patients with cirrhosis between 2013 and 2019. We conducted comparisons of the area under the receiver operating characteristic curve (AUROC) of the MELD3.0 and other models for predicting 3-month mortality. Additionally, we assessed the risk of cirrhosis-related complications according to the MELD3.0 score. Results: A total of 3,314 patients were included. The mean age was 55.9±11.3 years, and 70.2% of the patients were male. Within the initial 3 months, 220 patients (6.6%) died, and the MELD3.0had the best predictive performance among the tested models, with an AUROC of 0.851, outperforming the Child-Pugh classification, ALBI grade, MELD, and MELDNa. A high MELD3.0score was associated with an increased risk of mortality. Compared with that of the group with a MELD3.0 score <10 points, the adjusted hazard ratio of the group with a score of 10–20 pointswas 2.176, and that for the group with a score of ≥20 points was 4.892. Each 1-point increase inthe MELD3.0 score increased the risk of cirrhosis-related complications by 1.033-fold. The risk of hepatorenal syndrome showed the highest increase, with an adjusted hazard ratio of 1.149, followed by hepatic encephalopathy and ascites. Conclusions The MELD3.0 demonstrated robust prognostic performance in predicting mortality in patients with cirrhosis. Moreover, the MELD3.0 score was linked to cirrhosis-related complications, particularly those involving kidney function, such as hepatorenal syndrome and ascites.

Background: Carbapenem-resistant Acinetobacter baumannii (CRAB) represents a devastating and growing global threat, calling for new antibiotic treatments. In Korea, the challenge of treating CRAB is compounded by high nosocomial acquisition rates and limited availability of novel antibiotics. Minocycline, a semisynthetic tetracycline derivative, has been proposed as a therapeutic option for CRAB infections. Nonsusceptibility to minocycline may occur through the efflux pump, TetB. The prevalence of tetB in A. baumannii has increased, along with higher minocycline minimum inhibitory concentrations (MICs). We aimed to evaluate minocycline susceptibility rates in clinical strains of CRAB, and the association between tetB carriage and minocycline susceptibility across different genotypes. Materials and Methods: Representative CRAB blood isolates were collected from Asan Medical Center, Seoul.Minocycline susceptibility was assessed using the Clinical and Laboratory Standards Institute (CLSI) breakpoint (≤4 mg/L) and the proposed pharmacokinetics (PK)/pharmacodynamics (PD) breakpoint (≤1 mg/L). Tigecycline was used as a comparator, and its susceptibility breakpoint for Enterobacterales defined by EUCAST was applied (≤0.5 mg/L).The presence of tetB was detected by PCR, and multilocus sequence typing (MLST) was performed using seven housekeeping genes. Results: Of the 160 CRAB blood isolates, 83.8% were susceptible to minocycline by the CLSI criteria, and 50.6% were PK-PD susceptible by the PK-PD criteria. The minocycline minimum inhibitory concentration (MIC)50 /MIC90 was 1/8 mg/L. tetB was present in 49% of isolates and was associated with a higher minocycline MIC (MIC50/90 2/8 mg/L vs. 1/2 mg/L). No clear correlation was observed between tetB positivity and tigecycline MIC. Nine MLSTs were identified, with significant differences in tetB carriage rates between the major sequence types. Notably, ST191, associated with non-tetB carriage and greater susceptibility to minocycline, declined over the study period (P=0.004), while ST451, associated with tetB carriage, increased. Conclusion tetB was present in 49% of CRAB isolates and was associated with higher MICs and non-susceptibility by both CLSI and PK-PD criteria. However, absence of tetB was not a reliable predictor of minocycline PK-PD susceptibility. Additionally, shifts over time towards genotypes with reduced minocycline susceptibility were observed. Further research is needed to correlate these findings with clinical outcomes and identify additional resistance mechanisms.

Single-cell omics technologies have transformed our investigation of genomic, transcriptomic, and proteomic landscapes at the individual cell level. In particular, the application of single-cell RNA sequencing has unveiled the complex transcriptional variations inherent in cardiac cells, offering valuable perspectives into their dynamics. This review focuses on the integration of single-cell omics with induced pluripotent stem cells (iPSCs) in the context of cardiovascular research, offering a unique avenue to deepen our understanding of cardiac biology. By synthesizing insights from various single-cell technologies, we aim to elucidate the molecular intricacies of heart health and diseases. Beyond current methodologies, we explore the potential of emerging paradigms such as single-cell/spatial omics, delving into their capacity to reveal the spatial organization of cellular components within cardiac tissues. Furthermore, we anticipate their transformative role in shaping the future of cardiovascular research. This review aims to contribute to the advancement of knowledge in the field, offering a comprehensive perspective on the synergistic potential of transcriptomic analyses, iPSC applications, and the evolving frontier of spatial omics.