{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,20]],"date-time":"2026-02-20T16:06:39Z","timestamp":1771603599902,"version":"3.50.1"},"reference-count":58,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2023,3,2]],"date-time":"2023-03-02T00:00:00Z","timestamp":1677715200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"The Emerson & Barbara Kampen Foundation"},{"name":"Lucas Garrett Pompe Foundation"},{"name":"Sanofi Genzyme and Amicus Therapeutics"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,3,20]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The survival of infantile-onset Pompe disease (IOPD) patients has improved dramatically since the introduction of enzyme replacement therapy (ERT) with a1glucosidase alfa. However, long-term IOPD survivors on ERT demonstrate motor deficits indicating that current therapy cannot completely prevent disease progression in skeletal muscle. We hypothesized that in IOPD, skeletal muscle endomysial stroma and capillaries would show consistent changes that could impede the movement of infused ERT from blood to muscle fibers. We retrospectively examined 9 skeletal muscle biopsies from 6 treated IOPD patients using light and electron microscopy. We found consistent ultrastructural endomysial stromal and capillary changes. The endomysial interstitium was expanded by lysosomal material, glycosomes\/glycogen, cellular debris, and organelles, some exocytosed by viable muscle fibers and some released on fiber lysis. Endomysial scavenger cells phagocytosed this material. Mature fibrillary collagen was seen in the endomysium, and both muscle fibers and endomysial capillaries showed basal laminar reduplication and\/or expansion. Capillary endothelial cells showed hypertrophy and degeneration, with narrowing of the vascular lumen. Ultrastructurally defined stromal and vascular changes likely constitute obstacles to movement of infused ERT from capillary lumen to muscle fiber sarcolemma, contributing to the incomplete efficacy of infused ERT in skeletal muscle. Our observations can inform approaches to overcoming these barriers to therapy.<\/jats:p>","DOI":"10.1093\/jnen\/nlad012","type":"journal-article","created":{"date-parts":[[2023,3,3]],"date-time":"2023-03-03T06:16:15Z","timestamp":1677824175000},"page":"345-362","source":"Crossref","is-referenced-by-count":1,"title":["Outside the fiber: Endomysial stromal and capillary pathology in skeletal muscle may impede infusion therapy in infantile-onset Pompe disease"],"prefix":"10.1093","volume":"82","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1209-5791","authenticated-orcid":false,"given":"Anne F","family":"Buckley","sequence":"first","affiliation":[{"name":"Department of Pathology, Duke University Medical Center , Durham, North Carolina, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ankit K","family":"Desai","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Medical Genetics, Duke University Medical Center , Durham, North Carolina, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christine I","family":"Ha","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Medical Genetics, Duke University Medical Center , Durham, North Carolina, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maureen A","family":"Petersen","sequence":"additional","affiliation":[{"name":"Department of Pathology, Duke University Medical Center , Durham, North Carolina, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Januario C","family":"Estrada","sequence":"additional","affiliation":[{"name":"Department of Pathology, Duke University Medical Center , Durham, North Carolina, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Justin R","family":"Water\ufb01eld","sequence":"additional","affiliation":[{"name":"Department of Pathology, Duke University Medical Center , Durham, North Carolina, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Edward H","family":"Bossen","sequence":"additional","affiliation":[{"name":"Department of Pathology, Duke University Medical Center , Durham, North Carolina, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Priya S","family":"Kishnani","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Medical Genetics, Duke University Medical Center , Durham, North Carolina, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2023,3,2]]},"reference":[{"key":"2024032523511314400_nlad012-B1","doi-asserted-by":"crossref","first-page":"1208","DOI":"10.1038\/labinvest.3700484","article-title":"Characterization of pre- and post-treatment pathology after enzyme replacement therapy for Pompe disease","volume":"86","author":"Thurberg","year":"2006","journal-title":"Lab Invest"},{"key":"2024032523511314400_nlad012-B2","doi-asserted-by":"crossref","first-page":"355","DOI":"10.3928\/01913913-20140813-01","article-title":"Ocular and histologic findings in a series of children with infantile Pompe disease treated with enzyme replacement therapy","volume":"51","author":"Prakalapakorn","year":"2014","journal-title":"J Pediatr Ophthalmol Strabismus"},{"key":"2024032523511314400_nlad012-B3","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1007\/8904_2015_426","article-title":"Postmortem findings and clinical correlates in individuals with infantile-onset Pompe disease","volume":"23","author":"Pena","year":"2015","journal-title":"JIMD Rep"},{"key":"2024032523511314400_nlad012-B4","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1016\/j.jpeds.2005.11.033","article-title":"A retrospective, multinational, multicenter study on the natural history of infantile-onset Pompe disease","volume":"148","author":"Kishnani","year":"2006","journal-title":"J Pediatr"},{"key":"2024032523511314400_nlad012-B5","volume-title":"The Online Metabolic & Molecular Bases of Inherited Disease","author":"Reuser","year":"2019"},{"key":"2024032523511314400_nlad012-B6","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1016\/S0140-6736(00)02533-2","article-title":"Recombinant human alpha-glucosidase from rabbit milk in Pompe patients","volume":"356","author":"Van den Hout","year":"2000","journal-title":"Lancet"},{"key":"2024032523511314400_nlad012-B7","first-page":"132","article-title":"Recombinant human acid alpha-glucosidase enzyme therapy for infantile glycogen storage disease type II: Results of a phase I\/II clinical trial","volume":"3","author":"Amalfitano","year":"2001","journal-title":"Genet Med"},{"key":"2024032523511314400_nlad012-B8","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/j.jpeds.2006.02.035","article-title":"Chinese hamster ovary cell-derived recombinant human acid alpha-glucosidase in infantile-onset Pompe disease","volume":"149","author":"Kishnani","year":"2006","journal-title":"J Pediatr"},{"key":"2024032523511314400_nlad012-B9","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1203\/PDR.0b013e3181b24e94","article-title":"Early treatment with alglucosidase alpha prolongs long-term survival of infants with Pompe disease","volume":"66","author":"Kishnani","year":"2009","journal-title":"Pediatr Res"},{"key":"2024032523511314400_nlad012-B10","doi-asserted-by":"crossref","first-page":"e1116\u201325","DOI":"10.1542\/peds.2008-3667","article-title":"Pompe disease in infants: Improving the prognosis by newborn screening and early treatment","volume":"124","author":"Chien","year":"2009","journal-title":"Pediatrics"},{"key":"2024032523511314400_nlad012-B11","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1016\/j.pedneo.2013.03.009","article-title":"Pompe disease: Early diagnosis and early treatment make a difference","volume":"54","author":"Chien","year":"2013","journal-title":"Pediatr Neonatol"},{"key":"2024032523511314400_nlad012-B12","doi-asserted-by":"crossref","first-page":"985","DOI":"10.1016\/j.jpeds.2014.10.068","article-title":"Long-term prognosis of patients with infantile-onset Pompe disease diagnosed by newborn screening and treated since birth","volume":"166","author":"Chien","year":"2015","journal-title":"J Pediatr"},{"key":"2024032523511314400_nlad012-B13","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1016\/j.jpeds.2015.10.078","article-title":"Very early treatment for infantile-onset Pompe disease contributes to better outcomes","volume":"169","author":"Yang","year":"2016","journal-title":"J Pediatr"},{"key":"2024032523511314400_nlad012-B14","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1016\/j.ymgme.2009.08.003","article-title":"Cross-reactive immunologic material status affects treatment outcomes in Pompe disease infants","volume":"99","author":"Kishnani","year":"2010","journal-title":"Mol Genet Metab"},{"key":"2024032523511314400_nlad012-B15","doi-asserted-by":"crossref","first-page":"729","DOI":"10.1097\/GIM.0b013e3182174703","article-title":"The impact of antibodies on clinical outcomes in diseases treated with therapeutic protein: Lessons learned from infantile Pompe disease","volume":"13","author":"Banugaria","year":"2011","journal-title":"Genet Med"},{"key":"2024032523511314400_nlad012-B16","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1002\/ajmg.c.31319","article-title":"Predicting cross-reactive immunological material (CRIM) status in Pompe disease using GAA mutations: Lessons learned from 10 years of clinical laboratory testing experience","volume":"160C","author":"Bali","year":"2012","journal-title":"Am J Med Genet C Semin Med Genet"},{"key":"2024032523511314400_nlad012-B17","doi-asserted-by":"crossref","first-page":"100475","DOI":"10.1016\/j.ymgmr.2019.100475","article-title":"Characterization of immune response in cross-reactive immunological material (CRIM)-positive infantile Pompe disease patients treated with enzyme replacement therapy","volume":"20","author":"Desai","year":"2019","journal-title":"Mol Genet Metab Rep"},{"key":"2024032523511314400_nlad012-B18","doi-asserted-by":"crossref","first-page":"887","DOI":"10.1038\/s41436-018-0270-7","article-title":"An immune tolerance approach using transient low-dose methotrexate in the ERT-naive setting of patients treated with a therapeutic protein: Experience in infantile-onset Pompe disease","volume":"21","author":"Kazi","year":"2019","journal-title":"Genet Med"},{"key":"2024032523511314400_nlad012-B19","doi-asserted-by":"crossref","first-page":"285","DOI":"10.21037\/atm.2019.05.27","article-title":"Immunological challenges and approaches to immunomodulation in Pompe disease: A literature review","volume":"7","author":"Desai","year":"2019","journal-title":"Ann Transl Med"},{"key":"2024032523511314400_nlad012-B20","doi-asserted-by":"crossref","first-page":"898","DOI":"10.1038\/s41436-019-0738-0","article-title":"Higher dosing of alglucosidase alfa improves outcomes in children with Pompe disease: A clinical study and review of the literature","volume":"22","author":"Khan","year":"2020","journal-title":"Genet Med"},{"key":"2024032523511314400_nlad012-B21","doi-asserted-by":"crossref","first-page":"1727","DOI":"10.3389\/fimmu.2020.01727","article-title":"Benefits of prophylactic short-course immune tolerance induction in patients with infantile Pompe disease: Demonstration of long-term safety and efficacy in an expanded cohort","volume":"11","author":"Desai","year":"2020","journal-title":"Front Immunol"},{"key":"2024032523511314400_nlad012-B22","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1002\/ajmg.c.31321","article-title":"Infantile Pompe disease on ERT: Update on clinical presentation, musculoskeletal management, and exercise considerations","volume":"160C","author":"Case","year":"2012","journal-title":"Am J Med Genet C Semin Med Genet"},{"key":"2024032523511314400_nlad012-B23","doi-asserted-by":"crossref","first-page":"800","DOI":"10.1038\/gim.2012.44","article-title":"The emerging phenotype of long-term survivors with infantile Pompe disease","volume":"14","author":"Prater","year":"2012","journal-title":"Genet Med"},{"key":"2024032523511314400_nlad012-B24","doi-asserted-by":"crossref","first-page":"674","DOI":"10.1002\/ppul.24621","article-title":"Pulmonary outcome measures in long-term survivors of infantile Pompe disease on enzyme replacement therapy: A case series","volume":"55","author":"ElMallah","year":"2020","journal-title":"Pediatr Pulmonol"},{"key":"2024032523511314400_nlad012-B25","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1212\/01.wnl.0000251268.41188.04","article-title":"Recombinant human acid [alpha]-glucosidase: Major clinical benefits in infantile-onset Pompe disease","volume":"68","author":"Kishnani","year":"2007","journal-title":"Neurology"},{"key":"2024032523511314400_nlad012-B26","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1007\/8904_2014_392","article-title":"Outcome of patients with classical infantile Pompe disease receiving enzyme replacement therapy in Germany","volume":"20","author":"Hahn","year":"2015","journal-title":"JIMD Rep"},{"key":"2024032523511314400_nlad012-B27","doi-asserted-by":"crossref","first-page":"743","DOI":"10.1002\/mus.10381","article-title":"Morphological changes in muscle tissue of patients with infantile Pompe\u2019s disease receiving enzyme replacement therapy","volume":"27","author":"Winkel","year":"2003","journal-title":"Muscle Nerve"},{"key":"2024032523511314400_nlad012-B28","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1186\/1750-1172-8-90","article-title":"Skeletal muscle pathology of infantile Pompe disease during long-term enzyme replacement therapy","volume":"8","author":"Prater","year":"2013","journal-title":"Orphanet J Rare Dis"},{"key":"2024032523511314400_nlad012-B29","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1016\/j.ymgme.2003.08.022","article-title":"Enzyme replacement therapy in the mouse model of Pompe disease","volume":"80","author":"Raben","year":"2003","journal-title":"Mol Gen Metab"},{"key":"2024032523511314400_nlad012-B30","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1007\/BF02889849","article-title":"Infantile acid maltase deficiency. I. Muscle fiber destruction after lysosomal rupture","volume":"45","author":"Griffin","year":"1984","journal-title":"Virchows Arch B Cell Pathol Incl Mol Pathol"},{"key":"2024032523511314400_nlad012-B31","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1016\/S0925-4439(02)00229-6","article-title":"Lysosomal dysfunction in muscle with special reference to glycogen storage disease type II","volume":"1637","author":"Hesselink","year":"2003","journal-title":"Biochim Biophys Acta"},{"key":"2024032523511314400_nlad012-B32","doi-asserted-by":"crossref","first-page":"831","DOI":"10.1016\/j.ymthe.2006.08.009","article-title":"Autophagy and mistargeting of therapeutic enzyme in skeletal muscle in Pompe disease","volume":"14","author":"Fukuda","year":"2006","journal-title":"Mol Ther"},{"key":"2024032523511314400_nlad012-B33","first-page":"723","article-title":"Expression of the insulin-like growth factor-II\/mannose-6-phosphate receptor in multiple human tissues during fetal life and early infancy","volume":"23","author":"Funk","year":"1992","journal-title":"J Clin Endocrinol Metab"},{"key":"2024032523511314400_nlad012-B34","first-page":"723","article-title":"Quantitation of Mr 46000 and Mr 300000 mannose 6-phosphate receptors in human cells and tissues","volume":"23","author":"Wenk","year":"1991","journal-title":"Biochem Int"},{"key":"2024032523511314400_nlad012-B35","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1007\/s00441-018-2955-2","article-title":"Skeletal muscle fibrosis: An overview","volume":"375","author":"Mahdy","year":"2019","journal-title":"Cell Tissue Res"},{"key":"2024032523511314400_nlad012-B36","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1016\/j.ymgme.2014.07.014","article-title":"Methods of diagnosis of patients with Pompe disease: Data from the Pompe Registry","volume":"113","author":"Kishnani","year":"2014","journal-title":"Mol Genet Metab"},{"key":"2024032523511314400_nlad012-B37","doi-asserted-by":"crossref","first-page":"7089","DOI":"10.1074\/jbc.R117.802843","article-title":"The dynamic life of the glycogen granule","volume":"293","author":"Prats","year":"2018","journal-title":"J Biol Chem"},{"key":"2024032523511314400_nlad012-B38","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1002\/ajmg.c.31320","article-title":"Assessing disease severity in Pompe disease: The roles of a urinary glucose tetrasaccharide biomarker and imaging techniques","volume":"160C","author":"Young","year":"2012","journal-title":"Am J Med Genet C Semin Med Genet"},{"key":"2024032523511314400_nlad012-B39","doi-asserted-by":"crossref","first-page":"989","DOI":"10.2214\/ajr.179.4.1790989","article-title":"MR imaging of primary skeletal muscle diseases in children","volume":"179","author":"Chan","year":"2002","journal-title":"AJR Am J Roentgenol"},{"key":"2024032523511314400_nlad012-B40","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1007\/s11948-010-9201-y","article-title":"Avoiding twisted pixels: Ethical guidelines for the appropriate use and manipulation of scientific digital images","volume":"16","author":"Cromey","year":"2010","journal-title":"Sci Eng Ethics"},{"key":"2024032523511314400_nlad012-B41","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1007\/BF02889851","article-title":"Infantile acid maltase deficiency. III. Ultrastructure of metachromatic material and glycogen in muscle fibers","volume":"45","author":"Griffin","year":"1984","journal-title":"Virchows Arch B Cell Pathol Incl Mol Pathol"},{"key":"2024032523511314400_nlad012-B42","volume-title":"Lysosomes: Biology, Diseases, and Therapeutics","author":"Singh","year":"2016"},{"key":"2024032523511314400_nlad012-B43","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1016\/j.ymgme.2012.05.004","article-title":"Transcriptional response to GAA deficiency (Pompe disease) in infantile-onset patients","volume":"106","author":"Palermo","year":"2012","journal-title":"Mol Genet Metab"},{"key":"2024032523511314400_nlad012-B44","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1016\/j.matbio.2017.11.010","article-title":"Inflammation and fibrosis","volume":"68\u201369","author":"Mack","year":"2018","journal-title":"Matrix Biol"},{"key":"2024032523511314400_nlad012-B45","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/j.biocel.2018.04.002","article-title":"Perivascular cell \u03b1v integrins as a target to treat skeletal muscle fibrosis","volume":"99","author":"Prazeres","year":"2018","journal-title":"Int J Biochem Cell Biol"},{"key":"2024032523511314400_nlad012-B46","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1007\/BF02889850","article-title":"Infantile acid maltase deficiency. II. Muscle fiber hypertrophy and the ultrastructure of end-stage fibers","volume":"45","author":"Griffin","year":"1984","journal-title":"Virchows Arch B Cell Pathol Incl Mol Pathol"},{"key":"2024032523511314400_nlad012-B47","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/j.matbio.2018.01.019","article-title":"The big five in fibrosis: Macrophages, myofibroblasts, matrix, mechanics, and miscommunication","volume":"68\u201369","author":"Pakshir","year":"2018","journal-title":"Matrix Biol"},{"key":"2024032523511314400_nlad012-B48","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1016\/j.addr.2018.02.009","article-title":"Tackling muscle fibrosis: From molecular mechanisms to next generation engineered models to predict drug delivery","volume":"129","author":"Bersini","year":"2018","journal-title":"Adv Drug Deliv Rev"},{"key":"2024032523511314400_nlad012-B49","doi-asserted-by":"crossref","first-page":"906","DOI":"10.1097\/NEN.0b013e3182a7f0b8","article-title":"Skeletal muscle microvasculature in the diagnosis of neuromuscular disease","volume":"72","author":"Buckley","year":"2013","journal-title":"J Neuropathol Exp Neurol"},{"key":"2024032523511314400_nlad012-B50","doi-asserted-by":"crossref","first-page":"15089","DOI":"10.1038\/s41598-017-15352-2","article-title":"AAV-mediated transcription factor EB (TFEB) gene delivery ameliorates muscle pathology and function in the murine model of Pompe disease","volume":"7","author":"Gatto","year":"2017","journal-title":"Sci Rep"},{"key":"2024032523511314400_nlad012-B51","doi-asserted-by":"crossref","first-page":"2576","DOI":"10.3390\/ijms21072576","article-title":"Lysosomal exocytosis, exosome release and secretory autophagy: The autophagic- and endo-lysosomal systems go extracellular","volume":"21","author":"Buratta","year":"2020","journal-title":"Int J Mol Sci"},{"key":"2024032523511314400_nlad012-B52","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1016\/j.cmet.2016.11.003","article-title":"Transcription factor EB controls metabolic flexibility during exercise","volume":"25","author":"Mansueto","year":"2017","journal-title":"Cell Metab"},{"key":"2024032523511314400_nlad012-B53","doi-asserted-by":"crossref","first-page":"928","DOI":"10.1007\/s13311-018-0655-y","article-title":"Pompe disease: From basic science to therapy","volume":"15","author":"Kohler","year":"2018","journal-title":"Neurotherapeutics"},{"key":"2024032523511314400_nlad012-B54","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1186\/1755-8417-1-6","article-title":"Abnormal mannose-6-phosphate receptor trafficking impairs recombinant alpha-glucosidase uptake in Pompe disease fibroblasts","volume":"1","author":"Cardone","year":"2008","journal-title":"PathoGenetics"},{"key":"2024032523511314400_nlad012-B55","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/j.ymgme.2011.02.006","article-title":"Enhanced efficacy of enzyme replacement therapy in Pompe disease through mannose-6-phosphate receptor expression in skeletal muscle","volume":"103","author":"Koeberl","year":"2011","journal-title":"Mol Genet Metab"},{"key":"2024032523511314400_nlad012-B56","doi-asserted-by":"crossref","first-page":"2171","DOI":"10.1096\/fj.13-241893","article-title":"Adjunctive albuterol enhances the response to enzyme replacement therapy in late-onset Pompe disease","volume":"28","author":"Koeberl","year":"2014","journal-title":"FASEB J"},{"key":"2024032523511314400_nlad012-B57","doi-asserted-by":"crossref","first-page":"50336","DOI":"10.1074\/jbc.M409676200","article-title":"Conjugation of mannose 6-phosphate-containing oligosaccharides to acid alpha-glucosidase improves the clearance of glycogen in Pompe mice","volume":"279","author":"Zhu","year":"2004","journal-title":"J Biol Chem"},{"key":"2024032523511314400_nlad012-B58","doi-asserted-by":"crossref","first-page":"1245","DOI":"10.1089\/hum.2019.109","article-title":"Gene therapy for Pompe disease: The time is now","volume":"30","author":"Colella","year":"2019","journal-title":"Hum Gene Ther"}],"container-title":["Journal of Neuropathology &amp; Experimental Neurology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jnen\/article-pdf\/82\/4\/345\/49535001\/nlad012.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jnen\/article-pdf\/82\/4\/345\/49535001\/nlad012.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,10,15]],"date-time":"2024-10-15T17:22:00Z","timestamp":1729012920000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jnen\/article\/82\/4\/345\/7067904"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,3,2]]},"references-count":58,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2023,3,2]]},"published-print":{"date-parts":[[2023,3,20]]}},"URL":"https:\/\/doi.org\/10.1093\/jnen\/nlad012","relation":{},"ISSN":["0022-3069","1554-6578"],"issn-type":[{"value":"0022-3069","type":"print"},{"value":"1554-6578","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2023,4,1]]},"published":{"date-parts":[[2023,3,2]]}}}