{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T21:19:41Z","timestamp":1791235181644,"version":"4.1.0"},"reference-count":60,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2024,7,11]],"date-time":"2024-07-11T00:00:00Z","timestamp":1720656000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Acute limb ischemia (ALI) is defined as a sudden reduction in blood flow to a limb, resulting in cessation of blood flow and, therefore, cessation of the delivery of nutrients and oxygen to the tissues of the lower limb. Despite optimal treatment to restore blood flow to ischemic tissues, some patients may suffer from ischemia\/reperfusion (I\/R) syndrome, the most severe complication after a revascularization procedure used to restore blood flow. There are multiple molecular and cellular factors that are involved in each phase of ALI. This review focuses firstly on molecular and cellular factors of arterial thrombosis, highlighting the role of atherosclerotic plaques, smooth muscle cells (SMCs), and cytokine which may alter key components of the extracellular matrix (ECM). Then, molecular and cellular factors of arterial embolism will be discussed, highlighting the importance of thrombi composition. Molecular and cellular factors of ischemia\/reperfusion syndrome are analyzed in depth, highlighting several important mechanisms related to tissue damage, such as inflammation, apoptosis, autophagy, necrosis, and necroptosis. Furthermore, local and general complications of ALI are discussed in the context of molecular alterations. Ultimately, the role of novel biomarkers and targeted therapies is discussed.<\/jats:p>","DOI":"10.3390\/biom14070838","type":"journal-article","created":{"date-parts":[[2024,7,12]],"date-time":"2024-07-12T14:04:35Z","timestamp":1720793075000},"page":"838","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Molecular Insight into Acute Limb Ischemia"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9199-8755","authenticated-orcid":false,"given":"Davide","family":"Costa","sequence":"first","affiliation":[{"name":"Department of Medical and Surgical Sciences, Magna Graecia University of Catanzaro, 88100 Catanzaro, Italy"},{"name":"Interuniversity Center of Phlebolymphology (CIFL), \u201cMagna Graecia\u201d University, 88100 Catanzaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1011-9844","authenticated-orcid":false,"given":"Nicola","family":"Ielapi","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Sciences, Magna Graecia University of Catanzaro, 88100 Catanzaro, Italy"},{"name":"Interuniversity Center of Phlebolymphology (CIFL), \u201cMagna Graecia\u201d University, 88100 Catanzaro, Italy"},{"name":"Department of Public Health and Infectious Disease, \u201cSapienza\u201d University of Rome, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paolo","family":"Perri","sequence":"additional","affiliation":[{"name":"Department of Vascular and Endovascular Surgery, Annunziata Hospital, 1 Via Migliori, 87100 Cosenza, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7680-0851","authenticated-orcid":false,"given":"Roberto","family":"Minici","sequence":"additional","affiliation":[{"name":"Department of Experimental and Clinical Medicine, Magna Graecia University of Catanzaro, 88100 Catanzaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teresa","family":"Faga","sequence":"additional","affiliation":[{"name":"Department of Health Sciences, Magna Graecia University of Catanzaro, 88100 Catanzaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashour","family":"Michael","sequence":"additional","affiliation":[{"name":"Department of Health Sciences, Magna Graecia University of Catanzaro, 88100 Catanzaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9507-9791","authenticated-orcid":false,"given":"Umberto Marcello","family":"Bracale","sequence":"additional","affiliation":[{"name":"Department of Public Health, University Federico II of Naples, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7974-3792","authenticated-orcid":false,"given":"Michele","family":"Andreucci","sequence":"additional","affiliation":[{"name":"Department of Health Sciences, Magna Graecia University of Catanzaro, 88100 Catanzaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4477-7412","authenticated-orcid":false,"given":"Raffaele","family":"Serra","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Sciences, Magna Graecia University of Catanzaro, 88100 Catanzaro, Italy"},{"name":"Interuniversity Center of Phlebolymphology (CIFL), \u201cMagna Graecia\u201d University, 88100 Catanzaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,7,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2198","DOI":"10.1056\/NEJMcp1006054","article-title":"Clinical practice. Acute limb ischemia","volume":"366","author":"Creager","year":"2012","journal-title":"N. Engl. J. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1016\/j.ajem.2023.09.052","article-title":"High risk and low prevalence diseases: Acute limb ischemia","volume":"74","author":"Arnold","year":"2023","journal-title":"Am. J. Emerg. Med."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Simon, F., Oberhuber, A., Floros, N., Busch, A., Wagenh\u00e4user, M.U., Schelzig, H., and Duran, M. (2018). Acute Limb Ischemia-Much More Than Just a Lack of Oxygen. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19020374"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"S5","DOI":"10.1016\/j.jvs.2006.12.037","article-title":"TASC II Working Group Inter-Society Consensus for the Management of Peripheral Arterial Disease (TASC II)","volume":"45","author":"Norgren","year":"2007","journal-title":"J. Vasc. Surg."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"669","DOI":"10.1016\/j.jvs.2014.03.244","article-title":"Trends in the incidence, treatment, and outcomes of acute lower extremity ischemia in the United States Medicare population","volume":"60","author":"Baril","year":"2014","journal-title":"J. Vasc. Surg."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1016\/j.avsg.2022.04.040","article-title":"Mechanisms and Interventions on Acute Lower Limb Ischemia\/Reperfusion Injury: A Review and Insights from Cell to Clinical Investigations","volume":"86","author":"Apichartpiyakul","year":"2022","journal-title":"Ann. Vasc. Surg."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"854","DOI":"10.1111\/iwj.12392","article-title":"Biomarkers in post-reperfusion syndrome after acute lower limb ischaemia","volume":"13","author":"Massara","year":"2016","journal-title":"Int. Wound J."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Lorentzen, L.G., Yeung, K., Eldrup, N., Eiberg, J.P., Sillesen, H.H., and Davies, M.J. (2024). Proteomic analysis of the extracellular matrix of human atherosclerotic plaques shows marked changes between plaque types. Matrix Biol. Plus, 21.","DOI":"10.1016\/j.mbplus.2024.100141"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1016\/j.vph.2012.02.011","article-title":"Crosstalk between macrophages and smooth muscle cells in atherosclerotic vascular diseases","volume":"57","author":"Koga","year":"2012","journal-title":"Vasc. Pharmacol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1262","DOI":"10.1161\/01.ATV.20.5.1262","article-title":"Lessons from sudden coronary death: A comprehensive morphological classification scheme for atherosclerotic lesions","volume":"20","author":"Virmani","year":"2000","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1111\/j.1749-6632.2012.06497.x","article-title":"Plaque neovascularization: Defense mechanisms, betrayal, or a war in progress","volume":"1254","author":"Moreno","year":"2012","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"921","DOI":"10.1001\/jama.281.10.921","article-title":"Plaque rupture and sudden death related to exertion in men with coronary artery disease","volume":"281","author":"Burke","year":"1999","journal-title":"JAMA"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1055\/s-0037-1616240","article-title":"Apoptosis as a determinant of atherothrombosis","volume":"86","author":"Tedgui","year":"2001","journal-title":"Thromb. Haemost."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"77","DOI":"10.4103\/2229-5151.109429","article-title":"Arterial embolism","volume":"3","author":"Lyaker","year":"2013","journal-title":"Int. J. Crit. Illn. Inj. Sci."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2370","DOI":"10.1161\/ATVBAHA.120.315754","article-title":"Thrombus Structural Composition in Cardiovascular Disease","volume":"41","author":"Alkarithi","year":"2021","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/j.biocel.2014.02.013","article-title":"Mitochondria: Mitochondrial participation in ischemia-reperfusion injury in skeletal muscle","volume":"50","author":"Lejay","year":"2014","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/0741-5214(90)90360-M","article-title":"The effect of ischemia\/reperfusion on adenine nucleotide metabolism and xanthine oxidase production in skeletal muscle","volume":"12","author":"Lindsay","year":"1990","journal-title":"J. Vasc. Surg."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1062","DOI":"10.1126\/science.1219855","article-title":"Mitochondrial fission, fusion, and stress","volume":"337","author":"Youle","year":"2012","journal-title":"Science"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2908","DOI":"10.1007\/s11999-015-4332-8","article-title":"Can Cytoprotective Cobalt Protoporphyrin Protect Skeletal Muscle and Muscle-derived Stem Cells From Ischemic Injury?","volume":"473","author":"Wilson","year":"2015","journal-title":"Clin. Orthop. Relat. Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1016\/S0022-2828(85)80017-1","article-title":"Xanthine oxidase as a source of free radical damage in myocardial ischemia","volume":"17","author":"Chambers","year":"1985","journal-title":"J. Mol. Cell. Cardiol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1016\/j.bbrc.2017.05.053","article-title":"Glycine-nitronyl nitroxide conjugate protects human umbilical vein endothelial cells against hypoxia\/reoxygenation injury via multiple mechanisms and ameliorates hind limb ischemia\/reperfusion injury in rats","volume":"488","author":"Gao","year":"2017","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"H1923","DOI":"10.1152\/ajpheart.00935.2003","article-title":"Differential contribution of necrosis and apoptosis in myocardial ischemia-reperfusion injury","volume":"286","author":"McCully","year":"2004","journal-title":"Am. J. Physiol.-Heart Circ. Physiol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1111\/iwj.12247","article-title":"Fatal early peripheral post-reperfusion syndrome and the role of cutaneous signs","volume":"13","author":"Serra","year":"2016","journal-title":"Int. Wound J."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1159\/000072226","article-title":"Development of \u2018no-reflow\u2019 phenomenon in ischemia\/reperfusion injury: Failure of active vasomotility and not simply passive vasoconstriction","volume":"35","author":"Nanobashvili","year":"2003","journal-title":"Eur. Surg. Res."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1097\/ALN.0b013e3182289988","article-title":"Sevoflurane reduces leukocyte and platelet adhesion after ischemia-reperfusion by protecting the endothelial glycocalyx","volume":"115","author":"Chappell","year":"2011","journal-title":"Anesthesiology"},{"key":"ref_26","first-page":"229","article-title":"Clinical implications of ischaemia-reperfusion injury","volume":"9","author":"Abela","year":"2003","journal-title":"Pathophysiol. Off. J. Int. Soc. Pathophysiol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1016\/j.carpath.2013.02.006","article-title":"Rapidly progressing fatal reperfusion syndrome caused by acute critical ischemia of the lower limb","volume":"22","author":"Kaliszky","year":"2013","journal-title":"Cardiovasc. Pathol. Off. J. Soc. Cardiovasc. Pathol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1016\/j.amjsurg.2003.07.027","article-title":"Major lower extremity amputations at a Veterans Affairs hospital","volume":"186","author":"Cruz","year":"2003","journal-title":"Am. J. Surg."},{"key":"ref_29","first-page":"192","article-title":"Oxygen free radicals mediate ischemia-induced lung injury","volume":"105","author":"Klausner","year":"1989","journal-title":"Surgery"},{"key":"ref_30","first-page":"122","article-title":"Pathophysiology and related studies of the no reflow phenomenon in skeletal muscle","volume":"314","author":"Allen","year":"1995","journal-title":"Clin. Orthop. Relat. Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1023\/A:1006832207864","article-title":"Inflammatory responses to ischemia and reperfusion in skeletal muscle","volume":"179","author":"Gute","year":"1998","journal-title":"Mol. Cell. Biochem."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1016\/B978-0-12-394309-5.00006-7","article-title":"Cell biology of ischemia\/reperfusion injury","volume":"298","author":"Kalogeris","year":"2012","journal-title":"Int. Rev. Cell Mol. Biol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"e331","DOI":"10.1161\/STROKEAHA.108.531632","article-title":"Apoptotic mechanisms after cerebral ischemia","volume":"40","author":"Broughton","year":"2009","journal-title":"Stroke"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1152\/physrev.00013.2006","article-title":"Mitochondrial membrane permeabilization in cell death","volume":"87","author":"Kroemer","year":"2007","journal-title":"Physiol. Rev."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1146\/annurev.physiol.010908.163111","article-title":"Cell death in the pathogenesis of heart disease: Mechanisms and significance","volume":"72","author":"Whelan","year":"2010","journal-title":"Annu. Rev. Physiol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1146\/annurev-physiol-021909-135757","article-title":"Autophagy during cardiac stress: Joys and frustrations of autophagy","volume":"72","author":"Gottlieb","year":"2010","journal-title":"Annu. Rev. Physiol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1146\/annurev-genet-102808-114910","article-title":"Regulation mechanisms and signaling pathways of autophagy","volume":"43","author":"He","year":"2009","journal-title":"Annu. Rev. Genet."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.cell.2007.12.018","article-title":"Autophagy in the pathogenesis of disease","volume":"132","author":"Levine","year":"2008","journal-title":"Cell"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1038\/cr.2008.31","article-title":"TNFalpha and reactive oxygen species in necrotic cell death","volume":"18","author":"Morgan","year":"2008","journal-title":"Cell Res."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1053\/j.semvascsurg.2015.01.007","article-title":"Biochemical markers of acute limb ischemia, rhabdomyolysis, and impact on limb salvage","volume":"27","author":"Watson","year":"2014","journal-title":"Semin. Vasc. Surg."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1705","DOI":"10.2147\/IJGM.S285262","article-title":"Precision Medicine and Precision Nursing: The Era of Biomarkers and Precision Health","volume":"13","author":"Ielapi","year":"2020","journal-title":"Int. J. Gen. Med."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"173","DOI":"10.2174\/1574887115999201027145406","article-title":"Neutrophil-to-lymphocyte Ratio and Platelet-to-lymphocyte Ratio as Biomarkers for Cardiovascular Surgery Procedures: A Literature Review","volume":"16","author":"Serra","year":"2021","journal-title":"Rev. Recent Clin. Trials"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1177\/1538574410396590","article-title":"Neutrophil-lymphocyte ratio predicts medium-term survival following elective major vascular surgery: A cross-sectional study","volume":"45","author":"Bhutta","year":"2011","journal-title":"Vasc. Endovasc. Surg."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1016\/j.jvs.2014.03.277","article-title":"Neutrophil-lymphocyte ratio as a prognostic marker of outcome in infrapopliteal percutaneous interventions for critical limb ischemia","volume":"60","author":"Chan","year":"2014","journal-title":"J. Vasc. Surg."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Taurino, M., Aloisi, F., Del Porto, F., Nespola, M., Dezi, T., Pranteda, C., Rizzo, L., and Sirignano, P. (2021). Neutrophil-to-Lymphocyte Ratio Could Predict Outcome in Patients Presenting with Acute Limb Ischemia. J. Clin. Med., 10.","DOI":"10.3390\/jcm10194343"},{"key":"ref_46","first-page":"115","article-title":"Pulmonary embolism, metalloproteinsases and neutrophil gelatinase associated lipocalin","volume":"14","author":"Busceti","year":"2013","journal-title":"Acta Phlebol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"378","DOI":"10.1016\/j.avsg.2023.04.008","article-title":"Vascular Biology of Arterial Aneurysms","volume":"94","author":"Costa","year":"2023","journal-title":"Ann. Vasc. Surg."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Costa, D., Scalise, E., Ielapi, N., Bracale, U.M., Andreucci, M., and Serra, R. (2024). Metalloproteinases as Biomarkers and Sociomarkers in Human Health and Disease. Biomolecules, 14.","DOI":"10.3390\/biom14010096"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"10740","DOI":"10.1038\/s41598-019-47217-1","article-title":"A Pro-Inflammatory Biomarker-Profile Predicts Amputation-Free Survival in Patients with Severe Limb Ischemia","volume":"9","author":"Gremmels","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_50","first-page":"e11488","article-title":"Acute Limb Ischemia: A Rare Complication of COVID-19","volume":"12","author":"Hasan","year":"2020","journal-title":"Cureus"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1055\/a-1544-5431","article-title":"Circulating Cytokines and Growth Factors in Acute Cerebral Large Vessel Occlusion-Association with Success of Endovascular Treatment","volume":"122","author":"Grosse","year":"2022","journal-title":"Thromb. Haemost."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Saenz-Pipaon, G., Martinez-Aguilar, E., Orbe, J., Gonz\u00e1lez Miqueo, A., Fernandez-Alonso, L., Paramo, J.A., and Roncal, C. (2021). The Role of Circulating Biomarkers in Peripheral Arterial Disease. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22073601"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"203","DOI":"10.4103\/0974-2700.115346","article-title":"The role of allopurinol\u2019s timing in the ischemia reperfusion injury of small intestine","volume":"6","author":"Sapalidis","year":"2013","journal-title":"J. Emergencies Trauma Shock."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"841","DOI":"10.1042\/BST0380841","article-title":"A pore way to die: The role of mitochondria in reperfusion injury and cardioprotection","volume":"38","author":"Halestrap","year":"2010","journal-title":"Biochem. Soc. Trans."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"I251","DOI":"10.1161\/CIRCULATIONAHA.105.000794","article-title":"A novel strategy for myocardial protection by combined antibody therapy inhibiting both P-selectin and intercellular adhesion molecule-1 via retrograde intracoronary route","volume":"114","author":"Fukushima","year":"2006","journal-title":"Circulation"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"e501","DOI":"10.1002\/ams2.501","article-title":"Therapeutic strategies for ischemia reperfusion injury in emergency medicine","volume":"7","author":"Naito","year":"2020","journal-title":"Acute Med. Surg."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"971","DOI":"10.3109\/10715762.2010.500328","article-title":"Recent advances in hydrogen research as a therapeutic medical gas","volume":"44","author":"Huang","year":"2010","journal-title":"Free. Radic. Res."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3164\/jcbn.08-193R","article-title":"Therapeutic antioxidant medical gas","volume":"44","author":"Nakao","year":"2009","journal-title":"J. Clin. Biochem. Nutr."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"2867","DOI":"10.2174\/138161206777947597","article-title":"The role of cytokines in pharmacological modulation of hepatic ischemia\/reperfusion injury","volume":"12","author":"Husted","year":"2006","journal-title":"Curr. Pharm. Des."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"414","DOI":"10.4300\/JGME-D-22-00480.1","article-title":"Narrative Reviews: Flexible, Rigorous, and Practical","volume":"14","author":"Sukhera","year":"2022","journal-title":"J. Grad. Med. Educ."}],"container-title":["Biomolecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-273X\/14\/7\/838\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T15:15:26Z","timestamp":1760109326000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-273X\/14\/7\/838"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,7,11]]},"references-count":60,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2024,7]]}},"alternative-id":["biom14070838"],"URL":"https:\/\/doi.org\/10.3390\/biom14070838","relation":{},"ISSN":["2218-273X"],"issn-type":[{"value":"2218-273X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,7,11]]}}}