347 research outputs found

    Colorectal cancer stages transcriptome analysis

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    Colorectal cancer (CRC) is the third most common cancer and the second leading cause of cancer-related deaths in the United States. The purpose of this study was to evaluate the gene expression differences in different stages of CRC. Gene expression data on 433 CRC patient samples were obtained from The Cancer Genome Atlas (TCGA). Gene expression differences were evaluated across CRC stages using linear regression. Genes with p 0.001 in expression differences were evaluated further in principal component analysis and genes with p 0.0001 were evaluated further in gene set enrichment analysis. A total of 377 patients with gene expression data in 20,532 genes were included in the final analysis. The numbers of patients in stage I through IV were 59, 147, 116 and 55, respectively. NEK4 gene, which encodes for NIMA related kinase 4, was differentially expressed across the four stages of CRC. The stage I patients had the highest expression of NEK4 genes, while the stage IV patients had the lowest expressions (p = 9*10−6 ). Ten other genes (RNF34, HIST3H2BB, NUDT6, LRCh4, GLB1L, HIST2H4A, TMEM79, AMIGO2, C20orf135 and SPSB3) had p value of 0.0001 in the differential expression analysis. Principal component analysis indicated that the patients from the 4 clinical stages do not appear to have distinct gene expression pattern. Network-based and pathway-based gene set enrichment analyses showed that these 11 genes map to multiple pathways such as meiotic synapsis and packaging of telomere ends, etc. Ten of these 11 genes were linked to Gene Ontology terms such as nucleosome, DNA packaging complex and protein-DNA interactions. The protein complex-based gene set analysis showed that four genes were involved in H2AX complex II. This study identified a small number of genes that might be associated with clinical stages of CRC. Our analysis was not able to find a molecular basis for the current clinical staging for CRC based on the gene expression patterns

    Principal component 1 and principle component 2 by cancer stage.

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    <p>Principal component 1 and principle component 2 by cancer stage.</p

    Preference of birth mode and postnatal health related quality of life after one previous caesarean section in three European countries

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    Objectives: Women who have had a caesarean section may have a preference for birth mode during their subsequent pregnancy, either 'vaginal birth after caesarean' (VBAC) or 'elective repeat caesarean section' (ERCS). A mismatch between the preferred and actual birth mode may result in an impaired postnatal Health Related Quality of Life (HRQoL). This study examined the associations between antenatal birth mode preferences, the actual birth mode and postnatal HRQoL in women with one previous caesarean section in three European countries. Design: Prospective longitudinal survey, as a part of a cluster randomised trial (OptiBIRTH) Setting: Fifteen maternity units in three European countries: Germany (5), Ireland (5) and Italy (5). Participants: Women (≄ aged 18 years) living in Germany, Ireland and Italy with one previous caesarean section. The sample consisted of 862 women with complete antenatal and postpartum data. Measurements: Women's preference for birth mode after one previous caesarean section was assessed at inclusion to the trial, and HRQoL was assessed antenatally and at three months postpartum using the Short-Form Six-Dimension health survey. Based on women's preferences and actual birth mode six groups were determined: "match VBAC-VBAC" (preference for vaginal birth, actual mode of birth vaginal birth), "match ERCS-ERCS" (preference for caesarean section, actual mode of birth elective repeat caesarean section), "match ERCS-EMCS" (preference for caesarean section, actual mode of birth emergency repeat caesarean section), "mismatch VBAC-ERCS" (preference for vaginal birth, actual mode of birth elective repeat caesarean section), "mismatch VBAC-EMCS" (preference for vaginal birth, actual mode of birth emergency repeat caesarean section) and "no preference". Associations between the preferred and actual birth mode were examined using univariate and multivariate analyses. Findings: Women with preference for vaginal birth but who gave birth by elective repeat caesarean section (mismatch VBAC-ERCS) had a lower postnatal HRQoL compared to women with a preference for vaginal birth who actually had a birth vaginally (match VBAC-VBAC, p = 0.02). Poor antenatal HRQoL scores (p < 0.01) and maternal readmission postpartum (p = 0.03) are cofounding factors for poorer postnatal HRQoL scores. Key Conclusions: The results show that women with a preference for a vaginal birth who gave birth by an elective repeat caesarean section had a significantly lower HRQoL at three months postnatal. The long-term consequences and psychological health of women who do not achieve a vaginal birth after caesarean require further consideration and research. Implications for Practice: Attention should be given to the long-term impact of a mismatch in preferred and actual mode on the psychological health of wome

    Integrating DNA Methylation and Gene Expression Data in the Development of the Soybean-Bradyrhizobium N2-Fixing Symbiosis

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    Eukaryote-bacteria symbioses are common in nature and several have been extensively studied. However, very little is known about the role of epigenetics in the differentiation of a bacterium from the free-living to the symbiotic state. Here the first genome-wide analysis of DNA methylation changes between these states is described using the model of symbiosis between soybean (Glycine max (L.) Merr.) and its root nodule-forming, nitrogen-fixing symbiont, Bradyrhizobium diazoefficiens. Resequencing the genome of B. diazoefficiens from both states using the Pacific Biosciences sequencing platform revealed 43,061 sites representing five motifs with the potential to be methylated in the 9.2 Mb genome. Of those sites, 3,276 changed methylation states in 2,921 genes or 35.5% of all genes in the genome. Over ten percent (10.9%) of the methylation changes occurred in the 681-kb sized symbiosis island that comprises just 7.4% of the genome. The CCTTGAG motif was methylated only during symbiosis with 1,361 adenosines methylated among the 1,700 possible sites. Published microarray data was used to correlate the methylation status with gene expression. Another 89 genes within the symbiotic island and 768 genes throughout the genome were found to have methylation and significant expression changes during symbiotic development. Of those, nine known symbiosis genes involved in all phases of symbiotic development including early infection events, nodule development, and nitrogenase production. These associations between methylation and expression changes in many B. diazoefficiens genes suggest an important role of the epigenome in bacterial differentiation to the symbiotic state

    Association Between Early-Life Antibiotic Use and the Risk of Islet or Celiac Disease Autoimmunity

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    Importance: Evidence is lacking regarding the consequences of antibiotic use in early life and the risk of certain autoimmune diseases.Objective: To test the association between early-life antibiotic use and islet or celiac disease (CD) autoimmunity in genetically at-risk children prospectively followed up for type 1 diabetes (T1D) or CD.Design, Setting, and Participants: HLA-genotyped newborns from Finland, Germany, Sweden, and the United States were enrolled in the prospective birth cohort of The Environmental Determinants of Diabetes in the Young (TEDDY) study between November 20, 2004, and July 8, 2010. The dates of analysis were November 20, 2004, to August 31, 2014. Individuals from the general population and those having a first-degree relative with T1D were enrolled if they had 1 of 9 HLA genotypes associated with a risk for T1D.Exposures: Parental reports of the most common antibiotics (cephalosporins, penicillins, and macrolides) used between age 3 months and age 4 years were recorded prospectively.Main Outcomes and Measures: Islet autoimmunity and CD autoimmunity were defined as being positive for islet or tissue transglutaminase autoantibodies at 2 consecutive clinic visits at least 3 months apart. Hazard ratios and 95% CIs calculated from Cox proportional hazards regression models were used to assess the relationship between antibiotic use in early life before seroconversion and the development of autoimmunity.Results: Participants were 8495 children (49.0% female) and 6558 children (48.7% female) enrolled in the TEDDY study who were tested for islet and tissue transglutaminase autoantibodies, respectively. Exposure to and frequency of use of any antibiotic assessed in this study in early life or before seroconversion did not influence the risk of developing islet autoimmunity or CD autoimmunity. Cumulative use of any antibiotic during the first 4 years of life was not associated with the appearance of any autoantibody (hazard ratio [HR], 0.98; 95% CI, 0.95-1.01), multiple islet autoantibodies (HR, 0.99; 95% CI, 0.95-1.03), or the transglutaminase autoantibody (HR, 1.00; 95% CI, 0.98-1.02).Conclusions and Relevance: The use of the most prescribed antibiotics during the first 4 years of life, regardless of geographic region, was not associated with the development of autoimmunity for T1D or CD. These results suggest that a risk of islet or tissue transglutaminase autoimmunity need not influence the recommendations for clinical use of antibiotics in young children at risk for T1D or CD

    The International Linear Collider: Report to Snowmass 2021

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    The International Linear Collider (ILC) is on the table now as a new global energy-frontier accelerator laboratory taking data in the 2030s. The ILC addresses key questions for our current understanding of particle physics. It is based on a proven accelerator technology. Its experiments will challenge the Standard Model of particle physics and will provide a new window to look beyond it. This document brings the story of the ILC up to date, emphasizing its strong physics motivation, its readiness for construction, and the opportunity it presents to the US and the global particle physics community

    The International Linear Collider:Report to Snowmass 2021

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    The International Linear Collider: Report to Snowmass 2021

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    International audienceThe International Linear Collider (ILC) is on the table now as a new global energy-frontier accelerator laboratory taking data in the 2030s. The ILC addresses key questions for our current understanding of particle physics. It is based on a proven accelerator technology. Its experiments will challenge the Standard Model of particle physics and will provide a new window to look beyond it. This document brings the story of the ILC up to date, emphasizing its strong physics motivation, its readiness for construction, and the opportunity it presents to the US and the global particle physics community
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