Enhancing Genomic Prediction Accuracy for Body Conformation Traits in Korean Holstein Cattle.

The Holstein breed is the mainstay of dairy production in Korea. In this study, we evaluated the genomic prediction accuracy for body conformation traits in Korean Holstein cattle, using a range of π levels (0.75, 0.90, 0.99, and 0.995) in Bayesian methods (BayesB and BayesC). Focusing on 24 traits, we analyzed the impact of different π levels on prediction accuracy. We observed a general increase in accuracy at higher levels for specific traits, with variations depending on the Bayesian method applied. Notably, the highest accuracy was achieved for rear teat angle when using deregressed estimated breeding values including parent average as a response variable. We further demonstrated that incorporating parent average into deregressed estimated breeding values enhances genomic prediction accuracy, showcasing the effectiveness of the model in integrating both offspring and parental genetic information. Additionally, we identified 18 significant window regions through genome-wide association studies, which are crucial for future fine mapping and discovery of causal mutations. These findings provide valuable insights into the efficiency of genomic selection for body conformation traits in Korean Holstein cattle and highlight the potential for advancements in the prediction accuracy using larger datasets and more sophisticated genomic models.

ZBTB7A suppresses glioblastoma tumorigenesis through the transcriptional repression of EPB41L5.

Glioblastoma multiforme (GBM), the most aggressive and malignant glioma, has a poor prognosis. Although patients with GBM are treated with surgery, chemotherapy, and radiation therapy, GBM is highly resistant to treatment, making it difficult and expensive to treat. In this study, we analyzed the Gene Expression Profiling Interactive Analysis dataset, the Cancer Genome Atlas dataset, and Gene Expression Omnibus array data. ZBTB7A (also called FBI1/POKEMON/LRF) was found to be highly expressed in low-grade glioma but significantly downregulated in patients with GBM. ZBTB7A is a transcription factor that plays an important role in many developmental stages, including cell proliferation. The activation of epithelial-mesenchymal transition (EMT) is a key process in cancer progression and metastasis. Erythrocyte membrane protein band 4.1 like 5 (EPB41L5) is an essential protein for EMT progression and metastasis in various types of cancer. We found that ZBTB7A depletion in U87 cells induced GBM progression and metastasis. Based on RNA sequencing data, ZBTB7A directly binds to the promoter of the EPB41L5 gene, reducing its expression and inhibiting GBM progression. We demonstrated that ZBTB7A dramatically inhibits GBM tumor growth through transcriptional repression of EPB41L5. Thus, both ZBTB7A and EPB41L5 may be potential biomarkers and novel therapeutic targets for GBM treatment. Overall, we discovered the role of a novel tumor suppressor that directly inhibits GBM progression (ZBTB7A) and identified EPB41L5 as a therapeutic target protein for patients with GBM.

Heat shock protein family D member 1 in boar spermatozoa is strongly related to the litter size of inseminated sows.

BACKGROUND: Sperm quality evaluation is the logical first step in increasing field fertility. Spermatozoa contain cytoplasmic organelles and biomolecules known as sperm-intrinsic factors, which play key roles in sperm maturation, sperm-oocyte fusion, and embryo development. In particular, sperm membrane proteins [e.g., arginine vasopressin receptor 2, beta-actin, prohibitin, and heat shock protein family D member 1 (HSPD1)] and RNA could be used as functional indicators of male fertility. We sought to clarify the effects of differential mRNA expression of selected genes on several fertilisation parameters, including sperm motility, motion kinematics, capacitation, and litter size, in a porcine model. RESULTS: Our results demonstrated that HSPD1 expression was significantly correlated with male fertility, as measured by the litter size of inseminated sows. The expression of HSPD1 mRNA was linked to sperm motility and other motion kinematic characteristics. Furthermore, HSPD1 had a 66.7% overall accuracy in detecting male fertility, and the high-litter size group which was selected with the HSPD1 marker had a 1.34 greater litter size than the low-litter size group. CONCLUSIONS: Our findings indicate that HSPD1 might be a helpful biomarker for superior boar selection for artificial insemination, which could boost field fertility.

Serum levels of carbohydrate antigen 125 in combination with N-terminal pro-brain natriuretic peptide in patients with acute decompensated heart failure.

BACKGROUND/AIMS: Carbohydrate antigen 125 (CA-125) is an emerging prognostic biomarker for heart failure. We aimed to test the long-term prognostic value of CA-125 in combination with N-terminal pro-brain natriuretic peptide (NT-proBNP) in patients with acute decompensated heart failure (ADHF). METHODS: This observational study included a total of 413 patients (64.1 ± 15.6 yearold, 214 men) with ADHF. All-cause mortality during the 2-year follow-up was investigated for the prognosis. RESULTS: During the follow-up (mean follow-up, 591 ± 233 days), 109 deaths (26.0%) were recorded. In the multivariable analysis model, CA-125 was an independent factor associated with all-cause mortality (log CA-125: hazard ratio, 1.23; 95% confidence interval, 1.02 to 1.48; p = 0.030) together with age, sex, New York Heart Association class, ß-blocker, and NT-proBNP. The Kaplan-Meier survival analysis demonstrated that the group with both low marker levels showed the best 2-year survival (87.9%) followed by the group with low NT-proBNP and high CA-125 (76.1%), high NT-proBNP and low CA-125 (64.7%) and high NT-proBNP and high CA-125 levels (54.3%) (p < 0.001). Addition of CA-125 in combination with NT-proBNP and established risk factors further increased the predictive power for mortality in patients with ADHF. CONCLUSION: CA-125 was an independent factor associated with all-cause mortality in patients with ADHF. Combination of CA-125 with NT-proBNP significantly improved the prediction of mortality in patients with ADHF.

Random Regression Models Using Legendre Polynomials to Estimate Genetic Parameters for Test-day Milk Protein Yields in Iranian Holstein Dairy Cattle.

The objective of this study was to estimate the genetic parameters of milk protein yields in Iranian Holstein dairy cattle. A total of 1,112,082 test-day milk protein yield records of 167,269 first lactation Holstein cows, calved from 1990 to 2010, were analyzed. Estimates of the variance components, heritability, and genetic correlations for milk protein yields were obtained using a random regression test-day model. Milking times, herd, age of recording, year, and month of recording were included as fixed effects in the model. Additive genetic and permanent environmental random effects for the lactation curve were taken into account by applying orthogonal Legendre polynomials of the fourth order in the model. The lowest and highest additive genetic variances were estimated at the beginning and end of lactation, respectively. Permanent environmental variance was higher at both extremes. Residual variance was lowest at the middle of the lactation and contrarily, heritability increased during this period. Maximum heritability was found during the 12th lactation stage (0.213±0.007). Genetic, permanent, and phenotypic correlations among test-days decreased as the interval between consecutive test-days increased. A relatively large data set was used in this study; therefore, the estimated (co)variance components for random regression coefficients could be used for national genetic evaluation of dairy cattle in Iran.

Association between harmful alcohol use and periodontal status according to gender and smoking.

BACKGROUND: the aim of this study is to assess the association of harmful alcohol use based on the alcohol use disorders identification test (AUDIT) score with periodontal status according to gender and smoking in a representative sample of Korean adults. METHODS: This study analyzed 5,291 participants older than 19 years whose data of harmful alcohol use and periodontal status were available. Harmful alcohol use was defined by the WHO guidelines for the administration of AUDIT. The periodontal status was assessed by the Community Periodontal Index (CPI). Multivariate logistic regression analysis was performed with adjustment for socio-demographic variables, oral and general health behavior, oral health status and systemic conditions. All analyses considered a complex sampling design, and multivariate analysis was also performed in the subgroups. RESULTS: Multivariate logistic regression analysis revealed a marginal association between harmful alcohol use and higher CPI in the total sample. The adjusted odds ratio (OR) of harmful alcohol use was 1.16 (0.97 to 1.38) for higher CPI. Higher CPI was significantly associated with harmful alcohol use in men (OR: 1.28; 95% CI: 1.03-1.60) and non-smokers (OR: 1.29; 95% CI: 1.06-1.57). CONCLUSION: Periodontal status is significantly associated with harmful alcohol use in men and non-smokers in a representative sample of Korean adults.

The impact of moderate to severe renal insufficiency on patients with acute myocardial infarction.

BACKGROUND AND OBJECTIVES: Renal insufficiency (RI) has been reported to be associated with unfavorable clinical outcomes in patients undergoing percutaneous coronary interventions (PCI). However, little data is available regarding the impact of moderate to severe RI on clinical outcomes in patients with acute myocardial infarction (AMI) undergoing PCI. SUBJECTS AND METHODS: Between March 2003 and July 2007, 878 patients with AMI who underwent PCI were enrolled. Based on estimated glomerular filtration rate (eGFR) using the Modification of Diet in Renal Disease (MDRD) equation, patients were divided into two groups: eGFR <60 mL/min·m(2) (moderate to severe RI, group A) and eGFR ≥60 mL/min·m(2) (normal to mild RI, group B). The primary endpoint was all-cause mortality at 1-year after successful PCI. The secondary endpoints were non-fatal myocardial infarction (MI), target lesion revascularization (TLR), target vessel revascularization (TVR), stent thrombosis (ST) and major adverse cardiac events (MACE) at 1-year. RESULTS: In group A, patients were more often male and older, with diabetes and hypertension. Compared to patients in group B, group A showed significantly higher incidences of all-cause mortality, cardiac mortality, non-fatal MI and MACE. The needs of TLR and TVR, and the incidence of ST were not significantly different between the two groups. Independent predictors of 1-year mortality were eGFR <60 mL/min·m(2), male gender, older age and a lower left ventricular ejection fraction. CONCLUSION: In patients with AMI, moderate to severe RI was associated with mortality and MACE at 1-year after successful PCI. In addition, eGFR <60 mL/min·m(2) was a strong independent predictor of 1-year mortality.

Two-dimensional strain or strain rate findings in mild to moderate diastolic dysfunction with preserved ejection fraction.

Left ventricular (LV) diastolic dysfunction with preserved ejection fraction is frequently encountered in clinical practice. However, the relations between LV filling patterns and myocardial function by using two-dimensional (2D) speckle tracking imaging are not well known. One hundred thirteen individuals (mean age 59 ± 12 years), referred for a clinically indicated echocardiogram, underwent standard and 2D strain echocardiography. The subjects were divided into groups on the basis of diastolic function by using standard Doppler indices, and we compared 2D strain/strain rate parameters between groups. Subjects with mild to moderate LV diastolic dysfunction showed a high left atrial volume index (LAVI) and early mitral inflow to annular velocity ratio. With regard to 2D strain/strain rate, the severity of diastolic dysfunction was associated with low peak strain, and low systolic and early diastolic strain rate of longitudinal, circumferential and radial deformations, whereas the late diastolic strain rate was not. In multivariate analysis, LAVI and circumferential early diastolic strain rate were most associated with the severity of diastolic dysfunction, although longitudinal and circumferential peak strains were also of significant correlation. In addition to LAVI, the circumferential early diastolic strain rate would be a useful parameter in the assessment of the severity of diastolic dysfunction with preserved ejection fraction.

Uric Acid as prognostic marker in advanced nonischemic dilated cardiomyopathy: comparison with N-terminal pro B-type natriuretic peptide level.

Although uric acid (UA) level has been associated with an increased risk of cardiovascular events, it is unclear whether UA can provide greater prognostic information than N-terminal pro B-type natriuretic peptide (NT-proBNP) in advanced heart failure with nonischemic dilated cardiomyopathy (DCM). UA and NT-proBNP values were obtained from a total of 122 DCM patients. Development of clinical events during follow-up was defined as the composite of cardiac death and readmission for heart failure. During follow-up, there were 18 cardiac events. UA and NT-proBNP values were significantly higher in patients with events. The receiver operating characteristics curve showed the area under the curve for UA was greater than that for NT-proBNP. On multivariate analysis, UA remained the only independent predictor of prognosis. UA concentrations > or =8.7 mg/dL rather than NT-proBNP > or =3800 pg/mL were associated with significantly decreased event-free survival. The authors' findings demonstrated that UA value could be an informative predictor in nonischemic DCM.

Tissue Doppler imaging as a prognostic marker for cardiovascular events in heart failure with preserved ejection fraction and atrial fibrillation.

BACKGROUND: Although atrial fibrillation (AF) is associated with adverse cardiovascular (CV) outcomes, the prognosis of heart failure (HF) with preserved ejection fraction (HFPEF) with AF is still uncertain. This study was designed to evaluate whether the occurrence of CV events in patients with HFPEF and AF could be predicted by tissue Doppler imaging (TDI) of mitral annular velocity. METHODS: Clinical and echocardiographic data from January 2004 to December 2005 in patients with HFPEF and AF were investigated in this retrospective study. The development of CV events was defined as the composite of CV death, recurrent HF, and ischemic stroke. RESULTS: Of 148 patients (mean age 68+/-10 years; 64% were men), 35 clinical events, including 2 cardiac deaths, 22 recurrent HFs, and 11 ischemic strokes, were identified during a median follow-up of 27 months. In univariate analyses, age, ejection fraction, left atrial dimension, systolic (s'), and early diastolic (e') mitral annular velocities were correlated with clinical events. Multivariate analyses revealed that old age, enlarged left atrial dimension, and lower s' and e' remained independent predictors of outcomes. Furthermore, patients with both s'<5 cm/s and e'<7 cm/s experienced more frequent clinical events (hazard ratio 12.2; 95% confidence interval, 1.62-92.5; P=.015). CONCLUSION: s' and e', particularly their combination, seem to be useful predictors of CV events in patients with HFPEF with AF.