Elevated CSF and plasma complement proteins in genetic frontotemporal dementia: results from the GENFI study
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Data de Publicação: | 2022 |
Outros Autores: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/10451/54421 |
Resumo: | © The Author(s) 2022 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
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Elevated CSF and plasma complement proteins in genetic frontotemporal dementia: results from the GENFI studyBiomarkerComplementFrontotemporal dementiaNeuroinflammation© The Author(s) 2022 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.Background: Neuroinflammation is emerging as an important pathological process in frontotemporal dementia (FTD), but biomarkers are lacking. We aimed to determine the value of complement proteins, which are key components of innate immunity, as biomarkers in cerebrospinal fluid (CSF) and plasma of presymptomatic and symptomatic genetic FTD mutation carriers. Methods: We measured the complement proteins C1q and C3b in CSF by ELISAs in 224 presymptomatic and symptomatic GRN, C9orf72 or MAPT mutation carriers and non-carriers participating in the Genetic Frontotemporal Dementia Initiative (GENFI), a multicentre cohort study. Next, we used multiplex immunoassays to measure a panel of 14 complement proteins in plasma of 431 GENFI participants. We correlated complement protein levels with corresponding clinical and neuroimaging data, neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP). Results: CSF C1q and C3b, as well as plasma C2 and C3, were elevated in symptomatic mutation carriers compared to presymptomatic carriers and non-carriers. In genetic subgroup analyses, these differences remained statistically significant for C9orf72 mutation carriers. In presymptomatic carriers, several complement proteins correlated negatively with grey matter volume of FTD-related regions and positively with NfL and GFAP. In symptomatic carriers, correlations were additionally observed with disease duration and with Mini Mental State Examination and Clinical Dementia Rating scale® plus NACC Frontotemporal lobar degeneration sum of boxes scores. Conclusions: Elevated levels of CSF C1q and C3b, as well as plasma C2 and C3, demonstrate the presence of complement activation in the symptomatic stage of genetic FTD. Intriguingly, correlations with several disease measures in presymptomatic carriers suggest that complement protein levels might increase before symptom onset. Although the overlap between groups precludes their use as diagnostic markers, further research is needed to determine their potential to monitor dysregulation of the complement system in FTD.This study was supported in the Netherlands by Memorabel grants from Deltaplan Dementie (ZonMw and Alzheimer Nederland; grant numbers 733050813, 733050103, 733050513), the Bluefield Project to Cure Frontotemporal Dementia, the Dioraphte foundation (grant number 1402 1300), and the European Joint Programme—Neurodegenerative Disease Research and the Netherlands Organisation for Health Research and Development (PreFrontALS: 733051042, RiMod-FTD: 733051024); in Belgium by the Mady Browaeys Fonds voor Onderzoek naar Frontotemporale Degeneratie; in the UK by the MRC UK GENFI grant (MR/M023664/1) and the JPND GENFI-PROX grant (2019-02248); JDR is supported by an MRC Clinician Scientist Fellowship (MR/M008525/1) and has received funding from the NIHR Rare Disease Translational Research Collaboration (BRC149/NS/MH); ASE supported by the UK Dementia Research Institute which receives its funding from DRI Ltd, funded by the UK Medical Research Council, Alzheimer’s Society and Alzheimer’s Research UK; IJS is supported by the Alzheimer’s Association; JBR is supported by the Wellcome Trust (103838); in Spain by the Fundació Marató de TV3 (20143810 to RSV); in Germany by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany’s Excellence Strategy within the framework of the Munich Cluster for Systems Neurology (EXC 2145 SyNergy—ID 390857198) and by grant 779357 “Solve-RD” from the Horizon 2020 Research and Innovation Programme (to MS); in Sweden by grants from the Swedish FTD Initiative funded by the Schörling Foundation, grants from JPND PreFrontALS Swedish Research Council (VR) 529–2014-7504, Swedish Research Council (VR) 2015–02926, Swedish Research Council (VR) 2018–02754, Swedish Brain Foundation, Swedish Alzheimer Foundation, Stockholm County Council ALF, Swedish Demensfonden, Stohnes foundation, Gamla Tjänarinnor, Karolinska Institutet Doctoral Funding, and StratNeuro. HZ is a Wallenberg Scholar.Springer NatureRepositório da Universidade de Lisboavan der Ende, Emma L.Heller, CarolinSogorb-Esteve, AitanaSwift, Imogen J.McFall, DavidPeakman, GeorgiaBouzigues, ArabellaPoos, Jackie M.Jiskoot, Lize C.Panman, Jessica L.Papma, Janne M.Bargalló, NuriaRohrer, Jonathan D.Seelaar, HarroAfonso, SóniaAlmeida, Maria RosarioAnderl-Straub, SarahAndersson, ChristinAntonell, AnnaArchetti, SilvanaBartha, RobartIndakoetxea, BegoñaBender, BenjaminBenussi, AlbertoBenussi, LuisaBessi, ValentinaBinetti, GiulianoMead, SimonBlack, SandraBorrego-Ecija, SergiBras, JoseBruffaerts, RoseMitchell, SaraCañada, MartaCantoni, ValentinaCaroppo, PaolaCastelo-Branco, MiguelConvery, RhianMiltenberger-Miltenyi, GabrielCope, ThomasDi Fede, GiuseppeDíez, AlinaDuro, DianaJelic, VesnaFenoglio, ChiaraFerrari, CamillaFerreira, Catarina B.Fox, NickFreedman, MorrisFumagalli, Giorgiovan Minkelen, RickGabilondo, AlazneGasparotti, RobertoGauthier, SergeKarnath, Hans-OttoGazzina, StefanoGiaccone, GiorgioGorostidi, AnaGreaves, CarolineGuerreiro, RitaHoegen, TobiasKeren, RonLangheinrich, TobiasLeitão, Maria JoãoLladó, AlbertLombardi, GemmaLoosli, SandraTiraboschi, PietroMaruta, CarolinaMoore, KatrinaNacmias, BenedettaNicholas, JenniferÖijerstedt, LinnOlives, JaumeOurselin, SebastienMeeter, Lieke H.Padovani, AlessandroPievani, MichelaTodd, EmilyPolito, CristinaPremi, EnricoPrioni, SaraPrix, CatharinaRademakers, RosaRedaelli, VeronicaRittman, TimDopper, Elise G. P.Rogaeva, EkaterinaRosa-Neto, PedroRossi, GiacominaRosser, MartinSantiago, BeatrizScarpini, ElioSchönecker, SonjaSemler, ElisaShafei, RachelleShoesmith, ChristenBocchetta, MartinaTábuas-Pereira, MiguelVan Damme, PhilipTainta, MikelTaipa, RicardoTang-Wai, DavidThomas, David L.Thompson, PaulThonberg, HakanTimberlake, CarolynVandenbulcke, MathieuVeldsman, MicheleVerdelho, AnaVillanua, JorgeWarren, JasonWilke, CarloArighi, AndreaWoollacott, IoneWlasich, ElisabethZulaica, MirenCash, DavidGraff, CarolineSynofzik, MatthisMoreno, FerminFinger, ElizabethSanchez-Valle, RaquelVandenberghe, RikBalasa, MirceaLaforce, RobertMasellis, MarioTartaglia, Maria CarmelaRowe, James B.Butler, ChrisDucharme, SimonGerhard, AlexanderDanek, AdrianLevin, JohannesPijnenburg, Yolande A. L.Barandiaran, MyriamOtto, MarkusBorroni, BarbaraTagliavini, FabrizioDe Mendonça, AlexandreSantana, IsabelGalimberti, DanielaSorbi, SandroZetterberg, HenrikHuang, Ericvan Swieten, John C.2022-09-09T14:42:57Z20222022-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10451/54421eng10.1186/s12974-022-02573-01742-2094info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-11-08T17:00:45Zoai:repositorio.ul.pt:10451/54421Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T22:05:13.911929Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
Elevated CSF and plasma complement proteins in genetic frontotemporal dementia: results from the GENFI study |
title |
Elevated CSF and plasma complement proteins in genetic frontotemporal dementia: results from the GENFI study |
spellingShingle |
Elevated CSF and plasma complement proteins in genetic frontotemporal dementia: results from the GENFI study van der Ende, Emma L. Biomarker Complement Frontotemporal dementia Neuroinflammation |
title_short |
Elevated CSF and plasma complement proteins in genetic frontotemporal dementia: results from the GENFI study |
title_full |
Elevated CSF and plasma complement proteins in genetic frontotemporal dementia: results from the GENFI study |
title_fullStr |
Elevated CSF and plasma complement proteins in genetic frontotemporal dementia: results from the GENFI study |
title_full_unstemmed |
Elevated CSF and plasma complement proteins in genetic frontotemporal dementia: results from the GENFI study |
title_sort |
Elevated CSF and plasma complement proteins in genetic frontotemporal dementia: results from the GENFI study |
author |
van der Ende, Emma L. |
author_facet |
van der Ende, Emma L. Heller, Carolin Sogorb-Esteve, Aitana Swift, Imogen J. McFall, David Peakman, Georgia Bouzigues, Arabella Poos, Jackie M. Jiskoot, Lize C. Panman, Jessica L. Papma, Janne M. Bargalló, Nuria Rohrer, Jonathan D. Seelaar, Harro Afonso, Sónia Almeida, Maria Rosario Anderl-Straub, Sarah Andersson, Christin Antonell, Anna Archetti, Silvana Bartha, Robart Indakoetxea, Begoña Bender, Benjamin Benussi, Alberto Benussi, Luisa Bessi, Valentina Binetti, Giuliano Mead, Simon Black, Sandra Borrego-Ecija, Sergi Bras, Jose Bruffaerts, Rose Mitchell, Sara Cañada, Marta Cantoni, Valentina Caroppo, Paola Castelo-Branco, Miguel Convery, Rhian Miltenberger-Miltenyi, Gabriel Cope, Thomas Di Fede, Giuseppe Díez, Alina Duro, Diana Jelic, Vesna Fenoglio, Chiara Ferrari, Camilla Ferreira, Catarina B. Fox, Nick Freedman, Morris Fumagalli, Giorgio van Minkelen, Rick Gabilondo, Alazne Gasparotti, Roberto Gauthier, Serge Karnath, Hans-Otto Gazzina, Stefano Giaccone, Giorgio Gorostidi, Ana Greaves, Caroline Guerreiro, Rita Hoegen, Tobias Keren, Ron Langheinrich, Tobias Leitão, Maria João Lladó, Albert Lombardi, Gemma Loosli, Sandra Tiraboschi, Pietro Maruta, Carolina Moore, Katrina Nacmias, Benedetta Nicholas, Jennifer Öijerstedt, Linn Olives, Jaume Ourselin, Sebastien Meeter, Lieke H. Padovani, Alessandro Pievani, Michela Todd, Emily Polito, Cristina Premi, Enrico Prioni, Sara Prix, Catharina Rademakers, Rosa Redaelli, Veronica Rittman, Tim Dopper, Elise G. P. Rogaeva, Ekaterina Rosa-Neto, Pedro Rossi, Giacomina Rosser, Martin Santiago, Beatriz Scarpini, Elio Schönecker, Sonja Semler, Elisa Shafei, Rachelle Shoesmith, Christen Bocchetta, Martina Tábuas-Pereira, Miguel Van Damme, Philip Tainta, Mikel Taipa, Ricardo Tang-Wai, David Thomas, David L. Thompson, Paul Thonberg, Hakan Timberlake, Carolyn Vandenbulcke, Mathieu Veldsman, Michele Verdelho, Ana Villanua, Jorge Warren, Jason Wilke, Carlo Arighi, Andrea Woollacott, Ione Wlasich, Elisabeth Zulaica, Miren Cash, David Graff, Caroline Synofzik, Matthis Moreno, Fermin Finger, Elizabeth Sanchez-Valle, Raquel Vandenberghe, Rik Balasa, Mircea Laforce, Robert Masellis, Mario Tartaglia, Maria Carmela Rowe, James B. Butler, Chris Ducharme, Simon Gerhard, Alexander Danek, Adrian Levin, Johannes Pijnenburg, Yolande A. L. Barandiaran, Myriam Otto, Markus Borroni, Barbara Tagliavini, Fabrizio De Mendonça, Alexandre Santana, Isabel Galimberti, Daniela Sorbi, Sandro Zetterberg, Henrik Huang, Eric van Swieten, John C. |
author_role |
author |
author2 |
Heller, Carolin Sogorb-Esteve, Aitana Swift, Imogen J. McFall, David Peakman, Georgia Bouzigues, Arabella Poos, Jackie M. Jiskoot, Lize C. Panman, Jessica L. Papma, Janne M. Bargalló, Nuria Rohrer, Jonathan D. Seelaar, Harro Afonso, Sónia Almeida, Maria Rosario Anderl-Straub, Sarah Andersson, Christin Antonell, Anna Archetti, Silvana Bartha, Robart Indakoetxea, Begoña Bender, Benjamin Benussi, Alberto Benussi, Luisa Bessi, Valentina Binetti, Giuliano Mead, Simon Black, Sandra Borrego-Ecija, Sergi Bras, Jose Bruffaerts, Rose Mitchell, Sara Cañada, Marta Cantoni, Valentina Caroppo, Paola Castelo-Branco, Miguel Convery, Rhian Miltenberger-Miltenyi, Gabriel Cope, Thomas Di Fede, Giuseppe Díez, Alina Duro, Diana Jelic, Vesna Fenoglio, Chiara Ferrari, Camilla Ferreira, Catarina B. Fox, Nick Freedman, Morris Fumagalli, Giorgio van Minkelen, Rick Gabilondo, Alazne Gasparotti, Roberto Gauthier, Serge Karnath, Hans-Otto Gazzina, Stefano Giaccone, Giorgio Gorostidi, Ana Greaves, Caroline Guerreiro, Rita Hoegen, Tobias Keren, Ron Langheinrich, Tobias Leitão, Maria João Lladó, Albert Lombardi, Gemma Loosli, Sandra Tiraboschi, Pietro Maruta, Carolina Moore, Katrina Nacmias, Benedetta Nicholas, Jennifer Öijerstedt, Linn Olives, Jaume Ourselin, Sebastien Meeter, Lieke H. Padovani, Alessandro Pievani, Michela Todd, Emily Polito, Cristina Premi, Enrico Prioni, Sara Prix, Catharina Rademakers, Rosa Redaelli, Veronica Rittman, Tim Dopper, Elise G. P. Rogaeva, Ekaterina Rosa-Neto, Pedro Rossi, Giacomina Rosser, Martin Santiago, Beatriz Scarpini, Elio Schönecker, Sonja Semler, Elisa Shafei, Rachelle Shoesmith, Christen Bocchetta, Martina Tábuas-Pereira, Miguel Van Damme, Philip Tainta, Mikel Taipa, Ricardo Tang-Wai, David Thomas, David L. Thompson, Paul Thonberg, Hakan Timberlake, Carolyn Vandenbulcke, Mathieu Veldsman, Michele Verdelho, Ana Villanua, Jorge Warren, Jason Wilke, Carlo Arighi, Andrea Woollacott, Ione Wlasich, Elisabeth Zulaica, Miren Cash, David Graff, Caroline Synofzik, Matthis Moreno, Fermin Finger, Elizabeth Sanchez-Valle, Raquel Vandenberghe, Rik Balasa, Mircea Laforce, Robert Masellis, Mario Tartaglia, Maria Carmela Rowe, James B. Butler, Chris Ducharme, Simon Gerhard, Alexander Danek, Adrian Levin, Johannes Pijnenburg, Yolande A. L. Barandiaran, Myriam Otto, Markus Borroni, Barbara Tagliavini, Fabrizio De Mendonça, Alexandre Santana, Isabel Galimberti, Daniela Sorbi, Sandro Zetterberg, Henrik Huang, Eric van Swieten, John C. |
author2_role |
author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author |
dc.contributor.none.fl_str_mv |
Repositório da Universidade de Lisboa |
dc.contributor.author.fl_str_mv |
van der Ende, Emma L. Heller, Carolin Sogorb-Esteve, Aitana Swift, Imogen J. McFall, David Peakman, Georgia Bouzigues, Arabella Poos, Jackie M. Jiskoot, Lize C. Panman, Jessica L. Papma, Janne M. Bargalló, Nuria Rohrer, Jonathan D. Seelaar, Harro Afonso, Sónia Almeida, Maria Rosario Anderl-Straub, Sarah Andersson, Christin Antonell, Anna Archetti, Silvana Bartha, Robart Indakoetxea, Begoña Bender, Benjamin Benussi, Alberto Benussi, Luisa Bessi, Valentina Binetti, Giuliano Mead, Simon Black, Sandra Borrego-Ecija, Sergi Bras, Jose Bruffaerts, Rose Mitchell, Sara Cañada, Marta Cantoni, Valentina Caroppo, Paola Castelo-Branco, Miguel Convery, Rhian Miltenberger-Miltenyi, Gabriel Cope, Thomas Di Fede, Giuseppe Díez, Alina Duro, Diana Jelic, Vesna Fenoglio, Chiara Ferrari, Camilla Ferreira, Catarina B. Fox, Nick Freedman, Morris Fumagalli, Giorgio van Minkelen, Rick Gabilondo, Alazne Gasparotti, Roberto Gauthier, Serge Karnath, Hans-Otto Gazzina, Stefano Giaccone, Giorgio Gorostidi, Ana Greaves, Caroline Guerreiro, Rita Hoegen, Tobias Keren, Ron Langheinrich, Tobias Leitão, Maria João Lladó, Albert Lombardi, Gemma Loosli, Sandra Tiraboschi, Pietro Maruta, Carolina Moore, Katrina Nacmias, Benedetta Nicholas, Jennifer Öijerstedt, Linn Olives, Jaume Ourselin, Sebastien Meeter, Lieke H. Padovani, Alessandro Pievani, Michela Todd, Emily Polito, Cristina Premi, Enrico Prioni, Sara Prix, Catharina Rademakers, Rosa Redaelli, Veronica Rittman, Tim Dopper, Elise G. P. Rogaeva, Ekaterina Rosa-Neto, Pedro Rossi, Giacomina Rosser, Martin Santiago, Beatriz Scarpini, Elio Schönecker, Sonja Semler, Elisa Shafei, Rachelle Shoesmith, Christen Bocchetta, Martina Tábuas-Pereira, Miguel Van Damme, Philip Tainta, Mikel Taipa, Ricardo Tang-Wai, David Thomas, David L. Thompson, Paul Thonberg, Hakan Timberlake, Carolyn Vandenbulcke, Mathieu Veldsman, Michele Verdelho, Ana Villanua, Jorge Warren, Jason Wilke, Carlo Arighi, Andrea Woollacott, Ione Wlasich, Elisabeth Zulaica, Miren Cash, David Graff, Caroline Synofzik, Matthis Moreno, Fermin Finger, Elizabeth Sanchez-Valle, Raquel Vandenberghe, Rik Balasa, Mircea Laforce, Robert Masellis, Mario Tartaglia, Maria Carmela Rowe, James B. Butler, Chris Ducharme, Simon Gerhard, Alexander Danek, Adrian Levin, Johannes Pijnenburg, Yolande A. L. Barandiaran, Myriam Otto, Markus Borroni, Barbara Tagliavini, Fabrizio De Mendonça, Alexandre Santana, Isabel Galimberti, Daniela Sorbi, Sandro Zetterberg, Henrik Huang, Eric van Swieten, John C. |
dc.subject.por.fl_str_mv |
Biomarker Complement Frontotemporal dementia Neuroinflammation |
topic |
Biomarker Complement Frontotemporal dementia Neuroinflammation |
description |
© The Author(s) 2022 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
publishDate |
2022 |
dc.date.none.fl_str_mv |
2022-09-09T14:42:57Z 2022 2022-01-01T00:00:00Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
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publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10451/54421 |
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http://hdl.handle.net/10451/54421 |
dc.language.iso.fl_str_mv |
eng |
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eng |
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10.1186/s12974-022-02573-0 1742-2094 |
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info:eu-repo/semantics/openAccess |
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openAccess |
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application/pdf |
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Springer Nature |
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Springer Nature |
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