{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,8]],"date-time":"2026-04-08T21:40:25Z","timestamp":1775684425758,"version":"3.50.1"},"reference-count":26,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2021,5,27]],"date-time":"2021-05-27T00:00:00Z","timestamp":1622073600000},"content-version":"vor","delay-in-days":1,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,8,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Intraepidermal nerve fiber density (IENFD) measurements in skin biopsy are performed manually by 1\u20133 operators. To improve diagnostic accuracy and applicability in clinical practice, we developed an automated method for fast IENFD determination with low operator-dependency. Sixty skin biopsy specimens were stained with the axonal marker PGP9.5 and imaged using a widefield fluorescence microscope. IENFD was first determined manually by 3 independent observers. Subsequently, images were processed in their Z-max projection and the intradermal line was delineated automatically. IENFD was calculated automatically (fluorescent images automated counting [FIAC]) and compared with manual counting on the same fluorescence images (fluorescent images manual counting [FIMC]), and with classical manual counting (CMC) data. A FIMC showed lower variability among observers compared with CMC (interclass correlation [ICC] = 0.996 vs 0.950). FIMC and FIAC showed high reliability (ICC = 0.999). A moderate-to-high (ICC = 0.705) was observed between CMC and FIAC counting. The algorithm process took on average 15\u2009seconds to perform FIAC counting, compared with 10\u2009minutes for FIMC counting. This automated method rapidly and reliably detects small nerve fibers in skin biopsies with clear advantages over the classical manual technique.<\/jats:p>","DOI":"10.1093\/jnen\/nlab045","type":"journal-article","created":{"date-parts":[[2021,5,27]],"date-time":"2021-05-27T02:49:34Z","timestamp":1622083774000},"page":"685-694","source":"Crossref","is-referenced-by-count":5,"title":["Advantages of an Automated Method Compared With Manual Methods for the Quantification of Intraepidermal Nerve Fiber in Skin Biopsy"],"prefix":"10.1093","volume":"80","author":[{"given":"Marta Francisca","family":"Corr\u00e0","sequence":"first","affiliation":[{"name":"From the Instituto de Ci\u00eancias Biom\u00e9dicas Abel Salazar (ICBAS), Universidade do Porto"}]},{"given":"Mafalda","family":"Sousa","sequence":"additional","affiliation":[{"name":"Instituto de investiga\u00e7\u00e3o e inova\u00e7\u00e3o em Sa\u00fade da Universidade do Porto (i3S) , Porto, Portugal"}]},{"given":"In\u00eas","family":"Reis","sequence":"additional","affiliation":[{"name":"Department of Neurology, Centro Hospitalar Universit\u00e1rio do Porto (CHUP)"}]},{"given":"Fabiana","family":"Tanganelli","sequence":"additional","affiliation":[{"name":"Department of Medicine IV, Geriatrics, University Hospital, LMU Munich , Munich, Germany"}]},{"given":"Nuno","family":"Vila-Ch\u00e3","sequence":"additional","affiliation":[{"name":"Department of Neurology, Centro Hospitalar Universit\u00e1rio do Porto (CHUP)"}]},{"given":"Ana Paula","family":"Sousa","sequence":"additional","affiliation":[{"name":"Department of Neurology, Centro Hospitalar Universit\u00e1rio do Porto (CHUP)"}]},{"given":"Rui","family":"Magalh\u00e3es","sequence":"additional","affiliation":[{"name":"Department of Neurology, Centro Hospitalar Universit\u00e1rio do Porto (CHUP)"}]},{"given":"Paula","family":"Sampaio","sequence":"additional","affiliation":[{"name":"Instituto de investiga\u00e7\u00e3o e inova\u00e7\u00e3o em Sa\u00fade da Universidade do Porto (i3S) , Porto, Portugal"}]},{"given":"Ricardo","family":"Taipa","sequence":"additional","affiliation":[{"name":"From the Instituto de Ci\u00eancias Biom\u00e9dicas Abel Salazar (ICBAS), Universidade do Porto"},{"name":"Department of Neurology, Centro Hospitalar Universit\u00e1rio do Porto (CHUP)"}]},{"given":"Lu\u00eds","family":"Maia","sequence":"additional","affiliation":[{"name":"From the Instituto de Ci\u00eancias Biom\u00e9dicas Abel Salazar (ICBAS), Universidade do Porto"},{"name":"Department of Neurology, Centro Hospitalar Universit\u00e1rio do Porto (CHUP)"},{"name":"Instituto de investiga\u00e7\u00e3o e inova\u00e7\u00e3o em Sa\u00fade da Universidade do Porto (i3S) , Porto, Portugal"}]}],"member":"286","published-online":{"date-parts":[[2021,5,26]]},"reference":[{"key":"2024032523402565000_nlab045-B1","doi-asserted-by":"crossref","first-page":"1059","DOI":"10.1097\/nen.0b013e31815c8989","article-title":"Assessment of epidermal nerve fibers: A new diagnostic and predictive tool for peripheral neuropathies","volume":"66","author":"Ebenezer","year":"2007","journal-title":"J Neuropathol Exp Neurol"},{"key":"2024032523402565000_nlab045-B2","doi-asserted-by":"crossref","first-page":"8796519","DOI":"10.1155\/2020\/8796519","article-title":"Small fiber neuropathy: Clinicopathological correlations","volume":"2020","author":"P\u00e1l","year":"2020","journal-title":"Behav Neurol"},{"key":"2024032523402565000_nlab045-B3","doi-asserted-by":"crossref","first-page":"1356","DOI":"10.1212\/WNL.0b013e3182a8236e","article-title":"Incidence and prevalence of small-fiber neuropathy: A survey in the Netherlands","volume":"81","author":"Peters","year":"2013","journal-title":"Neurology"},{"key":"2024032523402565000_nlab045-B4","doi-asserted-by":"crossref","first-page":"789","DOI":"10.1007\/s00415-005-0743-x","article-title":"A quantitative method for the assessment of intraepidermal nerve fibers in small-fiber neuropathy","volume":"252","author":"Koskinen","year":"2005","journal-title":"J Neurol"},{"key":"2024032523402565000_nlab045-B5","doi-asserted-by":"crossref","first-page":"546","DOI":"10.1038\/ncpneuro0630","article-title":"Skin biopsy as a diagnostic tool in peripheral neuropathy","volume":"3","author":"Lauria","year":"2007","journal-title":"Nat Clin Pract Neurol"},{"key":"2024032523402565000_nlab045-B6","doi-asserted-by":"crossref","first-page":"1159","DOI":"10.1136\/bmj.39192.488125.BE","article-title":"Skin biopsy: A new tool for diagnosing peripheral neuropathy","volume":"334","author":"Lauria","year":"2007","journal-title":"BMJ"},{"key":"2024032523402565000_nlab045-B7","doi-asserted-by":"crossref","first-page":"903","DOI":"10.1111\/j.1468-1331.2010.03023.x","article-title":"European Federation of Neurological Societies\/Peripheral Nerve Society Guideline on the use of skin biopsy in the diagnosis of small fiber neuropathy. 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