{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T06:38:05Z","timestamp":1791959885624,"version":"4.3.4"},"reference-count":75,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,8,10]],"date-time":"2021-08-10T00:00:00Z","timestamp":1628553600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,8,10]],"date-time":"2021-08-10T00:00:00Z","timestamp":1628553600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100010665","name":"H2020 Marie Sk\u0142odowska-Curie Actions","doi-asserted-by":"publisher","award":["752470"],"award-info":[{"award-number":["752470"]}],"id":[{"id":"10.13039\/100010665","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003196","name":"Italian Ministry of Health","doi-asserted-by":"crossref","award":["GR-2016-02361552"],"award-info":[{"award-number":["GR-2016-02361552"]}],"id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Intesa San Paolo S.p.A.","award":["B\/2018\/0061"],"award-info":[{"award-number":["B\/2018\/0061"]}]},{"name":"Regione Lombardia \u201cBANDO Call HUB Ricerca e Innovazione\u201d","award":["1157625"],"award-info":[{"award-number":["1157625"]}]},{"name":"Italian Ministry of Education, University and Research","award":["PRIN, grant 2017SNW5MB"],"award-info":[{"award-number":["PRIN, grant 2017SNW5MB"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Mol Neurodegeneration"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Amyotrophic lateral sclerosis (ALS) is a multifactorial, multisystem motor neuron disease for which currently there is no effective treatment. There is an urgent need to identify biomarkers to tackle the disease\u2019s complexity and help in early diagnosis, prognosis, and therapy. Extracellular vesicles (EVs) are nanostructures released by any cell type into body fluids. Their biophysical and biochemical characteristics vary with the parent cell\u2019s physiological and pathological state and make them an attractive source of multidimensional data for patient classification and stratification.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We analyzed plasma-derived EVs of ALS patients (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u2009106) and controls (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200996), and SOD1\n                      <jats:sup>G93A<\/jats:sup>\n                      and TDP-43\n                      <jats:sup>Q331K<\/jats:sup>\n                      mouse models of ALS. We purified plasma EVs by nickel-based isolation, characterized their EV size distribution and morphology respectively by nanotracking analysis and transmission electron microscopy, and analyzed EV markers and protein cargos by Western blot and proteomics. We used machine learning techniques to predict diagnosis and prognosis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Our procedure resulted in high-yield isolation of intact and polydisperse plasma EVs, with minimal lipoprotein contamination. EVs in the plasma of ALS patients and the two mouse models of ALS had a distinctive size distribution and lower HSP90 levels compared to the controls. In terms of disease progression, the levels of cyclophilin A with the EV size distribution distinguished fast and slow disease progressors, a possibly new means for patient stratification. Immuno-electron microscopy also suggested that phosphorylated TDP-43 is not an intravesicular cargo of plasma-derived EVs.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our analysis unmasked features in plasma EVs of ALS patients with potential straightforward clinical application. We conceived an innovative mathematical model based on machine learning which, by integrating EV size distribution data with protein cargoes, gave very high prediction rates for disease diagnosis and prognosis.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s13024-021-00470-3","type":"journal-article","created":{"date-parts":[[2021,8,10]],"date-time":"2021-08-10T05:03:38Z","timestamp":1628571818000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":47,"title":["Decoding distinctive features of plasma extracellular vesicles in amyotrophic lateral sclerosis"],"prefix":"10.1186","volume":"16","author":[{"given":"Laura","family":"Pasetto","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefano","family":"Callegaro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandro","family":"Corbelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabio","family":"Fiordaliso","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deborah","family":"Ferrara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Brunelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanna","family":"Sestito","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberta","family":"Pastorelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisa","family":"Bianchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina","family":"Cretich","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcella","family":"Chiari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Potrich","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Moglia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Massimo","family":"Corbo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gianni","family":"Sorar\u00f9","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Lunetta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Calvo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adriano","family":"Chi\u00f2","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriele","family":"Mora","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Pennuto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandro","family":"Quattrone","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Rinaldi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vito Giuseppe","family":"D\u2019Agostino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuela","family":"Basso","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0456-2054","authenticated-orcid":false,"given":"Valentina","family":"Bonetto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,8,10]]},"reference":[{"issue":"9","key":"470_CR1","doi-asserted-by":"publisher","first-page":"1097","DOI":"10.1001\/jamaneurol.2017.1387","volume":"74","author":"A Chi\u00f2","year":"2017","unstructured":"Chi\u00f2 A, Mora G, Moglia C, Manera U, Canosa A, Cammarosano S, et al. Secular trends of amyotrophic lateral sclerosis: the Piemonte and Valle d\u2019Aosta register. JAMA Neurol. 2017;74(9):1097\u2013104. https:\/\/doi.org\/10.1001\/jamaneurol.2017.1387.","journal-title":"JAMA Neurol"},{"issue":"1","key":"470_CR2","doi-asserted-by":"publisher","first-page":"17085","DOI":"10.1038\/nrdp.2017.85","volume":"3","author":"O Hardiman","year":"2017","unstructured":"Hardiman O, Al-Chalabi A, Chio A, Corr EM, Logroscino G, Robberecht W, et al. Amyotrophic lateral sclerosis. Nat Rev Dis Primer. 2017;3(1):17085. https:\/\/doi.org\/10.1038\/nrdp.2017.85.","journal-title":"Nat Rev Dis Primer"},{"issue":"7266","key":"470_CR3","doi-asserted-by":"publisher","first-page":"916","DOI":"10.1038\/nature08538","volume":"461","author":"RJ Perrin","year":"2009","unstructured":"Perrin RJ, Fagan AM, Holtzman DM. Multimodal techniques for diagnosis and prognosis of Alzheimer\u2019s disease. Nature. 2009;461(7266):916\u201322. https:\/\/doi.org\/10.1038\/nature08538.","journal-title":"Nature."},{"issue":"10","key":"470_CR4","doi-asserted-by":"publisher","first-page":"7789","DOI":"10.1007\/s12035-018-0947-6","volume":"55","author":"E Feneberg","year":"2018","unstructured":"Feneberg E, Gray E, Ansorge O, Talbot K, Turner MR. Towards a TDP-43-based biomarker for ALS and FTLD. Mol Neurobiol. 2018;55(10):7789\u2013801. https:\/\/doi.org\/10.1007\/s12035-018-0947-6.","journal-title":"Mol Neurobiol"},{"key":"470_CR5","doi-asserted-by":"publisher","first-page":"fcaa142","DOI":"10.1093\/braincomms\/fcaa142","volume":"2","author":"C Scial\u00f2","year":"2020","unstructured":"Scial\u00f2 C, Tran TH, Salzano G, Novi G, Caponnetto C, Chi\u00f2 A, et al. TDP-43 real-time quaking induced conversion reaction optimization and detection of seeding activity in CSF of amyotrophic lateral sclerosis and frontotemporal dementia patients. Brain Commun. 2020;2:fcaa142.","journal-title":"Brain Commun"},{"issue":"1","key":"470_CR6","doi-asserted-by":"publisher","first-page":"130","DOI":"10.1002\/ana.25276","volume":"84","author":"M Benatar","year":"2018","unstructured":"Benatar M, Wuu J, Andersen PM, Lombardi V, Malaspina A. Neurofilament light: a candidate biomarker of presymptomatic amyotrophic lateral sclerosis and phenoconversion. Ann Neurol. 2018;84(1):130\u20139. https:\/\/doi.org\/10.1002\/ana.25276.","journal-title":"Ann Neurol"},{"key":"470_CR7","doi-asserted-by":"publisher","unstructured":"Benatar M, Wuu J, Lombardi V, Jeromin A, Bowser R, Andersen PM, et al. Neurofilaments in pre-symptomatic ALS and the impact of genotype. Amyotroph Lateral Scler Front Degener. 2019;20(7-8):538\u201348. https:\/\/doi.org\/10.1080\/21678421.2019.1646769.","DOI":"10.1080\/21678421.2019.1646769"},{"issue":"10","key":"470_CR8","doi-asserted-by":"publisher","first-page":"1971","DOI":"10.1002\/acn3.50890","volume":"6","author":"M De Schaepdryver","year":"2019","unstructured":"De Schaepdryver M, Goossens J, De Meyer S, Jeromin A, Masrori P, Brix B, et al. Serum neurofilament heavy chains as early marker of motor neuron degeneration. Ann Clin Transl Neurol. 2019;6(10):1971\u20139. https:\/\/doi.org\/10.1002\/acn3.50890.","journal-title":"Ann Clin Transl Neurol"},{"issue":"8","key":"470_CR9","doi-asserted-by":"publisher","first-page":"870","DOI":"10.1136\/jnnp-2018-320106","volume":"90","author":"L Gaetani","year":"2019","unstructured":"Gaetani L, Blennow K, Calabresi P, Di Filippo M, Parnetti L, Zetterberg H. Neurofilament light chain as a biomarker in neurological disorders. J Neurol Neurosurg Psychiatry. 2019;90(8):870\u201381. https:\/\/doi.org\/10.1136\/jnnp-2018-320106.","journal-title":"J Neurol Neurosurg Psychiatry"},{"issue":"4","key":"470_CR10","doi-asserted-by":"publisher","first-page":"213","DOI":"10.1038\/nrm.2017.125","volume":"19","author":"G van Niel","year":"2018","unstructured":"van Niel G, D\u2019Angelo G, Raposo G. Shedding light on the cell biology of extracellular vesicles. Nat Rev Mol Cell Biol. 2018;19(4):213\u201328. https:\/\/doi.org\/10.1038\/nrm.2017.125.","journal-title":"Nat Rev Mol Cell Biol"},{"key":"470_CR11","doi-asserted-by":"publisher","first-page":"26913","DOI":"10.3402\/jev.v3.26913","volume":"3","author":"J L\u00f6tvall","year":"2014","unstructured":"L\u00f6tvall J, Hill AF, Hochberg F, Buz\u00e1s EI, Di Vizio D, Gardiner C, et al. Minimal experimental requirements for definition of extracellular vesicles and their functions: a position statement from the International Society for Extracellular Vesicles. J Extracell Vesicles. 2014;3:26913.","journal-title":"J Extracell Vesicles"},{"key":"470_CR12","doi-asserted-by":"publisher","first-page":"428","DOI":"10.1016\/j.cell.2019.02.029","volume":"177","author":"DK Jeppesen","year":"2019","unstructured":"Jeppesen DK, Fenix AM, Franklin JL, Higginbotham JN, Zhang Q, Zimmerman LJ, et al. Reassessment of exosome composition. Cell. 2019;177:428\u2013445.e18.","journal-title":"Cell"},{"key":"470_CR13","doi-asserted-by":"publisher","first-page":"127","DOI":"10.3389\/fnins.2016.00127","volume":"10","author":"M Basso","year":"2016","unstructured":"Basso M, Bonetto V. Extracellular vesicles and a novel form of communication in the brain. Front Neurosci. 2016;10:127.","journal-title":"Front Neurosci"},{"key":"470_CR14","doi-asserted-by":"publisher","first-page":"574","DOI":"10.3389\/fnins.2018.00574","volume":"12","author":"D Ferrara","year":"2018","unstructured":"Ferrara D, Pasetto L, Bonetto V, Basso M. Role of extracellular vesicles in amyotrophic lateral sclerosis. Front Neurosci. 2018;12:574. https:\/\/doi.org\/10.3389\/fnins.2018.00574.","journal-title":"Front Neurosci"},{"issue":"22","key":"470_CR15","doi-asserted-by":"publisher","first-page":"15699","DOI":"10.1074\/jbc.M112.425066","volume":"288","author":"M Basso","year":"2013","unstructured":"Basso M, Pozzi S, Tortarolo M, Fiordaliso F, Bisighini C, Pasetto L, et al. Mutant copper-zinc superoxide dismutase (SOD1) induces protein secretion pathway alterations and exosome release in astrocytes: implications for disease spreading and motor neuron pathology in amyotrophic lateral sclerosis. J Biol Chem. 2013;288(22):15699\u2013711. https:\/\/doi.org\/10.1074\/jbc.M112.425066.","journal-title":"J Biol Chem"},{"key":"470_CR16","doi-asserted-by":"publisher","first-page":"487","DOI":"10.3389\/fnins.2018.00487","volume":"12","author":"D Sproviero","year":"2018","unstructured":"Sproviero D, La Salvia S, Giannini M, Crippa V, Gagliardi S, Bernuzzi S, et al. Pathological proteins are transported by extracellular vesicles of sporadic amyotrophic lateral sclerosis patients. Front Neurosci. 2018;12:487. https:\/\/doi.org\/10.3389\/fnins.2018.00487.","journal-title":"Front Neurosci"},{"issue":"1","key":"470_CR17","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1186\/2045-8118-10-4","volume":"10","author":"AS Haqqani","year":"2013","unstructured":"Haqqani AS, Delaney CE, Tremblay T-L, Sodja C, Sandhu JK, Stanimirovic DB. Method for isolation and molecular characterization of extracellular microvesicles released from brain endothelial cells. Fluids Barriers CNS. 2013;10(1):4. https:\/\/doi.org\/10.1186\/2045-8118-10-4.","journal-title":"Fluids Barriers CNS"},{"key":"470_CR18","doi-asserted-by":"publisher","first-page":"8545347","DOI":"10.1155\/2018\/8545347","volume":"2018","author":"MY Konoshenko","year":"2018","unstructured":"Konoshenko MY, Lekchnov EA, Vlassov AV, Laktionov PP. Isolation of extracellular vesicles: general methodologies and latest trends. Biomed Res Int. 2018;2018:8545347.","journal-title":"Biomed Res Int"},{"key":"470_CR19","doi-asserted-by":"publisher","first-page":"114","DOI":"10.1016\/j.ebiom.2019.04.039","volume":"43","author":"M Notarangelo","year":"2019","unstructured":"Notarangelo M, Zucal C, Modelska A, Pesce I, Scarduelli G, Potrich C, et al. Ultrasensitive detection of cancer biomarkers by nickel-based isolation of polydisperse extracellular vesicles from blood. EBioMedicine. 2019;43:114\u201326. https:\/\/doi.org\/10.1016\/j.ebiom.2019.04.039.","journal-title":"EBioMedicine."},{"issue":"1","key":"470_CR20","doi-asserted-by":"publisher","first-page":"492","DOI":"10.1016\/j.neurobiolaging.2014.06.026","volume":"36","author":"M Marino","year":"2015","unstructured":"Marino M, Papa S, Crippa V, Nardo G, Peviani M, Cheroni C, et al. Differences in protein quality control correlate with phenotype variability in 2 mouse models of familial amyotrophic lateral sclerosis. Neurobiol Aging. 2015;36(1):492\u2013504. https:\/\/doi.org\/10.1016\/j.neurobiolaging.2014.06.026.","journal-title":"Neurobiol Aging"},{"issue":"8","key":"470_CR21","doi-asserted-by":"publisher","first-page":"E736","DOI":"10.1073\/pnas.1222809110","volume":"110","author":"ES Arnold","year":"2013","unstructured":"Arnold ES, Ling S-C, Huelga SC, Lagier-Tourenne C, Polymenidou M, Ditsworth D, et al. ALS-linked TDP-43 mutations produce aberrant RNA splicing and adult-onset motor neuron disease without aggregation or loss of nuclear TDP-43. Proc Natl Acad Sci U S A. 2013;110(8):E736\u201345. https:\/\/doi.org\/10.1073\/pnas.1222809110.","journal-title":"Proc Natl Acad Sci U S A"},{"key":"470_CR22","doi-asserted-by":"publisher","first-page":"e3512","DOI":"10.21769\/BioProtoc.3512","volume":"10","author":"M Notarangelo","year":"2020","unstructured":"Notarangelo M, Ferrara D, Potrich C, Lunelli L, Vanzetti L, Provenzani A, et al. Rapid nickel-based isolation of extracellular vesicles from different biological fluids. BIO-Protoc. 2020;10:e3512.","journal-title":"BIO-Protoc."},{"issue":"7","key":"470_CR23","doi-asserted-by":"publisher","first-page":"671","DOI":"10.1038\/nmeth.2089","volume":"9","author":"CA Schneider","year":"2012","unstructured":"Schneider CA, Rasband WS, Eliceiri KW. NIH image to ImageJ: 25 years of image analysis. Nat Methods. 2012;9(7):671\u20135. https:\/\/doi.org\/10.1038\/nmeth.2089.","journal-title":"Nat Methods"},{"key":"470_CR24","first-page":"1302","volume":"2013","author":"A Llorente","year":"1831","unstructured":"Llorente A, Skotland T, Sylv\u00e4nne T, Kauhanen D, R\u00f3g T, Or\u0142owski A, et al. Molecular lipidomics of exosomes released by PC-3 prostate cancer cells. Biochim Biophys Acta. 1831;2013:1302\u20139.","journal-title":"Biochim Biophys Acta"},{"issue":"1","key":"470_CR25","doi-asserted-by":"publisher","first-page":"32570","DOI":"10.3402\/jev.v5.32570","volume":"5","author":"RA Haraszti","year":"2016","unstructured":"Haraszti RA, Didiot M-C, Sapp E, Leszyk J, Shaffer SA, Rockwell HE, et al. High-resolution proteomic and lipidomic analysis of exosomes and microvesicles from different cell sources. J Extracell Vesicles. 2016;5(1):32570. https:\/\/doi.org\/10.3402\/jev.v5.32570.","journal-title":"J Extracell Vesicles"},{"issue":"8","key":"470_CR26","doi-asserted-by":"publisher","first-page":"2417","DOI":"10.1016\/j.jprot.2012.02.023","volume":"75","author":"L Brunelli","year":"2012","unstructured":"Brunelli L, Llansola M, Felipo V, Campagna R, Airoldi L, De Paola M, et al. Insight into the neuroproteomics effects of the food-contaminant non-dioxin like polychlorinated biphenyls. J Proteome. 2012;75(8):2417\u201330. https:\/\/doi.org\/10.1016\/j.jprot.2012.02.023.","journal-title":"J Proteome"},{"issue":"12","key":"470_CR27","doi-asserted-by":"publisher","first-page":"1367","DOI":"10.1038\/nbt.1511","volume":"26","author":"J Cox","year":"2008","unstructured":"Cox J, Mann M. MaxQuant enables high peptide identification rates, individualized p.p.b.-range mass accuracies and proteome-wide protein quantification. Nat Biotechnol. 2008;26(12):1367\u201372. https:\/\/doi.org\/10.1038\/nbt.1511.","journal-title":"Nat Biotechnol"},{"issue":"9","key":"470_CR28","doi-asserted-by":"publisher","first-page":"731","DOI":"10.1038\/nmeth.3901","volume":"13","author":"S Tyanova","year":"2016","unstructured":"Tyanova S, Temu T, Sinitcyn P, Carlson A, Hein MY, Geiger T, et al. The Perseus computational platform for comprehensive analysis of (prote) omics data. Nat Methods. 2016;13(9):731\u201340. https:\/\/doi.org\/10.1038\/nmeth.3901.","journal-title":"Nat Methods"},{"key":"470_CR29","doi-asserted-by":"publisher","unstructured":"Buhmann M. Radial Basis Functions: Theory and Implementations (Cambridge Monographs on Applied and Computational Mathematics). Cambridge: Cambridge University Press;\u00a02003. https:\/\/doi.org\/10.1017\/CBO9780511543241.","DOI":"10.1017\/CBO9780511543241"},{"issue":"1","key":"470_CR30","doi-asserted-by":"publisher","first-page":"243","DOI":"10.1016\/j.amc.2009.03.013","volume":"213","author":"A De Gaetano","year":"2009","unstructured":"De Gaetano A, Panunzi S, Rinaldi F, Risi A, Sciandrone M. A patient adaptable ECG beat classifier based on neural networks. Appl Math Comput. 2009;213(1):243\u20139. https:\/\/doi.org\/10.1016\/j.amc.2009.03.013.","journal-title":"Appl Math Comput"},{"issue":"2","key":"470_CR31","doi-asserted-by":"publisher","first-page":"405","DOI":"10.1109\/TKDE.2012.232","volume":"26","author":"S Barua","year":"2014","unstructured":"Barua S, Islam MM, Yao X, Murase K. MWMOTE\u2013majority weighted minority oversampling technique for imbalanced data set learning. IEEE Trans Knowl Data Eng. 2014;26(2):405\u201325. https:\/\/doi.org\/10.1109\/TKDE.2012.232.","journal-title":"IEEE Trans Knowl Data Eng"},{"issue":"4","key":"470_CR32","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1109\/MCI.2018.2866730","volume":"13","author":"MS Santos","year":"2018","unstructured":"Santos MS, Soraes J, Araujo H, Santos J. Cross-validation for imbalanced datasets: avoiding overoptimistic and Overfitting approaches [research frontier]. IEEE Comput Intell Mag. 2018;13(4):59\u201376. https:\/\/doi.org\/10.1109\/MCI.2018.2866730.","journal-title":"IEEE Comput Intell Mag"},{"key":"470_CR33","doi-asserted-by":"publisher","first-page":"102","DOI":"10.1111\/j.2517-6161.1976.tb01573.x","volume":"38","author":"M Stone","year":"1976","unstructured":"Stone M. Cross-Validatory choice and assessment of statistical predictions (with discussion). J R Stat Soc Ser B Methodol. 1976;38:102.","journal-title":"J R Stat Soc Ser B Methodol"},{"key":"470_CR34","doi-asserted-by":"publisher","unstructured":"Van Deun J, Mestdagh P, Sormunen R, Cocquyt V, Vermaelen K, Vandesompele J, et al. The impact of disparate isolation methods for extracellular vesicles on downstream RNA profiling. J Extracell Vesicles.\u00a02014;3. https:\/\/doi.org\/10.3402\/jev.v3.24858.","DOI":"10.3402\/jev.v3.24858."},{"issue":"1","key":"470_CR35","doi-asserted-by":"publisher","first-page":"1396823","DOI":"10.1080\/20013078.2017.1396823","volume":"6","author":"KW Witwer","year":"2017","unstructured":"Witwer KW, Soekmadji C, Hill AF, Wauben MH, Buz\u00e1s EI, Di Vizio D, et al. Updating the MISEV minimal requirements for extracellular vesicle studies: building bridges to reproducibility. J Extracell Vesicles. 2017;6(1):1396823. https:\/\/doi.org\/10.1080\/20013078.2017.1396823.","journal-title":"J Extracell Vesicles."},{"issue":"1","key":"470_CR36","doi-asserted-by":"publisher","first-page":"32945","DOI":"10.3402\/jev.v5.32945","volume":"5","author":"C Gardiner","year":"2016","unstructured":"Gardiner C, Di Vizio D, Sahoo S, Th\u00e9ry C, Witwer KW, Wauben M, et al. Techniques used for the isolation and characterization of extracellular vesicles: results of a worldwide survey. J Extracell Vesicles. 2016;5(1):32945. https:\/\/doi.org\/10.3402\/jev.v5.32945.","journal-title":"J Extracell Vesicles."},{"key":"470_CR37","doi-asserted-by":"publisher","unstructured":"Webber J, Clayton A. How pure are your vesicles? J Extracell Vesicles. 2013;2(1). https:\/\/doi.org\/10.3402\/jev.v2i0.19861.","DOI":"10.3402\/jev.v2i0.19861"},{"issue":"4","key":"470_CR38","doi-asserted-by":"publisher","first-page":"879","DOI":"10.1016\/j.nano.2015.01.003","volume":"11","author":"JZ Nordin","year":"2015","unstructured":"Nordin JZ, Lee Y, Vader P, M\u00e4ger I, Johansson HJ, Heusermann W, et al. Ultrafiltration with size-exclusion liquid chromatography for high yield isolation of extracellular vesicles preserving intact biophysical and functional properties. Nanomedicine Nanotechnol Biol Med. 2015;11(4):879\u201383. https:\/\/doi.org\/10.1016\/j.nano.2015.01.003.","journal-title":"Nanomedicine Nanotechnol Biol Med"},{"key":"470_CR39","doi-asserted-by":"publisher","unstructured":"Yuana Y, Levels J, Grootemaat A, Sturk A, Nieuwland R. Co-isolation of extracellular vesicles and high-density lipoproteins using density gradient ultracentrifugation. J Extracell Vesicles. 2014;3(1). https:\/\/doi.org\/10.3402\/jev.v3.23262.","DOI":"10.3402\/jev.v3.23262"},{"issue":"1","key":"470_CR40","doi-asserted-by":"publisher","first-page":"24316","DOI":"10.1038\/srep24316","volume":"6","author":"BW S\u00f3dar","year":"2016","unstructured":"S\u00f3dar BW, Kittel \u00c1, P\u00e1l\u00f3czi K, Vukman KV, Osteikoetxea X, Szab\u00f3-Taylor K, et al. Low-density lipoprotein mimics blood plasma-derived exosomes and microvesicles during isolation and detection. Sci Rep. 2016;6(1):24316. https:\/\/doi.org\/10.1038\/srep24316.","journal-title":"Sci Rep"},{"issue":"8","key":"470_CR41","doi-asserted-by":"publisher","first-page":"920","DOI":"10.1161\/CIRCRESAHA.117.311767","volume":"121","author":"JB Simonsen","year":"2017","unstructured":"Simonsen JB. What are we looking at? Extracellular vesicles, lipoproteins, or both? Circ Res. 2017;121(8):920\u20132. https:\/\/doi.org\/10.1161\/CIRCRESAHA.117.311767.","journal-title":"Circ Res"},{"issue":"12","key":"470_CR42","doi-asserted-by":"publisher","first-page":"e8130","DOI":"10.1371\/journal.pone.0008130","volume":"4","author":"M Basso","year":"2009","unstructured":"Basso M, Samengo G, Nardo G, Massignan T, D\u2019Alessandro G, Tartari S, et al. Characterization of detergent-insoluble proteins in ALS indicates a causal link between nitrative stress and aggregation in pathogenesis. PLoS One. 2009;4(12):e8130. https:\/\/doi.org\/10.1371\/journal.pone.0008130.","journal-title":"PLoS One"},{"key":"470_CR43","doi-asserted-by":"publisher","first-page":"99","DOI":"10.3389\/fnmol.2017.00099","volume":"10","author":"M Filareti","year":"2017","unstructured":"Filareti M, Luotti S, Pasetto L, Pignataro M, Paolella K, Messina P, et al. Decreased Levels of Foldase and chaperone proteins are associated with an early-onset amyotrophic lateral sclerosis. Front Mol Neurosci. 2017;10:99.","journal-title":"Front Mol Neurosci"},{"issue":"4","key":"470_CR44","doi-asserted-by":"publisher","first-page":"974","DOI":"10.1093\/brain\/awv005","volume":"138","author":"E Lauranzano","year":"2015","unstructured":"Lauranzano E, Pozzi S, Pasetto L, Stucchi R, Massignan T, Paolella K, et al. Peptidylprolyl isomerase a governs TARDBP function and assembly in heterogeneous nuclear ribonucleoprotein complexes. Brain. 2015;138(4):974\u201391. https:\/\/doi.org\/10.1093\/brain\/awv005.","journal-title":"Brain."},{"key":"470_CR45","doi-asserted-by":"publisher","first-page":"104815","DOI":"10.1016\/j.nbd.2020.104815","volume":"139","author":"S Luotti","year":"2020","unstructured":"Luotti S, Pasetto L, Porcu L, Torri V, Elezgarai SR, Pantalone S, et al. Diagnostic and prognostic values of PBMC proteins in amyotrophic lateral sclerosis. Neurobiol Dis. 2020;139:104815. https:\/\/doi.org\/10.1016\/j.nbd.2020.104815.","journal-title":"Neurobiol Dis"},{"issue":"23-24","key":"470_CR46","doi-asserted-by":"publisher","first-page":"3036","DOI":"10.1002\/elps.201800526","volume":"40","author":"S Ayala-Mar","year":"2019","unstructured":"Ayala-Mar S, Donoso-Quezada J, Gallo-Villanueva RC, Perez-Gonzalez VH, Gonz\u00e1lez-Valdez J. Recent advances and challenges in the recovery and purification of cellular exosomes. Electrophoresis. 2019;40(23-24):3036\u201349. https:\/\/doi.org\/10.1002\/elps.201800526.","journal-title":"Electrophoresis."},{"issue":"15","key":"470_CR47","doi-asserted-by":"publisher","first-page":"2873","DOI":"10.1007\/s00018-018-2773-4","volume":"75","author":"N Karimi","year":"2018","unstructured":"Karimi N, Cvjetkovic A, Jang SC, Crescitelli R, Hosseinpour Feizi MA, Nieuwland R, et al. Detailed analysis of the plasma extracellular vesicle proteome after separation from lipoproteins. Cell Mol Life Sci CMLS. 2018;75(15):2873\u201386. https:\/\/doi.org\/10.1007\/s00018-018-2773-4.","journal-title":"Cell Mol Life Sci CMLS"},{"issue":"7","key":"470_CR48","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.3000363","volume":"17","author":"L Margolis","year":"2019","unstructured":"Margolis L, Sadovsky Y. The biology of extracellular vesicles: the known unknowns. PLoS Biol. 2019;17(7):e3000363. https:\/\/doi.org\/10.1371\/journal.pbio.3000363.","journal-title":"PLoS Biol"},{"issue":"1","key":"470_CR49","doi-asserted-by":"publisher","first-page":"3854","DOI":"10.1038\/s41467-019-11486-1","volume":"10","author":"D Wu","year":"2019","unstructured":"Wu D, Yan J, Shen X, Sun Y, Thulin M, Cai Y, et al. Profiling surface proteins on individual exosomes using a proximity barcoding assay. Nat Commun. 2019;10(1):3854. https:\/\/doi.org\/10.1038\/s41467-019-11486-1.","journal-title":"Nat Commun"},{"issue":"1","key":"470_CR50","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1212\/WNL.0000000000001702","volume":"85","author":"EJ Goetzl","year":"2015","unstructured":"Goetzl EJ, Boxer A, Schwartz JB, Abner EL, Petersen RC, Miller BL, et al. Altered lysosomal proteins in neural-derived plasma exosomes in preclinical Alzheimer disease. Neurology. 2015;85(1):40\u20137. https:\/\/doi.org\/10.1212\/WNL.0000000000001702.","journal-title":"Neurology."},{"key":"470_CR51","doi-asserted-by":"publisher","first-page":"929","DOI":"10.3389\/fphys.2019.00929","volume":"10","author":"S Rome","year":"2019","unstructured":"Rome S, Forterre A, Mizgier ML, Bouzakri K. Skeletal muscle-released extracellular vesicles: state of the art. Front Physiol. 2019;10:929. https:\/\/doi.org\/10.3389\/fphys.2019.00929.","journal-title":"Front Physiol"},{"issue":"11","key":"470_CR52","doi-asserted-by":"publisher","first-page":"1584","DOI":"10.1038\/nn.4132","volume":"18","author":"H Asai","year":"2015","unstructured":"Asai H, Ikezu S, Tsunoda S, Medalla M, Luebke J, Haydar T, et al. Depletion of microglia and inhibition of exosome synthesis halt tau propagation. Nat Neurosci. 2015;18(11):1584\u201393. https:\/\/doi.org\/10.1038\/nn.4132.","journal-title":"Nat Neurosci"},{"issue":"6","key":"470_CR53","doi-asserted-by":"publisher","first-page":"836","DOI":"10.1016\/j.ccell.2016.10.009","volume":"30","author":"A Becker","year":"2016","unstructured":"Becker A, Thakur BK, Weiss JM, Kim HS, Peinado H, Lyden D. Extracellular vesicles in Cancer: cell-to-cell mediators of metastasis. Cancer Cell. 2016;30(6):836\u201348. https:\/\/doi.org\/10.1016\/j.ccell.2016.10.009.","journal-title":"Cancer Cell"},{"issue":"4","key":"470_CR54","doi-asserted-by":"publisher","first-page":"897","DOI":"10.1083\/jcb.201504057","volume":"211","author":"MS Feiler","year":"2015","unstructured":"Feiler MS, Strobel B, Freischmidt A, Helferich AM, Kappel J, Brewer BM, et al. TDP-43 is intercellularly transmitted across axon terminals. J Cell Biol. 2015;211(4):897\u2013911. https:\/\/doi.org\/10.1083\/jcb.201504057.","journal-title":"J Cell Biol"},{"issue":"139","key":"470_CR55","doi-asserted-by":"publisher","first-page":"3187","DOI":"10.1093\/brain\/aww237","volume":"2016","author":"Y Iguchi","year":"2016","unstructured":"Iguchi Y, Eid L, Parent M, Soucy G, Bareil C, Riku Y, et al. Exosome secretion is a key pathway for clearance of pathological TDP-43. Brain J Neurol. 2016;2016(139):3187\u2013201.","journal-title":"Brain J Neurol"},{"key":"470_CR56","first-page":"2004","volume":"2016","author":"M Kamelgarn","year":"1862","unstructured":"Kamelgarn M, Chen J, Kuang L, Arenas A, Zhai J, Zhu H, et al. Proteomic analysis of FUS interacting proteins provides insights into FUS function and its role in ALS. Biochim Biophys Acta. 1862;2016:2004\u201314.","journal-title":"Biochim Biophys Acta"},{"issue":"3","key":"470_CR57","doi-asserted-by":"publisher","first-page":"645","DOI":"10.1016\/j.celrep.2016.09.032","volume":"17","author":"T Westergard","year":"2016","unstructured":"Westergard T, Jensen BK, Wen X, Cai J, Kropf E, Iacovitti L, et al. Cell-to-cell transmission of dipeptide repeat proteins linked to C9orf72-ALS\/FTD. Cell Rep. 2016;17(3):645\u201352. https:\/\/doi.org\/10.1016\/j.celrep.2016.09.032.","journal-title":"Cell Rep"},{"issue":"1","key":"470_CR58","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1038\/s41593-018-0294-y","volume":"22","author":"F Laferri\u00e8re","year":"2019","unstructured":"Laferri\u00e8re F, Maniecka Z, P\u00e9rez-Berlanga M, Hruska-Plochan M, Gilhespy L, Hock E-M, et al. TDP-43 extracted from frontotemporal lobar degeneration subject brains displays distinct aggregate assemblies and neurotoxic effects reflecting disease progression rates. Nat Neurosci. 2019;22(1):65\u201377. https:\/\/doi.org\/10.1038\/s41593-018-0294-y.","journal-title":"Nat Neurosci"},{"issue":"8","key":"470_CR59","doi-asserted-by":"publisher","first-page":"e0236439","DOI":"10.1371\/journal.pone.0236439","volume":"15","author":"M Palviainen","year":"2020","unstructured":"Palviainen M, Saraswat M, Varga Z, Kitka D, Neuvonen M, Puhka M, et al. Extracellular vesicles from human plasma and serum are carriers of extravesicular cargo-implications for biomarker discovery. PLoS One. 2020;15(8):e0236439. https:\/\/doi.org\/10.1371\/journal.pone.0236439.","journal-title":"PLoS One"},{"issue":"38","key":"470_CR60","doi-asserted-by":"publisher","first-page":"14265","DOI":"10.1073\/pnas.0805135105","volume":"105","author":"M Lundqvist","year":"2008","unstructured":"Lundqvist M, Stigler J, Elia G, Lynch I, Cedervall T, Dawson KA. Nanoparticle size and surface properties determine the protein corona with possible implications for biological impacts. Proc Natl Acad Sci U S A. 2008;105(38):14265\u201370. https:\/\/doi.org\/10.1073\/pnas.0805135105.","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"5-6","key":"470_CR61","doi-asserted-by":"publisher","first-page":"351","DOI":"10.3109\/21678421.2014.905606","volume":"15","author":"E Feneberg","year":"2014","unstructured":"Feneberg E, Steinacker P, Lehnert S, Schneider A, Walther P, Thal DR, et al. Limited role of free TDP-43 as a diagnostic tool in neurodegenerative diseases. Amyotroph Lateral Scler Front Degener. 2014;15(5-6):351\u20136. https:\/\/doi.org\/10.3109\/21678421.2014.905606.","journal-title":"Amyotroph Lateral Scler Front Degener"},{"issue":"2","key":"470_CR62","doi-asserted-by":"publisher","first-page":"164","DOI":"10.1016\/j.tcb.2018.10.004","volume":"29","author":"T Mor\u00e1n Luengo","year":"2019","unstructured":"Mor\u00e1n Luengo T, Mayer MP, R\u00fcdiger SGD. The Hsp70-Hsp90 chaperone Cascade in protein folding. Trends Cell Biol. 2019;29(2):164\u201377. https:\/\/doi.org\/10.1016\/j.tcb.2018.10.004.","journal-title":"Trends Cell Biol"},{"issue":"2","key":"470_CR63","doi-asserted-by":"publisher","first-page":"215","DOI":"10.1136\/jnnp-2019-320624","volume":"91","author":"V Lombardi","year":"2020","unstructured":"Lombardi V, Bombaci A, Zampedri L, Lu C-H, Malik B, Zetterberg H, et al. Plasma pNfH levels differentiate SBMA from ALS. J Neurol Neurosurg Psychiatry. 2020;91(2):215\u20137. https:\/\/doi.org\/10.1136\/jnnp-2019-320624.","journal-title":"J Neurol Neurosurg Psychiatry"},{"issue":"5","key":"470_CR64","doi-asserted-by":"publisher","first-page":"565","DOI":"10.1136\/jnnp-2014-307672","volume":"86","author":"CH Lu","year":"2015","unstructured":"Lu CH, Petzold A, Topping J, Allen K, Macdonald-Wallis C, Clarke J, et al. Plasma neurofilament heavy chain levels and disease progression in amyotrophic lateral sclerosis: insights from a longitudinal study. J Neurol Neurosurg Psychiatry. 2015;86(5):565\u201373. https:\/\/doi.org\/10.1136\/jnnp-2014-307672.","journal-title":"J Neurol Neurosurg Psychiatry"},{"issue":"2","key":"470_CR65","doi-asserted-by":"publisher","first-page":"157","DOI":"10.1136\/jnnp-2018-318704","volume":"90","author":"F Verde","year":"2019","unstructured":"Verde F, Steinacker P, Weishaupt JH, Kassubek J, Oeckl P, Halbgebauer S, et al. Neurofilament light chain in serum for the diagnosis of amyotrophic lateral sclerosis. J Neurol Neurosurg Psychiatry. 2019;90(2):157\u201364. https:\/\/doi.org\/10.1136\/jnnp-2018-318704.","journal-title":"J Neurol Neurosurg Psychiatry"},{"issue":"1","key":"470_CR66","doi-asserted-by":"publisher","first-page":"e59","DOI":"10.1212\/WNL.0000000000009559","volume":"95","author":"M Benatar","year":"2020","unstructured":"Benatar M, Zhang L, Wang L, Granit V, Statland J, Barohn R, et al. Validation of serum neurofilaments as prognostic and potential pharmacodynamic biomarkers for ALS. Neurology. 2020;95(1):e59\u201369. https:\/\/doi.org\/10.1212\/WNL.0000000000009559.","journal-title":"Neurology."},{"key":"470_CR67","doi-asserted-by":"publisher","first-page":"135","DOI":"10.3389\/fnins.2019.00135","volume":"13","author":"V Grollemund","year":"2019","unstructured":"Grollemund V, Pradat P-F, Querin G, Delbot F, Le Chat G, Pradat-Peyre J-F, et al. Machine learning in amyotrophic lateral sclerosis: achievements, pitfalls, and future directions. Front Neurosci. 2019;13:135. https:\/\/doi.org\/10.3389\/fnins.2019.00135.","journal-title":"Front Neurosci"},{"issue":"11","key":"470_CR68","doi-asserted-by":"publisher","first-page":"866","DOI":"10.1002\/acn3.348","volume":"3","author":"AA Taylor","year":"2016","unstructured":"Taylor AA, Fournier C, Polak M, Wang L, Zach N, Keymer M, et al. Predicting disease progression in amyotrophic lateral sclerosis. Ann Clin Transl Neurol. 2016;3(11):866\u201375. https:\/\/doi.org\/10.1002\/acn3.348.","journal-title":"Ann Clin Transl Neurol."},{"issue":"12","key":"470_CR69","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.1005887","volume":"13","author":"Z Huang","year":"2017","unstructured":"Huang Z, Zhang H, Boss J, Goutman SA, Mukherjee B, Dinov ID, et al. Complete hazard ranking to analyze right-censored data: an ALS survival study. PLoS Comput Biol. 2017;13(12):e1005887. https:\/\/doi.org\/10.1371\/journal.pcbi.1005887.","journal-title":"PLoS Comput Biol"},{"key":"470_CR70","doi-asserted-by":"publisher","first-page":"36","DOI":"10.3389\/fninf.2018.00036","volume":"12","author":"SR Pfohl","year":"2018","unstructured":"Pfohl SR, Kim RB, Coan GS, Mitchell CS. Unraveling the complexity of amyotrophic lateral sclerosis survival prediction. Front Neuroinformatics. 2018;12:36. https:\/\/doi.org\/10.3389\/fninf.2018.00036.","journal-title":"Front Neuroinformatics"},{"issue":"10","key":"470_CR71","doi-asserted-by":"publisher","first-page":"3104","DOI":"10.1177\/0962280217693034","volume":"27","author":"H Seibold","year":"2018","unstructured":"Seibold H, Zeileis A, Hothorn T. Individual treatment effect prediction for amyotrophic lateral sclerosis patients. Stat Methods Med Res. 2018;27(10):3104\u201325. https:\/\/doi.org\/10.1177\/0962280217693034.","journal-title":"Stat Methods Med Res"},{"issue":"9","key":"470_CR72","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0044401","volume":"7","author":"N von Neuhoff","year":"2012","unstructured":"von Neuhoff N, Oumeraci T, Wolf T, Kollewe K, Bewerunge P, Neumann B, et al. Monitoring CSF proteome alterations in amyotrophic lateral sclerosis: obstacles and perspectives in translating a novel marker panel to the clinic. PLoS One. 2012;7(9):e44401. https:\/\/doi.org\/10.1371\/journal.pone.0044401.","journal-title":"PLoS One"},{"issue":"1","key":"470_CR73","doi-asserted-by":"publisher","first-page":"16334","DOI":"10.1038\/s41598-018-34642-x","volume":"8","author":"MS Bereman","year":"2018","unstructured":"Bereman MS, Beri J, Enders JR, Nash T. Machine learning reveals protein signatures in CSF and plasma fluids of clinical value for ALS. Sci Rep. 2018;8(1):16334. https:\/\/doi.org\/10.1038\/s41598-018-34642-x.","journal-title":"Sci Rep"},{"key":"470_CR74","doi-asserted-by":"publisher","unstructured":"Bendotti C, Bonetto V, Pupillo E, Logroscino G, Al-Chalabi A, Lunetta C, et al. Focus on the heterogeneity of amyotrophic lateral sclerosis. Amyotroph Lateral Scler Front Degener.\u00a02020;21(7-8):485-95. https:\/\/doi.org\/10.1080\/21678421.2020.1779298.","DOI":"10.1080\/21678421.2020.1779298"},{"issue":"8","key":"470_CR75","doi-asserted-by":"publisher","first-page":"440","DOI":"10.1038\/s41582-020-0377-8","volume":"16","author":"MA Myszczynska","year":"2020","unstructured":"Myszczynska MA, Ojamies PN, Lacoste AMB, Neil D, Saffari A, Mead R, et al. Applications of machine learning to diagnosis and treatment of neurodegenerative diseases. Nat Rev Neurol. 2020;16(8):440\u201356. https:\/\/doi.org\/10.1038\/s41582-020-0377-8.","journal-title":"Nat Rev Neurol"}],"updated-by":[{"DOI":"10.1186\/s13024-026-00955-z","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T00:00:00Z","timestamp":1779840000000}}],"container-title":["Molecular Neurodegeneration"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13024-021-00470-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s13024-021-00470-3","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13024-021-00470-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T10:28:07Z","timestamp":1779877687000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1186\/s13024-021-00470-3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,8,10]]},"references-count":75,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2021,12]]}},"alternative-id":["470"],"URL":"https:\/\/doi.org\/10.1186\/s13024-021-00470-3","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2020.08.06.20169300","asserted-by":"object"}]},"ISSN":["1750-1326"],"issn-type":[{"value":"1750-1326","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,8,10]]},"assertion":[{"value":"17 September 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"5 July 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"10 August 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"27 May 2026","order":5,"name":"change_date","label":"Change Date","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Correction","order":6,"name":"change_type","label":"Change Type","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"A Correction to this paper has been published:","order":7,"name":"change_details","label":"Change Details","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"https:\/\/doi.org\/10.1186\/s13024-026-00955-z","URL":"https:\/\/doi.org\/10.1186\/s13024-026-00955-z","order":8,"name":"change_details","label":"Change Details","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The study was performed according to the ethical principles of the Declaration of Helsinki and was approved by the local ethics committees. Written informed consent was obtained from all subjects.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"All authors have given their consent for publication.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"VDA and AQ declare competing interests for the patent application of the NBI procedure (WO2019122003).","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"52"}}