Age- and ethnic-driven molecular and clinical disparity of East Asian breast cancers.

BACKGROUND: Breast cancer (BC) is a complex disease with profound genomic aberrations. However, the underlying molecular disparity influenced by age and ethnicity remains elusive. METHODS: In this study, we aimed to investigate the molecular properties of 843 primary and metastatic BC patients enrolled in the K-MASTER program. By categorizing patients into two distinct age subgroups, we explored their unique molecular properties. Additionally, we leveraged large-scale genomic data from the TCGA and MSK-IMPACT studies to examine the ethnic-driven molecular and clinical disparities. RESULTS: We observed a high prevalence of PI3KCA mutations in K-MASTER HER2 + tumors, particularly in older patients. Moreover, we identified increased mutation rates in DNA damage response molecules, including ARID1A, MSH6, and MLH1. The K-MASTER patients were mainly comprised of triple-negative breast cancer (TNBC) and HER2-positive tumors, while the TCGA and MSK-IMPACT cohorts exhibited a predominance of hormone receptor-positive (HR +) subtype tumors. Importantly, GATA3 mutations were less frequently observed in East Asian patients, which correlated with poor clinical outcomes. In addition to characterizing the molecular disparities, we developed a gradient-boosting multivariable model to identify a new molecular signature that could predict the therapeutic response to platinum-based chemotherapy. CONCLUSIONS: Our findings collectively provide unprecedented insights into the significance of age and ethnicity on the molecular and clinical characteristics of BC patients.

Safety and impact of the Mediterranean diet in patients with chronic kidney disease: a pilot randomized crossover trial.

Introduction: Emerging evidence highlights the potential advantages of the Mediterranean diet (MD) in preserving kidney function and slowing chronic kidney disease (CKD) progression. However, interventional studies on the MD are scarce in East Asian populations. Methods: This randomized crossover trial aimed to assess the safety and short-term impact of the Mediterranean Proper Optimal Balance (MEDi-POB) diet in Korean patients with stage 3-4 CKD. Kidney function was assessed using the estimated glomerular filtration rate, which was calculated using the CKD Epidemiology Collaboration equation. Fifty patients with CKD were randomly assigned to two groups, each starting with a different 4-week intervention, followed by a 4-week washout period, followed by a switch to the other 4-week intervention. During the MEDi-POB intervention, patients received home delivery of meals twice daily, 5 days a week, while the control intervention comprised a conventional diet. Forty-six patients successfully completed the entire 12-week trial. Paired t-tests were conducted to assess mean differences between the two groups. A linear mixed model was used to adjust for sequence and period. Results: Dietary fat, fiber, and niacin intake were significantly higher following the MEDi-POB diet than following the control diet (p = 0.001 for fat, p < 0.001 for fiber, and p = 0.007 for niacin). The MEDi-POB diet also yielded slightly increased total CO2 levels (p = 0.043), indicating effective management of metabolic acidosis. Conversely, sodium and copper intake were significantly lower with the MEDi-POB diet (p = 0.032 and p = 0.037, respectively). Caloric intake increased, but body mass index slightly decreased from baseline after consuming the MEDi-POB diet. Dietary potassium intake exhibited a non-significant increase (p = 0.053), and no significant changes in serum (p = 0.883) and urine potassium levels (p = 0.087) occurred. Kidney function remained well-preserved following the MEDi-POB diet. Conclusion: These results indicate that the MEDi-POB diet is safe even in patients with advanced CKD, as it does not adversely affect serum and urine potassium levels and helps maintain kidney function.

Association of dietary habits with general and abdominal obesity in Korean children and adolescents: cluster analysis of nationwide population survey data.

Introduction: Childhood obesity is a growing global health concern, but few studies have investigated dietary factors specifically related to obesity and abdominal obesity in children and adolescents. Herein, we aimed to identify the dietary factors affecting childhood obesity in Korean children and adolescents. Methods: Data from the Korea National Health and Nutrition Survey (KNHANES) VIII were analyzed using K-means clustering analysis to identify distinct clusters based on nine variables related to dietary habit, nutritional status, and nutritional education. Multiple logistic regression analysis was used to examine the association between incident obesity risk and the different clusters. We enrolled 2,290 participants aged 6-18 years, and separated them into two distinct clusters; Healthy and Unhealthy Dietary Habit Groups, clusters 1 and 2, respectively. Results: Cluster 1 was characterized by a lower obesity prevalence, healthier dietary habits (regular breakfast consumption; fruit and vegetable, reduced total energy, and lower protein and fat intakes), and greater nutritional education than Cluster 2. After adjusting for confounders, compared with Cluster 1, Cluster 2 demonstrated a significantly higher prevalence (OR [95% CI]) of both general and abdominal obesity (1.49 [1.05-2.13], p=0.027 and 1.43 [1.09-1.88], p=0.009). Discussion: Maintaining optimal dietary quality and patterns are crucial to prevent childhood obesity. Further research is warranted to explore specific dietary interventions tailored to different clusters to effectively address childhood obesity.

Investigation of Residue Dissipation of Fluxapyroxad and Its Metabolites in Chinese Cabbage and Spring Scallion Using Different Application Methods.

Fluxapyroxad, a persistent fungicide in soil, was investigated for differences in residue dissipation in Chinese cabbage and spring scallion through the application methods of soil, foliar, and systemic treatment. Soil application of 0.4% granule fluxapyroxad resulted in residues up to 0.09 mg kg-1 in the scallion, while it did not contribute to the residues in the harvested cabbage. The 50% dissipation time (DT50) of fluxapyroxad in the scallion was 6.8 days. The residues from systemic treatment were highly correlated with foliar application in both the cabbage and the scallion, and the initial residue and DT50 values were similar for foliar and systemic treatments. In comparing the residues from the systemic treatments between the two crops, the initial residue was 3.11 and 0.22 mg kg-1 in the cabbage and the scallion after the systemic treatment, respectively. The DT50 values were 2.6 and 12.2 days in the cabbage and the scallion, respectively. The theoretical dilution effect due to crop growth was higher for the cabbage (4-fold) than for the scallion (1.2-fold), and the half-lives of fluxapyroxad without considering the dilution effect were 6.4 days in the cabbage and 17.8 days in the scallion. Thus, the residue difference was drastically reduced after 14 days from the last treatment.

Mature microRNA-binding protein QKI suppresses extracellular microRNA let-7b release.

Argonaute (AGO), a component of RNA-induced silencing complexes (RISCs), is a representative RNA-binding protein (RBP) known to bind with mature microRNA (miRNA) and is directly involved in post-transcriptional gene silencing. However, despite the biological significance of miRNA, the roles of other micro RNA-binding proteins (miRBPs) remain unclear in regulation of miRNA loading, dissociation from RISC, and extracellular release. In this study, we perform protein arrays to profile miRBPs and identify 118 RNA-binding proteins directly binding with miRNAs. Among those proteins, RBP quaking (QKI) inhibits extracellular release of mature microRNA let-7b by controlling the loading of let-7b into extracellular vesicles via additional miRBPs such as hnRNPD/AUF1 and hnRNPK. The enhanced extracellular release of let-7b after QKI depletion activates the Toll-like Receptor 7 (TLR7) and promotes the production of proinflammatory cytokines in recipient cells, leading to brain inflammation in mouse cortex. Thus, this study reveals contribution of QKI to the inhibition of brain inflammation via regulation of extracellular let-7b release.

Germline functional variants contribute to somatic mutation and outcomes in neuroblastoma.

Germline genetic context may play a significant role in the development and evolution of cancer, particularly in childhood cancers such as neuroblastoma. This study investigates the role of putatively functional germline variants in neuroblastoma, even if they do not directly increase disease risk. Our whole-exome sequencing analysis of 125 patients with neuroblastoma reveals a positive correlation between germline variant burden and somatic mutations. Moreover, patients with higher germline variant burden exhibit worse outcomes. Similar findings are observed in the independent neuroblastoma cohort where a higher germline variant burden correlates with a higher somatic mutational burden and a worse overall survival outcome. However, contrasting results emerge in adult-onset cancer, emphasizing the importance of germline genetics in neuroblastoma. The enrichment of putatively functional germline variants in cancer predisposition genes is borderline significant when compared to healthy populations (P = 0.077; Odds Ratio, 1.45; 95% confidence intervals, 0.94-2.21) and significantly more pronounced against adult-onset cancers (P = 0.016; Odds Ratio, 2.13; 95% confidence intervals, 1.10-3.91). Additionally, the presence of these variants proves to have prognostic significance in neuroblastoma (log-rank P < 0.001), and combining germline with clinical risk factors notably improves survival predictions.

Association between carbohydrate to protein or fat ratio and mortality: A prospective cohort study.

BACKGROUND & AIMS: The effect of dietary macronutrient balance on longevity and metabolic health remains a subject of considerable interest. We aimed to investigate the association of carbohydrate-to-protein and carbohydrate-to-fat ratios with all-cause and cardiovascular mortalities. METHODS: In this population-based study, data from the Korean Genome and Epidemiology Study were integrated with those from national data sources, including mortality records from the Korea National Statistical Office. The primary outcomes were all-cause and cardiovascular mortalities. Carbohydrate-to-protein and carbohydrate-to-fat ratios were evaluated based on dietary habits assessed through a food frequency questionnaire. Harrell's C-index was employed to determine optimal cut-off points for carbohydrate-to-protein and carbohydrate-to-fat ratios. Cox proportional hazards regression models were used to assess associations. RESULTS: A total of 143,050 participants aged ≥40 years were included in the analyses. Compared with individuals with non-elevated carbohydrate-to-protein ratios (<5.2), those with elevated carbohydrate-to-protein ratios (>9.9) exhibited a higher all-cause mortality (hazard ratio 1.09, 95% confidence interval 1.01-1.17); however, no correlation between carbohydrate-to-protein ratio and cardiovascular mortality (hazard ratio 1.13, 95% confidence interval 0.96-1.32) was observed. Compared with those with non-elevated carbohydrate-to-fat ratios (<5.1), those with higher carbohydrate-to-fat ratios (>7.1) exhibited increased all-cause (hazard ratio 1.08, 95% confidence interval 1.00-1.16) and cardiovascular (hazard ratio 1.27, 95% confidence interval 1.06-1.52) mortalities. CONCLUSIONS: Our findings regarding macronutrient ratios and their association with mortality suggest that reducing excessive carbohydrate intake and increasing the consumption of protein and fats may have beneficial effects on longevity and cardiovascular health. Further studies are needed to understand the underlying mechanisms of these effects.

Association between antibiotics use and osteoporotic fracture risk: a nationally representative retrospective cohort study.

This population-based retrospective cohort study aimed to estimate the association between antibiotic exposure and osteoporotic fracture risk. Long-term antibiotic use was associated with the risk of osteoporotic fracture. An increase in the number of antibiotic classes prescribed may also be associated with an increased osteoporotic fracture risk. PURPOSE: This study aims to examine the association between antibiotic usage and osteoporotic fractures in a large cohort of Korean adults, with a specific focus on the duration of antibiotic exposure and the number of antibiotic classes used. METHODS: This retrospective cohort study from the National Health Insurance Service-National Health Screening Cohort (NHIS-HEALS) database from January 1, 2002, to December 31, 2019, included 167,370 Korean adults aged 50 years or older (mean [SD] age, 59.3 [7.82] years; 65,425 [39.09%] women). The cumulative antibiotic prescription days and the classes of antibiotics prescribed between 2004 and 2008 were exposure variables, respectively. The main outcome was a newly diagnosed osteoporotic fracture during follow-up. Cox proportional hazard regression was used to determine the adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for the incident osteoporotic fractures associated with antibiotic exposure. RESULTS: The antibiotic user group with 91 days had a higher risk of osteoporotic fracture in comparison to the antibiotic non-user group (aHR, 1.12; 95% CI, 1.03-1.21). Additionally, those who used more than four different antibiotic classes had an elevated risk of osteoporotic fracture compared to the non-user group (aHR, 1.10; 95% CI, 1.02-1.18). CONCLUSION: This extensive population-based cohort study conducted on a large population has identified an association between the utilization of antibiotics and an elevated risk of osteoporotic fractures. The cumulative days exposed to antibiotics and osteoporotic fractures may be positively associated.

Development and Validation of a Questionnaire to Measure Adherence to a Mediterranean-Type Diet in Youth.

Proper nutrition during childhood is crucial for preventing chronic diseases and ensuring optimal growth. This study aimed to develop and validate the Korean version of the KIDMED (K-KIDMED) questionnaire to accurately measure Mediterranean diet (MD) adherence among Korean children and adolescents. A total of 226 parents, representing their children and adolescents, completed the K-KIDMED, a 112-item food frequency questionnaire (FFQ), and a 24-h dietary recall method through an anonymous online survey. The K-KIDMED comprised 11 questions, with five excluded from the original scoring as they did not apply to the FFQ. Scores were categorized into three levels of adherence to the MD: low (1 or less), average (2-4), and good (5 or more). The agreement between total MD scores from the Korean version of the Mediterranean diet adherence screener and the FFQ was moderate (intraclass correlation coefficient = 0.455, 95% confidence interval: 0.346, 0.553). Among the 226 children and adolescents, 36.7% had low adherence to the KIDMED, 43.3% had intermediate adherence, and 19.9% had good adherence. Higher K-KIDMED scores were correlated with greater intakes of fiber, vitamin K, vitamin B6, and potassium (all p < 0.05). We developed the K-KIDMED as a valid tool to assess MD adherence in Korean children and adolescents.

Deep Learning-Based Reconstruction Algorithm With Lung Enhancement Filter for Chest CT: Effect on Image Quality and Ground Glass Nodule Sharpness.

OBJECTIVE: To assess the effect of a new lung enhancement filter combined with deep learning image reconstruction (DLIR) algorithm on image quality and ground-glass nodule (GGN) sharpness compared to hybrid iterative reconstruction or DLIR alone. MATERIALS AND METHODS: Five artificial spherical GGNs with various densities (-250, -350, -450, -550, and -630 Hounsfield units) and 10 mm in diameter were placed in a thorax anthropomorphic phantom. Four scans at four different radiation dose levels were performed using a 256-slice CT (Revolution Apex CT, GE Healthcare). Each scan was reconstructed using three different reconstruction algorithms: adaptive statistical iterative reconstruction-V at a level of 50% (AR50), Truefidelity (TF), which is a DLIR method, and TF with a lung enhancement filter (TF + Lu). Thus, 12 sets of reconstructed images were obtained and analyzed. Image noise, signal-to-noise ratio, and contrast-to-noise ratio were compared among the three reconstruction algorithms. Nodule sharpness was compared among the three reconstruction algorithms using the full-width at half-maximum value. Furthermore, subjective image quality analysis was performed. RESULTS: AR50 demonstrated the highest level of noise, which was decreased by using TF + Lu and TF alone (P = 0.001). TF + Lu significantly improved nodule sharpness at all radiation doses compared to TF alone (P = 0.001). The nodule sharpness of TF + Lu was similar to that of AR50. Using TF alone resulted in the lowest nodule sharpness. CONCLUSION: Adding a lung enhancement filter to DLIR (TF + Lu) significantly improved the nodule sharpness compared to DLIR alone (TF). TF + Lu can be an effective reconstruction technique to enhance image quality and GGN evaluation in ultralow-dose chest CT scans.