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/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/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: Pre-diabetes can develop into type 2 diabetes mellitus, but can prevented by regular exercise.However, the outcomes when combining unsupervised Kinect-based mixed-reality (KMR) exercise with continuous glucose monitoring (CGM) remain unclear. Therefore, this single-arm pilot trial examined changes in blood glucose (BG) concentrations over 672 hours (4 weeks), including a 2-week period of KMR exercise and CGM in individuals with pre-diabetes. Methods: This was a pre-and post-treatment case-control study with nine participants. General questionnaires were administered and body composition, fasting BG concentrations, and 2-hour oral glucose tolerance test (2-OGTT) results were measured pre-and post-treatment. Weekly average glucose concentrations, hyperglycemia rate, hypoglycemia rate, average glucose concentration over time, amount of physical activity, amount of food intake, and pre- and postprandial BG (immediately and 30, 60, 90, and 120 minutes after lunch) were measured over 4 weeks (pre-test, exercise, and post -test weeks). Glucose concentrations were measured before exercising, between sets, and 30 and 60 minutes after exercise during the 2 weeks of unsupervised exercise (3 days/week). Results: In all participants, body mass index (27.16±2.92 kg/m²), fasting BG (108.00±7.19 mg/dL), 2-OGTT (162.56±18.12 mg/dL), hyperglycemia rate (P= 0.040), and 90-minute postprandial BG (P= 0.035) were significantly reduced during the 2 exercise weeks, and the 2-OGTT result (P= 0.044) and diastolic blood pressure (DBP) (P= 0.046) were significantly reduced at the post- test as compared with the pre-test. Conclusion This study found that 2 weeks of unsupervised KMR exercise reduced 2-OGTT, DBP, hyperglycemia rate, and 90-minute postprandial BG concentration. We believed this effect could be identified more clearly in studies involving a larger number of participants and longer durations of exercise.

Background: Pre-diabetes can develop into type 2 diabetes mellitus, but can prevented by regular exercise.However, the outcomes when combining unsupervised Kinect-based mixed-reality (KMR) exercise with continuous glucose monitoring (CGM) remain unclear. Therefore, this single-arm pilot trial examined changes in blood glucose (BG) concentrations over 672 hours (4 weeks), including a 2-week period of KMR exercise and CGM in individuals with pre-diabetes. Methods: This was a pre-and post-treatment case-control study with nine participants. General questionnaires were administered and body composition, fasting BG concentrations, and 2-hour oral glucose tolerance test (2-OGTT) results were measured pre-and post-treatment. Weekly average glucose concentrations, hyperglycemia rate, hypoglycemia rate, average glucose concentration over time, amount of physical activity, amount of food intake, and pre- and postprandial BG (immediately and 30, 60, 90, and 120 minutes after lunch) were measured over 4 weeks (pre-test, exercise, and post -test weeks). Glucose concentrations were measured before exercising, between sets, and 30 and 60 minutes after exercise during the 2 weeks of unsupervised exercise (3 days/week). Results: In all participants, body mass index (27.16±2.92 kg/m²), fasting BG (108.00±7.19 mg/dL), 2-OGTT (162.56±18.12 mg/dL), hyperglycemia rate (P= 0.040), and 90-minute postprandial BG (P= 0.035) were significantly reduced during the 2 exercise weeks, and the 2-OGTT result (P= 0.044) and diastolic blood pressure (DBP) (P= 0.046) were significantly reduced at the post- test as compared with the pre-test. Conclusion This study found that 2 weeks of unsupervised KMR exercise reduced 2-OGTT, DBP, hyperglycemia rate, and 90-minute postprandial BG concentration. We believed this effect could be identified more clearly in studies involving a larger number of participants and longer durations of exercise.

Background: Pre-diabetes can develop into type 2 diabetes mellitus, but can prevented by regular exercise.However, the outcomes when combining unsupervised Kinect-based mixed-reality (KMR) exercise with continuous glucose monitoring (CGM) remain unclear. Therefore, this single-arm pilot trial examined changes in blood glucose (BG) concentrations over 672 hours (4 weeks), including a 2-week period of KMR exercise and CGM in individuals with pre-diabetes. Methods: This was a pre-and post-treatment case-control study with nine participants. General questionnaires were administered and body composition, fasting BG concentrations, and 2-hour oral glucose tolerance test (2-OGTT) results were measured pre-and post-treatment. Weekly average glucose concentrations, hyperglycemia rate, hypoglycemia rate, average glucose concentration over time, amount of physical activity, amount of food intake, and pre- and postprandial BG (immediately and 30, 60, 90, and 120 minutes after lunch) were measured over 4 weeks (pre-test, exercise, and post -test weeks). Glucose concentrations were measured before exercising, between sets, and 30 and 60 minutes after exercise during the 2 weeks of unsupervised exercise (3 days/week). Results: In all participants, body mass index (27.16±2.92 kg/m²), fasting BG (108.00±7.19 mg/dL), 2-OGTT (162.56±18.12 mg/dL), hyperglycemia rate (P= 0.040), and 90-minute postprandial BG (P= 0.035) were significantly reduced during the 2 exercise weeks, and the 2-OGTT result (P= 0.044) and diastolic blood pressure (DBP) (P= 0.046) were significantly reduced at the post- test as compared with the pre-test. Conclusion This study found that 2 weeks of unsupervised KMR exercise reduced 2-OGTT, DBP, hyperglycemia rate, and 90-minute postprandial BG concentration. We believed this effect could be identified more clearly in studies involving a larger number of participants and longer durations of exercise.

Purpose: Delirium is a common neurocognitive disorder in patients with advanced cancer and is associated with poor clinical outcomes. As a potentially reversible phenomenon, early recognition of delirium by identifying the risk factors demands attention. We aimed to develop a model to predict the occurrence of delirium in hospitalized patients with advanced cancer. Materials and Methods: This retrospective study included patients with advanced cancer admitted to the oncology ward of four tertiary cancer centers in Korea for supportive cares and excluded those discharged due to death. The primary endpoint was occurrence of delirium. Sociodemographic characteristics, clinical characteristics, laboratory findings, and concomitant medication were investigated for associating variables. The predictive model developed using multivariate logistic regression was internally validated by bootstrapping. Results: From January 2019 to December 2020, 2,152 patients were enrolled. The median age of patients was 64 years, and 58.4% were male. A total of 127 patients (5.9%) developed delirium during hospitalization. In multivariate logistic regression, age, body mass index, hearing impairment, previous delirium history, length of hospitalization, chemotherapy during hospitalization, blood urea nitrogen and calcium levels, and concomitant antidepressant use were significantly associated with the occurrence of delirium. The predictive model combining all four categorized variables showed the best performance among the developed models (area under the curve 0.831, sensitivity 80.3%, and specificity 72.0%). The calibration plot showed optimal agreement between predicted and actual probabilities through internal validation of the final model. Conclusion We proposed a successful predictive model for the risk of delirium in hospitalized patients with advanced cancer.

Cytomegalovirus (CMV) is the most important opportunistic viral pathogen in solid organ transplant (SOT) recipients.The Korean guideline for the prevention of CMV infection in SOT recipients was developed jointly by the Korean Society for Infectious Diseases and the Korean Society of Transplantation. CMV serostatus of both donors and recipients should be screened before transplantation to best assess the risk of CMV infection after SOT. Seronegative recipients receiving organs from seropositive donors face the highest risk, followed by seropositive recipients. Either antiviral prophylaxis or preemptive therapy can be used to prevent CMV infection. While both strategies have been demonstrated to prevent CMV infection post-transplant, each has its own advantages and disadvantages. CMV serostatus, transplant organ, other risk factors, and practical issues should be considered for the selection of preventive measures. There is no universal viral load threshold to guide treatment in preemptive therapy. Each institution should define and validate its own threshold.Valganciclovir is the favored agent for both prophylaxis and preemptive therapy. The evaluation of CMV-specific cellmediated immunity and the monitoring of viral load kinetics are gaining interest, but there was insufficient evidence to issue recommendations. Specific considerations on pediatric transplant recipients are included.

Background and Objectives: The association between bilirubin and atrial fibrillation (AF) has been evaluated previously in observational studies but with contradictory results. This study evaluated the causal association between serum bilirubin level and AF using Mendelian randomization (MR) analysis. Methods: This cross-sectional study includes 8,977 participants from the Dong-gu Study.In the observational analysis, multivariate logistic regression was performed to evaluate the association between bilirubin and prevalent AF. To evaluate the causal association between bilirubin and AF, MR analysis was conducted by using the UGT1A1 rs11891311 and rs4148323 polymorphisms as instrumental variables. Results: Elevated serum bilirubin levels were associated with an increased risk for AF in observational analysis (total bilirubin: odds ratio [OR], 1.31; 95% confidence interval [95% CI], 1.15–1.48 per 1 standard deviation [SD]; direct bilirubin: OR, 1.31; 95% CI, 1.18–1.46 per 1 SD), whereas the genetically predicted serum bilirubin levels in MR analysis did not show this association (total bilirubin: OR, 1.02; 95% CI, 0.67–1.53 per 1 SD; direct bilirubin: OR, 1.03; 95% CI, 0.61–1.73 per 1 SD). Conclusions Genetically predicted bilirubin levels were not associated with prevalent AF.Thus, the observational association between serum bilirubin levels and AF may be noncausal and affected by reverse causality or unmeasured confounding.

The objective of this study was to investigate the effect of different cooling rates and subsequent post-firing heat treatment on the final hardness of a metal-ceramic alloy. For this, Specimens of Pd-Ag-In-Sn alloy underwent simulated firing at two different cooling rates, followed by post-firing heat treatment. Hardness measurement, microstructure observation, and crystal structure analysis were conducted on the firing simulated and post-firing heat-treated specimens to analyze the causes of hardness variations. The experimental results showed that the difference in cooling rates during simulated firing had an impact on the final hardness of the alloy, and the specimens cooled at the slowest rate (Stage 3) exhibited higher hardness at all firing Stages compared to the specimens cooled at the highest rate (Stage 0). Regardless of the difference in cooling rates during the firing process, the hardness of the alloy significantly increased by the post-firing heat treatment. The increase in hardness by the post-firing heat treatment was attributed to the formation of fine precipitates in the matrix, and the precipitation reaction occurred as a result of the decrease in solubility of (Pd, Ag, Au) 3 (In, Sn, Zn) phase in the Pd-Ag-rich matrix. The clinical significance of this study is that performing the post-firing heat treatment demonstrates effectiveness in increasing the reduced hardness after porcelain firing in metal-ceramic alloys.