Pathomorphological Analysis of Fibrillary Astrocytoma of the Brain Identified by Magnetic Resonance Imaging

Pathomorphological Analysis of Fibrillary Astrocytoma of the Brain Identified by Magnetic Resonance Imaging | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Pathomorphological Analysis of Fibrillary Astrocytoma of the Brain Identified by Magnetic Resonance Imaging Gaybullaev Sherzod, Khamidov Obid This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6311339/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract To conduct a pathomorphological analysis of fibrillary astrocytoma of the brain identified using magnetic resonance imaging (MRI), tumor tissue surgically removed from 23 patients was examined. It was found that fibrillary astrocytoma consists of a small number of cells and a large number of glial fibers. These fibers, varying in thickness, distinctly differentiate fibrillary astrocytomas from tumors with thin, indistinct astrocytic contours. Rosenthal dystrophy actively develops within the glial fibers, contributing to the extensive spread of fibrillary astrocytoma in the brain. Health sciences/Medical research Health sciences/Oncology Figures Figure 1 Figure 2 Introduction Astrocytomas are among the most common tumors of the brain, originating from astrocytes (6). According to the latest edition of the WHO classification [7], astrocytomas are distinguished based on their molecular characteristics. In terms of growth rate, astrocytic tumors are categorized as slow-growing (low-grade) and rapidly growing (high-grade), while their malignancy is classified into four degrees [3]. Astrocytomas belong to a group of glial neoplasms originating from astroglial cells and are considered the most prevalent primary blastomas of the nervous system. These brain tumors account for 30–50% of all neoplasms [13]. Fibrillary astrocytoma is a low-grade glioma; however, according to some authors, malignant transformation is observed in 48–80% of cases [5]. Following surgical treatment of fibrillary astrocytomas, the average life expectancy of patients, based on representative statistical studies, is up to 5 years [21]. Objective of the Study To conduct a pathomorphological analysis of fibrillary astrocytoma of the brain identified using magnetic resonance imaging. Materials and Methods The study was conducted at the Neurosurgery Department of the Multidisciplinary Clinic of Samarkand State Medical University. A total of 23 patients—13 men and 10 women—underwent MRI-based identification of astrocytomas. Tumor samples measuring 1×1×0.5 cm were surgically excised. The tissue samples were fixed in 10% neutral formalin, processed through an alcohol series, and embedded in paraffin blocks. Histological sections of 7–10 microns in thickness were stained with hematoxylin and eosin, as well as Nissl stain. The prepared histological specimens were analyzed morphologically. Results and Discussion Microscopic examination of fibrillary astrocytoma revealed a low cellular density and a high concentration of glial fibers. The cytoplasm of the cells appeared faint, with oval and elongated nuclei (Fig. 1 ). Astrocytes and Glial Fibers Astrocytes and glial fibers are arranged in parallel, following a consistent orientation, and sometimes form bundle-like structures. In certain cases, these bundles merge with a reticular structure. In other specimens, glial fibers appear to be randomly arranged. Some histological preparations show sparsely distributed glial fibers with wide inter-fiber spaces, whereas others reveal densely packed fibers. Glial fibers are generally uniform in thickness and have well-defined contours; however, in certain microscopic fields, variations in fiber thickness can be observed. These fibers distinctly stand out from the thin and indistinct astrocytic processes. The inter-fiber spaces are filled with tissue fluid. In some preparations, these regions do not absorb stain, whereas in many hematoxylin and eosin-stained specimens, the inter-fiber spaces appear light pink due to protein accumulation. Rosenthal dystrophy, characterized by thickening of both astrocytic processes and cell bodies, is commonly observed in glial fibers (Fig. 2 ). A defining characteristic of glial tumors is their invasive growth, during which tumor cells penetrate the surrounding brain tissue to varying depths, forming an infiltration zone. The extent of this infiltration depends on the histobiological properties of the tumor, including its degree of malignancy, as well as the topographic and anatomical features of the affected area [9]. In our study, histological examination of tumor tissue excised from MRI-identified lesions revealed glial fibers interspersed among normal brain tissue, differing from astrocytic processes. Fibrillary astrocytoma initially exhibits glial fiber formation, followed by the incorporation of cellular structures. Conclusion In summary, fibrillary astrocytoma consists of a low number of cells and a high density of glial fibers. These fibers, varying in thickness, clearly distinguish the tumor from astrocytic processes with thin and indistinct contours. Rosenthal dystrophy actively develops within glial fibers, facilitating the tumor’s expansion within the brain. Given the high prevalence and distinct pathomorphological features of fibrillary astrocytoma, further in-depth scientific studies on this tumor type are warranted. Declarations Author Contribution All authors reviewed the manuscript. Ethics Statement: This study was conducted at the multidisciplinary clinic of Samarkand State Medical University. All procedures involving human participants were performed in accordance with the ethical standards of the institutional ethics committee and the 1964 Helsinki Declaration and its later amendments. Ethical approval was obtained from the university's ethics committee prior to the start of the research. References Bain B. N., Shardakov V. I., Selyukova M. V. Antitumor Immunity and Its Disorders in Cerebral Tumors: A Textbook for Physicians. Kirov State Medical Academy, 2004. – 49 p. Kolosov A. E. Life Expectancy in Cancer, Sarcoma, Melanoma, Leukemia, and Lymphogranulomatosis: A Guide for Physicians. St. Petersburg – Kirov, 2007. – 432 p. Matsko D. E., Korshunov A. G. Atlas of Central Nervous System Tumors (Histological Structure). St. Petersburg: R. N. Khi Publishing House, 1998. – 200 p. Yakhno N. N., Shtulman D. R. Diseases of the Nervous System in Two Volumes. Moscow: Medicine, 2003. – Vol. 1. Buckner C., Brown P. D., O’Neill B. P., et al. Central Nervous System Tumors. Mayo Clinic Proceedings , 2007: 1271-1286. Babu R., Sharma R., Karikari I. O., Owens T. R., Friedman A. H., Adamson C. Outcome and Prognostic Factors in Adult Cerebellar Glioblastoma. Journal of Clinical Neuroscience , 2013 Aug; 20(8):1117-1121. doi: 10.1016/joen.2012.12.006. PMID: 23706183. Louis D. N., Perry A., Reifenberger G., von Deimling A., Figarella-Branger D., Ohgaki H., Wiestler O. D., Kleihues P., Ellison D. W. The 2016 World Health Organization Classification of Tumors of the Central Nervous System: A Summary. Acta Neuropathologica , 2016 Jun; 131(6):803-820. doi: 10.1007/s00401-016-1545-1. PMID: 27157931. Strauss I., Jonas-Kimchi T., Bokstein F., Blumenthal D., Roth J., Sit R., Wilson J., Ram Z. Gliomas of the Posterior Fossa in Adults. Journal of Neuro-Oncology , 2013 Dec; 115(3):401-409. doi: 10.1007/s11060-013-1231-2. PMID: 23979683. Khominskiy B. S., Shamayey M. I., Rasheyeva I. C. Rustika Gliomas of the Medial and Paramedial Regions of the Brain. Problemy Neyrokhirurgii , 1970; 3:14-27. (In Russian). Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6311339","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":434232942,"identity":"11af3e94-4210-4d2b-a08b-be9352ccb725","order_by":0,"name":"Gaybullaev Sherzod","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAzElEQVRIiWNgGAWjYNACNgYGfhCdUECKFskGkBYDUrQYHAAxiNFicP6M4eOKMrto4/OrEz88MGCQ5xc7QEDLgTPGhmfOJeduu/F2swTQYYYzZycQ0HKwx0yysY0ZqOXsBpCWBIPbhLQc5gFpqc/dPOPs5h/EaTkG1nI4dwN/7zbibJE8w1Zs2HDueO6MG7zbLBIMJAj7he/84Y0PG8qqc/v7z26++aPCRp5fmoAWBgYOaFxIgFVKEFIOAuwPIDT/AWJUj4JRMApGwUgEAF0lRzg1F7BPAAAAAElFTkSuQmCC","orcid":"","institution":"Samarkand state medical university","correspondingAuthor":true,"prefix":"","firstName":"Gaybullaev","middleName":"","lastName":"Sherzod","suffix":""},{"id":434232944,"identity":"562be902-0893-4b54-9ac8-40a1d46b9f6f","order_by":1,"name":"Khamidov Obid","email":"","orcid":"","institution":"Samarkand state medical university","correspondingAuthor":false,"prefix":"","firstName":"Khamidov","middleName":"","lastName":"Obid","suffix":""}],"badges":[],"createdAt":"2025-03-26 10:23:22","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6311339/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6311339/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":79586556,"identity":"87782a6e-282b-4a9d-b0ad-4bec49485b9e","added_by":"auto","created_at":"2025-03-31 12:33:44","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":66020,"visible":true,"origin":"","legend":"\u003cp\u003eFibrillary astrocytoma with oval and elongated nuclei. Hematoxylin and eosin staining. Objective 40x, Ocular 10x\u003c/p\u003e","description":"","filename":"floatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-6311339/v1/cdce5a2a504aad1789e627ae.png"},{"id":79587577,"identity":"d539e597-fa1d-40f5-b38f-d7fa6ab57f53","added_by":"auto","created_at":"2025-03-31 12:41:44","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":44254,"visible":true,"origin":"","legend":"\u003cp\u003eRosenthal dystrophy in fibrillary astrocytoma. Hematoxylin and eosin staining. Objective 40x, Ocular 10x.\u003c/p\u003e","description":"","filename":"floatimage2.png","url":"https://assets-eu.researchsquare.com/files/rs-6311339/v1/9ab9d534fcbe28604cf5d55a.png"},{"id":80297061,"identity":"2fd5d75b-4b50-4271-a718-c617527522f0","added_by":"auto","created_at":"2025-04-10 08:39:06","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":381279,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6311339/v1/85092771-6802-4bdb-ad98-ac87a41615aa.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"\u003cp\u003ePathomorphological Analysis of Fibrillary Astrocytoma of the Brain Identified by Magnetic Resonance Imaging\u003c/p\u003e","fulltext":[{"header":"Introduction","content":"\u003cp\u003eAstrocytomas are among the most common tumors of the brain, originating from astrocytes (6). According to the latest edition of the WHO classification [7], astrocytomas are distinguished based on their molecular characteristics. In terms of growth rate, astrocytic tumors are categorized as slow-growing (low-grade) and rapidly growing (high-grade), while their malignancy is classified into four degrees [3]. Astrocytomas belong to a group of glial neoplasms originating from astroglial cells and are considered the most prevalent primary blastomas of the nervous system. These brain tumors account for 30\u0026ndash;50% of all neoplasms [13]. Fibrillary astrocytoma is a low-grade glioma; however, according to some authors, malignant transformation is observed in 48\u0026ndash;80% of cases [5]. Following surgical treatment of fibrillary astrocytomas, the average life expectancy of patients, based on representative statistical studies, is up to 5 years [21].\u003c/p\u003e\n\u003ch3\u003eObjective of the Study\u003c/h3\u003e\n\u003cp\u003eTo conduct a pathomorphological analysis of fibrillary astrocytoma of the brain identified using magnetic resonance imaging.\u003c/p\u003e"},{"header":"Materials and Methods","content":"\u003cp\u003eThe study was conducted at the Neurosurgery Department of the Multidisciplinary Clinic of Samarkand State Medical University. A total of 23 patients\u0026mdash;13 men and 10 women\u0026mdash;underwent MRI-based identification of astrocytomas. Tumor samples measuring 1\u0026times;1\u0026times;0.5 cm were surgically excised. The tissue samples were fixed in 10% neutral formalin, processed through an alcohol series, and embedded in paraffin blocks. Histological sections of 7\u0026ndash;10 microns in thickness were stained with hematoxylin and eosin, as well as Nissl stain. The prepared histological specimens were analyzed morphologically.\u003c/p\u003e"},{"header":"Results and Discussion","content":"\u003cp\u003eMicroscopic examination of fibrillary astrocytoma revealed a low cellular density and a high concentration of glial fibers. The cytoplasm of the cells appeared faint, with oval and elongated nuclei (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e\n\u003ch3\u003eAstrocytes and Glial Fibers\u003c/h3\u003e\n\u003cp\u003eAstrocytes and glial fibers are arranged in parallel, following a consistent orientation, and sometimes form bundle-like structures. In certain cases, these bundles merge with a reticular structure. In other specimens, glial fibers appear to be randomly arranged. Some histological preparations show sparsely distributed glial fibers with wide inter-fiber spaces, whereas others reveal densely packed fibers. Glial fibers are generally uniform in thickness and have well-defined contours; however, in certain microscopic fields, variations in fiber thickness can be observed. These fibers distinctly stand out from the thin and indistinct astrocytic processes.\u003c/p\u003e \u003cp\u003eThe inter-fiber spaces are filled with tissue fluid. In some preparations, these regions do not absorb stain, whereas in many hematoxylin and eosin-stained specimens, the inter-fiber spaces appear light pink due to protein accumulation. Rosenthal dystrophy, characterized by thickening of both astrocytic processes and cell bodies, is commonly observed in glial fibers (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eA defining characteristic of glial tumors is their invasive growth, during which tumor cells penetrate the surrounding brain tissue to varying depths, forming an infiltration zone. The extent of this infiltration depends on the histobiological properties of the tumor, including its degree of malignancy, as well as the topographic and anatomical features of the affected area [9]. In our study, histological examination of tumor tissue excised from MRI-identified lesions revealed glial fibers interspersed among normal brain tissue, differing from astrocytic processes. Fibrillary astrocytoma initially exhibits glial fiber formation, followed by the incorporation of cellular structures.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eIn summary, fibrillary astrocytoma consists of a low number of cells and a high density of glial fibers. These fibers, varying in thickness, clearly distinguish the tumor from astrocytic processes with thin and indistinct contours. Rosenthal dystrophy actively develops within glial fibers, facilitating the tumor\u0026rsquo;s expansion within the brain. Given the high prevalence and distinct pathomorphological features of fibrillary astrocytoma, further in-depth scientific studies on this tumor type are warranted.\u003c/p\u003e"},{"header":"Declarations","content":"\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eAll authors reviewed the manuscript.\u003c/p\u003e\u003cp\u003eEthics Statement: This study was conducted at the multidisciplinary clinic of Samarkand State Medical University. All procedures involving human participants were performed in accordance with the ethical standards of the institutional ethics committee and the 1964 Helsinki Declaration and its later amendments. Ethical approval was obtained from the university\u0026apos;s ethics committee prior to the start of the research.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eBain B. N., Shardakov V. I., Selyukova M. V. \u003cem\u003eAntitumor Immunity and Its Disorders in Cerebral Tumors: A Textbook for Physicians.\u003c/em\u003e Kirov State Medical Academy, 2004. \u0026ndash; 49 p.\u003c/li\u003e\n\u003cli\u003eKolosov A. E. \u003cem\u003eLife Expectancy in Cancer, Sarcoma, Melanoma, Leukemia, and Lymphogranulomatosis: A Guide for Physicians.\u003c/em\u003e St. Petersburg \u0026ndash; Kirov, 2007. \u0026ndash; 432 p.\u003c/li\u003e\n\u003cli\u003eMatsko D. E., Korshunov A. G. \u003cem\u003eAtlas of Central Nervous System Tumors (Histological Structure).\u003c/em\u003e St. Petersburg: R. N. Khi Publishing House, 1998. \u0026ndash; 200 p.\u003c/li\u003e\n\u003cli\u003eYakhno N. N., Shtulman D. R. \u003cem\u003eDiseases of the Nervous System in Two Volumes.\u003c/em\u003e Moscow: Medicine, 2003. \u0026ndash; Vol. 1.\u003c/li\u003e\n\u003cli\u003eBuckner C., Brown P. D., O\u0026rsquo;Neill B. P., et al. \u003cem\u003eCentral Nervous System Tumors.\u003c/em\u003e\u003cem\u003eMayo Clinic Proceedings\u003c/em\u003e, 2007: 1271-1286.\u003c/li\u003e\n\u003cli\u003eBabu R., Sharma R., Karikari I. O., Owens T. R., Friedman A. H., Adamson C. \u003cem\u003eOutcome and Prognostic Factors in Adult Cerebellar Glioblastoma.\u003c/em\u003e\u003cem\u003eJournal of Clinical Neuroscience\u003c/em\u003e, 2013 Aug; 20(8):1117-1121. doi: 10.1016/joen.2012.12.006. PMID: 23706183.\u003c/li\u003e\n\u003cli\u003eLouis D. N., Perry A., Reifenberger G., von Deimling A., Figarella-Branger D., Ohgaki H., Wiestler O. D., Kleihues P., Ellison D. W. \u003cem\u003eThe 2016 World Health Organization Classification of Tumors of the Central Nervous System: A Summary.\u003c/em\u003e\u003cem\u003eActa Neuropathologica\u003c/em\u003e, 2016 Jun; 131(6):803-820. doi: 10.1007/s00401-016-1545-1. PMID: 27157931.\u003c/li\u003e\n\u003cli\u003eStrauss I., Jonas-Kimchi T., Bokstein F., Blumenthal D., Roth J., Sit R., Wilson J., Ram Z. \u003cem\u003eGliomas of the Posterior Fossa in Adults.\u003c/em\u003e\u003cem\u003eJournal of Neuro-Oncology\u003c/em\u003e, 2013 Dec; 115(3):401-409. doi: 10.1007/s11060-013-1231-2. PMID: 23979683.\u003c/li\u003e\n\u003cli\u003eKhominskiy B. S., Shamayey M. I., Rasheyeva I. C. \u003cem\u003eRustika Gliomas of the Medial and Paramedial Regions of the Brain.\u003c/em\u003e\u003cem\u003eProblemy Neyrokhirurgii\u003c/em\u003e, 1970; 3:14-27. (In Russian).\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"","lastPublishedDoi":"10.21203/rs.3.rs-6311339/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6311339/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eTo conduct a pathomorphological analysis of fibrillary astrocytoma of the brain identified using magnetic resonance imaging (MRI), tumor tissue surgically removed from 23 patients was examined. It was found that fibrillary astrocytoma consists of a small number of cells and a large number of glial fibers. These fibers, varying in thickness, distinctly differentiate fibrillary astrocytomas from tumors with thin, indistinct astrocytic contours. Rosenthal dystrophy actively develops within the glial fibers, contributing to the extensive spread of fibrillary astrocytoma in the brain.\u003c/p\u003e","manuscriptTitle":"Pathomorphological Analysis of Fibrillary Astrocytoma of the Brain Identified by Magnetic Resonance Imaging","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-03-31 12:33:39","doi":"10.21203/rs.3.rs-6311339/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"5caadbc2-684b-4c2d-8388-36b58c701d5f","owner":[],"postedDate":"March 31st, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":46430696,"name":"Health sciences/Medical research"},{"id":46430697,"name":"Health sciences/Oncology"}],"tags":[],"updatedAt":"2025-04-10T08:38:49+00:00","versionOfRecord":[],"versionCreatedAt":"2025-03-31 12:33:39","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-6311339","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6311339","identity":"rs-6311339","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}