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Inclusion: prospective and retrospective observational studies and randomized trials. Participants were humans with vital permanent teeth and a well\u2010defined pulpal diagnosis. Exclusion: deciduous teeth,\n                      <jats:italic>in vitro<\/jats:italic>\n                      and animal studies. Risk of bias was assessed with modified\u2010Downs and Black quality assessment checklist. Meta\u2010analysis was performed using bivariate random effect model in Meta\u2010DiSc 2.0 and RevMan and the quality of the evidence was assessed using Grading of Recommendations Assessment, Development and Evaluation.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Fifty\u2010six studies were selected, reporting &gt;70 individual biomolecules investigating pulpal health and disease at the gene and protein level. Most studies were of low and fair quality. Among the biomolecules investigated, IL\u20108 and IL\u20106 demonstrated a level of diagnostic accuracy with high sensitivity, specificity and DOR to discriminate between healthy pulps and those exhibiting spontaneous pain suggestive of IRP (low\u2010certainty evidence). However, none was shown to have high DOR and the ability to discriminate between pulpitic states (very low certainty evidence). Limited data suggests high levels of matrix metalloproteinase 9 correlate with poorer outcomes of full pulpotomy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>The inability of identified molecular inflammatory markers to discriminate between dental pulps with spontaneous and non\u2010spontaneous pain should shift the focus to improved study quality or the pursuit of other molecules potentially associated with healing and repair.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Low\u2010quality evidence suggests IL\u20108 and IL\u20106 demonstrated level of diagnostic accuracy to discriminate between healthy pulps and those exhibiting spontaneous pain. There is a need for standardized biomarker diagnostic and prognostic studies focusing on solutions that can accurately determine the degree of pulp inflammation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Registration<\/jats:title>\n                    <jats:p>PROSPERO CRD42021259305.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/iej.13950","type":"journal-article","created":{"date-parts":[[2023,7,1]],"date-time":"2023-07-01T06:18:55Z","timestamp":1688192335000},"page":"1160-1177","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":37,"title":["Molecular biomarkers for objective assessment of symptomatic pulpitis: A systematic review and meta\u2010analysis"],"prefix":"10.1111","volume":"56","author":[{"given":"Riham N.","family":"Karrar","sequence":"first","affiliation":[{"name":"Faculty of Dentistry University of Khartoum  Khartoum Sudan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1623-8641","authenticated-orcid":false,"given":"Siobhan","family":"Cushley","sequence":"additional","affiliation":[{"name":"School of Medicine Dentistry and Biomedical Sciences Queen's University Belfast  Belfast UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8690-2379","authenticated-orcid":false,"given":"Henry F.","family":"Duncan","sequence":"additional","affiliation":[{"name":"Division of Restorative Dentistry &amp; Periodontology Dublin Dental University Hospital, Trinity College Dublin, University of Dublin  Dublin Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3150-1150","authenticated-orcid":false,"given":"Fionnuala T.","family":"Lundy","sequence":"additional","affiliation":[{"name":"School of Medicine Dentistry and Biomedical Sciences Queen's University Belfast  Belfast UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salma A.","family":"Abushouk","sequence":"additional","affiliation":[{"name":"Faculty of Dentistry University of Khartoum  Khartoum Sudan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2926-7257","authenticated-orcid":false,"given":"Mike","family":"Clarke","sequence":"additional","affiliation":[{"name":"School of Medicine Dentistry and Biomedical Sciences Queen's University Belfast  Belfast UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5314-7378","authenticated-orcid":false,"given":"Ikhlas A.","family":"El\u2010Karim","sequence":"additional","affiliation":[{"name":"School of Medicine Dentistry and Biomedical Sciences Queen's University Belfast  Belfast UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,7,17]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.joen.2012.12.035"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.joen.2012.11.011"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1177\/154405910708601215"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.joen.2020.07.013"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/iej.13547"},{"key":"e_1_2_11_7_1","unstructured":"American Association of Endodontists. 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