{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,11]],"date-time":"2026-02-11T13:12:50Z","timestamp":1770815570574,"version":"3.50.1"},"reference-count":58,"publisher":"Public Library of Science (PLoS)","issue":"10","license":[{"start":{"date-parts":[[2021,10,21]],"date-time":"2021-10-21T00:00:00Z","timestamp":1634774400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>Pediatric optic pathway glioma (OPG) can seriously decrease visual function in the case of progression. Systemic anticancer therapy (SAT) is considered the treatment of first choice for unresectable OPG. New SAT modalities for the treatment of progressive OPG have been introduced in the last decade, including VEGF and MAPK pathway inhibition. This systematic review evaluated the effect of SAT on change in visual acuity and visual field in OPG. A systematic review was performed on SAT for OPG (January 1990 to August 2020). MEDLINE and EMBASE (Ovid) were searched for studies reporting on change in visual acuity and visual field after treatment with SAT for OPG. Overall, 11 series, including 358 patients, fulfilled the eligibility criteria. After follow-up of median 3.7 years (range: cessation of SAT\u2013 8.2 years), improvement in binocular VA was found in 0\u201345% of studies, stability in 18\u201377% and a decrease in 0\u201382%. Two studies reported on change in visual field (improvement in 19% and 71% of patients), although either the change was not defined or the testing strategy was lacking. Considerable heterogeneity was present among the included studies, such as variety in the combinations of SAT administered, status of neurofibromatosis type 1, definition regarding change in visual acuity, 1- or 2-eye analysis, diversity in anatomic location, and extent of follow-up, all of which made meta-analysis inappropriate. This systematic review suggests that the impact of SAT in OPG on visual function is still unclear. The wide ranges reported on the efficacy of SAT and the observed heterogeneity highlight the need for prospective studies with uniform definitions of outcome parameters.<\/jats:p>","DOI":"10.1371\/journal.pone.0258548","type":"journal-article","created":{"date-parts":[[2021,10,21]],"date-time":"2021-10-21T18:00:54Z","timestamp":1634839254000},"page":"e0258548","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":10,"title":["Impact of systemic anticancer\u00a0therapy in pediatric optic pathway glioma on visual function: A systematic review"],"prefix":"10.1371","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4733-2120","authenticated-orcid":true,"given":"Carlien A. M.","family":"Bennebroek","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura. E.","family":"Wijninga","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jaqueline","family":"Limpens","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antoinette Y. N.","family":"Schouten-van Meeteren","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peerooz","family":"Saeed","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2021,10,21]]},"reference":[{"key":"pone.0258548.ref001","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1016\/j.ejca.2017.04.019","article-title":"A European randomised controlled trial of the addition of etoposide to standard vincristine and carboplatin induction as part of an 18-month treatment programme for childhood (<\/ = 16 years) low grade glioma\u2013A final report","volume":"81","author":"AK Gnekow","year":"2017","journal-title":"Eur J Cancer"},{"issue":"9","key":"pone.0258548.ref002","doi-asserted-by":"crossref","first-page":"692","DOI":"10.1007\/s004310000531","article-title":"When do children with optic pathway tumours need treatment? An oncological perspective in 106 patients treated in a single centre","volume":"159","author":"J Grill","year":"2000","journal-title":"Eur J Pediatr"},{"issue":"7","key":"pone.0258548.ref003","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1177\/08830738030180070401","article-title":"Optic pathway gliomas in children with and without neurofibromatosis 1","volume":"18","author":"E Czyzyk","year":"2003","journal-title":"J Child Neurol"},{"issue":"4","key":"pone.0258548.ref004","doi-asserted-by":"crossref","first-page":"516","DOI":"10.1001\/archopht.119.4.516","article-title":"Spontaneous regression of optic gliomas: Thirteen cases documented by serial neuroimaging","volume":"119","author":"CF Parsa","year":"2001","journal-title":"Arch Ophthalmol"},{"issue":"6","key":"pone.0258548.ref005","doi-asserted-by":"crossref","first-page":"e0127676","DOI":"10.1371\/journal.pone.0127676","article-title":"Mortality in children with optic pathway glioma treated with up-front BB-SFOP chemotherapy","volume":"10","author":"J Rakotonjanahary","year":"2015","journal-title":"PloS One"},{"issue":"24","key":"pone.0258548.ref006","doi-asserted-by":"crossref","first-page":"4572","DOI":"10.1200\/JCO.2003.03.043","article-title":"Progression-free survival in children with optic pathway tumors: dependence on age and the quality of the response to chemotherapy\u2014results of the first French prospective study for the French Society of Pediatric Oncology","volume":"21","author":"V Laithier","year":"2003","journal-title":"J Clin Oncol"},{"issue":"6","key":"pone.0258548.ref007","first-page":"331","article-title":"Low grade chiasmatic-hypothalamic glioma-carboplatin and vincristin chemotherapy effectively defers radiotherapy within a comprehensive treatment strategy\u2014report from the multicenter treatment study for children and adolescents with a low grade glioma\u2014HIT-LGG 1996\u2014of the Society of Pediatric Oncology and Hematology (GPOH)","volume":"216","author":"AK Gnekow","year":"2004","journal-title":"Klin P\u00e4diatr."},{"issue":"5","key":"pone.0258548.ref008","doi-asserted-by":"crossref","first-page":"747","DOI":"10.3171\/jns.1997.86.5.0747","article-title":"Carboplatin and vincristine chemotherapy for children with newly diagnosed progressive low-grade gliomas","volume":"86","author":"RJ Packer","year":"1997","journal-title":"J Neurosurg"},{"issue":"23","key":"pone.0258548.ref009","doi-asserted-by":"crossref","first-page":"4190","DOI":"10.1002\/cncr.29649","article-title":"Long-term visual outcome after chemotherapy for optic pathway glioma in children: Site and age are strongly predictive","volume":"121","author":"AJ Dodgshun","year":"2015","journal-title":"Cancer"},{"issue":"6","key":"pone.0258548.ref010","doi-asserted-by":"crossref","first-page":"1083","DOI":"10.1002\/pbc.22748","article-title":"Optic pathway glioma: Long-term visual outcome in children without neurofibromatosis type-1","volume":"55","author":"M Campagna","year":"2010","journal-title":"Pediatr Blood Cancer"},{"issue":"1","key":"pone.0258548.ref011","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1007\/s11060-016-2163-4","article-title":"Long-term visual outcomes of optic pathway gliomas in pediatric patients without neurofibromatosis type 1","volume":"129","author":"MJ Wan","year":"2016","journal-title":"J Neuro-oncol"},{"issue":"3","key":"pone.0258548.ref012","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1097\/ICU.0000000000000370","article-title":"Optic pathway glioma of childhood.","volume":"28","author":"N Rasool","year":"2017","journal-title":"Curr Opin Ophthalmol"},{"issue":"12","key":"pone.0258548.ref013","doi-asserted-by":"crossref","first-page":"825","DOI":"10.1007\/BF02072067","article-title":"Growth and endocrine disorders in optic glioma","volume":"149","author":"R Brauner","year":"1990","journal-title":"Eur J Pediatr"},{"issue":"3","key":"pone.0258548.ref014","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1002\/1531-8249(199903)45:3<393::AID-ANA17>3.0.CO;2-B","article-title":"Radiation-induced cerebral vasculopathy in children with neurofibromatosis and optic pathway glioma","volume":"45","author":"J Grill","year":"1999","journal-title":"Ann Neurol"},{"issue":"9","key":"pone.0258548.ref015","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1007\/s00066-003-8104-0","article-title":"Current and future strategies in radiotherapy of childhood low-grade glioma of the brain. Part II: Treatment-related late toxicity","volume":"179","author":"RD Kortmann","year":"2003","journal-title":"Strahlentherapie und Onkologie"},{"issue":"2","key":"pone.0258548.ref016","doi-asserted-by":"crossref","first-page":"135","DOI":"10.3171\/jns.1976.45.2.0135","article-title":"Response to vincristine of recurrent brain tumors in children","volume":"45","author":"JG Rosenstock","year":"1976","journal-title":"J Neurosurg"},{"issue":"20","key":"pone.0258548.ref017","doi-asserted-by":"crossref","first-page":"4209","DOI":"10.1200\/JCO.2002.08.087","article-title":"High response rate to cisplatin\/etoposide regimen in childhood low-grade glioma.","volume":"20","author":"M Massimino","year":"2002","journal-title":"J Clin Oncol"},{"issue":"29","key":"pone.0258548.ref018","doi-asserted-by":"crossref","first-page":"3537","DOI":"10.1200\/JCO.2016.68.1585","article-title":"Phase II Weekly vinblastine for chemotherapy-naive children with progressive low-grade glioma: A Canadian Pediatric Brain Tumor Consortium Study","volume":"34","author":"A Lassaletta","year":"2016","journal-title":"J Clin Oncol"},{"issue":"1","key":"pone.0258548.ref019","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1007\/s11060-017-2630-6","article-title":"Current and emerging treatment strategies for children with progressive chiasmatic-hypothalamic glioma diagnosed as infants: A web-based survey","volume":"136","author":"AA Azizi","year":"2018","journal-title":"J Neuro-oncol"},{"issue":"7","key":"pone.0258548.ref020","doi-asserted-by":"crossref","first-page":"791","DOI":"10.1002\/pbc.21935","article-title":"Objective response of multiply recurrent low-grade gliomas to bevacizumab and irinotecan","volume":"52","author":"RJ Packer","year":"2009","journal-title":"Pediatr Blood Cancer"},{"issue":"5","key":"pone.0258548.ref021","doi-asserted-by":"crossref","first-page":"776","DOI":"10.1002\/pbc.24297","article-title":"Long-term efficacy and toxicity of bevacizumab-based therapy in children with recurrent low-grade gliomas","volume":"60","author":"EI Hwang","year":"2013","journal-title":"Pediatr Blood Cancer"},{"issue":"1","key":"pone.0258548.ref022","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1001\/jamaophthalmol.2013.5819","article-title":"Marked recovery of vision in children with optic pathway gliomas treated with bevacizumab","volume":"132","author":"RA Avery","year":"2014","journal-title":"JAMA Ophthalmol"},{"issue":"1","key":"pone.0258548.ref023","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1002\/cam4.1799","article-title":"Use of bevacizumab as a single agent or in adjunct with traditional chemotherapy regimens in children with unresectable or progressive low-grade glioma","volume":"8","author":"N Zhukova","year":"2019","journal-title":"Cancer Med"},{"issue":"9","key":"pone.0258548.ref024","doi-asserted-by":"crossref","first-page":"e27234","DOI":"10.1002\/pbc.27234","article-title":"Single-agent bevacizumab in the treatment of recurrent or refractory pediatric low-grade glioma: A single institutional experience","volume":"65","author":"HS Gorsi","year":"2018","journal-title":"Pediatr Blood Cancer"},{"issue":"2","key":"pone.0258548.ref025","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1093\/neuonc\/not154","article-title":"Efficacy of bevacizumab plus irinotecan in children with recurrent low-grade gliomas. A Pediatric Brain Tumor Consortium study","volume":"16","author":"S Gururangan","year":"2014","journal-title":"J Neuro-oncol"},{"issue":"2","key":"pone.0258548.ref026","first-page":"435","article-title":"Trametinib for progressive pediatric low-grade gliomas","volume":"140","author":"M Kondyli","year":"2018","journal-title":"JNeuro-oncol."},{"issue":"7","key":"pone.0258548.ref027","doi-asserted-by":"crossref","first-page":"1011","DOI":"10.1016\/S1470-2045(19)30277-3","article-title":"Selumetinib in paediatric patients with BRAF-aberrant or neurofibromatosis type 1-associated recurrent, refractory, or progressive low-grade glioma: a multicentre, phase 2 trial","volume":"20","author":"J Fangusaro","year":"2019","journal-title":"Lancet Oncol"},{"key":"pone.0258548.ref028","article-title":"Trametinib for the treatment of recurrent\/progressive pediatric low-grade glioma","author":"N Manoharan","year":"2020","journal-title":"J Neuro-oncol"},{"issue":"10","key":"pone.0258548.ref029","doi-asserted-by":"crossref","first-page":"1367","DOI":"10.1136\/bjophthalmol-2017-311305","article-title":"Visual outcomes after chemotherapy for optic pathway glioma in children with and without neurofibromatosis type 1: Results of the International Society of Paediatric Oncology (SIOP) Low-Grade Glioma 2004 trial UK cohort","volume":"102","author":"K Falzon","year":"2018","journal-title":"Br J Ophthalmol"},{"issue":"6","key":"pone.0258548.ref030","doi-asserted-by":"crossref","first-page":"790","DOI":"10.1093\/neuonc\/nos076","article-title":"Visual outcomes in children with neurofibromatosis type 1-associated optic pathway glioma following chemotherapy: A multicenter retrospective analysis","volume":"14","author":"MJ Fisher","year":"2012","journal-title":"J Neuro-oncol"},{"issue":"2","key":"pone.0258548.ref031","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1002\/pbc.24726","article-title":"Visual acuity of children treated with chemotherapy for optic pathway gliomas","volume":"61","author":"E Kalin-Hajdu","year":"2014","journal-title":"Pediatr Blood Cancer"},{"issue":"12","key":"pone.0258548.ref032","doi-asserted-by":"crossref","first-page":"2253","DOI":"10.1016\/j.ejca.2010.03.028","article-title":"Does chemotherapy affect the visual outcome in children with optic pathway glioma? A systematic review of the evidence","volume":"46","author":"L Moreno","year":"2010","journal-title":"Eur J Cancer"},{"issue":"2","key":"pone.0258548.ref033","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1002\/ana.410410204","article-title":"Optic pathway gliomas in children with neurofibromatosis 1: Consensus statement from the NF1 Optic Pathway Glioma Task Force","volume":"41","author":"R Listernick","year":"1997","journal-title":"Ann Neurol"},{"issue":"3","key":"pone.0258548.ref034","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1002\/ana.21107","article-title":"Optic pathway gliomas in neurofibromatosis-1: Controversies and recommendations","volume":"61","author":"R Listernick","year":"2007","journal-title":"Ann Neurol"},{"issue":"Suppl 1","key":"pone.0258548.ref035","doi-asserted-by":"crossref","first-page":"S23","DOI":"10.1097\/WNO.0000000000000550","article-title":"Optic pathway gliomas in neurofibromatosis Type 1: An update: Surveillance, treatment indications, and biomarkers of vision.","volume":"37","author":"PMK de Blank","year":"2017","journal-title":"J Neuro-ophthalmol"},{"issue":"3","key":"pone.0258548.ref036","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1055\/a-0889-8256","article-title":"SIOP-E-BTG and GPOH guidelines for diagnosis and treatment of children and adolescents with low grade glioma","volume":"231","author":"AK Gnekow","year":"2019","journal-title":"Klin P\u00e4diatr."},{"issue":"6","key":"pone.0258548.ref037","doi-asserted-by":"crossref","first-page":"e305","DOI":"10.1016\/S1470-2045(20)30064-4","article-title":"Response assessment in paediatric low-grade glioma: Recommendations from the Response Assessment in Pediatric Neuro-Oncology (RAPNO) working group","volume":"21","author":"J Fangusaro","year":"2020","journal-title":"Lancet Oncol."},{"key":"pone.0258548.ref038","unstructured":"JBI-CA: Joanna Briggs Institute Critical Appraisal Institute JB (2017). https:\/\/joannabriggs.org\/sites\/default\/files\/2019-05\/JBI_Critical_Appraisal-Checklist_for_Case_Series2017_0.pdf. 2017."},{"issue":"7","key":"pone.0258548.ref039","doi-asserted-by":"crossref","first-page":"1231","DOI":"10.1002\/pbc.22198","article-title":"Natural history and outcome of optic pathway gliomas in children","volume":"53","author":"G Nicolin","year":"2009","journal-title":"Pediatr Blood Cancer"},{"issue":"21 Suppl 1","key":"pone.0258548.ref040","doi-asserted-by":"crossref","first-page":"S15","DOI":"10.1212\/01.wnl.0000435745.95155.b8","article-title":"Functional outcome measures for NF1-associated optic pathway glioma clinical trials","volume":"81","author":"MJ Fisher","year":"2013","journal-title":"Neurology"},{"key":"pone.0258548.ref041","unstructured":"Oxford Centre of Evidence Based Medicine (2011). https:\/\/www.cebm.net\/2009\/06\/oxford-centre-evidence-based-medicine-levels-evidence-march-2009."},{"issue":"4","key":"pone.0258548.ref042","doi-asserted-by":"crossref","first-page":"430","DOI":"10.1215\/15228517-2007-031","article-title":"Visual outcome of a cohort of children with neurofibromatosis type 1 and optic pathway glioma followed by a pediatric neuro-oncology program","volume":"9","author":"P Dalla Via","year":"2007","journal-title":"J Neuro-oncol"},{"issue":"1","key":"pone.0258548.ref043","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1007\/s11060-010-0136-6","article-title":"A lower-dose, lower-toxicity cisplatin-etoposide regimen for childhood progressive low-grade glioma","volume":"100","author":"M Massimino","year":"2010","journal-title":"J Neuro-oncol"},{"issue":"2","key":"pone.0258548.ref044","doi-asserted-by":"crossref","first-page":"102","DOI":"10.3109\/08880018.2016.1155101","article-title":"Optic pathway glioma in children: 10 years of experience in a single institution","volume":"33","author":"D Doganis","year":"2016","journal-title":"Pediatr Hematol Oncol"},{"issue":"3","key":"pone.0258548.ref045","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1002\/pbc.22967","article-title":"Visual outcome following chemotherapy for progressive optic pathway gliomas","volume":"57","author":"B Shofty","year":"2011","journal-title":"Pediatr Blood Cancer"},{"issue":"4","key":"pone.0258548.ref046","doi-asserted-by":"crossref","first-page":"1051","DOI":"10.1002\/1097-0142(19950215)75:4<1051::AID-CNCR2820750423>3.0.CO;2-S","article-title":"Optic pathway and hypothalamic\/chiasmatic gliomas in children younger than age 5 years with a 6-year follow-up","volume":"75","author":"AJ Janss","year":"1995","journal-title":"Cancer"},{"issue":"9","key":"pone.0258548.ref047","doi-asserted-by":"crossref","first-page":"572","DOI":"10.1097\/00043426-200112000-00004","article-title":"Visual improvement despite radiologically stable disease after treatment with carboplatin in children with progressive low-grade optic\/thalamic gliomas","volume":"23","author":"AE Mitchell","year":"2001","journal-title":"J Pediatr Hematol\/Oncol"},{"issue":"3","key":"pone.0258548.ref048","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1159\/000028996","article-title":"Optic pathway hypothalamic gliomas in children under three years of age: The role of chemotherapy.","volume":"33","author":"MM Silva","year":"2000","journal-title":"Pediatr Neurosurg."},{"issue":"5","key":"pone.0258548.ref049","doi-asserted-by":"crossref","first-page":"701","DOI":"10.3171\/jns.1991.74.5.0701","article-title":"Management of chiasmal and hypothalamic gliomas of infancy and childhood with chemotherapy","volume":"74","author":"J Petronio","year":"1991","journal-title":"J Neurosurg"},{"issue":"5","key":"pone.0258548.ref050","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1001\/archneur.1995.00540290099024","article-title":"Recurrent chiasmatic-hypothalamic glioma treated with oral etoposide","volume":"52","author":"MC Chamberlain","year":"1995","journal-title":"Arch Neurol"},{"key":"pone.0258548.ref051","unstructured":"NCT03871257 CgI. A study of the drugs selumetinib versus carboplatin\/vincristine in patients with neurofibromatosis and low-Grade glioma. https:\/\/clinicaltrials.gov\/ct2\/show\/record\/NCT03871257?cond=Optic+pathway+glioma&draw=2&rank=9."},{"issue":"12","key":"pone.0258548.ref052","doi-asserted-by":"crossref","first-page":"1807","DOI":"10.1016\/j.ejca.2006.02.022","article-title":"Prognostic factors for progression of childhood optic pathway glioma: a systematic review","volume":"42","author":"E Opocher","year":"2006","journal-title":"EurJ Cancer"},{"issue":"5","key":"pone.0258548.ref053","doi-asserted-by":"crossref","first-page":"944","DOI":"10.1016\/j.ajo.2015.07.036","article-title":"Longitudinal change of Circumpapillary Retinal Nerve Fiber Layer Thickness in Children With Optic Pathway Gliomas","volume":"160","author":"RA Avery","year":"2015","journal-title":"Am J Ophthalmol"},{"issue":"3","key":"pone.0258548.ref054","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1007\/s00381-019-04407-6","article-title":"Bevacizumab for optic pathway glioma with worsening visual field in absence of imaging progression: 2 case reports and literature review","volume":"36","author":"F Yamasaki","year":"2020","journal-title":"Child Nerv Syst."},{"key":"pone.0258548.ref055","unstructured":"NCT03326388 CgI. Intermittent dosing of selumetinib in childhood NF1 associated tumours. https:\/\/clinicaltrialsgov\/ct2\/show\/NCT03326388?cond=Optic+pathway+glioma&draw=2&rank=7."},{"issue":"4","key":"pone.0258548.ref056","doi-asserted-by":"crossref","first-page":"851","DOI":"10.1016\/j.jpeds.2015.07.001","article-title":"The use of magnetic resonance imaging screening for optic pathway gliomas in children with neurofibromatosis Type 1","volume":"167","author":"CE Prada","year":"2015","journal-title":"J Pediatr"},{"issue":"12","key":"pone.0258548.ref057","first-page":"1257","article-title":"A multivariate analysis of factors determining tumor progression in childhood low-grade glioma: a population-based cohort study (CCLG CNS9702).","volume":"12","author":"T Stokland","year":"2010","journal-title":"J Neuro-oncol"},{"issue":"2","key":"pone.0258548.ref058","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1002\/pbc.21563","article-title":"Outcome analysis of childhood low-grade astrocytomas","volume":"51","author":"PG Fisher","year":"2008","journal-title":"Pediatr Blood Cancer"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0258548","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,10,21]],"date-time":"2021-10-21T18:02:01Z","timestamp":1634839321000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0258548"}},"subtitle":[],"editor":[{"given":"Jonathan H.","family":"Sherman","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2021,10,21]]},"references-count":58,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2021,10,21]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0258548","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,10,21]]}}}