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B\u00e4ckryd reports grants from ALF Grants, Region \u00d6sterg\u00f6tland, and from NEURO Sweden"},{"DOI":"10.13039\/501100003945","name":"Link\u00f6ping University","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100003945","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>About 20% of patients with diabetes suffer from chronic pain with neuropathic characteristics. We investigated the multivariate associations between 92 neurology-related proteins measured in serum from 190 patients with painful and painless diabetic neuropathy. Participants were recruited from the Pain in Neuropathy Study, an observational cross-sectional multicentre study in which participants underwent deep phenotyping. In the exploration cohort, two groups were defined by hierarchical cluster analyses of protein data. The proportion of painless vs painful neuropathy did not differ between the two groups, but one group had a significantly higher grade of neuropathy as measured by the Toronto Clinical Scoring System (TCSS). This finding was replicated in the replication cohort. Analyzing both groups together, we found that a group of 11 inter-correlated proteins (TNFRSF12A, SCARB2, N2DL-2, SKR3, EFNA4, LAYN, CLM-1, CD38, UNC5C, GFR-alpha-1, and JAM-B) were positively associated with TCSS values. Notably, EFNA4 and UNC5C are known to be part of axon guidance pathways. To conclude, although cluster analysis of 92 neurology-related proteins did not distinguish painful from painless diabetic neuropathy, we identified 11 proteins which positively correlated to neuropathy severity and warrant further investigation as potential biomarkers.<\/jats:p>","DOI":"10.1038\/s41598-024-66471-6","type":"journal-article","created":{"date-parts":[[2024,7,24]],"date-time":"2024-07-24T05:02:47Z","timestamp":1721797367000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Eleven neurology-related proteins measured in serum are positively correlated to the severity of diabetic neuropathy"],"prefix":"10.1038","volume":"14","author":[{"given":"Emmanuel","family":"B\u00e4ckryd","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Themistocleous","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anders","family":"Larsson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Torsten","family":"Gordh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew S. 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Andrew SC Rice (ASCR) was a Principal Investigator\/director of the Wellcome Trust funded London Pain Consortium through which the PiNS study was funded. ASCR declares the following interests unrelated to this manuscript occurring in last 36 months: Employee Imperial College London. Hon Consultant Chelsea and Westminster Hospital NHS Foundation Trust. ASCR undertakes consultancy and advisory board work for Imperial College Consultants- in the last 36 months this has included remunerated work for: Confo, Combigene, Vertex, Novartis, Orion, Shanghai SIMR Biotech & Science Practice (Wellcome Trust). ASCR is named as an inventor on patents: Rice A.S.C., Vandevoorde S. and Lambert D.M Methods using N-(2-propenyl)hexadecanamide and related amides to relieve pain. WO 2005\/079771. Okuse K. et al. Methods of treating pain by inhibition of vgf activity EP13702262.0\/ WO2013 110945. Member Joint Committee on Vaccine and Immunisation- varicella sub-committee. Analgesic Clinical Trial Translation: Innovations, Opportunities, and Networks (ACTTION) steering committee member. Medicines and Healthcare products Regulatory Agency (MHRA), Commission on Human Medicines\u2014Neurology, Pain & Psychiatry Expert Advisory Group. Grants and studentships\u2014UKRI (Medical Research Council & BBSRC), Versus Arthritis, Alan and Sheila Diamond Trust, Royal British Legion, European Commission, Ministry of Defence, Dr Jennie Gwynn Bequests, The British Pain Society, Royal Society of Medicine. Royal College of Anaesthetists\u2014Heritage and Archives Committee (2020\u2014date). Lecture honoraria: MD Cancer Cancer Center -2021, University California San Francisco. CSF12th Pediatric Pain Master Class (USA) Dec 2021, Bioevents \u2013 Controversies in Neuropathic pain \u2013 2021, Royal Marsden Hospital 2019, Indonesian Neurological Association Pain Study Group International Lecture Series Donated to (Association of Southeast Asian Pain Societies (ASEAPS) \u2013Oct 2022, Malaysian Society of Anaesthesiologists \u2013 July 2022, Siriraj Hospital Bangkok international relations programme- visiting Professorship Nov 2022 \u2013 used for expenses. Royal Pharmaceutical Society- British National Formulary- ongoing. International Association Study of Pain: Executive Committee (President-elect). David L Bennett (DLB) was a Principal Investigator\/director of the Wellcome Trust funded London Pain Consortium through which the PiNS study was funded. DLB declares the following interests unrelated to this manuscript occurring in last 36 months: DLB is a member of the NeupSIG executive committee. DLB has received grant funding from UKRI, Lilly, AstraZeneca, Wellcome, EU and Diabetes UK. DLB has acted as a consultant in the last 2 years for AditumBio, Amgen, Biointervene, Bristows, LatigoBio, GSK, Ionis, Lexicon therapeutics, Lilly, Neuvati, Olipass, Regeneron, Replay and Theranexus on behalf of Oxford University Innovation. DLB has been named on a patent \u2018a method for the treatment or prevention of pain, or excessive neuronal activity, or epilepsy\u2019 Application No. 16\/337,428. Solomon Tesfaye has received: honoraria from Procter & Gamble, Viatris, Grunenthal, Novo Nordisk, Pfizer, Merck, Eva Pharma, Hikma, Astellas Pharma, Abbott, AstraZeneca, Berlin-Chemie, Worwag Pharma, Nevro, Haisco Pharmaceutical Group, for educational meetings; consultancy fees for advisor board membership from Angelini, Bayer, GSK, Worwag Phrama and Nevro; research equipment donated to Sheffield Teaching Hospitals from Impeto Medical and Neurometrix; and unrestricted, competitive research grants from Viatris and Procter and Gamble.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"17068"}}