{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T22:27:31Z","timestamp":1791844051705,"version":"4.3.4"},"reference-count":39,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,11,6]],"date-time":"2025-11-06T00:00:00Z","timestamp":1762387200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,11,6]],"date-time":"2025-11-06T00:00:00Z","timestamp":1762387200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100000848","name":"University of Edinburgh","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000848","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Adiso Therapeutics Inc."},{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["MR\/K013386\/1"],"award-info":[{"award-number":["MR\/K013386\/1"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Inflamm"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Minimizing unintended granulocyte activation while measuring functional responsiveness is essential, as the use of external probes, antibodies, or fluorescent dyes can potentially alter cellular responsiveness. To address this, we employed an antibody-free flow cytometry approach that measures forward scatter (FSC) to detect variations in cell-size, morphology, and shape; some key indicators of neutrophil and eosinophil activation. Human peripheral blood neutrophils, containing contaminating eosinophils, were isolated using discontinuous Percoll gradients and pre-treated with receptor antagonists [e.g., cyclosporin-H (an FPR1 antagonist) and CP105696 (a BLT1 receptor antagonist)] prior to stimulation with agonists such as fMLF (an FPR1 agonist) and LTB\n                    <jats:sub>4<\/jats:sub>\n                    (a BLT1 agonist). Furthermore, fMLF stimulation resulted in a loss of CD62L and an increase in CD11b expression along with an increase in intracellular ROS production compared to control, as analysed using flow cytometry. Imaging flow cytometry, together with FSC analysis, enabled assessment of cell polarization and associated morphological changes. Importantly, autofluorescence-based gating allowed for the identification of contaminating eosinophils within the mixed granulocyte population, allowing parallel assessment of shape-change in both neutrophils and eosinophils in response to the same ligands. Stimulation of neutrophils with fMLF resulted in distinct FSC shifts compared to unstimulated controls across all flow cytometers tested, which were inhibited by cyclosporin-H, but not CP105696. Morphological analysis confirmed these changes corresponded with increased cell area and perimeter and decreased circularity, hallmarks of cell polarisation. Additionally, selective activation of eosinophils (but not neutrophils) by eotaxin, and dual activation of both cell types by the arachidonic acid metabolite 5-oxo-ETE, were confirmed through specific gating strategies. Taken together, these findings support the use of FSC-based flow cytometry as a rapid, scalable and effective method for evaluating granulocyte polarisation and screening candidate therapeutics targeting immune cell activation in disease contexts.\n                  <\/jats:p>","DOI":"10.1186\/s12950-025-00472-8","type":"journal-article","created":{"date-parts":[[2025,11,6]],"date-time":"2025-11-06T12:27:42Z","timestamp":1762432062000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Rapid autofluorescence flow cytometric analysis of agonist-induced neutrophil and eosinophil polarization reveals novel insights into 5-oxo-ETE-mediated granulocyte activation"],"prefix":"10.1186","volume":"22","author":[{"given":"Anuruddika J.","family":"Fernando","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fiona","family":"Rossi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Destiny","family":"Docherty","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Popravko","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucy","family":"Masters","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Boydd","family":"Houston","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renu","family":"Gupta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin","family":"Dhaliwal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adriano G.","family":"Rossi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,11,6]]},"reference":[{"issue":"8","key":"472_CR1","doi-asserted-by":"publisher","first-page":"399","DOI":"10.1093\/intimm\/dxac029","volume":"34","author":"HB Shim","year":"2022","unstructured":"Shim HB, Deniset JF, Kubes P. Neutrophils in homeostasis and tissue repair. Int Immunol. 2022;34(8):399\u2013407.","journal-title":"Int Immunol"},{"issue":"5","key":"472_CR2","doi-asserted-by":"publisher","first-page":"672","DOI":"10.1002\/path.5221","volume":"247","author":"PM Potey","year":"2019","unstructured":"Potey PM, Rossi AG, Lucas CD, Dorward DA. Neutrophils in the initiation and resolution of acute pulmonary inflammation: understanding biological function and therapeutic potential. J Pathol. 2019;247(5):672\u201385.","journal-title":"J Pathol"},{"issue":"10","key":"472_CR3","doi-asserted-by":"publisher","first-page":"2694","DOI":"10.1016\/j.mayocp.2021.04.025","volume":"96","author":"ME Wechsler","year":"2021","unstructured":"Wechsler ME, Munitz A, Ackerman SJ, Drake MG, Jackson DJ, Wardlaw AJ, et al. Eosinophils in health and disease: a state-of-the-art review. Mayo Clin Proc. 2021;96(10):2694\u2013707.","journal-title":"Mayo Clin Proc"},{"issue":"5","key":"472_CR4","doi-asserted-by":"publisher","first-page":"1172","DOI":"10.1016\/j.ajpath.2015.01.020","volume":"185","author":"DA Dorward","year":"2015","unstructured":"Dorward DA, Lucas CD, Chapman GB, Haslett C, Dhaliwal K, Rossi AG. The role of formylated peptides and formyl peptide receptor 1 in governing neutrophil function during acute inflammation. Am J Pathol. 2015;185(5):1172\u201384.","journal-title":"Am J Pathol"},{"issue":"2","key":"472_CR5","doi-asserted-by":"publisher","first-page":"137","DOI":"10.1016\/j.smim.2016.03.007","volume":"28","author":"HR Jones","year":"2016","unstructured":"Jones HR, Robb CT, Perretti M, Rossi AG. The role of neutrophils in inflammation resolution. Semin Immunol. 2016;28(2):137\u201345.","journal-title":"Semin Immunol"},{"issue":"2","key":"472_CR6","doi-asserted-by":"publisher","first-page":"117","DOI":"10.1002\/jlb.53.2.117","volume":"53","author":"AG Rossi","year":"1993","unstructured":"Rossi AG, MacIntyre DE, Jones CJ, McMillan RM. Stimulation of human polymorphonuclear leukocytes by leukotriene B4 and platelet-activating factor: an ultrastructural and pharmacological study. J Leukoc Biol. 1993;53(2):117\u201325.","journal-title":"J Leukoc Biol"},{"issue":"3","key":"472_CR7","doi-asserted-by":"publisher","first-page":"1167","DOI":"10.1006\/bbrc.1993.2599","volume":"197","author":"DA Griffiths-Johnson","year":"1993","unstructured":"Griffiths-Johnson DA, Collins PD, Rossi AG, Jose PJ, Williams TJ. The chemokine, eotaxin, activates guinea-pig eosinophils in vitro and causes their accumulation into the lung in vivo. Biochem Biophys Res Commun. 1993;197(3):1167\u201372.","journal-title":"Biochem Biophys Res Commun"},{"issue":"3","key":"472_CR8","doi-asserted-by":"publisher","first-page":"881","DOI":"10.1084\/jem.179.3.881","volume":"179","author":"PJ Jose","year":"1994","unstructured":"Jose PJ, Griffiths-Johnson DA, Collins PD, Walsh DT, Moqbel R, Totty NF, et al. Eotaxin: a potent eosinophil chemoattractant cytokine detected in a guinea pig model of allergic airways inflammation. J Exp Med. 1994;179(3):881\u20137.","journal-title":"J Exp Med"},{"issue":"13","key":"472_CR9","doi-asserted-by":"publisher","first-page":"7725","DOI":"10.1074\/jbc.271.13.7725","volume":"271","author":"M Kitaura","year":"1996","unstructured":"Kitaura M, Nakajima T, Imai T, Harada S, Combadiere C, Tiffany HL, et al. Molecular cloning of human eotaxin, an eosinophil-selective CC chemokine, and identification of a specific eosinophil eotaxin receptor, CC chemokine receptor 3. J Biol Chem. 1996;271(13):7725\u201330.","journal-title":"J Biol Chem"},{"issue":"4","key":"472_CR10","doi-asserted-by":"publisher","first-page":"651","DOI":"10.1016\/j.plipres.2013.09.001","volume":"52","author":"WS Powell","year":"2013","unstructured":"Powell WS, Rokach J. The eosinophil chemoattractant 5-oxo-ETE and the OXE receptor. Prog Lipid Res. 2013;52(4):651\u201365.","journal-title":"Prog Lipid Res"},{"issue":"30","key":"472_CR11","doi-asserted-by":"publisher","first-page":"eaat4579","DOI":"10.1126\/sciimmunol.aat4579","volume":"3","author":"K Ley","year":"2018","unstructured":"Ley K, Hoffman HM, Kubes P, Cassatella MA, Zychlinsky A, Hedrick CC, et al. Neutrophils: New insights and open questions. Sci Immunol. 2018;3(30):eaat4579.","journal-title":"Sci Immunol"},{"issue":"10","key":"472_CR12","doi-asserted-by":"publisher","first-page":"4715","DOI":"10.4049\/jimmunol.1290017","volume":"188","author":"DL Jaye","year":"2012","unstructured":"Jaye DL, Bray RA, Gebel HM, Harris WA, Waller EK. Translational applications of low cytometry in clinical practice. J Immunol. 2012;188(10):4715\u20139.","journal-title":"J Immunol"},{"key":"472_CR13","doi-asserted-by":"publisher","first-page":"113308","DOI":"10.1016\/j.jim.2022.113308","volume":"507","author":"J Pioch","year":"2022","unstructured":"Pioch J, Blomgran R. Optimized flow cytometry protocol for dihydrorhodamine 123-based detection of reactive oxygen species in leukocyte subpopulations in whole blood. J Immunol Methods. 2022;507:113308.","journal-title":"J Immunol Methods"},{"issue":"1","key":"472_CR14","first-page":"101","volume":"119","author":"C Haslett","year":"1985","unstructured":"Haslett C, Guthrie LA, Kopaniak MM, Johnston RB Jr, Henson PM. Modulation of multiple neutrophil functions by preparative methods or trace concentrations of bacterial lipopolysaccharide. Am J Pathol. 1985;119(1):101\u201310.","journal-title":"Am J Pathol"},{"issue":"2","key":"472_CR15","doi-asserted-by":"publisher","first-page":"211","DOI":"10.1016\/0022-1759(95)00003-S","volume":"181","author":"MG Macey","year":"1995","unstructured":"Macey MG, McCarthy DA, Vordermeier S, Newland AC, Brown KA. Effects of cell purification methods on CD11b and L-selectin expression as well as the adherence and activation of leucocytes. J Immunol Methods. 1995;181(2):211\u20139.","journal-title":"J Immunol Methods"},{"issue":"Pt3","key":"472_CR16","doi-asserted-by":"publisher","first-page":"452","DOI":"10.1042\/bst0320452","volume":"32","author":"AG Rossi","year":"2004","unstructured":"Rossi AG, Ward C, Dransfield I. Getting to grips with the granulocyte: manipulation of granulocyte behaviour and apoptosis by protein transduction methods. Biochem Soc Trans. 2004;32(Pt3):452-5. 571 28 572.","journal-title":"Biochem Soc Trans"},{"key":"472_CR17","doi-asserted-by":"publisher","first-page":"101","DOI":"10.1007\/978-1-61779-527-5_7","volume":"844","author":"Y Hu","year":"2012","unstructured":"Hu Y. Isolation of human and mouse neutrophils ex vivo and in vitro. Methods Mol Biol. 2012;844:101\u201313.","journal-title":"Methods Mol Biol"},{"key":"472_CR18","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1016\/j.jim.2017.06.005","volume":"449","author":"K Son","year":"2017","unstructured":"Son K, Mukherjee M, McIntyre BAS, Eguez JC, Radford K, LaVigne N, et al. Improved recovery of functionally active eosinophils and neutrophils using novel immunomagnetic technology. J Immunol Methods. 2017;449:44\u201355.","journal-title":"J Immunol Methods"},{"issue":"6","key":"472_CR19","doi-asserted-by":"publisher","first-page":"1099","DOI":"10.1182\/blood.V57.6.1099.1099","volume":"57","author":"GJ Weil","year":"1981","unstructured":"Weil GJ, Chused TM. Eosinophil autofluorescence and its use in isolation and analysis of human eosinophils using low microfluorometry. Blood. 1981;57(6):1099\u2013104.","journal-title":"Blood"},{"issue":"1","key":"472_CR20","doi-asserted-by":"publisher","first-page":"193","DOI":"10.1189\/jlb.0113040","volume":"94","author":"DA Dorward","year":"2013","unstructured":"Dorward DA, Lucas CD, Alessandri AL, Marwick JA, Rossi F, Dransfield I, et al. Technical advance: autofluorescence-based sorting: rapid and nonperturbing isolation of ultrapure neutrophils to determine cytokine production. J Leukoc Biol. 2013;94(1):193\u2013202.","journal-title":"J Leukoc Biol"},{"issue":"5","key":"472_CR21","doi-asserted-by":"publisher","first-page":"2946","DOI":"10.4049\/jimmunol.162.5.2946","volume":"162","author":"I Sabroe","year":"1999","unstructured":"Sabroe I, Hartnell A, Jopling LA, Bel S, Ponath PD, Pease JE, et al. Differential regulation of eosinophil chemokine signaling via CCR3 and non-CCR3 pathways. J Immunol. 1999;162(5):2946\u201355.","journal-title":"J Immunol"},{"issue":"331","key":"472_CR22","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1016\/j.morpho.2016.05.001","volume":"100","author":"AE Depince-Berger","year":"2016","unstructured":"Depince-Berger AE, Aanei C, Iobagiu C, Jeraiby M, Lambert C. New tools in cytometry. Morphologie. 2016;100(331):199\u2013209.","journal-title":"Morphologie"},{"issue":"3","key":"472_CR23","doi-asserted-by":"publisher","first-page":"181","DOI":"10.4155\/bio-2020-0267","volume":"13","author":"SM Manohar","year":"2021","unstructured":"Manohar SM, Shah P, Nair A. Flow cytometry: principles, applications and recent advances. Bioanalysis. 2021;13(3):181\u201398.","journal-title":"Bioanalysis"},{"issue":"1","key":"472_CR24","doi-asserted-by":"publisher","first-page":"129","DOI":"10.1006\/bbrc.1993.1391","volume":"192","author":"JT O\u2019Flaherty","year":"1993","unstructured":"O\u2019Flaherty JT, Cordes J, Redman J, Thomas MJ. 5-oxo-eicosatetraenoate, a potent human neutrophil stimulus. Biochem Biophys Res Commun. 1993;192(1):129\u201334.","journal-title":"Biochem Biophys Res Commun"},{"key":"472_CR25","doi-asserted-by":"crossref","unstructured":"Willetts L, Ochkur SI, Jacobsen EA, Lee JJ, Lacy P. Eosinophil Shape Change and Secretion. In: Walsh GM, editor. Eosinophils: Methods and Protocols. New York, NY: Springer New York; 2014. p. 111\u201328. 596 29 597","DOI":"10.1007\/978-1-4939-1016-8_11"},{"issue":"2","key":"472_CR26","doi-asserted-by":"publisher","first-page":"388","DOI":"10.1038\/sj.bjp.0705265","volume":"139","author":"J Murray","year":"2003","unstructured":"Murray J, Ward C, O\u2019Flaherty JT, Dransfield I, Haslett C, Chilvers ER, et al. Role of leukotrienes in the regulation of human granulocyte behaviour: dissociation between agonist-induced activation and retardation of apoptosis. Br J Pharmacol. 2003;139(2):388\u201398.","journal-title":"Br J Pharmacol"},{"issue":"6","key":"472_CR27","doi-asserted-by":"publisher","first-page":"1143","DOI":"10.1002\/JLB.MA0718-295RR","volume":"105","author":"KR Bashant","year":"2019","unstructured":"Bashant KR, Vassallo A, Herold C, Berner R, Menschner L, Subburayalu J, et al. Real time deformability cytometry reveals sequential contraction and expansion during neutrophil priming. J Leukoc Biol. 2019;105(6):1143\u201353.","journal-title":"J Leukoc Biol"},{"issue":"3","key":"472_CR28","doi-asserted-by":"publisher","first-page":"290","DOI":"10.1021\/ac60111a002","volume":"28","author":"M Dimbat","year":"1956","unstructured":"Dimbat M, Porter PE, Stross FH. Apparatus requirements for quantitative applications. Anal Chem. 1956;28(3):290\u20137.","journal-title":"Anal Chem"},{"issue":"10","key":"472_CR29","doi-asserted-by":"publisher","first-page":"928","DOI":"10.1136\/thoraxjnl-2017-210030","volume":"72","author":"DA Dorward","year":"2017","unstructured":"Dorward DA, Lucas CD, Doherty MK, Chapman GB, Scholefield EJ, Conway Morris A, et al. Novel role for endogenous mitochondrial formylated peptide-driven formyl peptide receptor 1 signalling in acute respiratory distress syndrome. Thorax. 2017;72(10):928\u201336.","journal-title":"Thorax"},{"issue":"1","key":"472_CR30","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1006\/bbrc.1996.1463","volume":"227","author":"A Burke-Gaffney","year":"1996","unstructured":"Burke-Gaffney A, Hellewell PG. Eotaxin stimulates eosinophil adhesion to human lung microvascular endothelial cells. Biochem Biophys Res Commun. 1996;227(1):35\u201340.","journal-title":"Biochem Biophys Res Commun"},{"key":"472_CR31","doi-asserted-by":"publisher","first-page":"2014583","DOI":"10.1155\/2017\/2014583","volume":"2017","author":"M Plagge","year":"2017","unstructured":"Plagge M, Laskay T. Early production of the neutrophil-derived lipid mediators LTB(4) and LXA(4) is modulated by intracellular infection with Leishmania major. Biomed Res Int. 2017;2017:2014583.","journal-title":"Biomed Res Int"},{"issue":"5","key":"472_CR32","doi-asserted-by":"publisher","first-page":"425","DOI":"10.1002\/jlb.51.5.425","volume":"51","author":"R Hidi","year":"1992","unstructured":"Hidi R, Co\u00ebffier E, Vargaftig BB. Formation of LTB4 by fMLP-stimulated alveolar macrophages accounts for eosinophil migration in vitro. J Leukoc Biol. 1992;51(5):425\u201331.","journal-title":"J Leukoc Biol"},{"issue":"1","key":"472_CR33","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1016\/S0163-7258(96)00203-3","volume":"74","author":"ER Prossnitz","year":"1997","unstructured":"Prossnitz ER, Ye RD. The N-formyl peptide receptor: a model for the study of chemoattractant receptor structure and function. Pharmacol Ther. 1997;74(1):73\u2013102.","journal-title":"Pharmacol Ther"},{"issue":"6","key":"472_CR34","doi-asserted-by":"publisher","first-page":"610","DOI":"10.1002\/cyto.a.24036","volume":"97","author":"GJA Arkesteijn","year":"2020","unstructured":"Arkesteijn GJA, Lozano-Andr\u00e9s E, Libregts S, Wauben MHM. Improved flow cytometric light scatter detection of submicron-sized particles by reduction of optical background signals. Cytometry A. 2020;97(6):610\u20139.","journal-title":"Cytometry A"},{"issue":"3","key":"472_CR35","doi-asserted-by":"publisher","first-page":"150","DOI":"10.1186\/rr52","volume":"2","author":"DM Conroy","year":"2001","unstructured":"Conroy DM, Williams TJ. Eotaxin and the attraction of eosinophils to the asthmatic lung. Respir Res. 2001;2(3):150\u20136.","journal-title":"Respir Res"},{"key":"472_CR36","doi-asserted-by":"publisher","first-page":"185","DOI":"10.1007\/978-3-319-27766-0_9","volume-title":"Lipoxygenases in Inflammation","author":"WS Powell","year":"2016","unstructured":"Powell WS, Rokach J. 5-Oxo-ETE and Inflammation. In: Steinhilber D, editor. Lipoxygenases in Inflammation. Cham: Springer International Publishing; 2016. p. 185\u2013210."},{"key":"472_CR37","doi-asserted-by":"publisher","first-page":"237","DOI":"10.1242\/jcs.38.1.237","volume":"38","author":"JE Beesley","year":"1979","unstructured":"Beesley JE, Pearson JD, Hutchings A, Carleton JS, Gordon JL. Granulocyte migration through endothelium in culture. J Cell Sci. 1979;38:237\u201348.","journal-title":"J Cell Sci"},{"issue":"1","key":"472_CR38","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1006\/exmp.2002.2439","volume":"73","author":"SS Cheng","year":"2002","unstructured":"Cheng SS, Lukacs NW, Kunkel SL. Eotaxin\/CCL11 is a negative regulator of neutrophil recruitment in a murine model of endotoxemia. Exp Mol Pathol. 2002;73(1):1\u20138.","journal-title":"Exp Mol Pathol"},{"key":"472_CR39","doi-asserted-by":"publisher","first-page":"102160","DOI":"10.1155\/2014\/102160","volume":"2014","author":"RA Luz","year":"2014","unstructured":"Luz RA, Xavier-Elsas P, de Luca B, Masid-de-Brito D, Cauduro PS, Arcanjo LC, et al. 5-lipoxygenase-dependent recruitment of neutrophils and macrophages by eotaxin-stimulated murine eosinophils. Mediators Inflamm. 2014;2014:102160.","journal-title":"Mediators Inflamm"}],"container-title":["Journal of Inflammation"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12950-025-00472-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12950-025-00472-8\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12950-025-00472-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,6]],"date-time":"2025-11-06T12:27:45Z","timestamp":1762432065000},"score":1,"resource":{"primary":{"URL":"https:\/\/journal-inflammation.biomedcentral.com\/articles\/10.1186\/s12950-025-00472-8"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,6]]},"references-count":39,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["472"],"URL":"https:\/\/doi.org\/10.1186\/s12950-025-00472-8","relation":{"has-preprint":[{"id-type":"doi","id":"10.21203\/rs.3.rs-7204746\/v1","asserted-by":"object"}]},"ISSN":["1476-9255"],"issn-type":[{"value":"1476-9255","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,6]]},"assertion":[{"value":"24 July 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"1 October 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"6 November 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":"Not applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"47"}}