{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T04:14:44Z","timestamp":1773288884754,"version":"3.50.1"},"reference-count":34,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2016,5,23]],"date-time":"2016-05-23T00:00:00Z","timestamp":1463961600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2016,5,23]],"date-time":"2016-05-23T00:00:00Z","timestamp":1463961600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Amyotrophic lateral sclerosis (ALS) is an incurable neurological degenerative disease. It can cause irreversible neurological damage to motor neurons; typical symptoms include muscle weakness and atrophy, bulbar paralysis and pyramidal tract signs. The ALS-mimicking disease cervical spondylotic myelopathy (CSM) presents similar symptoms, but analysis of breath volatile organic compounds (VOCs) can potentially be used to distinguish ALS from CSM. In this study, breath samples were collected from 28 ALS and 13 CSM patients. Subsequently, gas chromatography\/mass spectrometry (GCMS) was used to analyze breath VOCs. Principal component analysis (PCA) and orthogonal partial least-squares discriminant analysis (OPLSDA) were the statistical methods used to process the final data. We identified 4 compounds with significantly decreased levels in ALS patients compared with CSM controls: (1) carbamic acid, monoammonium salt; (2) 1-alanine ethylamide, (S)-; (3) guanidine, N,N-dimethyl-; and (4) phosphonic acid, (p-hydroxyphenyl)-. Currently, the metabolic origin of the VOCs remains unclear; however, several pathways might explain the decreasing trends observed. The results of this study demonstrate that there are specific VOC profiles associated with ALS and CSM patients that can be used to differentiate between the two. In addition, these metabolites could contribute to a better understanding of the underlying pathophysiological mechanisms of ALS.<\/jats:p>","DOI":"10.1038\/srep26120","type":"journal-article","created":{"date-parts":[[2016,5,24]],"date-time":"2016-05-24T07:18:04Z","timestamp":1464074284000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Comparative Analysis of VOCs in Exhaled Breath of Amyotrophic Lateral Sclerosis and Cervical Spondylotic Myelopathy Patients"],"prefix":"10.1038","volume":"6","author":[{"given":"Changsong","family":"Wang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mingjuan","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hongquan","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hongshuang","family":"Tong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yue","family":"Feng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yue","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xin","family":"Pi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lei","family":"Guo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maomao","family":"Nie","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Honglin","family":"Feng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Enyou","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2016,5,23]]},"reference":[{"key":"BFsrep26120_CR1","doi-asserted-by":"publisher","first-page":"385","DOI":"10.1136\/jnnp.2009.183525","volume":"81","author":"G Logroscino","year":"2010","unstructured":"Logroscino, G. et al. Incidence of amyotrophic lateral sclerosis in Europe. J Neurol Neurosurg Psychiatry 81, 385\u201390 (2010).","journal-title":"J Neurol Neurosurg Psychiatry"},{"key":"BFsrep26120_CR2","doi-asserted-by":"publisher","first-page":"28","DOI":"10.1186\/1750-1326-8-28","volume":"8","author":"S Chen","year":"2013","unstructured":"Chen, S., Sayana, P., Zhang, X. & Le, W. Genetics of amyotrophic lateral sclerosis: an update. Mol Neurodegener. 8, 28 (2013).","journal-title":"Mol Neurodegener."},{"key":"BFsrep26120_CR3","doi-asserted-by":"publisher","first-page":"271","DOI":"10.1002\/ana.410180302","volume":"18","author":"R Tandan","year":"1985","unstructured":"Tandan, R. & Bradley, W. G. Amyotrophic lateral sclerosis: Part 1. Clinical features, pathology, and ethical issues in management. Ann Neurol. 18, 271\u2013280 (1985).","journal-title":"Ann Neurol."},{"key":"BFsrep26120_CR4","doi-asserted-by":"publisher","first-page":"78","DOI":"10.1016\/j.jocn.2004.04.011","volume":"13","author":"MC Zoing","year":"2006","unstructured":"Zoing, M. C., Burke, D., Pamphlett, R. & Kiernan, M. C. Riluzole therapy for motor neurone disease: an early Australian experience (1996-2002). J Clin Neurosci. 13, 78\u201383 (2006).","journal-title":"J Clin Neurosci."},{"key":"BFsrep26120_CR5","doi-asserted-by":"publisher","first-page":"293","DOI":"10.1080\/146608200300079536","volume":"1","author":"BR Brooks","year":"2000","unstructured":"Brooks, B. R., Miller, R. G., Swash, M. & Munsat, T. L. World Federation of Neurology Research Group on Motor Neuron Diseases. El Escorial revisited: revised criteria for the diagnosis of amyotrophic lateral sclerosis. Amyotroph Lateral Scler Other Motor Neuron Disord. 1, 293\u20139 (2000).","journal-title":"Amyotroph Lateral Scler Other Motor Neuron Disord."},{"key":"BFsrep26120_CR6","first-page":"229","volume":"66","author":"S Misawa","year":"2014","unstructured":"Misawa, S. Utility of muscle ultrasonography for the diagnosis of amyotrophic lateral sclerosis. Brain Nerve. 66, 229\u201336 (2014).","journal-title":"Brain Nerve."},{"key":"BFsrep26120_CR7","doi-asserted-by":"publisher","first-page":"027106","DOI":"10.1088\/1752-7155\/6\/2\/027106","volume":"6","author":"PJ Mazzone","year":"2012","unstructured":"Mazzone, P. J. Exhaled breath volatile organic compound biomarkers in lung cancer. J Breath Res. 6, 027106 (2012).","journal-title":"J Breath Res."},{"key":"BFsrep26120_CR8","doi-asserted-by":"publisher","first-page":"5949","DOI":"10.1021\/cr300174a","volume":"112","author":"M Hakim","year":"2012","unstructured":"Hakim, M. et al. Volatile organic compounds of lung cancer and possible biochemical pathways. Chem Rev. 112, 5949\u201366 (2012).","journal-title":"Chem Rev."},{"key":"BFsrep26120_CR9","doi-asserted-by":"publisher","first-page":"733","DOI":"10.3390\/metabo2040733","volume":"2","author":"AC Hauschild","year":"2012","unstructured":"Hauschild, A. C. et al. Computational methods for metabolomic data analysis of ion mobility spectrometry data-reviewing the state of the art. Metabolites. 2, 733\u201355 (2012).","journal-title":"Metabolites."},{"key":"BFsrep26120_CR10","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1093\/biostatistics\/kxt032","volume":"15","author":"Y Benjamini","year":"2014","unstructured":"Benjamini, Y. & Hechtlinger, Y. Discussion: An estimate of the science-wise false discovery rate and applications to top medical journals by Jager and Leek. Biostatistics 15, 13\u20136, discussion 39\u201345 (2014).","journal-title":"Biostatistics"},{"key":"BFsrep26120_CR11","doi-asserted-by":"publisher","first-page":"012001","DOI":"10.1088\/1752-7155\/8\/1\/012001","volume":"8","author":"SP Eckel","year":"2014","unstructured":"Eckel, S. P., Baumbach, J. & Hauschild, A. C. On the importance of statistics in breath analysis--hope or curse? J Breath Res. 8, 012001 (2014).","journal-title":"J Breath Res."},{"key":"BFsrep26120_CR12","doi-asserted-by":"publisher","first-page":"e95668","DOI":"10.1371\/journal.pone.0095668","volume":"9","author":"A Smolinska","year":"2014","unstructured":"Smolinska, A. et al. Profiling of volatile organic compounds in exhaled breath as a strategy to find early predictive signatures of asthma in children. PLos One 9, e95668 (2014).","journal-title":"PLos One"},{"key":"BFsrep26120_CR13","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1007\/s12031-014-0297-4","volume":"55","author":"H Jiang","year":"2015","unstructured":"Jiang, H. et al. Blood volatile organic compounds as potential biomarkers for amyotrophic lateral sclerosis: an animal study in the SOD1 G93A mouse. J Mol Neurosci. 55, 167\u201373 (2015).","journal-title":"J Mol Neurosci."},{"key":"BFsrep26120_CR14","doi-asserted-by":"publisher","first-page":"5835","DOI":"10.1158\/1078-0432.CCR-10-1434","volume":"16","author":"CM Slupsky","year":"2010","unstructured":"Slupsky, C. M. et al. Urine metabolite analysis offers potential early diagnosis of ovarian and breast cancers. Clin Cancer Res. 16, 5835\u201341 (2010).","journal-title":"Clin Cancer Res."},{"key":"BFsrep26120_CR15","first-page":"410","volume":"28","author":"X Li","year":"2011","unstructured":"Li, X., Ma, L., Wang, J. & Zhao, C. An overview of feature selection algorithm in bioinformatics. Sheng Wu Yi Xue Gong Cheng Xue Za Zhi. 28, 410\u20134 (2011). Review. Chinese.","journal-title":"Sheng Wu Yi Xue Gong Cheng Xue Za Zhi."},{"key":"BFsrep26120_CR16","doi-asserted-by":"publisher","first-page":"318","DOI":"10.1016\/j.chroma.2007.04.021","volume":"1158","author":"M Katajamaa","year":"2007","unstructured":"Katajamaa, M. & Oresic, M. Data processing for mass spectrometry-based metabolomics. J Chromatogr A. 1158, 318\u2013328 (2007).","journal-title":"J Chromatogr A."},{"key":"BFsrep26120_CR17","doi-asserted-by":"publisher","first-page":"469","DOI":"10.1021\/pr060594q","volume":"6","author":"J Trygg","year":"2007","unstructured":"Trygg, J., Holmes, E. & Lundstedt, T. Chemometrics in metabonomics. J Proteome Res. 6, 469\u2013479 (2007).","journal-title":"J Proteome Res."},{"key":"BFsrep26120_CR18","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1007\/s11306-007-0099-6","volume":"4","author":"JA Westerhuis","year":"2008","unstructured":"Westerhuis, J. A. et al. Assessment of PLSDA cross validation. Metabolomics. 4, 81\u201389 (2008).","journal-title":"Metabolomics."},{"key":"BFsrep26120_CR19","doi-asserted-by":"publisher","first-page":"66","DOI":"10.1016\/j.forsciint.2015.01.017","volume":"249","author":"L Lindberg","year":"2015","unstructured":"Lindberg, L. et al. Detection of mouth alcohol during breath alcohol analysis. Forensic Sci Int. 249, 66\u201372 (2015).","journal-title":"Forensic Sci Int."},{"key":"BFsrep26120_CR20","doi-asserted-by":"crossref","unstructured":"Niedzielska, E. et al. Oxidative Stress in Neurodegenerative Diseases. Mol Neurobiol, 10.1007\/s12035-015-9337-5 (2015).","DOI":"10.1007\/s12035-015-9337-5"},{"key":"BFsrep26120_CR21","doi-asserted-by":"publisher","first-page":"529","DOI":"10.1046\/j.0305-1846.2003.00518.x","volume":"29","author":"JD Wood","year":"2003","unstructured":"Wood, J. D., Beaujeux, T. P. & Shaw, P. J. Protein aggregation in motor neurone disorders. Neuropathol Appl Neurobil. 29, 529\u201345 (2003).","journal-title":"Neuropathol Appl Neurobil."},{"key":"BFsrep26120_CR22","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1016\/j.tins.2003.11.001","volume":"27","author":"SD Rao","year":"2004","unstructured":"Rao, S. D. & Weiss, J. H. Excitotoxic and oxidative cross-talk between motor neurons and glia in ALS pathogenesis. Trends Neurosci. 27, 17\u201323 (2004).","journal-title":"Trends Neurosci."},{"key":"BFsrep26120_CR23","doi-asserted-by":"publisher","first-page":"336","DOI":"10.1111\/j.1365-2990.2011.01166.x","volume":"37","author":"LM Duffy","year":"2011","unstructured":"Duffy, L. M., Chapman, A. L., Shaw, P. J. & Grierson, A. J. Review: The role of mitochondria in the pathogenesis of amyotrophic lateral sclerosis. Neuropathol Appl Neurobiol. 37, 336\u201352 (2011).","journal-title":"Neuropathol Appl Neurobiol."},{"key":"BFsrep26120_CR24","doi-asserted-by":"publisher","first-page":"402","DOI":"10.3389\/fncel.2014.00402","volume":"8","author":"M Jaronen","year":"2014","unstructured":"Jaronen, M., Goldsteins, G. & Koistinaho, J. ER stress and unfolded protein response in amyotrophic lateral sclerosis-a controversial role of protein disulphide isomerase. Front Cell Neurosci. 8, 402 (2014).","journal-title":"Front Cell Neurosci."},{"key":"BFsrep26120_CR25","doi-asserted-by":"publisher","first-page":"241","DOI":"10.1002\/glia.20210","volume":"51","author":"SA Sargsyan","year":"2005","unstructured":"Sargsyan, S. A., Monk, P. N. & Shaw, P. J. Microglia as potential contributors to motor neuron injury in amyotrophic lateral sclerosis. Glia. 51, 241\u201353 (2005).","journal-title":"Glia."},{"key":"BFsrep26120_CR26","doi-asserted-by":"publisher","first-page":"1251","DOI":"10.1002\/glia.20848","volume":"57","author":"D Blackburn","year":"2009","unstructured":"Blackburn, D., Sargsyan, S., Monk, P. N. & Shaw, P. J. Astrocyte function and role in motor neuron disease: a future therapeutic target? Glia. 57, 1251\u201364 (2009).","journal-title":"Glia."},{"key":"BFsrep26120_CR27","doi-asserted-by":"publisher","first-page":"383","DOI":"10.1080\/10715760400027979","volume":"39","author":"N Aguirre","year":"2005","unstructured":"Aguirre, N., Beal, M. F., Matson, W. R. & Bogdanov, M. B. Increased oxidative damage to DNA in an animal model of amyotrophic lateral sclerosis. Free Radic Res. 39, 383\u20138 (2005).","journal-title":"Free Radic Res."},{"key":"BFsrep26120_CR28","doi-asserted-by":"publisher","first-page":"66","DOI":"10.1002\/(SICI)1097-4547(19980701)53:1<66::AID-JNR7>3.0.CO;2-H","volume":"53","author":"ED Hall","year":"1998","unstructured":"Hall, E. D., Andrus, P. K., Oostveen, J. A., Fleck, T. J. & Gurney, M. E. Relationship of oxygen radical-induced lipid peroxidative damage to disease onset and progression in a transgenic model of familial ALS. J Neurosci Res. 53, 66\u201377 (1998).","journal-title":"J Neurosci Res."},{"key":"BFsrep26120_CR29","doi-asserted-by":"publisher","first-page":"275","DOI":"10.1016\/S0925-4439(99)00046-0","volume":"1454","author":"AG McBride","year":"1999","unstructured":"McBride, A. G., Borutait\u00e9, V. & Brown, G. C. Superoxide dismutase and hydrogen peroxide cause rapid nitric oxide breakdown, peroxynitrite production and subsequent cell death. Biochim Biophys Acta. 1454, 275\u201388 (1999).","journal-title":"Biochim Biophys Acta."},{"key":"BFsrep26120_CR30","doi-asserted-by":"publisher","first-page":"88","DOI":"10.1016\/j.freeradbiomed.2011.03.027","volume":"51","author":"A Neymotin","year":"2011","unstructured":"Neymotin, A. et al. Neuroprotective effect of Nrf2\/ARE activators, CDDO ethylamide and CDDO trifluoroethylamide, in a mouse model of amyotrophic lateral sclerosis. Free Radic Biol Med. 51, 88\u201396 (2011).","journal-title":"Free Radic Biol Med."},{"key":"BFsrep26120_CR31","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1016\/S0022-3565(24)29332-0","volume":"299","author":"T Canton","year":"2001","unstructured":"Canton, T. et al. RPR 119990, a novel alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid antagonist: synthesis, pharmacological properties, and activity in an animal model of amyotrophic lateral sclerosis. J Pharmacol Exp Ther. 299, 314\u201322 (2001).","journal-title":"J Pharmacol Exp Ther."},{"key":"BFsrep26120_CR32","doi-asserted-by":"publisher","first-page":"43","DOI":"10.2217\/nnm.12.105","volume":"8","author":"U Tisch","year":"2013","unstructured":"Tisch, U. et al. Detection of Alzheimer\u2019s and Parkinson\u2019s disease from exhaled breath using nanomaterial-based sensors. Nanomedicine (Lond). 8, 43\u201356 (2013).","journal-title":"Nanomedicine (Lond)."},{"key":"BFsrep26120_CR33","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1016\/j.cccn.2004.04.023","volume":"347","author":"W Miekisch","year":"2004","unstructured":"Miekisch, W., Schubert, J. K. & Noeldge-Schomburg, G. F. Diagnostic potential of breath analysis\u2013focus on volatile organic compounds. Clin Chim Acta. 347, 25\u201339 (2004).","journal-title":"Clin Chim Acta."},{"key":"BFsrep26120_CR34","doi-asserted-by":"publisher","first-page":"281","DOI":"10.2217\/bmm.09.71","volume":"4","author":"J Ganesalingam","year":"2010","unstructured":"Ganesalingam, J. & Bowser, R. The application of biomarkers in clinical trials for motor neuron disease. Biomark Med. 4, 281\u201397 (2010).","journal-title":"Biomark Med."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/srep26120.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/srep26120","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/srep26120.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,6,3]],"date-time":"2025-06-03T19:06:39Z","timestamp":1748977599000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/srep26120"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,5,23]]},"references-count":34,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2016,5,31]]}},"alternative-id":["BFsrep26120"],"URL":"https:\/\/doi.org\/10.1038\/srep26120","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,5,23]]},"assertion":[{"value":"4 February 2016","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"27 April 2016","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"23 May 2016","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing financial interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"26120"}}