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      Metabolic Signatures of Performance in Elite World Tour Professional Male Cyclists

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          Abstract

          Background and Objective

          Metabolomics studies of recreational and elite athletes have been so far limited to venipuncture-dependent blood sample collection in the setting of controlled training and medical facilities. However, limited to no information is currently available to determine if findings in laboratory settings are translatable to a real-world scenario in elite competitions. The goal of this study was to define molecular signatures of exertion under controlled exercise conditions and use these signatures as a framework for assessing cycling performance in a World Tour competition.

          Methods

          To characterize molecular profiles of exertion in elite athletes during cycling, we performed metabolomics analyses on blood isolated from 28 international-level, elite, World Tour professional male athletes from a Union Cycliste Internationale World Team taken before and after a graded exercise test to volitional exhaustion and before and after a long aerobic training session. Moreover, established signatures were then used to characterize the metabolic physiology of five of these cyclists who were selected to represent the same Union Cycliste Internationale World Team during a seven-stage elite World Tour race.

          Results

          Using dried blood spot collection to circumvent logistical hurdles associated with field sampling, these studies defined metabolite signatures and fold change ranges of anaerobic or aerobic exertion in elite cyclists, respectively. Blood profiles of lactate, carboxylic acids, fatty acids, and acylcarnitines differed between exercise modes. The graded exercise test elicited significant two- to three-fold accumulations in lactate and succinate, in addition to significant elevations in free fatty acids and acylcarnitines. Conversely, the long aerobic training session elicited a larger magnitude of increase in fatty acids and acylcarnitines without appreciable increases in lactate or succinate. Comparable signatures were revealed after sprinting and climbing stages, respectively, in a World Tour race. In addition, signatures of elevated fatty acid oxidation capacity correlated with competitive performance.

          Conclusions

          Collectively, these studies provide a unique view of alterations in the blood metabolome of elite athletes during competition and at the peak of their performance capabilities. Furthermore, they demonstrate the utility of dried blood sampling for omics analysis, thereby enabling molecular monitoring of athletic performance in the field during training and competition.

          Supplementary Information

          The online version contains supplementary material available at 10.1007/s40279-023-01846-9.

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          Hallmarks of Cancer: New Dimensions

          The hallmarks of cancer conceptualization is a heuristic tool for distilling the vast complexity of cancer phenotypes and genotypes into a provisional set of underlying principles. As knowledge of cancer mechanisms has progressed, other facets of the disease have emerged as potential refinements. Herein, the prospect is raised that phenotypic plasticity and disrupted differentiation is a discrete hallmark capability, and that nonmutational epigenetic reprogramming and polymorphic microbiomes both constitute distinctive enabling characteristics that facilitate the acquisition of hallmark capabilities. Additionally, senescent cells, of varying origins, may be added to the roster of functionally important cell types in the tumor microenvironment. SIGNIFICANCE: Cancer is daunting in the breadth and scope of its diversity, spanning genetics, cell and tissue biology, pathology, and response to therapy. Ever more powerful experimental and computational tools and technologies are providing an avalanche of "big data" about the myriad manifestations of the diseases that cancer encompasses. The integrative concept embodied in the hallmarks of cancer is helping to distill this complexity into an increasingly logical science, and the provisional new dimensions presented in this perspective may add value to that endeavor, to more fully understand mechanisms of cancer development and malignant progression, and apply that knowledge to cancer medicine.
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            Diagnosis and management of the metabolic syndrome: an American Heart Association/National Heart, Lung, and Blood Institute Scientific Statement.

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              MetaboAnalyst 4.0: towards more transparent and integrative metabolomics analysis

              Abstract We present a new update to MetaboAnalyst (version 4.0) for comprehensive metabolomic data analysis, interpretation, and integration with other omics data. Since the last major update in 2015, MetaboAnalyst has continued to evolve based on user feedback and technological advancements in the field. For this year's update, four new key features have been added to MetaboAnalyst 4.0, including: (1) real-time R command tracking and display coupled with the release of a companion MetaboAnalystR package; (2) a MS Peaks to Pathways module for prediction of pathway activity from untargeted mass spectral data using the mummichog algorithm; (3) a Biomarker Meta-analysis module for robust biomarker identification through the combination of multiple metabolomic datasets and (4) a Network Explorer module for integrative analysis of metabolomics, metagenomics, and/or transcriptomics data. The user interface of MetaboAnalyst 4.0 has been reengineered to provide a more modern look and feel, as well as to give more space and flexibility to introduce new functions. The underlying knowledgebases (compound libraries, metabolite sets, and metabolic pathways) have also been updated based on the latest data from the Human Metabolome Database (HMDB). A Docker image of MetaboAnalyst is also available to facilitate download and local installation of MetaboAnalyst. MetaboAnalyst 4.0 is freely available at http://metaboanalyst.ca.
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                Author and article information

                Contributors
                travis.nemkov@cuanschutz.edu
                angelo.dalessandro@cuanschutz.edu
                Journal
                Sports Med
                Sports Med
                Sports Medicine (Auckland, N.z.)
                Springer International Publishing (Cham )
                0112-1642
                1179-2035
                6 May 2023
                : 1-15
                Affiliations
                [1 ]GRID grid.430503.1, ISNI 0000 0001 0703 675X, Department of Biochemistry and Molecular Genetics, Anschutz Medical Campus, , University of Colorado, ; 12801 East 17th Ave L18-9122, Aurora, CO 80045 USA
                [2 ]GRID grid.430503.1, ISNI 0000 0001 0703 675X, Department of Medicine, Division of Endocrinology, Metabolism and Diabetes, , University of Colorado, Anschutz Medical Campus, ; Aurora, CO USA
                [3 ]GRID grid.266186.d, ISNI 0000 0001 0684 1394, Department of Human Physiology and Nutrition, , University of Colorado, ; Colorado Springs, CO USA
                [4 ]GRID grid.430503.1, ISNI 0000 0001 0703 675X, Department of Biochemistry and Molecular Genetics, , University of Colorado, Anschutz Medical Campus, ; 12801 East 17Th Ave L18-9118, Aurora, CO 80045 USA
                Author information
                https://orcid.org/0000-0001-8566-7119
                https://orcid.org/0000-0002-8874-2150
                https://orcid.org/0000-0002-7756-6788
                https://orcid.org/0000-0001-5054-838X
                https://orcid.org/0000-0002-7975-917X
                http://orcid.org/0000-0002-2258-6490
                Article
                1846
                10.1007/s40279-023-01846-9
                10163861
                37148487
                81414821-ba76-4236-a8c4-8a13c3a9494a
                © The Author(s), under exclusive licence to Springer Nature Switzerland AG 2023, Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

                This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.

                History
                : 19 March 2023
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/100017540, NHLBI Division of Intramural Research;
                Award ID: R01HL146442
                Award ID: R01HL149714
                Award ID: R01HL148151
                Award ID: R01HL161004
                Award ID: R21HL150032
                Award Recipient :
                Categories
                Original Research Article

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