{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T02:33:06Z","timestamp":1789957986483,"version":"4.0.1"},"reference-count":82,"publisher":"Springer Science and Business Media LLC","issue":"3","license":[{"start":{"date-parts":[[2022,8,7]],"date-time":"2022-08-07T00:00:00Z","timestamp":1659830400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2022,8,7]],"date-time":"2022-08-07T00:00:00Z","timestamp":1659830400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Alma Mater Studiorum - Universit\u00e0 di Bologna"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Cell Mol Neurobiol"],"published-print":{"date-parts":[[2023,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Human cytomegalovirus (HCMV) causes congenital neurological lifelong disabilities. To date, the neuropathogenesis of brain injury related to congenital HCMV (cCMV) infection\u00a0is poorly understood. This study evaluates the characteristics and pathogenetic mechanisms of encephalic damage in cCMV infection. Ten HCMV-infected human fetuses at 21\u00a0weeks of gestation were examined. Specifically, tissues from different brain areas were analyzed by: (i) immunohistochemistry (IHC) to detect HCMV-infected cell distribution, (ii) hematoxylin\u2013eosin staining to evaluate histological damage and (iii) real-time PCR to quantify tissue viral load (HCMV-DNA). The differentiation stage of HCMV-infected neural\/neuronal cells was assessed by double IHC to detect simultaneously HCMV-antigens and neural\/neuronal markers: nestin (a marker of neural stem\/progenitor cells), doublecortin (DCX, marker of cells committed to the neuronal lineage) and neuronal nuclei (NeuN, identifying mature neurons). HCMV-positive cells and viral DNA were found in the brain of 8\/10 (80%) fetuses. For these cases, brain damage was classified as mild (<jats:italic>n<\/jats:italic>\u2009=\u20094, 50%), moderate (<jats:italic>n<\/jats:italic>\u2009=\u20093, 37.5%) and severe (<jats:italic>n<\/jats:italic>\u2009=\u20091, 12.5%) based on presence and frequency of pathological findings (necrosis, microglial nodules, microglial activation, astrocytosis, and vascular changes). The highest median HCMV-DNA level was found in the hippocampus (212 copies\/5\u00a0ng of human DNA [hDNA], range: 10\u20137,505) as well as the highest mean HCMV-infected cell value (2.9 cells, range: 0\u201323), followed by that detected in subventricular zone (1.7 cells, range: 0\u201319). These findings suggested a preferential viral tropism for both neural stem\/progenitor cells and neuronal committed cells, residing in these regions, confirmed by the expression of DCX and nestin in 94% and 63.3% of HCMV-positive cells, respectively. NeuN was not found among HCMV-positive cells and was nearly absent in the brain with severe damage, suggesting HCMV does not infect mature neurons and immature neural\/neuronal cells do not differentiate into neurons. This could lead to known structural and functional brain defects from cCMV infection.<\/jats:p>\n                <jats:p><jats:bold>Graphical Abstract<\/jats:bold><\/jats:p>","DOI":"10.1007\/s10571-022-01258-9","type":"journal-article","created":{"date-parts":[[2022,8,7]],"date-time":"2022-08-07T11:02:30Z","timestamp":1659870150000},"page":"1385-1399","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":34,"title":["Fetal Brain Damage in Human Fetuses with Congenital Cytomegalovirus Infection: Histological Features and Viral Tropism"],"prefix":"10.1007","volume":"43","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2596-2367","authenticated-orcid":false,"given":"Giulia","family":"Piccirilli","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5994-4749","authenticated-orcid":false,"given":"Liliana","family":"Gabrielli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4889-1944","authenticated-orcid":false,"given":"Maria Paola","family":"Bonasoni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7509-297X","authenticated-orcid":false,"given":"Angela","family":"Chiereghin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3662-570X","authenticated-orcid":false,"given":"Gabriele","family":"Turello","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9121-0430","authenticated-orcid":false,"given":"Eva Caterina","family":"Borgatti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7186-395X","authenticated-orcid":false,"given":"Giuliana","family":"Simonazzi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3820-1997","authenticated-orcid":false,"given":"Silvia","family":"Felici","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5394-0739","authenticated-orcid":false,"given":"Marta","family":"Leone","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4383-4972","authenticated-orcid":false,"given":"Nunzio Cosimo Mario","family":"Salfi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1692-6348","authenticated-orcid":false,"given":"Donatella","family":"Santini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3093-363X","authenticated-orcid":false,"given":"Tiziana","family":"Lazzarotto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,8,7]]},"reference":[{"key":"1258_CR1","doi-asserted-by":"publisher","first-page":"11159","DOI":"10.1128\/JVI.01742-15","volume":"89","author":"AA Berger","year":"2015","unstructured":"Berger AA, Gil Y, Panet A, Weisblum Y, Oiknine-Djian E, Gropp M, Steiner D, Reubinoff BE, Wolf DG (2015) Transition toward human cytomegalovirus susceptibility in early human embryonic stem cell-derived neural precursors. J Virol 89:11159\u201311164","journal-title":"J Virol"},{"issue":"12","key":"1258_CR2","doi-asserted-by":"publisher","first-page":"2177","DOI":"10.1007\/s00018-018-2794-z","volume":"75","author":"A Bernal","year":"2018","unstructured":"Bernal A, Arranz L (2018) Nestin-expressing progenitor cells: function, identity and therapeutic implications. Cell Mol Life Sci 75(12):2177\u20132195","journal-title":"Cell Mol Life Sci"},{"issue":"Suppl 4","key":"1258_CR3","doi-asserted-by":"publisher","first-page":"S178","DOI":"10.1093\/cid\/cit629","volume":"57","author":"SB Boppana","year":"2013","unstructured":"Boppana SB, Ross SA, Fowler KB (2013) Congenital cytomegalovirus infection: clinical outcome. Clin Infect Dis 57(Suppl 4):S178-181","journal-title":"Clin Infect Dis"},{"issue":"10","key":"1258_CR4","doi-asserted-by":"publisher","first-page":"1214","DOI":"10.1091\/mbc.E18-06-0361","volume":"30","author":"CJ Bott","year":"2019","unstructured":"Bott CJ, Johnson CG, Yap CC, Dwyer ND, Litwa KA, Winckler B (2019) Nestin in immature embryonic neurons affects axon growth cone morphology and Semaphorin3a sensitivity. Mol Biol Cell 30(10):1214\u20131229","journal-title":"Mol Biol Cell"},{"issue":"17","key":"1258_CR5","doi-asserted-by":"publisher","first-page":"e00957","DOI":"10.1128\/JVI.00957-19","volume":"93","author":"RM Brown","year":"2019","unstructured":"Brown RM, Rana PSJB, Jaeger HK, O\u2019Dowd JM, Balemba OB, Fortunato EA (2019) Human Cytomegalovirus compromises development of cerebral organoids. J Virol 93(17):e00957-e1019","journal-title":"J Virol"},{"issue":"1","key":"1258_CR6","first-page":"99","volume":"22","author":"MC Cheeran","year":"2009","unstructured":"Cheeran MC, Lokensgard JR, Schleiss MR (2009) Neuropathogenesis of congenital cytomegalovirus infection: disease mechanisms and prospects for intervention. ClinMicrobiol Rev 22(1):99\u2013126","journal-title":"ClinMicrobiol Rev"},{"issue":"5","key":"1258_CR7","first-page":"241","volume":"2","author":"X Chen","year":"2010","unstructured":"Chen X, Cho DB, Yang PC (2010) Double staining immunohistochemistry. N Am J Med Sci 2(5):241\u2013245","journal-title":"N Am J Med Sci"},{"key":"1258_CR8","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-019-1443-2)","author":"Z Chen","year":"2019","unstructured":"Chen Z, Zhong D, Li G (2019) The role of microglia in viral encephalitis: a review. J Neuroinflammation. https:\/\/doi.org\/10.1186\/s12974-019-1443-2)","journal-title":"J Neuroinflammation"},{"key":"1258_CR9","doi-asserted-by":"publisher","first-page":"296","DOI":"10.1016\/j.biomaterials.2015.02.094","volume":"53","author":"\u00c9 Cosset","year":"2015","unstructured":"Cosset \u00c9, Martinez Y, Preynat-Seauve O, Lobrinus JA, Tapparel C, Cordey S, Peterson H, Petty TJ, Colaianna M, Tieng V, Tirefort D, Dinnyes A, Dubois-Dauphin M, Kaiser L, Krause KH (2015) Human three-dimensional engineered neural tissue reveals cellular and molecular events following cytomegalovirus infection. Biomaterials 53:296\u2013308","journal-title":"Biomaterials"},{"issue":"4","key":"1258_CR10","doi-asserted-by":"publisher","first-page":"969","DOI":"10.1038\/ki.1989.80","volume":"35","author":"RS Cotran","year":"1989","unstructured":"Cotran RS, Pober JS (1989) Effects of cytokines on vascular endothelium: their role in vascular and immune injury. Kidney Int 35(4):969\u2013975","journal-title":"Kidney Int"},{"key":"1258_CR11","doi-asserted-by":"publisher","first-page":"e49700","DOI":"10.1371\/journal.pone.0049700","volume":"7","author":"L D'Aiuto","year":"2012","unstructured":"D\u2019Aiuto L, Di Maio R, Heath B, Raimondi G, Milosevic J, Watson AM, Bamne M, Parks WT, Yang L, Lin B, Miki T, Mich-Basso JD, Arav-Boger R, Sibille E, Sabunciyan S, Yolken R, Nimgaonkar V (2012) Human induced pluripotent stem cell-derived models to investigate human cytomegalovirus infection in neural cells. PLoS ONE 7:e49700","journal-title":"PLoS ONE"},{"issue":"4","key":"1258_CR12","doi-asserted-by":"publisher","first-page":"297","DOI":"10.1136\/jnnp.48.4.297","volume":"48","author":"AR Damasio","year":"1985","unstructured":"Damasio AR, Van Hoesen GW (1985) The limbic system and the localisation of herpes simplex encephalitis. J Neurol Neurosurg Psychiatry 48(4):297\u2013301","journal-title":"J Neurol Neurosurg Psychiatry"},{"key":"1258_CR13","doi-asserted-by":"publisher","first-page":"235","DOI":"10.3389\/fncel.2017.00235","volume":"11","author":"MDM Fern\u00e1ndez-Arjona","year":"2017","unstructured":"Fern\u00e1ndez-Arjona MDM, Grondona JM, Granados-Dur\u00e1n P, Fern\u00e1ndez-Llebrez P, L\u00f3pez-\u00c1valos MD (2017) Microglia morphological categorization in a rat model of neuroinflammation by hierarchical cluster and principal components analysis. Front Cell Neurosci 11:235","journal-title":"Front Cell Neurosci"},{"issue":"7","key":"1258_CR14","doi-asserted-by":"publisher","first-page":"1779","DOI":"10.1148\/rg.307105043","volume":"30","author":"KR Fink","year":"2010","unstructured":"Fink KR, Thapa MM, Ishak GE, Pruthi S (2010) Neuroimaging of pediatric central nervous system cytomegalovirus infection. Radiographics 30(7):1779\u20131796","journal-title":"Radiographics"},{"key":"1258_CR15","doi-asserted-by":"publisher","first-page":"1008","DOI":"10.1001\/jama.289.8.1008","volume":"289","author":"KB Fowler","year":"2003","unstructured":"Fowler KB, Stagno S, Pass RF (2003) Maternal immunity and prevention of congenital cytomegalovirus infection. JAMA 289:1008\u20131011","journal-title":"JAMA"},{"issue":"5","key":"1258_CR16","doi-asserted-by":"publisher","first-page":"779","DOI":"10.3390\/microorganisms8050779","volume":"8","author":"L Gabrielli","year":"2020","unstructured":"Gabrielli L, Bonasoni MP, Chiereghin A, Piccirilli G, Borgatti EC, Simonazzi G, Salfi NCM, Tamagnini I, Lazzarotto T (2020) Pathophysiology of hyperechogenic bowel in congenitally human cytomegalovirus infected fetuses. Microorganisms 8(5):779","journal-title":"Microorganisms"},{"issue":"2","key":"1258_CR17","doi-asserted-by":"publisher","first-page":"318","DOI":"10.1002\/jmv.24628","volume":"89","author":"L Gabrielli","year":"2017","unstructured":"Gabrielli L, Bonasoni MP, Chiereghin A, Piccirilli G, Santini D, Pavia C, Turello G, Squarzoni D, Lazzarotto T (2017) Salivary glands and human congenital cytomegalovirus infection: what happens in early fetal life? J Med Virol 89(2):318\u2013323","journal-title":"J Med Virol"},{"issue":"2","key":"1258_CR18","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1159\/000487302","volume":"45","author":"L Gabrielli","year":"2019","unstructured":"Gabrielli L, Bonasoni MP, Foschini MP, Silini EM, Spinillo A, Revello MG, Chiereghin A, Piccirilli G, Petrisli E, Turello G, Simonazzi G, Gibertoni D, Lazzarotto T (2019) Histological analysis of term placentas from hyperimmune globulin-treated and untreated mothers with primary cytomegalovirus infection. Fetal Diagn Ther 45(2):111\u2013117","journal-title":"Fetal Diagn Ther"},{"key":"1258_CR19","first-page":"S16","volume":"46","author":"L Gabrielli","year":"2009","unstructured":"Gabrielli L, Bonasoni MP, Lazzarotto T, Lega S, Santini D, Foschini MP, Guerra B, Baccolini F, Piccirilli G, Chiereghin A, Petrisli E, Gardini G, Lanari M, Landini MP (2009) Histological findings in fetuses congenitally infected by cytomegalovirus. J ClinVirol 46:S16-21","journal-title":"J ClinVirol"},{"key":"1258_CR20","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1186\/2051-5960-1-63","volume":"1","author":"L Gabrielli","year":"2013","unstructured":"Gabrielli L, Bonasoni MP, Santini D, Piccirilli G, Chiereghin A, Guerra B, Landini MP, Capretti MG, Lanari M, Lazzarotto T (2013) Human fetal inner ear involvement in congenital cytomegalovirus infection. Acta Neuropathol Commun 1:63","journal-title":"Acta Neuropathol Commun"},{"issue":"10","key":"1258_CR21","doi-asserted-by":"publisher","first-page":"E419","DOI":"10.1111\/j.1469-0691.2012.03983.x","volume":"18","author":"L Gabrielli","year":"2012","unstructured":"Gabrielli L, Bonasoni MP, Santini D, Piccirilli G, Chiereghin A, Petrisli E, Dolcetti R, Guerra B, Piccioli M, Lanari M, Landini MP, Lazzarotto T (2012) Congenital citomegalovirus infection: patterns of fetal brain damage. Clin Microbiol Infect 18(10):E419-427","journal-title":"Clin Microbiol Infect"},{"key":"1258_CR22","doi-asserted-by":"publisher","first-page":"245","DOI":"10.1097\/00006254-200204000-00024","volume":"57","author":"MA Gaytant","year":"2002","unstructured":"Gaytant MA, Steegers EA, Semmekrot BA, Merkus HM, Galama JM (2002) Congenital cytomegalovirus infection: review of the epidemiology and outcome. Obstet Gynecol Surv 57:245\u2013256","journal-title":"Obstet Gynecol Surv"},{"issue":"1","key":"1258_CR23","doi-asserted-by":"publisher","first-page":"86","DOI":"10.1016\/0002-9378(89)90093-8","volume":"160","author":"A Ghidini","year":"1989","unstructured":"Ghidini A, Sirtori M, Vergani P, Mariani S, Tucci E, Scola GC (1989) Fetal intracranial calcifications. Am J Obstet Gynecol 160(1):86\u201387","journal-title":"Am J Obstet Gynecol"},{"issue":"4","key":"1258_CR24","doi-asserted-by":"publisher","first-page":"346","DOI":"10.1007\/s13365-015-0315-5","volume":"21","author":"HM Gonz\u00e1lez-S\u00e1nchez","year":"2015","unstructured":"Gonz\u00e1lez-S\u00e1nchez HM, Monsiv\u00e1is-Urenda A, Salazar-Aldrete CA, Hern\u00e1ndez-Salinas A, Noyola DE, Jim\u00e9nez-Capdeville ME, Mart\u00ednez-Serrano A, Castillo CG (2015) Effects of cytomegalovirus infection in human neural precursor cells depend on their differentiation state. J Neurovirol 21(4):346\u2013357","journal-title":"J Neurovirol"},{"key":"1258_CR25","doi-asserted-by":"publisher","first-page":"380.e1","DOI":"10.1016\/j.ajog.2007.09.052","volume":"198","author":"B Guerra","year":"2008","unstructured":"Guerra B, Simonazzi G, Puccetti C, Lanari M, Farina A, Lazzarotto T, Rizzo N (2008) Ultrasound prediction of symptomatic congenital citomegalovirus infection. Am J Obstet Gynecol 198:380.e1\u20137","journal-title":"Am J Obstet Gynecol"},{"issue":"2","key":"1258_CR26","doi-asserted-by":"publisher","first-page":"154","DOI":"10.1016\/j.nbd.2009.02.008","volume":"38","author":"R Guerrini","year":"2010","unstructured":"Guerrini R, Parrini E (2010) Neuronal migration disorders. Neurobiol Dis 38(2):154\u2013166","journal-title":"Neurobiol Dis"},{"issue":"2","key":"1258_CR27","doi-asserted-by":"publisher","first-page":"42","DOI":"10.32607\/20758251-2015-7-2-42-47","volume":"7","author":"VV Gusel'nikova","year":"2015","unstructured":"Gusel\u2019nikova VV, Korzhevskiy DE (2015) NeuN as a neuronal nuclear antigen and neuron differentiation marker. Acta Naturae 7(2):42\u201347","journal-title":"Acta Naturae"},{"issue":"17","key":"1258_CR28","doi-asserted-by":"publisher","first-page":"e00799","DOI":"10.1128\/JVI.00799-17","volume":"91","author":"D Han","year":"2017","unstructured":"Han D, Byun SH, Kim J, Kwon M, Pleasure SJ, Ahn JH, Yoon K (2017) Human cytomegalovirus IE2 protein disturbs brain development by the dysregulation of neural stem cell maintenance and the polarization of migrating neurons. J Virol 91(17):e00799-e817","journal-title":"J Virol"},{"key":"1258_CR29","doi-asserted-by":"publisher","first-page":"48","DOI":"10.3389\/fnagi.2018.00048","volume":"10","author":"SA Harris","year":"2018","unstructured":"Harris SA, Harris EA (2018) Molecular mechanisms for herpes simplex virus type 1 pathogenesis in Alzheimer\u2019s disease. Front Aging Neurosci 10:48","journal-title":"Front Aging Neurosci"},{"issue":"13","key":"1258_CR30","doi-asserted-by":"publisher","first-page":"7286","DOI":"10.1128\/JVI.02501-06","volume":"81","author":"WS Ho","year":"2007","unstructured":"Ho WS, van den Pol AN (2007) Bystander attenuation of neuronal and astrocyte intercellular communication by murine cytomegalovirus infection of glia. J Virol 81(13):7286\u20137292","journal-title":"J Virol"},{"key":"1258_CR31","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.826091","volume":"13","author":"AO Ihunwo","year":"2022","unstructured":"Ihunwo AO, Perego J, Martino G, Vicenzi E, Panina-Bordignon P (2022) Neurogenesis and viral infection. Front Immunol 13:826091. https:\/\/doi.org\/10.3389\/fimmu.2022.826091","journal-title":"Front Immunol"},{"issue":"8","key":"1258_CR32","doi-asserted-by":"publisher","first-page":"1468","DOI":"10.3390\/v13081468","volume":"13","author":"YS Kamte","year":"2021","unstructured":"Kamte YS, Chandwani MN, Michaels AC, O\u2019Donnell LA (2021) Neural stem cells: what happens when they go viral? Viruses 13(8):1468","journal-title":"Viruses"},{"issue":"8","key":"1258_CR33","doi-asserted-by":"publisher","first-page":"447","DOI":"10.1016\/j.tins.2004.05.013","volume":"27","author":"G Kempermann","year":"2004","unstructured":"Kempermann G, Jessberger S, Steiner B, Kronenberg G (2004) Milestones of neuronal development in the adult hippocampus. Trends Neurosci 27(8):447\u2013452","journal-title":"Trends Neurosci"},{"key":"1258_CR34","doi-asserted-by":"publisher","first-page":"253","DOI":"10.1002\/rmv.535","volume":"17","author":"A Kenneson","year":"2007","unstructured":"Kenneson A, Cannon MJ (2007) Review and meta-analysis of the epidemiology of congenital cytomegalovirus (CMV) infection. Rev Med Virol 17:253\u2013257","journal-title":"Rev Med Virol"},{"issue":"42","key":"1258_CR35","doi-asserted-by":"publisher","first-page":"17916","DOI":"10.1073\/pnas.0908892106","volume":"106","author":"SJ Kopp","year":"2009","unstructured":"Kopp SJ, Banisadr G, Glajch K, Maurer UE, Gr\u00fcnewald K, Miller RJ, Osten P, Spear PG (2009) Infection of neurons and encephalitis after intracranial inoculation of herpes simplex virus requires the entry receptor nectin-1. Proc Natl Acad Sci USA 106(42):17916\u201317920","journal-title":"Proc Natl Acad Sci USA"},{"issue":"6","key":"1258_CR36","doi-asserted-by":"publisher","first-page":"1078","DOI":"10.3390\/v13061078","volume":"13","author":"F Krstanovi\u0107","year":"2021","unstructured":"Krstanovi\u0107 F, Britt WJ, Jonji\u0107 S, Brizi\u0107 I (2021) cytomegalovirus infection and inflammation in developing brain. Viruses 13(6):1078","journal-title":"Viruses"},{"key":"1258_CR37","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1016\/j.pediatrneurol.2018.03.008","volume":"83","author":"M Kwak","year":"2018","unstructured":"Kwak M, Yum MS, Yeh HR, Kim HJ, Ko TS (2018) Brain magnetic resonance imaging findings of congenital cytomegalovirus infection as a prognostic factor for neurological outcome. Pediatr Neurol 83:14\u201318","journal-title":"Pediatr Neurol"},{"key":"1258_CR38","doi-asserted-by":"publisher","first-page":"1019","DOI":"10.1097\/00002030-200205030-00008","volume":"16","author":"Langford TD, Letendre SL, Marcotte TD, Ellis RJ, McCutchan JA, Grant I, Mallory ME, Hansen LA, Archibald S, Jernigan T, Masliah E; HNRC Group","year":"2002","unstructured":"Langford TD, Letendre SL, Marcotte TD, Ellis RJ, McCutchan JA, Grant I, Mallory ME, Hansen LA, Archibald S, Jernigan T, Masliah E; HNRC Group (2002) Severe, demyelinating leukoencephalopathy in AIDS patients on antiretroviral therapy. AIDS 16:1019\u20131029","journal-title":"AIDS"},{"issue":"3","key":"1258_CR39","doi-asserted-by":"publisher","first-page":"376","DOI":"10.1007\/s13365-016-0504-x","volume":"23","author":"R Lathe","year":"2017","unstructured":"Lathe R, Haas JG (2017) Distribution of cellular HSV-1 receptor expression in human brain. J Neurovirol 23(3):376\u2013384","journal-title":"J Neurovirol"},{"issue":"1\u20132","key":"1258_CR40","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1016\/j.jns.2013.03.012","volume":"329","author":"AM Lavezzi","year":"2013","unstructured":"Lavezzi AM, Corna MF, Matturri L (2013) Neuronal nuclear antigen (NeuN): a useful marker of neuronal immaturity in sudden unexplained perinatal death. J Neurol Sci 329(1\u20132):45\u201350","journal-title":"J Neurol Sci"},{"issue":"16","key":"1258_CR41","doi-asserted-by":"publisher","first-page":"8876","DOI":"10.3390\/ijms22168876","volume":"22","author":"P Layrolle","year":"2021","unstructured":"Layrolle P, Payoux P, Chavanas S (2021) PPAR Gamma and viral infections of the brain. Int J Mol Sci 22(16):8876","journal-title":"Int J Mol Sci"},{"key":"1258_CR42","doi-asserted-by":"publisher","first-page":"34","DOI":"10.3109\/00365513.2014.936679","volume":"244","author":"T Lazzarotto","year":"2014","unstructured":"Lazzarotto T, Gabrielli L, Guerra B, Cervi F, Piccirilli G, Simonazzi G, Chiereghin A, Bellini F, Landini MP (2014) Diagnosis and prognosis of congenital CMV infection: a case report and review of the literature. Scand J Clin Lab Invest Suppl 244:34\u201340","journal-title":"Scand J Clin Lab Invest Suppl"},{"issue":"3","key":"1258_CR43","doi-asserted-by":"publisher","first-page":"330","DOI":"10.1016\/j.ajog.2020.02.018","volume":"223","author":"M Leruez-Ville","year":"2020","unstructured":"Leruez-Ville M, Foulon I, Pass R, Ville Y (2020) Cytomegalovirus infection during pregnancy: state of the science. Am J Obstet Gynecol 223(3):330\u2013349","journal-title":"Am J Obstet Gynecol"},{"key":"1258_CR44","doi-asserted-by":"publisher","first-page":"209","DOI":"10.1016\/S0147-9563(98)90009-7","volume":"27","author":"RE Levitz","year":"1998","unstructured":"Levitz RE (1998) Herpes simplex encephalitis: a review. Heart Lung 27:209\u2013212","journal-title":"Heart Lung"},{"issue":"6","key":"1258_CR45","doi-asserted-by":"publisher","first-page":"552","DOI":"10.1007\/s12250-009-3019-2","volume":"24","author":"L Li","year":"2009","unstructured":"Li L, Wang B, Li P, Bai ZQ, Wang HT, Song XX, Ding SY (2009) Human cytomegalovirus infection inhibits the differentiation of human hippocampus neural precursor cells into astrocytes. Virol Sin 24(6):552","journal-title":"Virol Sin"},{"key":"1258_CR46","first-page":"91","volume":"2","author":"JR Lokensgard","year":"1999","unstructured":"Lokensgard JR, Cheeran MC, Gekker G, Hu S, Chao CC, Peterson PK (1999) Human cytomegalovirus replication and modulation of apoptosis in astrocytes. J Hum Virol 2:91\u2013101","journal-title":"J Hum Virol"},{"issue":"2","key":"1258_CR47","doi-asserted-by":"publisher","first-page":"159","DOI":"10.1007\/s00401-015-1511-3","volume":"131","author":"M Ludlow","year":"2016","unstructured":"Ludlow M, Kortekaas J, Herden C, Hoffmann B, Tappe D, Trebst C, Griffin DE, Brindle HE, Solomon T, Brown AS, van Riel D, Wolthers KC, Pajkrt D, Wohlsein P, Martina BEE, Baumg\u00e4rtner W, Verjans GM, Osterhaus ADME (2016) Neurotropic virus infections as the cause of immediate and delayed neuropathology. Acta Neuropathol 131(2):159\u2013184","journal-title":"Acta Neuropathol"},{"key":"1258_CR48","doi-asserted-by":"publisher","first-page":"3528","DOI":"10.1128\/JVI.02161-09","volume":"84","author":"MH Luo","year":"2010","unstructured":"Luo MH, Hannemann H, Kulkarni AS, Schwartz PH, O\u2019Dowd JM, Fortunato EA (2010) Human cytomegalovirus infection causes premature and abnormal differentiation of human neural progenitor cells. J Virol 84:3528\u20133541","journal-title":"J Virol"},{"issue":"20","key":"1258_CR49","doi-asserted-by":"publisher","first-page":"9994","DOI":"10.1128\/JVI.00943-08","volume":"82","author":"MH Luo","year":"2008","unstructured":"Luo MH, Schwartz PH, Fortunato EA (2008) Neonatal neural progenitor cells and their neuronal and glial cell derivatives are fully permissive for human cytomegalovirus infection. J Virol 82(20):9994\u201310007","journal-title":"J Virol"},{"key":"1258_CR50","doi-asserted-by":"publisher","first-page":"134","DOI":"10.3389\/fped.2017.00134","volume":"5","author":"I Mack","year":"2017","unstructured":"Mack I, Burckhardt MA, Heininger U, Pr\u00fcfer F, Schulzke S, Wellmann S (2017) symptomatic congenital cytomegalovirus infection in children of seropositive women. Front Pediatr 5:134","journal-title":"Front Pediatr"},{"issue":"1","key":"1258_CR51","first-page":"28","volume":"24","author":"G Malinger","year":"2003","unstructured":"Malinger G, Lev D, Zahalka N, Ben Aroia Z, Watemberg N, Kidron D, Sira LB, Lerman-Sagie T (2003) Fetal cytomegalovirus infection of the brain: the spectrum of sonographic findings. AJNR Am J Neuroradiol 24(1):28\u201332","journal-title":"AJNR Am J Neuroradiol"},{"key":"1258_CR52","doi-asserted-by":"publisher","first-page":"86","DOI":"10.1128\/CMR.00062-12","volume":"26","author":"S Manicklal","year":"2013","unstructured":"Manicklal S, Emery VC, Lazzarotto T, Boppana SB, Gupta RK (2013) The \u201csilent\u201d global burden of congenital cytomegalovirus. Clin Microbiol Rev 26:86\u2013102","journal-title":"Clin Microbiol Rev"},{"key":"1258_CR53","doi-asserted-by":"publisher","first-page":"1514","DOI":"10.1111\/j.1532-5415.2009.02356.x","volume":"57","author":"B Mook-Kanamori","year":"2009","unstructured":"Mook-Kanamori B, van de Beek D, Wijdicks EF (2009) Herpes simplex encephalitis with normal initial cerebrospinal fluid examination. J Am Geriatr Soc 57:1514\u20131515","journal-title":"J Am Geriatr Soc"},{"issue":"1","key":"1258_CR54","doi-asserted-by":"publisher","first-page":"e16211","DOI":"10.1371\/journal.pone.0016211","volume":"6","author":"MB Mutnal","year":"2011","unstructured":"Mutnal MB, Cheeran MC, Hu S, Lokensgard JR (2011) Murine cytomegalovirus infection of neural stem cells alters neurogenesis in the developing brain. PLoS ONE 6(1):e16211","journal-title":"PLoS ONE"},{"key":"1258_CR55","doi-asserted-by":"publisher","first-page":"46","DOI":"10.3109\/13550280009006381","volume":"6","author":"M Nebuloni","year":"2000","unstructured":"Nebuloni M, Pellegrinelli A, Ferri A, Tosoni A, Bonetto S, Zerbi P, Boldorini R, Vago L, Costanzi G (2000) Etiology of microglial nodules in brains of patients with acquired immunodeficiency syndrome. J Neurovirol 6:46\u201350","journal-title":"J Neurovirol"},{"issue":"18","key":"1258_CR56","doi-asserted-by":"publisher","first-page":"8929","DOI":"10.1128\/JVI.00676-06","volume":"80","author":"J Odeberg","year":"2006","unstructured":"Odeberg J, Wolmer N, Falci S, Westgren M, Seiger A, S\u00f6derberg-Naucl\u00e9r C (2006) Human Cytomegalovirus inhibits neuronal differentiation and induces apoptosis in human neural precursor cells. J Virol 80(18):8929\u20138939","journal-title":"J Virol"},{"issue":"3","key":"1258_CR57","doi-asserted-by":"publisher","first-page":"583","DOI":"10.1002\/jnr.21144","volume":"85","author":"J Odeberg","year":"2007","unstructured":"Odeberg J, Wolmer N, Falci S, Westgren M, Sundtr\u00f6m E, Seiger A, S\u00f6derberg-Naucl\u00e9r C (2007) Late human cytomegalovirus (HCMV) proteins inhibit differentiation of human neural precursor cells into astrocytes. J Neurosci Res 85(3):583\u2013593","journal-title":"J Neurosci Res"},{"key":"1258_CR58","doi-asserted-by":"crossref","unstructured":"Pass RF, Arav-Boger R (2018) Maternal and fetal cytomegalovirus infection: diagnosis, management, and prevention. F1000Res 7:255","DOI":"10.12688\/f1000research.12517.1"},{"issue":"1","key":"1258_CR59","doi-asserted-by":"publisher","first-page":"64","DOI":"10.1002\/ana.410310112","volume":"31","author":"JM Perlman","year":"1992","unstructured":"Perlman JM, Argyle C (1992) Lethal cytomegalovirus infection in preterm infants: clinical, radiological, and neuropathological findings. Ann Neurol 31(1):64\u201368","journal-title":"Ann Neurol"},{"key":"1258_CR60","doi-asserted-by":"publisher","first-page":"2613","DOI":"10.1099\/vir.0.19279-0","volume":"84","author":"C Potel","year":"2003","unstructured":"Potel C, Kaelin K, Danglot L, Triller A, Vannier C, Rozenberg F (2003) Herpes simplex virus type 1 glycoprotein B sorting in hippocampal neurons. J Gen Virol 84:2613\u20132624","journal-title":"J Gen Virol"},{"issue":"1\u20132","key":"1258_CR61","doi-asserted-by":"publisher","first-page":"225","DOI":"10.1016\/S0006-8993(00)02099-0","volume":"863","author":"J Qin","year":"2000","unstructured":"Qin J, Mizuguchi M, Itoh M, Takashima S (2000) Immunohistochemical expression of doublecortin in the human cerebrum: comparison of normal development and neuronal migration disorders. Brain Res 863(1\u20132):225\u2013232","journal-title":"Brain Res"},{"issue":"6","key":"1258_CR62","doi-asserted-by":"publisher","first-page":"e177","DOI":"10.1016\/S1473-3099(17)30143-3","volume":"17","author":"WD Rawlinson","year":"2017","unstructured":"Rawlinson WD, Boppana SB, Fowler KB, Kimberlin DW, Lazzarotto T, Alain S, Daly K, Doutr\u00e9 S, Gibson L, Giles ML, Greenlee J, Hamilton ST, Harrison GJ, Hui L, Jones CA, Palasanthiran P, Schleiss MR, Shand AW, van Zuylen WJ (2017) Congenital cytomegalovirus infection in pregnancy and the neonate: consensus recommendations for prevention, diagnosis, and therapy. Lancet Infect Dis 17(6):e177-188","journal-title":"Lancet Infect Dis"},{"key":"1258_CR63","doi-asserted-by":"publisher","first-page":"60","DOI":"10.1016\/j.bbi.2016.01.006","volume":"55","author":"KN Robillard","year":"2016","unstructured":"Robillard KN, Lee KM, Chiu KB, MacLean AG (2016) Glial cell morphological and density changes through the lifespan of rhesus macaques. Brain Behav Immun 55:60\u201369","journal-title":"Brain Behav Immun"},{"issue":"4","key":"1258_CR64","doi-asserted-by":"publisher","first-page":"942","DOI":"10.1128\/CMR.17.4.942-964.2004","volume":"17","author":"RB Rock","year":"2004","unstructured":"Rock RB, Gekker G, Hu S, Sheng WS, Cheeran M, Lokensgard JR, Peterson PK (2004) Role of microglia in central nervous system infections. Clin Microbiol Rev 17(4):942\u2013964","journal-title":"Clin Microbiol Rev"},{"issue":"4","key":"1258_CR65","doi-asserted-by":"publisher","first-page":"e1005547","DOI":"10.1371\/journal.ppat.1005547","volume":"12","author":"M Rolland","year":"2016","unstructured":"Rolland M, Li X, Sellier Y, Martin H, Perez-Berezo T, Rauwel B, Benchoua A, Bessi\u00e8res B, Aziza J, Cenac N, Luo M, Casper C, Peschanski M, Gonzalez-Dunia D, Leruez-Ville M, Davrinche C, Chavanas S (2016) PPAR\u03b3 is activated during congenital cytomegalovirus infection and inhibits neuronogenesis from human neural stem cells. PLoS Pathog 12(4):e1005547","journal-title":"PLoS Pathog"},{"issue":"1","key":"1258_CR66","first-page":"92","volume":"254","author":"M Rolland","year":"2021","unstructured":"Rolland M, Martin H, Bergamelli M, Sellier Y, Bessi\u00e8res B, Aziza J, Benchoua A, Leruez-Ville M, Gonzalez-Dunia D, Chavanas S (2021) Human cytomegalovirus infection is associated with increased expression of the lissencephaly gene PAFAH1B1encoding LIS1 in neural stem cells and congenitally infected brains. J Pathol 254(1):92\u2013102","journal-title":"J Pathol"},{"issue":"2","key":"1258_CR67","doi-asserted-by":"publisher","first-page":"88","DOI":"10.1016\/S0387-7604(97)00111-3","volume":"20","author":"HB Sarnat","year":"1998","unstructured":"Sarnat HB, Nochlin D, Born DE (1998) Neuronal nuclear antigen (NeuN): a marker of neuronal maturation in early human fetal nervous system. Brain Dev 20(2):88\u201394","journal-title":"Brain Dev"},{"issue":"3","key":"1258_CR68","doi-asserted-by":"publisher","first-page":"186","DOI":"10.1007\/s11940-008-0020-2","volume":"10","author":"MR Schleiss","year":"2008","unstructured":"Schleiss MR (2008) Congenital cytomegalovirus infection: update on management strategies. Curr Treat Options Neurol 10(3):186\u2013192","journal-title":"Curr Treat Options Neurol"},{"issue":"2","key":"1258_CR69","doi-asserted-by":"publisher","first-page":"176","DOI":"10.3390\/microorganisms8020176","volume":"8","author":"Y Sellier","year":"2020","unstructured":"Sellier Y, Marliot F, Bessi\u00e8res B, Stirnemann J, Encha-Razavi F, Guilleminot T, Haicheur N, Pages F, Ville Y, Leruez-Ville M (2020) Adaptive and innate immune cells in fetal human cytomegalovirus-infected brains. Microorganisms 8(2):176","journal-title":"Microorganisms"},{"issue":"2","key":"1258_CR70","doi-asserted-by":"publisher","first-page":"180","DOI":"10.1038\/cmi.2014.51","volume":"12","author":"I Slavuljica","year":"2015","unstructured":"Slavuljica I, Kve\u0161tak D, Huszthy PC, Kosmac K, Britt WJ, Jonji\u0107 S (2015) Immunobiology of congenital cytomegalovirus infection of the central nervous system\u2014the murine cytomegalovirus model. Cell Mol Immunol 12(2):180\u2013191","journal-title":"Cell Mol Immunol"},{"issue":"3","key":"1258_CR71","doi-asserted-by":"publisher","first-page":"409","DOI":"10.1007\/s00430-015-0396-z","volume":"204","author":"DH Spector","year":"2015","unstructured":"Spector DH (2015) Human cytomegalovirus riding the cell cycle. Med Microbiol Immunol 204(3):409\u2013419","journal-title":"Med Microbiol Immunol"},{"issue":"Pt A","key":"1258_CR72","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1016\/j.nbd.2015.08.003","volume":"92","author":"MA Stouffer","year":"2016","unstructured":"Stouffer MA, Golden JA, Francis F (2016) Neuronal migration disorders: focus on the cytoskeleton and epilepsy. Neurobiol Dis 92(Pt A):18\u201345","journal-title":"Neurobiol Dis"},{"issue":"2","key":"1258_CR73","doi-asserted-by":"publisher","first-page":"143","DOI":"10.1097\/NEN.0000000000000038","volume":"73","author":"N Teissier","year":"2014","unstructured":"Teissier N, Fallet-Bianco C, Delezoide AL, Laquerri\u00e8re A, Marcorelles P, Khung-Savatovsky S, Nardelli J, Cipriani S, Csaba Z, Picone O, Golden JA, Van Den Abbeele T, Gressens P, Adle-Biassette H (2014) Cytomegalovirus-induced brain malformations in foetuses. J Neuropathol Exp Neurol 73(2):143\u2013158","journal-title":"J Neuropathol Exp Neurol"},{"issue":"4","key":"1258_CR74","doi-asserted-by":"publisher","first-page":"619","DOI":"10.1007\/s00401-019-01958-5","volume":"137","author":"WI Tr\u00f6scherAR","year":"2019","unstructured":"Tr\u00f6scherAR WI, Quemada-Garrido L, K\u00f6ck U, Gessl D, Verberk SGS, Martin B, Lassmann H, Bien CG, Bauer J (2019) Microglial nodules provide the environment for pathogenic T cells in human encephalitis. Acta Neuropathol 137(4):619\u2013635","journal-title":"Acta Neuropathol"},{"issue":"14","key":"1258_CR75","doi-asserted-by":"publisher","first-page":"7247","DOI":"10.1128\/JVI.76.14.7247-7254.2002","volume":"76","author":"Y Tsutsui","year":"2002","unstructured":"Tsutsui Y, Kawasaki H, Kosugi I (2002) Reactivation of latent cytomegalovirus infection in mouse brain cells detected after transfer to brain slice cultures. J Virol 76(14):7247\u20137254","journal-title":"J Virol"},{"issue":"5","key":"1258_CR76","doi-asserted-by":"publisher","first-page":"327","DOI":"10.1002\/rmv.475","volume":"15","author":"Y Tsutsui","year":"2005","unstructured":"Tsutsui Y, Kosugi I, Kawasaki H (2005) Neuropathogenesis in cytomegalovirus infection: indication of the mechanisms using mouse models. Rev Med Virol 15(5):327\u2013345","journal-title":"Rev Med Virol"},{"issue":"14","key":"1258_CR77","doi-asserted-by":"publisher","first-page":"3734","DOI":"10.1523\/JNEUROSCI.5060-06.2007","volume":"27","author":"TL Walker","year":"2007","unstructured":"Walker TL, Yasuda T, Adams DJ, Bartlett PF (2007) The doublecortin-expressing population in the developing and adult brain contains multipotential precursors in addition to neuronal-lineage cells. J Neurosci 27(14):3734\u20133742","journal-title":"J Neurosci"},{"issue":"3","key":"1258_CR78","doi-asserted-by":"publisher","first-page":"218","DOI":"10.1016\/j.pediatrneurol.2013.11.005","volume":"50","author":"AL White","year":"2014","unstructured":"White AL, Hedlund GL, Bale JF Jr (2014) Congenital cytomegalovirus infection and brain clefting. Pediatr Neurol 50(3):218\u2013223","journal-title":"Pediatr Neurol"},{"issue":"12","key":"1258_CR79","first-page":"2757","volume":"6","author":"X Yin","year":"2013","unstructured":"Yin X, Li L, Zhang X, Yang Y, Chai Y, Han X, Feng Z (2013) Development of neural stem cells at different sites of fetus brain of different gestational age. Int J ClinExpPathol 6(12):2757\u20132764","journal-title":"Int J ClinExpPathol"},{"issue":"5","key":"1258_CR80","first-page":"240","volume":"36","author":"JY Yoon","year":"2017","unstructured":"Yoon JY, Danielson B, Mathis D, Karamchandani J, Munoz DG (2017) Cytomegalovirus in the human dentate gyrus and its impact on neural progenitor cells: report of two cases. ClinNeuropathol 36(5):240\u2013245","journal-title":"ClinNeuropathol"},{"issue":"17","key":"1258_CR81","doi-asserted-by":"publisher","first-page":"2109","DOI":"10.1097\/CM9.0000000000000404","volume":"132","author":"XY Zhang","year":"2019","unstructured":"Zhang XY, Fang F (2019) Congenital human cytomegalovirus infection and neurologic diseases in newborns. Chin Med J 132(17):2109\u20132118","journal-title":"Chin Med J"},{"issue":"1","key":"1258_CR82","doi-asserted-by":"publisher","first-page":"e152551","DOI":"10.1172\/jci.insight.152551","volume":"7","author":"YP Zhou","year":"2022","unstructured":"Zhou YP, Mei MJ, Wang XZ, Huang SN, Chen L, Zhang M, Li XY, Qin HB, Dong X, Cheng S, Wen L, Yang B, An XF, He AD, Zhang B, Zeng WB, Li XJ, Lu Y, Li HC, Li H, Zou WG, Redwood AJ, Rayner S, Cheng H, McVoy MA, Tang Q, Britt WJ, Zhou X, Jiang X, Luo MH (2022) A congenital CMV infection model for follow-up studies of neurodevelopmental disorders, neuroimaging abnormalities, and treatment. JCI Insight 7(1):e152551","journal-title":"JCI Insight"}],"container-title":["Cellular and Molecular Neurobiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10571-022-01258-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s10571-022-01258-9\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10571-022-01258-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,3,26]],"date-time":"2023-03-26T21:50:16Z","timestamp":1679867416000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s10571-022-01258-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,8,7]]},"references-count":82,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2023,4]]}},"alternative-id":["1258"],"URL":"https:\/\/doi.org\/10.1007\/s10571-022-01258-9","relation":{},"ISSN":["0272-4340","1573-6830"],"issn-type":[{"value":"0272-4340","type":"print"},{"value":"1573-6830","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,8,7]]},"assertion":[{"value":"27 January 2022","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"8 July 2022","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"7 August 2022","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare that they have no conflicts of interest\/competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and\/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. The study was approved by the Ethical Committee of IRCCS S. Orsola Polyclinic, University Hospital, Bologna, Italy (approval numbers: 14\/2017\/U\/tess and 8\/2010\/O\/Sper).","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical Approval"}},{"value":"Informed consent was obtained from all individual participants included in the study.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Informed Consent"}},{"value":"Not applicable.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for Publication"}}]}}