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      Cross-sectional examination of metabolites and metabolic phenotypes in uremia.

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          Abstract

          Although metabolomic approaches have begun to document numerous changes that arise in end stage renal disease (ESRD), how these alterations relate to established metabolic phenotypes in uremia is unknown.

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          Most cited references 36

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          MetaboAnalyst: a web server for metabolomic data analysis and interpretation

          Metabolomics is a newly emerging field of ‘omics’ research that is concerned with characterizing large numbers of metabolites using NMR, chromatography and mass spectrometry. It is frequently used in biomarker identification and the metabolic profiling of cells, tissues or organisms. The data processing challenges in metabolomics are quite unique and often require specialized (or expensive) data analysis software and a detailed knowledge of cheminformatics, bioinformatics and statistics. In an effort to simplify metabolomic data analysis while at the same time improving user accessibility, we have developed a freely accessible, easy-to-use web server for metabolomic data analysis called MetaboAnalyst. Fundamentally, MetaboAnalyst is a web-based metabolomic data processing tool not unlike many of today's web-based microarray analysis packages. It accepts a variety of input data (NMR peak lists, binned spectra, MS peak lists, compound/concentration data) in a wide variety of formats. It also offers a number of options for metabolomic data processing, data normalization, multivariate statistical analysis, graphing, metabolite identification and pathway mapping. In particular, MetaboAnalyst supports such techniques as: fold change analysis, t-tests, PCA, PLS-DA, hierarchical clustering and a number of more sophisticated statistical or machine learning methods. It also employs a large library of reference spectra to facilitate compound identification from most kinds of input spectra. MetaboAnalyst guides users through a step-by-step analysis pipeline using a variety of menus, information hyperlinks and check boxes. Upon completion, the server generates a detailed report describing each method used, embedded with graphical and tabular outputs. MetaboAnalyst is capable of handling most kinds of metabolomic data and was designed to perform most of the common kinds of metabolomic data analyses. MetaboAnalyst is accessible at http://www.metaboanalyst.ca
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            Is Open Access

            MetaboAnalyst 2.0—a comprehensive server for metabolomic data analysis

            First released in 2009, MetaboAnalyst (www.metaboanalyst.ca) was a relatively simple web server designed to facilitate metabolomic data processing and statistical analysis. With continuing advances in metabolomics along with constant user feedback, it became clear that a substantial upgrade to the original server was necessary. MetaboAnalyst 2.0, which is the successor to MetaboAnalyst, represents just such an upgrade. MetaboAnalyst 2.0 now contains dozens of new features and functions including new procedures for data filtering, data editing and data normalization. It also supports multi-group data analysis, two-factor analysis as well as time-series data analysis. These new functions have also been supplemented with: (i) a quality-control module that allows users to evaluate their data quality before conducting any analysis, (ii) a functional enrichment analysis module that allows users to identify biologically meaningful patterns using metabolite set enrichment analysis and (iii) a metabolic pathway analysis module that allows users to perform pathway analysis and visualization for 15 different model organisms. In developing MetaboAnalyst 2.0 we have also substantially improved its graphical presentation tools. All images are now generated using anti-aliasing and are available over a range of resolutions, sizes and formats (PNG, TIFF, PDF, PostScript, or SVG). To improve its performance, MetaboAnalyst 2.0 is now hosted on a much more powerful server with substantially modified code to take advantage the server’s multi-core CPUs for computationally intensive tasks. MetaboAnalyst 2.0 also maintains a collection of 50 or more FAQs and more than a dozen tutorials compiled from user queries and requests. A downloadable version of MetaboAnalyst 2.0, along detailed instructions for local installation is now available as well.
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              Rosuvastatin and cardiovascular events in patients undergoing hemodialysis.

              Statins reduce the incidence of cardiovascular events in patients at high cardiovascular risk. However, a benefit of statins in such patients who are undergoing hemodialysis has not been proved. We conducted an international, multicenter, randomized, double-blind, prospective trial involving 2776 patients, 50 to 80 years of age, who were undergoing maintenance hemodialysis. We randomly assigned patients to receive rosuvastatin, 10 mg daily, or placebo. The combined primary end point was death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke. Secondary end points included death from all causes and individual cardiac and vascular events. After 3 months, the mean reduction in low-density lipoprotein (LDL) cholesterol levels was 43% in patients receiving rosuvastatin, from a mean baseline level of 100 mg per deciliter (2.6 mmol per liter). During a median follow-up period of 3.8 years, 396 patients in the rosuvastatin group and 408 patients in the placebo group reached the primary end point (9.2 and 9.5 events per 100 patient-years, respectively; hazard ratio for the combined end point in the rosuvastatin group vs. the placebo group, 0.96; 95% confidence interval [CI], 0.84 to 1.11; P=0.59). Rosuvastatin had no effect on individual components of the primary end point. There was also no significant effect on all-cause mortality (13.5 vs. 14.0 events per 100 patient-years; hazard ratio, 0.96; 95% CI, 0.86 to 1.07; P=0.51). In patients undergoing hemodialysis, the initiation of treatment with rosuvastatin lowered the LDL cholesterol level but had no significant effect on the composite primary end point of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke. (ClinicalTrials.gov number, NCT00240331.) 2009 Massachusetts Medical Society
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                Author and article information

                Journal
                BMC Nephrol
                BMC nephrology
                Springer Nature
                1471-2369
                1471-2369
                Jul 07 2015
                : 16
                Affiliations
                [1 ] Division of Nephrology, Massachusetts General Hospital (MGH), 165 Cambridge Street, Suite 302, Boston, MA, 02114, USA. skalim@mgh.harvard.edu.
                [2 ] Broad Institute, Cambridge, MA, USA. clary@broadinstitute.org.
                [3 ] Division of Nephrology, Massachusetts General Hospital (MGH), 165 Cambridge Street, Suite 302, Boston, MA, 02114, USA. joseph.deferio@downstate.edu.
                [4 ] Division of Nephrology, Massachusetts General Hospital (MGH), 165 Cambridge Street, Suite 302, Boston, MA, 02114, USA. gortiz@partners.org.
                [5 ] Division of Nephrology, Massachusetts General Hospital (MGH), 165 Cambridge Street, Suite 302, Boston, MA, 02114, USA. amoffet2@illinois.edu.
                [6 ] Broad Institute, Cambridge, MA, USA. rgerszten@partners.org.
                [7 ] Cardiology Division, MGH, Boston, MA, USA. rgerszten@partners.org.
                [8 ] Cardiovascular Research Center, MGH, Boston, MA, USA. rgerszten@partners.org.
                [9 ] Division of Nephrology, Massachusetts General Hospital (MGH), 165 Cambridge Street, Suite 302, Boston, MA, 02114, USA. rthadhani@partners.org.
                [10 ] Division of Nephrology, Massachusetts General Hospital (MGH), 165 Cambridge Street, Suite 302, Boston, MA, 02114, USA. eprhee@partners.org.
                [11 ] Broad Institute, Cambridge, MA, USA. eprhee@partners.org.
                Article
                10.1186/s12882-015-0100-y
                10.1186/s12882-015-0100-y
                4491861
                26149577

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