{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T02:13:28Z","timestamp":1791598408982,"version":"4.3.4"},"reference-count":41,"publisher":"Springer Science and Business Media LLC","issue":"11","license":[{"start":{"date-parts":[[2025,7,18]],"date-time":"2025-07-18T00:00:00Z","timestamp":1752796800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,7,18]],"date-time":"2025-07-18T00:00:00Z","timestamp":1752796800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100002352","name":"Ain Shams University","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100002352","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Mol Neurobiol"],"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:p>Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system (CNS), characterized by neuroinflammation and neurodegeneration. Emerging evidence links gut microbiota dysbiosis to immune dysregulation and MS progression. While extensive research has been conducted in Western populations, region-specific studies are needed to assess the influence of local genetic and environmental factors. This study investigates gut microbiota alterations in Egyptian MS patients using Oxford Nanopore sequencing to identify microbial signatures associated with disease progression. Fecal samples from 33 newly diagnosed MS patients (20 with relapsing\u2013remitting MS [RRM] and 13 with Progressive MS [PMS]) and 10 healthy controls were analyzed using long-read Oxford Nanopore sequencing of the full 16S rRNA gene. MS patients exhibited increased microbial richness but reduced evenness, with distinct gut microbiome profiles. Progressive MS was characterized by an abundance of pro-inflammatory bacteria (e.g., <jats:italic>Enterococcus faecium<\/jats:italic> and <jats:italic>Romboutsia timonensis<\/jats:italic>) and a depletion of short-chain fatty acid (SCFA)\u2013producing species (<jats:italic>Ruminococcus bromii<\/jats:italic> and <jats:italic>Faecalibacterium duncaniae<\/jats:italic>), potentially contributing to heightened neuroinflammation and disease progression. Relapsing MS exhibited microbial shifts indicative of immune dysregulation, including increased <jats:italic>Clostridium saudiense<\/jats:italic> and decreased levels of the gut-protective <jats:italic>Faecalibacterium butyricigenerans<\/jats:italic>. Functional analysis linked these microbial alterations to oxidative stress, neurotransmitter imbalance, and suppressed lipid and carbohydrate metabolism. These findings underscore the role of gut microbiota dysbiosis in MS pathogenesis and, by focusing on an underexplored Egyptian cohort, highlight region-specific microbial shifts that may inform targeted therapeutic strategies for both Progressive and Relapsing forms of MS.<\/jats:p>","DOI":"10.1007\/s12035-025-05194-9","type":"journal-article","created":{"date-parts":[[2025,7,18]],"date-time":"2025-07-18T13:40:49Z","timestamp":1752846049000},"page":"14245-14260","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Decoding the Gut Microbiota in Multiple Sclerosis Using Nanopore Long-Read Sequencing: Insights into Disease Severity and Subtypes"],"prefix":"10.1007","volume":"62","author":[{"given":"Ameera Saeed","family":"Alshinnawy","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elham A.","family":"Badiea","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahmoud Saad","family":"Swelam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed A.","family":"Sayed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9269-3128","authenticated-orcid":false,"given":"Mohamed R.","family":"Mohamed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,7,18]]},"reference":[{"key":"5194_CR1","doi-asserted-by":"publisher","first-page":"1443","DOI":"10.3390\/cimb45020094","volume":"45","author":"G Papiri","year":"2023","unstructured":"Papiri G, D\u2019Andreamatteo G, Cacchi\u00f2 G et al (2023) Multiple sclerosis: inflammatory and neuroglial aspects. Curr Issues Mol Biol 45:1443\u20131470","journal-title":"Curr Issues Mol Biol"},{"key":"5194_CR2","doi-asserted-by":"publisher","first-page":"1327","DOI":"10.2147\/CLEP.S376005","volume":"14","author":"V Perrone","year":"2022","unstructured":"Perrone V, Veronesi C, Giacomini E et al (2022) The epidemiology, treatment patterns and economic burden of different phenotypes of multiple sclerosis in Italy: relapsing-remitting multiple sclerosis and secondary progressive multiple sclerosis. Clin Epidemiol 14:1327\u20131337. https:\/\/doi.org\/10.2147\/CLEP.S376005","journal-title":"Clin Epidemiol"},{"key":"5194_CR3","doi-asserted-by":"publisher","first-page":"1816","DOI":"10.1177\/1352458520970841","volume":"26","author":"C Walton","year":"2020","unstructured":"Walton C, King R, Rechtman L et al (2020) Rising prevalence of multiple sclerosis worldwide: insights from the Atlas of MS, third edition. Multi Sclerosis J 26:1816\u20131821. https:\/\/doi.org\/10.1177\/1352458520970841","journal-title":"Multi Sclerosis J"},{"issue":"3","key":"5194_CR4","doi-asserted-by":"publisher","first-page":"100977","DOI":"10.1016\/j.lanepe.2024.100977","volume":"44","author":"E Portaccio","year":"2024","unstructured":"Portaccio E, Magyari M, Havrdova EK et al (2024) Multiple sclerosis: emerging epidemiological trends and redefining the clinical course. The Lancet Reg Health - Eur 44(3):100977. https:\/\/doi.org\/10.1016\/j.lanepe.2024.100977","journal-title":"The Lancet Reg Health - Eur"},{"issue":"40","key":"5194_CR5","doi-asserted-by":"publisher","first-page":"10713","DOI":"10.1073\/pnas.1711235114","volume":"114","author":"E Cekanaviciute","year":"2017","unstructured":"Cekanaviciute E, Yoo BB, Runia TF et al (2017) Gut bacteria from multiple sclerosis patients modulate human T cells and exacerbate symptoms in mouse models. Proc Natl Acad Sci USA 114(40):10713\u201310718. https:\/\/doi.org\/10.1073\/pnas.1711235114","journal-title":"Proc Natl Acad Sci USA"},{"issue":"40","key":"5194_CR6","doi-asserted-by":"publisher","first-page":"10719","DOI":"10.1073\/pnas.1711233114","volume":"114","author":"K Berer","year":"2017","unstructured":"Berer K, Gerdes LA, Cekanaviciute E et al (2017) Gut microbiota from multiple sclerosis patients enables spontaneous autoimmune encephalomyelitis in mice. Proc Natl Acad Sci USA 114(40):10719\u201310724. https:\/\/doi.org\/10.1073\/pnas.1711233114","journal-title":"Proc Natl Acad Sci USA"},{"key":"5194_CR7","doi-asserted-by":"publisher","unstructured":"Ochoa-Rep\u00e1raz J, Kirby TO, Kasper LH (2018) The gut microbiome and multiple sclerosis. Cold Spring Harb Perspect Med 8:. https:\/\/doi.org\/10.1101\/cshperspect.a029017","DOI":"10.1101\/cshperspect.a029017"},{"key":"5194_CR8","doi-asserted-by":"publisher","first-page":"1413","DOI":"10.2174\/1570159x19666210629145351","volume":"20","author":"X Wang","year":"2021","unstructured":"Wang X, Liang Z, Wang S et al (2021) Role of gut microbiota in multiple sclerosis and potential therapeutic implications. Curr Neuropharmacol 20:1413\u20131426. https:\/\/doi.org\/10.2174\/1570159x19666210629145351","journal-title":"Curr Neuropharmacol"},{"key":"5194_CR9","doi-asserted-by":"publisher","first-page":"4217","DOI":"10.3748\/wjg.v24.i37.4217","volume":"24","author":"CR Camara-Lemarroy","year":"2018","unstructured":"Camara-Lemarroy CR, Metz LM, Yong VW (2018) Focus on the gut-brain axis: multiple sclerosis, the intestinal barrier and the microbiome. World J Gastroenterol 24:4217\u20134223","journal-title":"World J Gastroenterol"},{"key":"5194_CR10","doi-asserted-by":"publisher","unstructured":"Al KF, Craven LJ, Gibbons S, et al (2022) Fecal microbiota transplantation is safe and tolerable in patients with multiple sclerosis: a pilot randomized controlled trial. Mult Scler J Exp Transl Clin 8:. https:\/\/doi.org\/10.1177\/20552173221086662","DOI":"10.1177\/20552173221086662"},{"key":"5194_CR11","doi-asserted-by":"publisher","first-page":"1905","DOI":"10.1002\/acn3.50862","volume":"6","author":"E Waubant","year":"2019","unstructured":"Waubant E, Lucas R, Mowry E et al (2019) Environmental and genetic risk factors for MS: an integrated review. Ann Clin Transl Neurol 6:1905\u20131922","journal-title":"Ann Clin Transl Neurol"},{"key":"5194_CR12","doi-asserted-by":"publisher","unstructured":"Johnson JS, Spakowicz DJ, Hong BY, et al (2019) Evaluation of 16S rRNA gene sequencing for species and strain-level microbiome analysis. Nat Commun 10:. https:\/\/doi.org\/10.1038\/s41467-019-13036-1","DOI":"10.1038\/s41467-019-13036-1"},{"key":"5194_CR13","doi-asserted-by":"publisher","first-page":"2371","DOI":"10.1093\/bioinformatics\/bty113","volume":"34","author":"RC Edgar","year":"2018","unstructured":"Edgar RC (2018) Updating the 97% identity threshold for 16S ribosomal RNA OTUs. Bioinformatics 34:2371\u20132375. https:\/\/doi.org\/10.1093\/bioinformatics\/bty113","journal-title":"Bioinformatics"},{"key":"5194_CR14","doi-asserted-by":"publisher","unstructured":"Ben\u00edtez-P\u00e1ez A, Portune KJ, Sanz Y (2016) Species-level resolution of 16S rRNA gene amplicons sequenced through the MinIONTM portable nanopore sequencer. Gigascience 5:. https:\/\/doi.org\/10.1186\/s13742-016-0111-z","DOI":"10.1186\/s13742-016-0111-z"},{"key":"5194_CR15","doi-asserted-by":"publisher","first-page":"845","DOI":"10.1038\/s41592-022-01520-4","volume":"19","author":"KD Curry","year":"2022","unstructured":"Curry KD, Wang Q, Nute MG et al (2022) Emu: species-level microbial community profiling of full-length 16S rRNA Oxford Nanopore sequencing data. Nat Methods 19:845\u2013853. https:\/\/doi.org\/10.1038\/s41592-022-01520-4","journal-title":"Nat Methods"},{"key":"5194_CR16","doi-asserted-by":"publisher","first-page":"2666","DOI":"10.1093\/bioinformatics\/bty149","volume":"34","author":"W De Coster","year":"2018","unstructured":"De Coster W, D\u2019Hert S, Schultz DT et al (2018) NanoPack: visualizing and processing long-read sequencing data. Bioinformatics 34:2666\u20132669. https:\/\/doi.org\/10.1093\/bioinformatics\/bty149","journal-title":"Bioinformatics"},{"key":"5194_CR17","doi-asserted-by":"publisher","first-page":"3094","DOI":"10.1093\/bioinformatics\/bty191","volume":"34","author":"H Li","year":"2018","unstructured":"Li H (2018) Minimap2: pairwise alignment for nucleotide sequences. Bioinformatics 34:3094\u20133100. https:\/\/doi.org\/10.1093\/bioinformatics\/bty191","journal-title":"Bioinformatics"},{"key":"5194_CR18","doi-asserted-by":"publisher","first-page":"2078","DOI":"10.1093\/bioinformatics\/btp352","volume":"25","author":"H Li","year":"2009","unstructured":"Li H, Handsaker B, Wysoker A et al (2009) The sequence alignment\/map format and SAMtools. Bioinformatics 25:2078\u20132079. https:\/\/doi.org\/10.1093\/bioinformatics\/btp352","journal-title":"Bioinformatics"},{"issue":"9","key":"5194_CR19","doi-asserted-by":"publisher","first-page":"844","DOI":"10.1016\/j.jgg.2021.03.006","volume":"48","author":"W Shen","year":"2019","unstructured":"Shen W, Xiong J (2019) TaxonKit: a cross-platform and efficient NCBI taxonomy toolkit. J Genet Genomics 48(9):844\u2013850. https:\/\/doi.org\/10.1016\/j.jgg.2021.03.006","journal-title":"J Genet Genomics"},{"key":"5194_CR20","doi-asserted-by":"publisher","first-page":"1100","DOI":"10.1093\/bioinformatics\/btv694","volume":"32","author":"C Lee","year":"2016","unstructured":"Lee C, Patil S, Sartor MA (2016) RNA-Enrich: a cut-off free functional enrichment testing method for RNA-seq with improved detection power. Bioinformatics 32:1100\u20131102. https:\/\/doi.org\/10.1093\/bioinformatics\/btv694","journal-title":"Bioinformatics"},{"key":"5194_CR21","doi-asserted-by":"publisher","unstructured":"McMurdie PJ, Holmes S (2013) Phyloseq: an R package for reproducible interactive analysis and graphics of microbiome census data. PLoS One 8:. https:\/\/doi.org\/10.1371\/journal.pone.0061217","DOI":"10.1371\/journal.pone.0061217"},{"key":"5194_CR22","doi-asserted-by":"publisher","first-page":"669","DOI":"10.1038\/s41587-020-0550-z","volume":"38","author":"HH Caicedo","year":"2020","unstructured":"Caicedo HH, Hashimoto DA, Caicedo JC et al (2020) Overcoming barriers to early disease intervention. Nat Biotechnol 38:669\u2013673","journal-title":"Nat Biotechnol"},{"key":"5194_CR23","doi-asserted-by":"publisher","first-page":"169","DOI":"10.1038\/ismej.2010.133","volume":"5","author":"C Lozupone","year":"2011","unstructured":"Lozupone C, Lladser ME, Knights D et al (2011) UniFrac: an effective distance metric for microbial community comparison. ISME J 5:169\u2013172","journal-title":"ISME J"},{"key":"5194_CR24","doi-asserted-by":"publisher","unstructured":"Ghimire S, Lehman PC, Aguilar Meza LS, et al (2025) Specific microbial ratio in the gut microbiome is associated with multiple sclerosis. Proc Natl Acad Sci U S A 122:. https:\/\/doi.org\/10.1073\/pnas.2413953122","DOI":"10.1073\/pnas.2413953122"},{"key":"5194_CR25","doi-asserted-by":"publisher","unstructured":"Miyake S, Kim S, Suda W, et al (2015) Dysbiosis in the gut microbiota of patients with multiple sclerosis, with a striking depletion of species belonging to clostridia XIVa and IV clusters. PLoS One 10:. https:\/\/doi.org\/10.1371\/journal.pone.0137429","DOI":"10.1371\/journal.pone.0137429"},{"key":"5194_CR26","doi-asserted-by":"publisher","unstructured":"Chen J, Chia N, Kalari KR, et al (2016) Multiple sclerosis patients have a distinct gut microbiota compared to healthy controls. Sci Rep 6:. https:\/\/doi.org\/10.1038\/srep28484","DOI":"10.1038\/srep28484"},{"key":"5194_CR27","doi-asserted-by":"publisher","unstructured":"Jangi S, Gandhi R, Cox LM, et al (2016) Alterations of the human gut microbiome in multiple sclerosis. Nat Commun 7:. https:\/\/doi.org\/10.1038\/ncomms12015","DOI":"10.1038\/ncomms12015"},{"key":"5194_CR28","doi-asserted-by":"publisher","unstructured":"Maaskant A, Voermans B, Levin E, et al (2024) Microbiome signature suggestive of lactose-intolerance in rhesus macaques (Macaca mulatta) with intermittent chronic diarrhea. Anim Microbiome 6:. https:\/\/doi.org\/10.1186\/s42523-024-00338-z","DOI":"10.1186\/s42523-024-00338-z"},{"key":"5194_CR29","doi-asserted-by":"publisher","unstructured":"Pr\u00f6bstel AK, Zhou X, Baumann R, et al (2020) Gut microbiota\u2013specific iga+ B cells traffic to the CNS in active multiple sclerosis. Sci Immunol 5:. https:\/\/doi.org\/10.1126\/SCIIMMUNOL.ABC7191","DOI":"10.1126\/SCIIMMUNOL.ABC7191"},{"key":"5194_CR30","doi-asserted-by":"publisher","first-page":"1507","DOI":"10.1177\/0963689719873890","volume":"28","author":"G Schepici","year":"2019","unstructured":"Schepici G, Silvestro S, Bramanti P, Mazzon E (2019) The gut microbiota in multiple sclerosis: an overview of clinical trials. Cell Transplant 28:1507\u20131527","journal-title":"Cell Transplant"},{"key":"5194_CR31","doi-asserted-by":"publisher","unstructured":"Li J, Feng S, Wang Z, et al (2023) Limosilactobacillus mucosae-derived extracellular vesicles modulates macrophage phenotype and orchestrates gut homeostasis in a diarrheal piglet model. NPJ Biofilms Microbiomes 9:. https:\/\/doi.org\/10.1038\/s41522-023-00403-6","DOI":"10.1038\/s41522-023-00403-6"},{"key":"5194_CR32","doi-asserted-by":"publisher","unstructured":"Ling Z, Cheng Y, Yan X, et al (2020) Alterations of the fecal microbiota in Chinese patients with multiple sclerosis. Front Immunol 11:. https:\/\/doi.org\/10.3389\/fimmu.2020.590783","DOI":"10.3389\/fimmu.2020.590783"},{"issue":"5","key":"5194_CR33","doi-asserted-by":"publisher","first-page":"4624","DOI":"10.3390\/ijerph20054624","volume":"20","author":"A Ordo\u00f1ez-Rodriguez","year":"2023","unstructured":"Ordo\u00f1ez-Rodriguez A, Roman P, Rueda-Ruzafa L et al (2023) Changes in gut microbiota and multiple sclerosis: a systematic review. Int J Environ Res Public Health 20(5):4624. https:\/\/doi.org\/10.3390\/ijerph20054624","journal-title":"Int J Environ Res Public Health"},{"key":"5194_CR34","doi-asserted-by":"publisher","first-page":"1195","DOI":"10.1002\/ana.26084","volume":"89","author":"LM Cox","year":"2021","unstructured":"Cox LM, Maghzi AH, Liu S et al (2021) Gut microbiome in progressive multiple sclerosis. Ann Neurol 89:1195\u20131211. https:\/\/doi.org\/10.1002\/ana.26084","journal-title":"Ann Neurol"},{"key":"5194_CR35","doi-asserted-by":"publisher","first-page":"169","DOI":"10.1002\/ana.1077","volume":"50","author":"P Werner","year":"2001","unstructured":"Werner P, Pitt D, Raine CS (2001) Multiple sclerosis: altered glutamate homeostasis in lesions correlates with oligodendrocyre and axonal damage. Ann Neurol 50:169\u2013180. https:\/\/doi.org\/10.1002\/ana.1077","journal-title":"Ann Neurol"},{"key":"5194_CR36","doi-asserted-by":"publisher","unstructured":"Thirion F, Sellebjerg F, Fan Y, et al (2023) The gut microbiota in multiple sclerosis varies with disease activity. Genome Med 15:. https:\/\/doi.org\/10.1186\/s13073-022-01148-1","DOI":"10.1186\/s13073-022-01148-1"},{"issue":"6","key":"5194_CR37","doi-asserted-by":"publisher","first-page":"e00083","DOI":"10.1128\/mSystems.00083-18","volume":"3","author":"E Cekanaviciute","year":"2018","unstructured":"Cekanaviciute E, Pr\u00f6bstel A-K, Thomann A et al (2018) Multiple sclerosis-associated changes in the composition and immune functions of spore-forming bacteria. mSystems 3(6):e00083-18. https:\/\/doi.org\/10.1128\/mSystems.00083-18","journal-title":"mSystems"},{"key":"5194_CR38","doi-asserted-by":"publisher","first-page":"1113","DOI":"10.1002\/1873-3468.13013","volume":"592","author":"G Campbell","year":"2018","unstructured":"Campbell G, Mahad DJ (2018) Mitochondrial dysfunction and axon degeneration in progressive multiple sclerosis. FEBS Lett 592:1113\u20131121","journal-title":"FEBS Lett"},{"key":"5194_CR39","doi-asserted-by":"publisher","first-page":"237","DOI":"10.1016\/j.ajhg.2019.06.005","volume":"105","author":"V Tiwari","year":"2019","unstructured":"Tiwari V, Wilson DM (2019) DNA damage and associated DNA repair defects in disease and premature aging. Am J Hum Genet 105:237\u2013257","journal-title":"Am J Hum Genet"},{"key":"5194_CR40","doi-asserted-by":"publisher","unstructured":"Montgomery TL, Wang Q, Mirza A, et al (2024) Identification of commensal gut microbiota signatures as predictors of clinical severity and disease progression in multiple sclerosis. Sci Rep 14:. https:\/\/doi.org\/10.1038\/s41598-024-64369-x","DOI":"10.1038\/s41598-024-64369-x"},{"key":"5194_CR41","doi-asserted-by":"publisher","first-page":"1067","DOI":"10.1016\/j.cell.2020.02.035","volume":"180","author":"A Duscha","year":"2020","unstructured":"Duscha A, Gisevius B, Hirschberg S et al (2020) Propionic acid shapes the multiple sclerosis disease course by an immunomodulatory mechanism. Cell 180:1067-1080.e16. https:\/\/doi.org\/10.1016\/j.cell.2020.02.035","journal-title":"Cell"}],"container-title":["Molecular Neurobiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12035-025-05194-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s12035-025-05194-9\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12035-025-05194-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T07:29:25Z","timestamp":1759994965000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s12035-025-05194-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,18]]},"references-count":41,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2025,11]]}},"alternative-id":["5194"],"URL":"https:\/\/doi.org\/10.1007\/s12035-025-05194-9","relation":{},"ISSN":["0893-7648","1559-1182"],"issn-type":[{"value":"0893-7648","type":"print"},{"value":"1559-1182","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7,18]]},"assertion":[{"value":"3 April 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"27 June 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"18 July 2025","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 no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}