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Assi N, Fages A, Vineis P, et\u00a0al. A statistical framework to model the meeting-in-the-middle principle using metabolomic data: application to hepatocellular carcinoma in the EPIC study. <i>Mutagenesis<\/i>. 2015;30(6):743\u2013753.","DOI":"10.1093\/mutage\/gev045"},{"key":"8","doi-asserted-by":"crossref","unstructured":"8. Vineis P, Demetriou CA, Probst-Hensch N. Long-term effects of air pollution: an exposome meet-in-the-middle approach. <i>Int J Public Health<\/i>. 2020;65(2):125\u2013127.","DOI":"10.1007\/s00038-019-01329-7"},{"key":"9","doi-asserted-by":"crossref","unstructured":"9. Vineis P, van Veldhoven K, Chadeau-Hyam M, Athersuch TJ. Advancing the application of omics-based biomarkers in environmental epidemiology. <i>Environ Mol Mutagen<\/i>. 2013;54(7):461\u2013467.","DOI":"10.1002\/em.21764"},{"key":"10","doi-asserted-by":"crossref","unstructured":"10. Ohmomo H, Harada S, Komaki S, et\u00a0al. DNA Methylation Abnormalities and Altered Whole Transcriptome Profiles after Switching from Combustible Tobacco Smoking to Heated Tobacco Products. <i>Cancer Epidemiol Biomarkers Prev<\/i>. 2022;31(1):269\u2013279.","DOI":"10.1158\/1055-9965.EPI-21-0444"},{"key":"11","doi-asserted-by":"crossref","unstructured":"11. Gu F, Derkach A, Freedman ND, et\u00a0al. Cigarette smoking behaviour and blood metabolomics. <i>Int J Epidemiol<\/i>. 2016;45(5):1421\u20131432.","DOI":"10.1093\/ije\/dyv330"},{"key":"12","doi-asserted-by":"crossref","unstructured":"12. Hsu PC, Lan RS, Brasky TM, et\u00a0al. Metabolomic profiles of current cigarette smokers. <i>Mol Carcinog<\/i>. 2017;56(2):594\u2013606.","DOI":"10.1002\/mc.22519"},{"key":"13","doi-asserted-by":"crossref","unstructured":"13. Xu T, Holzapfel C, Dong X, et\u00a0al. Effects of smoking and smoking cessation on human serum metabolite profile: results from the KORA cohort study. <i>BMC Med<\/i>. 2013;11(1):60.","DOI":"10.1186\/1741-7015-11-60"},{"key":"14","doi-asserted-by":"crossref","unstructured":"14. Zheng Y, Hu FB, Ruiz-Canela M, et\u00a0al. Metabolites of Glutamate Metabolism Are Associated With Incident Cardiovascular Events in the PREDIMED PREvenci\u00f3n con DIeta MEDiterr\u00e1nea (PREDIMED) Trial. <i>J Am Heart Assoc<\/i>. 2016;5(9):e003755.","DOI":"10.1161\/JAHA.116.003755"},{"key":"15","doi-asserted-by":"crossref","unstructured":"15. Shah SH, Bain JR, Muehlbauer MJ, et\u00a0al. Association of a Peripheral Blood Metabolic Profile With Coronary Artery Disease and Risk of Subsequent Cardiovascular Events. <i>Circ Cardiovasc Genet<\/i>. 2010;3(2):207\u2013214.","DOI":"10.1161\/CIRCGENETICS.109.852814"},{"key":"16","doi-asserted-by":"crossref","unstructured":"16. Harada S, Hirayama A, Chan Q, et\u00a0al. 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Hirayama A, Nakashima E, Sugimoto M, et\u00a0al. Metabolic profiling reveals new serum biomarkers for differentiating diabetic nephropathy. <i>Anal Bioanal Chem<\/i>. 2012;404(10):3101\u20133109.","DOI":"10.1007\/s00216-012-6412-x"},{"key":"20","doi-asserted-by":"crossref","unstructured":"20. Soga T, Igarashi K, Ito C, Mizobuchi K, Zimmermann HP, Tomita M. Metabolomic profiling of anionic metabolites by capillary electrophoresis mass spectrometry. <i>Anal Chem<\/i>. 2009;81(15):6165\u20136174.","DOI":"10.1021\/ac900675k"},{"key":"21","doi-asserted-by":"crossref","unstructured":"21. Sugimoto M, Wong DT, Hirayama A, Soga T, Tomita M. Capillary electrophoresis mass spectrometry-based saliva metabolomics identified oral, breast and pancreatic cancer-specific profiles. <i>Metabolomics<\/i>. 2010;6(1):78\u201395.","DOI":"10.1007\/s11306-009-0178-y"},{"key":"22","doi-asserted-by":"crossref","unstructured":"22. Hirayama A, Kami K, Sugimoto M, et\u00a0al. Quantitative metabolome profiling of colon and stomach cancer microenvironment by capillary electrophoresis time-of-flight mass spectrometry. <i>Cancer Res<\/i>. 2009;69(11):4918\u20134925.","DOI":"10.1158\/0008-5472.CAN-08-4806"},{"key":"23","doi-asserted-by":"crossref","unstructured":"23. Beane J, Sebastiani P, Liu G, Brody JS, Lenburg ME, Spira A. Reversible and permanent effects of tobacco smoke exposure on airway epithelial gene expression. <i>Genome Biol<\/i>. 2007;8(9):R201.","DOI":"10.1186\/gb-2007-8-9-r201"},{"key":"24","unstructured":"24. Bridges CC, Kekuda R, Wang H, et\u00a0al. Structure, function, and regulation of human cystine\/glutamate transporter in retinal pigment epithelial cells. <i>Invest Ophthalmol Vis Sci<\/i>. 2001;42(1):47\u201354."},{"key":"25","doi-asserted-by":"crossref","unstructured":"25. Brunner H, Cockcroft JR, Deanfield J, et\u00a0al. Endothelial function and dysfunction. Part II: Association with cardiovascular risk factors and diseases. 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