Grahammunro2950

The genetically heterogeneous triple-negative breast cancer (TNBC) continues to be an intractable disease, due to lack of effective targeted therapies. Gene amplification is a major event in tumorigenesis. Genes with amplification-dependent expression are being explored as therapeutic targets for cancer treatment. In this study, we have applied Analytical Multi-scale Identification of Recurring Events analysis and transcript quantification in the TNBC genome across 222 TNBC tumors and identified 138 candidate genes with positive correlation in copy number gain (CNG) and gene expression. siRNA-based loss-of-function screen of the candidate genes has validated EGFR, MYC, ASAP1, IRF2BP2, and CCT5 genes as drivers promoting proliferation in different TNBC cells. MYC, ASAP1, IRF2BP2, and CCT5 display frequent CNG and concurrent expression over 2173 breast cancer tumors (cBioPortal dataset). More frequently are MYC and ASAP1 amplified in TNBC tumors (>30%, n = 320). In particular, high expression of ASAP1, the ADP-ribosylation factor GTPase-activating protein, is significantly related to poor metastatic relapse-free survival of TNBC patients (n = 257, bc-GenExMiner). Furthermore, we have revealed that silencing of ASAP1 modulates numerous cytokine and apoptosis signaling components, such as IL1B, TRAF1, AIFM2, and MAP3K11 that are clinically relevant to survival outcomes of TNBC patients. ASAP1 has been reported to promote invasion and metastasis in various cancer cells. Our findings that ASAP1 is an amplification-dependent TNBC driver gene promoting TNBC cell proliferation, functioning upstream apoptosis components, and correlating to clinical outcomes of TNBC patients, support ASAP1 as a potential actionable target for TNBC treatment.BACKGROUND Nutritional knowledge assessment is an important component in nutrition research, and a prerequisite for the implementation of many policies and programs aimed at improving eating behavior. Tofacitinib In order to generate objective results, validated tools for a given population must be employed. The aim of this study was to determine the validity and reliability of a nutrition knowledge questionnaire for Romanian adults. METHODS Kleimann's version of a General Nutrition Knowledge Questionnaire, was translated and adapted to Romanian language, culture, and cuisine. The final format was developed in several steps and used four components internal and external reliability were assessed in a general population sample (n1 = 412), respectively in a subgroup (n2 = 46) from Component 1; Component 3 assessed construct validity (n3 = 96) using the "known-groups" method; Component 4 (convergent validity, n4 = 508) tested the association between socio-demographic characteristics and nutrition knowledge. RESULTS The overall internal reliability was 0.878 and the external reliability was >0.880 in all sections, and overall. Specialists had higher scores than nonspecialists, with a very large effect size. In the general population, females scored higher than males, and middle-aged and older adults scored higher than young adults. Higher scores were associated with higher levels of education. The characteristics of individuals prone to giving wrong answers were males (beta = 0.170), high school or less (beta = 0.167), and no training in nutrition (beta = 0.154). CONCLUSIONS The Romanian version of the General Nutrition Knowledge Questionnaire is a reliable and valid tool for measuring nutrition knowledge in adults.BACKGROUND/OBJECTIVES Maternal diet is critical to fetal development. This study aimed to explore the association between maternal dietary diversity during pregnancy and congenital heart defects (CHD) in Chinese population. METHODS A hospital-based case-control study was conducted including 474 cases and 948 controls in Northwest China. We recruited eligible women waiting for delivery in the hospital and gathered their diets during the whole pregnancy by a validated food frequency questionnaire. According to the FAO Minimum Dietary Diversity for Women (MDD-W) guideline, the participants were categorized into "inadequate dietary diversity score (DDS)" (DDS  less then  5) and "adequate DDS" (DDS ≥ 5) groups. The association between dietary diversity and CHD was estimated using the mixed logistic regression models. RESULTS Case mothers had a lower DDS during pregnancy than the controls (P  less then  0.001). The proportions of women consuming all the ten defined food groups were lower in the inadequate DDS group than in the adequate DDS group among both cases and controls (all P  less then  0.001). The prevalence of inadequate micronutrient intake was higher in the inadequate DDS group than in the adequate DDS group among both cases and controls (all P  less then  0.05). Women in the adequate DDS group had reduced risks of having fetuses with total CHD (OR = 0.62, 95% CI = 0.45-0.84) and ventricular septal defects (OR = 0.58, 95% CI = 0.38-0.88). CONCLUSIONS Adequate DDS during pregnancy might be associated with a lower risk of CHD in offspring. Efforts to promote dietary diversity during pregnancy need to be strengthened to reduce the prevalence of CHD in Chinese population.Imidacloprid (IMI) is one of the most frequently used neonicotinoid insecticides, but recent studies have shown adverse effects on mammals. IMI was found to be neurotoxic and hepatotoxic. In the present study, the effects of repeated oral administration of two doses of IMI (5 and 20 mg/kg/day) for 28 days on hippocampus and liver of female KM mice were studied. The histopathological and biochemical experiments indicated obvious damages to the hippocampus and liver of mice in the high-dose group (20 mg/kg/day). Using a high-throughput metabolomics platform based on ultrahigh performance liquid chromatography/hybrid quadrupole time-of-flight mass spectrometry (UPLC/Q-TOF MS), we studied effects of IMI on metabolic profiles in the hippocampus and liver of mice. Significant differences among the control group, the low-dose group and the high-dose group were clearly presented using multivariate analysis. The changed metabolic profile in the low-dose group (5 mg/kg/day) revealed that the metabolic disturbance in the hippocampus and liver of mice had been induced by low-dose of IMI, although no significant histopathological changes were observed in the low-dose group.