{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T13:19:30Z","timestamp":1785417570087,"version":"3.56.0"},"reference-count":56,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T00:00:00Z","timestamp":1785283200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000050","name":"National Heart Lung and Blood Institute","doi-asserted-by":"publisher","award":["HL163471"],"award-info":[{"award-number":["HL163471"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"award":["HL163471"],"award-info":[{"award-number":["HL163471"]}],"id":[{"id":"https:\/\/ror.org\/012pb6c26","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000968","name":"American Heart Association","doi-asserted-by":"publisher","award":["26BCDA1622687"],"award-info":[{"award-number":["26BCDA1622687"]}],"id":[{"id":"10.13039\/100000968","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000968","name":"American Heart Association","doi-asserted-by":"publisher","award":["26PRE1563350"],"award-info":[{"award-number":["26PRE1563350"]}],"id":[{"id":"10.13039\/100000968","id-type":"DOI","asserted-by":"publisher"}]},{"award":["26BCDA1622687"],"award-info":[{"award-number":["26BCDA1622687"]}],"id":[{"id":"https:\/\/ror.org\/013kjyp64","id-type":"ROR","asserted-by":"publisher"}]},{"award":["26PRE1563350"],"award-info":[{"award-number":["26PRE1563350"]}],"id":[{"id":"https:\/\/ror.org\/013kjyp64","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Background\/Objectives: ADAMTS13 is a plasma metalloprotease that cleaves von Willebrand Factor (vWF), a multimeric glycoprotein involved in platelet recruitment during primary hemostasis. Inhibition of ADAMTS13 activity by autoantibodies causes immune thrombotic thrombocytopenic purpura (iTTP). Growing evidence has established allostery as a key contributor to iTTP pathophysiology. This review summarizes the current understanding of how ADAMTS13 structure contributes to its function and regulation and examines anti-ADAMTS13 antibodies as pathological allosteric modulators in iTTP and their associated allosteric mechanisms. Methods: We searched the published literature investigating the role of allostery in iTTP, with special emphasis on studies that satisfy the functional definition of allostery, which addresses how a ligand binding to a protein influences a second ligand-binding event at a distinct site. Results: Anti-ADAMTS13 antibodies primarily affect catalytic turnover as opposed to substrate binding affinity, consistent with their characterization as V-type allosteric ligands. Biophysical studies have revealed extensive and distal structural changes upon antibody binding, including near the enzyme\u2019s active site. However, more recent work utilizing full-length Immunoglobulin G (IgG) molecules and polyclonal iTTP patient plasma suggests that the mechanistic complexity is greater than initially appreciated, with multiple mechanisms likely coexisting. Conclusions: While significant progress has been made to understand allostery in ADAMTS13 and iTTP, many questions remain unresolved. Further elucidation of these underlying mechanisms could help inform the development of diagnostic strategies and targeted therapies for this potentially fatal disorder.<\/jats:p>","DOI":"10.3390\/ph19081186","type":"journal-article","created":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T10:13:47Z","timestamp":1785320027000},"page":"1186","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Pathological Allostery in ADAMTS13: Autoantibody-Induced Modulation and Its Role in Immune Thrombotic Thrombocytopenic Purpura (iTTP)"],"prefix":"10.3390","volume":"19","author":[{"given":"Madison","family":"Gil","sequence":"first","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, The University of Kansas Medical Center, Kansas City, KS 66160, USA"},{"name":"Department of Internal Medicine, Division of Hematologic Malignancies and Cellular Therapeutics, The University of Kansas Medical Center, Kansas City, KS 66160, USA"},{"name":"Institute for Reproductive and Developmental Sciences, The University of Kansas Medical Center, Kansas City, KS 66160, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9594-1852","authenticated-orcid":false,"given":"Konstantine","family":"Halkidis","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, The University of Kansas Medical Center, Kansas City, KS 66160, USA"},{"name":"Department of Internal Medicine, Division of Hematologic Malignancies and Cellular Therapeutics, The University of Kansas Medical Center, Kansas City, KS 66160, USA"},{"name":"Institute for Reproductive and Developmental Sciences, The University of Kansas Medical Center, Kansas City, KS 66160, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"41059","DOI":"10.1074\/jbc.C100515200","article-title":"Structure of von Willebrand factor-cleaving protease (ADAMTS13), a metalloprotease involved in thrombotic thrombocytopenic purpura","volume":"276","author":"Zheng","year":"2001","journal-title":"J. Biol. Chem."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1097\/MBC.0000000000000065","article-title":"Update on von Willebrand factor multimers: Focus on high-molecular-weight multimers and their role in hemostasis","volume":"25","author":"Stockschlaeder","year":"2014","journal-title":"Blood Coagul. Fibrinolysis"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1585","DOI":"10.1056\/NEJM199811263392203","article-title":"Antibodies to von Willebrand factor-cleaving protease in acute thrombotic thrombocytopenic purpura","volume":"339","author":"Tsai","year":"1998","journal-title":"N. Eng. J. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1016\/j.tibs.2008.05.009","article-title":"Allostery: An illustrated definition for the \u2018second secret of life\u2019","volume":"33","author":"Fenton","year":"2008","journal-title":"Trends Biochem. Sci."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"105672","DOI":"10.1016\/j.jbc.2024.105672","article-title":"What is allosteric regulation? Exploring the exceptions that prove the rule!","volume":"300","author":"McCullagh","year":"2024","journal-title":"J. Biol. Chem."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1111\/jth.12221","article-title":"Structure-function and regulation of ADAMTS-13 protease","volume":"11","author":"Zheng","year":"2013","journal-title":"J. Thromb. Haemost."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2011","DOI":"10.1111\/jth.13445","article-title":"Conformational quiescence of ADAMTS13 prevents proteolytic promiscuity","volume":"14","author":"South","year":"2016","journal-title":"J. Thromb. Haemost."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1330","DOI":"10.1126\/science.1170905","article-title":"Mechanoenzymatic cleavage of the ultralarge vascular protein von Willebrand factor","volume":"324","author":"Zhang","year":"2009","journal-title":"Science"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"18584","DOI":"10.1073\/pnas.1413282112","article-title":"Allosteric activation of ADAMTS13 by von Willebrand factor","volume":"111","author":"Muia","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"5323","DOI":"10.1182\/blood-2008-07-169359","article-title":"The distal carboxyl-terminal domains of ADAMTS13 are required for regulation of in vivo thrombus formation","volume":"113","author":"Banno","year":"2009","journal-title":"Blood"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"3212","DOI":"10.1182\/blood-2011-02-306597","article-title":"Unraveling the scissile bond: How ADAMTS13 recognizes and cleaves von Willebrand factor","volume":"118","author":"Crawley","year":"2011","journal-title":"Blood"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1160\/TH17-06-0404","article-title":"Insights into 3D Structure of ADAMTS13: A Stepping Stone towards Novel Therapeutic Treatment of Thrombotic Thrombocytopenic Purpura","volume":"118","author":"Ercig","year":"2018","journal-title":"Thromb. Haemost."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"823","DOI":"10.1002\/pro.5560040502","article-title":"The metzincins\u2014Topological and sequential relations between the astacins, adamalysins, serralysins, and matrixins (collagenases) define a super family of zinc-peptidases","volume":"4","author":"Stocker","year":"1995","journal-title":"Protein Sci."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"3064","DOI":"10.1182\/blood-2009-12-258780","article-title":"The ADAMTS13 metalloprotease domain: Roles of subsites in enzyme activity and specificity","volume":"116","author":"Lane","year":"2010","journal-title":"Blood"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"11602","DOI":"10.1073\/pnas.1018559108","article-title":"Mechanism of von Willebrand factor scissile bond cleavage by a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 (ADAMTS13)","volume":"108","author":"Xiang","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"29428","DOI":"10.1074\/jbc.M505513200","article-title":"The proximal carboxyl-terminal domains of ADAMTS13 determine substrate specificity and are all required for cleavage of von Willebrand factor","volume":"280","author":"Ai","year":"2005","journal-title":"J. Biol. Chem."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1182\/blood-2003-08-2861","article-title":"VWF73, a region from D1596 to R1668 of von Willebrand factor, provides a minimal substrate for ADAMTS-13","volume":"103","author":"Kokame","year":"2004","journal-title":"Blood"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"30136","DOI":"10.1074\/jbc.M305331200","article-title":"Cleavage of von Willebrand factor requires the spacer domain of the metalloprotease ADAMTS13","volume":"278","author":"Zheng","year":"2003","journal-title":"J. Biol. Chem."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"19099","DOI":"10.1073\/pnas.0607264104","article-title":"Exosite interactions contribute to tension-induced cleavage of von Willebrand factor by the antithrombotic ADAMTS13 metalloprotease","volume":"103","author":"Gao","year":"2006","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"3781","DOI":"10.1038\/s41467-019-11474-5","article-title":"Crystal structure and substrate-induced activation of ADAMTS13","volume":"10","author":"Petri","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2300","DOI":"10.1182\/blood-2009-07-235101","article-title":"Amino acid residues Arg(659), Arg(660), and Tyr(661) in the spacer domain of ADAMTS13 are critical for cleavage of von Willebrand factor","volume":"115","author":"Jin","year":"2010","journal-title":"Blood"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"166954","DOI":"10.1016\/j.jmb.2021.166954","article-title":"An Integrative Structural Biology Analysis of Von Willebrand Factor Binding and Processing by ADAMTS-13 in Solution","volume":"433","author":"Sagar","year":"2021","journal-title":"J. Mol. Biol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"18578","DOI":"10.1073\/pnas.1411979112","article-title":"Conformational activation of ADAMTS13","volume":"111","author":"South","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2819","DOI":"10.1182\/blood-2009-05-224915","article-title":"A novel binding site for ADAMTS13 constitutively exposed on the surface of globular VWF","volume":"114","author":"Zanardelli","year":"2009","journal-title":"Blood"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"eabg4403","DOI":"10.1126\/sciadv.abg4403","article-title":"Crystal structure of ADAMTS13 CUB domains reveals their role in global latency","volume":"7","author":"Kim","year":"2021","journal-title":"Sci. Adv."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"3836","DOI":"10.1182\/blood-2011-12-399501","article-title":"Gain-of-function ADAMTS13 variants that are resistant to autoantibodies against ADAMTS13 in patients with acquired thrombotic thrombocytopenic purpura","volume":"119","author":"Jian","year":"2012","journal-title":"Blood"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1670","DOI":"10.3324\/haematol.2010.036327","article-title":"Residues Arg568 and Phe592 contribute to an antigenic surface for anti-ADAMTS13 antibodies in the spacer domain","volume":"96","author":"Pos","year":"2011","journal-title":"Haematologica"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2099","DOI":"10.1111\/jth.14602","article-title":"Identification of cysteine thiol-based linkages in ADAMTS13 in support of a non-proteolytic regulation of von Willebrand factor","volume":"17","author":"Rottensteiner","year":"2019","journal-title":"J. Thromb. Haemost."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1888","DOI":"10.1111\/jth.15332","article-title":"A human monoclonal antibody against the distal carboxyl terminus of ADAMTS-13 modulates its susceptibility to an inhibitor in thrombotic thrombocytopenic purpura","volume":"19","author":"Halkidis","year":"2021","journal-title":"J. Thromb. Haemost."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"172","DOI":"10.3324\/haematol.12701","article-title":"Acquired thrombotic thrombocytopenic purpura: ADAMTS13 activity, anti-ADAMTS13 autoantibodies and risk of recurrent disease","volume":"93","author":"Lammle","year":"2008","journal-title":"Haematologica"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1703","DOI":"10.1111\/j.1538-7836.2009.03568.x","article-title":"IgG subclass distribution of anti-ADAMTS13 antibodies in patients with acquired thrombotic thrombocytopenic purpura","volume":"7","author":"Ferrari","year":"2009","journal-title":"J. Thromb. Haemost."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"763","DOI":"10.1038\/s41577-023-00871-z","article-title":"The unique properties of IgG4 and its roles in health and disease","volume":"23","author":"Rispens","year":"2023","journal-title":"Nat. Rev. Immunol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1763","DOI":"10.1111\/trf.13584","article-title":"ADAMTS13 autoantibodies cloned from patients with acquired thrombotic thrombocytopenic purpura: 1. Structural and functional characterization in vitro","volume":"56","author":"Ostertag","year":"2016","journal-title":"Transfusion"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1160\/TH04-05-0301","article-title":"The spacer domain of ADAMTS13 contains a major binding site for antibodies in patients with thrombotic thrombocytopenic purpura","volume":"93","author":"Luken","year":"2005","journal-title":"Thromb. Haemost."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"4514","DOI":"10.1182\/blood-2003-12-4165","article-title":"Epitope mapping of ADAMTS13 autoantibodies in acquired thrombotic thrombocytopenic purpura","volume":"103","author":"Klaus","year":"2004","journal-title":"Blood"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1555","DOI":"10.3324\/haematol.2009.019299","article-title":"Multiple domains of ADAMTS13 are targeted by autoantibodies against ADAMTS13 in patients with acquired idiopathic thrombotic thrombocytopenic purpura","volume":"95","author":"Zheng","year":"2010","journal-title":"Haematologica"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"942","DOI":"10.1016\/j.ebiom.2015.06.007","article-title":"Pathogenicity of Anti-ADAMTS13 Autoantibodies in Acquired Thrombotic Thrombocytopenic Purpura","volume":"2","author":"Thomas","year":"2015","journal-title":"EBioMedicine"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1763","DOI":"10.1182\/bloodadvances.2024014950","article-title":"Unraveling antibody-induced structural dynamics in the ADAMTS13 CUB1-2 domains via HDX-MS","volume":"9","author":"Bonnez","year":"2025","journal-title":"Blood Adv."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"5350","DOI":"10.1182\/bloodadvances.2025017193","article-title":"Trp1250, Lys1252, and Arg1367 of ADAMTS13 comprise a hot spot for anti-CUB domain antibodies in patients with iTTP","volume":"9","author":"Postmus","year":"2025","journal-title":"Blood Adv."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"9620","DOI":"10.1073\/pnas.1512561112","article-title":"High-resolution epitope mapping by HX MS reveals the pathogenic mechanism and a possible therapy for autoimmune TTP syndrome","volume":"112","author":"Casina","year":"2015","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1072","DOI":"10.1182\/bloodadvances.2019001375","article-title":"Antibodies that conformationally activate ADAMTS13 allosterically enhance metalloprotease domain function","volume":"4","author":"Schelpe","year":"2020","journal-title":"Blood Adv."},{"key":"ref_42","first-page":"2993","article-title":"Mechanisms of inhibition of human monoclonal antibodies in immune thrombotic thrombocytopenic purpura","volume":"141","author":"Halkidis","year":"2023","journal-title":"Blood"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"102603","DOI":"10.1016\/j.rpth.2024.102603","article-title":"Mechanistic insight into multiple antibody binding to ADAMTS13 in immune thrombotic thrombocytopenic purpura","volume":"8","author":"Halkidis","year":"2024","journal-title":"Res. Pract. Thromb. Haemost."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1016\/0003-9861(83)90225-4","article-title":"The determination of thermodynamic allosteric parameters of an enzyme undergoing steady-state turnover","volume":"224","author":"Reinhart","year":"1983","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Meng, C., Halkidis, K., Gil, M., Liu, S., and Zheng, X.L. (2026). Human monoclonal and polyclonal anti-ADAMTS13 antibodies in immune thrombotic thrombocytopenic purpura: Variable mechanisms of inhibition. J. Thromb. Haemost.","DOI":"10.1016\/j.jtha.2026.05.018"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"059","DOI":"10.1055\/a-2223-9484","article-title":"100 Years of Thrombotic Thrombocytopenic Purpura: A Story of Death and Life","volume":"44","author":"Vanhoorelbeke","year":"2024","journal-title":"Hamostaseologie"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1038\/s41573-022-00501-8","article-title":"Avidity in antibody effector functions and biotherapeutic drug design","volume":"21","author":"Oostindie","year":"2022","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Dainese, C., Valeri, F., Bruno, B., and Borchiellini, A. (2023). Anti-ADAMTS13 Autoantibodies: From Pathophysiology to Prognostic Impact-A Review for Clinicians. J. Clin. Med., 12.","DOI":"10.3390\/jcm12175630"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"2815","DOI":"10.1182\/blood-2006-02-006064","article-title":"Prognostic value of anti-ADAMTS13 antibody features (Ig isotype, titer, and inhibitory effect) in a cohort of 35 adult French patients undergoing a first episode of thrombotic microangiopathy with undetectable ADAMTS13 activity","volume":"109","author":"Ferrari","year":"2007","journal-title":"Blood"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1556","DOI":"10.1111\/j.1538-7836.2012.04808.x","article-title":"ADAMTS-13 activity and autoantibodies classes and subclasses as prognostic predictors in acquired thrombotic thrombocytopenic purpura","volume":"10","author":"Bettoni","year":"2012","journal-title":"J. Thromb. Haemost."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1111\/j.1365-2141.2005.05837.x","article-title":"Prognostic value of inhibitory anti-ADAMTS13 antibodies in adult-acquired thrombotic thrombocytopenic purpura","volume":"132","author":"Coppo","year":"2006","journal-title":"Br. J. Haematol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"466","DOI":"10.1182\/blood-2016-12-758656","article-title":"Presenting ADAMTS13 antibody and antigen levels predict prognosis in immune-mediated thrombotic thrombocytopenic purpura","volume":"130","author":"Alwan","year":"2017","journal-title":"Blood"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"232","DOI":"10.3324\/haematol.11739","article-title":"ADAMTS13 and anti-ADAMTS13 antibodies as markers for recurrence of acquired thrombotic thrombocytopenic purpura during remission","volume":"93","author":"Peyvandi","year":"2008","journal-title":"Haematologica"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"953","DOI":"10.1002\/ajh.25845","article-title":"Low levels of ADAMTS-13 with high anti-ADAMTS-13 antibodies during remission of immune-mediated thrombotic thrombocytopenic purpura highly predict for disease relapse: A multi-institutional study","volume":"95","author":"Schieppati","year":"2020","journal-title":"Am. J. Hematol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"10760296221125785","DOI":"10.1177\/10760296221125785","article-title":"ADAMTS13 Autoantibodies and Burden of Care in Immune Thrombotic Thrombocytopenic purpura: New Evidence and Future Implications","volume":"28","author":"Dainese","year":"2022","journal-title":"Clin. Appl. Thromb. Hemost."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1111\/j.1365-2141.2008.07107.x","article-title":"Relationship between ADAMTS13 activity in clinical remission and the risk of TTP relapse","volume":"141","author":"Jin","year":"2008","journal-title":"Br. J. Haematol."}],"container-title":["Pharmaceuticals"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1424-8247\/19\/8\/1186\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T08:20:58Z","timestamp":1785399658000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1424-8247\/19\/8\/1186"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,29]]},"references-count":56,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2026,8]]}},"alternative-id":["ph19081186"],"URL":"https:\/\/doi.org\/10.3390\/ph19081186","relation":{},"ISSN":["1424-8247"],"issn-type":[{"value":"1424-8247","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,29]]}}}