Fentanyl decreases blood oxygen more than furanylfentanyl despite similar effects on breathing

Fentanyl decreases blood oxygen more than furanylfentanyl despite similar effects on breathing | 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 Research Article Fentanyl decreases blood oxygen more than furanylfentanyl despite similar effects on breathing Catherine Demery, Sierra C. Moore, Kelsey E. Kochan, Mengchu Li, and 7 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8398857/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 Rationale: Fatal opioid overdoses involving synthetic opioids have increased >10-fold over the past 8 years. Fentanyl, a potent synthetic opioid acting at the mu-opioid receptor (MOR), has largely replaced heroin as the predominant illicit opioid available. Various analogs have been synthesized from the fentanyl scaffold, including 2-furanylfentanyl, one of the most trafficked analogs from 2019 to 2024. Despite its prevalence, the in vivo effects of furanylfentanyl are not well characterized, especially regarding respiratory depression. Objectives: To characterize furanylfentanyl relative to fentanyl in vitro and compare the effects of both drugs in mouse models of antinociception and respiratory depression. Methods: The affinity and potency of fentanyl and furanylfentanyl were determined in CHO cells overexpressing MOR. Male and female mice were administered ( i.p. ) fentanyl or furanylfentanyl prior to measuring antinociception (warm-water tail withdrawal), respiration (whole-body plethysmography), or oxygen saturation (pulse oximetry). Results: Furanylfentanyl behaves as a partial agonist in vitro relative to fentanyl and morphine but with similar affinity and potency at MOR. In mice, fentanyl and furanylfentanyl produced similar effects on breathing parameters (including rate and inspiration time) that were greater than those induced by morphine, yet only fentanyl caused a drastic, long-lasting depletion of blood oxygen saturation. The discrepancy between effects on breathing and oxygen saturation may be explained by a greater number of apneas induced by fentanyl. Conclusions: These results highlight the complexity of fentanyl-induced respiratory depression and indicate that recreational use of 2-furanylfentanyl in humans may pose a greater risk of overdose than morphine but lesser than fentanyl. Furanylfentanyl fentanyl opioid mu-opioid receptor respiratory depression plethysmography oxygen saturation overdose apneas mouse Full Text Additional Declarations No competing interests reported. Supplementary Files FFSupplementaryMaterialNOVEMBERSUBMISSION.docx 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. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. 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-8398857","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":571055756,"identity":"12ba69d6-70e2-4d5b-b1c6-9532b7d838d0","order_by":0,"name":"Catherine Demery","email":"","orcid":"","institution":"University of Michigan Medical School","correspondingAuthor":false,"prefix":"","firstName":"Catherine","middleName":"","lastName":"Demery","suffix":""},{"id":571055757,"identity":"c2bdbb1c-0bcc-4ec9-9049-9cad8307656b","order_by":1,"name":"Sierra C. Moore","email":"","orcid":"","institution":"University of Michigan Medical School","correspondingAuthor":false,"prefix":"","firstName":"Sierra","middleName":"C.","lastName":"Moore","suffix":""},{"id":571055760,"identity":"823762c6-90b3-41bd-9e21-4c843372c245","order_by":2,"name":"Kelsey E. Kochan","email":"","orcid":"","institution":"University of Michigan Medical School","correspondingAuthor":false,"prefix":"","firstName":"Kelsey","middleName":"E.","lastName":"Kochan","suffix":""},{"id":571055763,"identity":"c9dffebc-6ec7-4a35-a7ad-85477e9f975a","order_by":3,"name":"Mengchu Li","email":"","orcid":"","institution":"University of Michigan Medical School","correspondingAuthor":false,"prefix":"","firstName":"Mengchu","middleName":"","lastName":"Li","suffix":""},{"id":571055766,"identity":"0408f176-a4d1-4ae9-9e4b-7b8d8ea8d151","order_by":4,"name":"Thomas D. Prince","email":"","orcid":"","institution":"University of Michigan Medical School","correspondingAuthor":false,"prefix":"","firstName":"Thomas","middleName":"D.","lastName":"Prince","suffix":""},{"id":571055769,"identity":"d4e3c90e-ce69-4a31-9889-4165bf39f72b","order_by":5,"name":"Benjamin M. Clements","email":"","orcid":"","institution":"University of Michigan Medical School","correspondingAuthor":false,"prefix":"","firstName":"Benjamin","middleName":"M.","lastName":"Clements","suffix":""},{"id":571055772,"identity":"16f9dea7-06be-4df9-8923-329149996fa1","order_by":6,"name":"Zhongqi Chen","email":"","orcid":"","institution":"University of Michigan College of Pharmacy","correspondingAuthor":false,"prefix":"","firstName":"Zhongqi","middleName":"","lastName":"Chen","suffix":""},{"id":571055776,"identity":"3b71ebad-0e87-416c-9901-a41c855c851d","order_by":7,"name":"Jessica R. Whitaker-Fornek","email":"","orcid":"","institution":"University of Michigan Medical School","correspondingAuthor":false,"prefix":"","firstName":"Jessica","middleName":"R.","lastName":"Whitaker-Fornek","suffix":""},{"id":571055783,"identity":"58ecbe1d-436c-4295-95c4-ddf2cc531fff","order_by":8,"name":"Erica S. Levitt","email":"","orcid":"","institution":"University of Michigan Medical School","correspondingAuthor":false,"prefix":"","firstName":"Erica","middleName":"S.","lastName":"Levitt","suffix":""},{"id":571055791,"identity":"5e6aa5ee-5f0f-4067-add1-29d8c760d0ac","order_by":9,"name":"Jessica P. Anand","email":"","orcid":"","institution":"University of Michigan Medical School","correspondingAuthor":false,"prefix":"","firstName":"Jessica","middleName":"P.","lastName":"Anand","suffix":""},{"id":571055793,"identity":"1c36a236-babd-447d-8c27-5bc8e3f500ac","order_by":10,"name":"John R. Traynor","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAy0lEQVRIiWNgGAWjYBACxgYogx+ID4B5BwhpaYMyJBuI1cLABqUNDsDsJKSFeX7vw8+8O2zyjW9kJx74uYNBju9GAiGHsRtL855Js9x2I3fDwd4zDMaShLWwMUjzth02MANqOQz0WeIGIrQw/wZpMZ4B0VJPjBY2sC0GEhAtCQaEtaSxWc5tSzOQOPMW6Jc2CcOZZx7g12LYfIz5xts2GwP+9tzNH3622cjzHSdgi2EDAwMTD4IvgV85CMiDHPeDsLpRMApGwSgYyQAAVAtHh0CnX+gAAAAASUVORK5CYII=","orcid":"","institution":"University of Michigan Medical School","correspondingAuthor":true,"prefix":"","firstName":"John","middleName":"R.","lastName":"Traynor","suffix":""}],"badges":[],"createdAt":"2025-12-18 21:08:15","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-8398857/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8398857/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":100364286,"identity":"2dca1d7b-30f6-42ad-b9a0-d9f3610f7c09","added_by":"auto","created_at":"2026-01-16 07:53:12","extension":"docx","order_by":0,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":2231720,"visible":true,"origin":"","legend":"","description":"","filename":"FFManuscriptwithFUNDINGstatement.docx","url":"https://assets-eu.researchsquare.com/files/rs-8398857/v1/0ca43a266e9d10e43361e609.docx"},{"id":100364070,"identity":"70f926ca-b073-4877-a01f-8b64b0ac4387","added_by":"auto","created_at":"2026-01-16 07:52:31","extension":"json","order_by":1,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":12089,"visible":true,"origin":"","legend":"","description":"","filename":"56034c77a191408996b7acdee70e7b5d.json","url":"https://assets-eu.researchsquare.com/files/rs-8398857/v1/9406f2d1e22836bf941101a3.json"},{"id":100062540,"identity":"685386da-4642-4fb8-b033-83ec566334a2","added_by":"auto","created_at":"2026-01-12 14:58:21","extension":"docx","order_by":2,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":1002885,"visible":true,"origin":"","legend":"","description":"","filename":"FFSupplementaryMaterialNOVEMBERSUBMISSION.docx","url":"https://assets-eu.researchsquare.com/files/rs-8398857/v1/ed1368e53df79605dfe708e9.docx"},{"id":100364233,"identity":"55690945-850f-4744-97cb-f1782a9847bb","added_by":"auto","created_at":"2026-01-16 07:53:01","extension":"xml","order_by":3,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":99736,"visible":true,"origin":"","legend":"","description":"","filename":"56034c77a191408996b7acdee70e7b5d1enriched.xml","url":"https://assets-eu.researchsquare.com/files/rs-8398857/v1/28d0a15550be7443286e6f64.xml"},{"id":100062532,"identity":"8cf1d06b-62e0-4e92-a647-5b84fb16487f","added_by":"auto","created_at":"2026-01-12 14:58:21","extension":"jpeg","order_by":4,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":428635,"visible":true,"origin":"","legend":"","description":"","filename":"floatimage1.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-8398857/v1/264fac481b52e9430d4239f9.jpeg"},{"id":100363967,"identity":"755886f5-1701-4c15-a716-97af1269c3ab","added_by":"auto","created_at":"2026-01-16 07:52:15","extension":"jpeg","order_by":5,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":267535,"visible":true,"origin":"","legend":"","description":"","filename":"floatimage2.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-8398857/v1/12f694de295f4c6a9b42af52.jpeg"},{"id":100364709,"identity":"ab15b084-080b-4e10-82e2-1c8c4f768f7e","added_by":"auto","created_at":"2026-01-16 07:54:14","extension":"jpeg","order_by":6,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":603007,"visible":true,"origin":"","legend":"","description":"","filename":"floatimage3.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-8398857/v1/fb3f6fe5981ba361ec1f7ff1.jpeg"},{"id":100062534,"identity":"603ac978-c494-4e65-a982-c0a80f86c347","added_by":"auto","created_at":"2026-01-12 14:58:21","extension":"jpeg","order_by":7,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":322374,"visible":true,"origin":"","legend":"","description":"","filename":"floatimage4.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-8398857/v1/c8d21a63efe474ee8a213001.jpeg"},{"id":100363411,"identity":"70c4b13f-d025-4c20-8325-2c76a2a8a909","added_by":"auto","created_at":"2026-01-16 07:49:40","extension":"jpeg","order_by":8,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":433375,"visible":true,"origin":"","legend":"","description":"","filename":"floatimage5.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-8398857/v1/adf8bf61be4733dc632b001b.jpeg"},{"id":100364242,"identity":"af2f41c7-c577-4e40-98f3-c2b52fb90e76","added_by":"auto","created_at":"2026-01-16 07:53:04","extension":"jpeg","order_by":9,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":369705,"visible":true,"origin":"","legend":"","description":"","filename":"floatimage6.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-8398857/v1/407f93a9671d9430fb408b5b.jpeg"},{"id":100363894,"identity":"9c8ee525-9b91-46f2-b6a8-20416a25cc01","added_by":"auto","created_at":"2026-01-16 07:51:59","extension":"jpeg","order_by":10,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":475600,"visible":true,"origin":"","legend":"","description":"","filename":"floatimage7.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-8398857/v1/899437bf1d44c1b49069cbae.jpeg"},{"id":100364747,"identity":"1d7481be-ffaa-4184-9f60-29607df61d0c","added_by":"auto","created_at":"2026-01-16 07:54:17","extension":"png","order_by":11,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":180450,"visible":true,"origin":"","legend":"","description":"","filename":"Onlinefloatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-8398857/v1/53ef77d0ff50f6a7b9185f01.png"},{"id":100364335,"identity":"969cc26a-4a4f-46c0-9b87-259c5c88f766","added_by":"auto","created_at":"2026-01-16 07:53:28","extension":"png","order_by":12,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":68000,"visible":true,"origin":"","legend":"","description":"","filename":"Onlinefloatimage2.png","url":"https://assets-eu.researchsquare.com/files/rs-8398857/v1/f90bdda8e9c50c5a1b18b5d5.png"},{"id":100363977,"identity":"15b8f6d2-4896-4c10-9a2b-67ba2f8508e3","added_by":"auto","created_at":"2026-01-16 07:52:16","extension":"png","order_by":13,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":167374,"visible":true,"origin":"","legend":"","description":"","filename":"Onlinefloatimage3.png","url":"https://assets-eu.researchsquare.com/files/rs-8398857/v1/ff50afa89ec0dea61e3b538b.png"},{"id":100364635,"identity":"0e3ffeb5-1fcb-47a1-af4d-13890df28f12","added_by":"auto","created_at":"2026-01-16 07:54:03","extension":"png","order_by":14,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":115701,"visible":true,"origin":"","legend":"","description":"","filename":"Onlinefloatimage4.png","url":"https://assets-eu.researchsquare.com/files/rs-8398857/v1/143987d55b927675db714381.png"},{"id":100363905,"identity":"f7b0db47-aab0-4e4e-b4dc-e2558a53703f","added_by":"auto","created_at":"2026-01-16 07:52:02","extension":"png","order_by":15,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":190627,"visible":true,"origin":"","legend":"","description":"","filename":"Onlinefloatimage5.png","url":"https://assets-eu.researchsquare.com/files/rs-8398857/v1/277c3b5d62966245a10b9c64.png"},{"id":100062551,"identity":"6b74e6bf-84c3-49ac-8016-c40684bbb877","added_by":"auto","created_at":"2026-01-12 14:58:22","extension":"png","order_by":16,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":143160,"visible":true,"origin":"","legend":"","description":"","filename":"Onlinefloatimage6.png","url":"https://assets-eu.researchsquare.com/files/rs-8398857/v1/fe52a58e3fb1e45c66e2a942.png"},{"id":100363669,"identity":"6b0a9cd5-718f-40e5-be82-9b3a1ad42eee","added_by":"auto","created_at":"2026-01-16 07:51:04","extension":"png","order_by":17,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":215050,"visible":true,"origin":"","legend":"","description":"","filename":"Onlinefloatimage7.png","url":"https://assets-eu.researchsquare.com/files/rs-8398857/v1/d5c2d203325da2419a7ca87e.png"},{"id":100062552,"identity":"2cdc94ec-dce8-482d-a1e8-17f38c821efe","added_by":"auto","created_at":"2026-01-12 14:58:22","extension":"xml","order_by":18,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":97561,"visible":true,"origin":"","legend":"","description":"","filename":"56034c77a191408996b7acdee70e7b5d1structuring.xml","url":"https://assets-eu.researchsquare.com/files/rs-8398857/v1/d6447220c398997509b4dc47.xml"},{"id":100062553,"identity":"bd3d10a6-e7a6-41cc-8273-0dd3cb45de82","added_by":"auto","created_at":"2026-01-12 14:58:22","extension":"html","order_by":19,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":106898,"visible":true,"origin":"","legend":"","description":"","filename":"earlyproof.html","url":"https://assets-eu.researchsquare.com/files/rs-8398857/v1/ff9ac36a2f76872acc29c627.html"},{"id":100381971,"identity":"c4b46396-a28e-4001-9cbf-ca37f10963e5","added_by":"auto","created_at":"2026-01-16 10:40:11","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2891098,"visible":true,"origin":"","legend":"","description":"","filename":"FFManuscriptwithFUNDINGstatement.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8398857/v1_covered_a4dd3fca-ed2b-4044-b3e2-66ee51c027d1.pdf"},{"id":100364017,"identity":"35095efe-6f0e-4f96-af9a-e53c119737f6","added_by":"auto","created_at":"2026-01-16 07:52:24","extension":"docx","order_by":0,"title":"","display":"","copyAsset":false,"role":"supplement","size":1002885,"visible":true,"origin":"","legend":"","description":"","filename":"FFSupplementaryMaterialNOVEMBERSUBMISSION.docx","url":"https://assets-eu.researchsquare.com/files/rs-8398857/v1/8846f4a7dcf0b144a07e09de.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Fentanyl decreases blood oxygen more than furanylfentanyl despite similar effects on breathing","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":true,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":true,"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":"Furanylfentanyl, fentanyl, opioid, mu-opioid receptor, respiratory depression, plethysmography, oxygen saturation, overdose, apneas, mouse","lastPublishedDoi":"10.21203/rs.3.rs-8398857/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8398857/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cem\u003eRationale:\u003c/em\u003e Fatal opioid overdoses involving synthetic opioids have increased \u0026gt;10-fold over the past 8 years. Fentanyl, a potent synthetic opioid acting at the mu-opioid receptor (MOR), has largely replaced heroin as the predominant illicit opioid available. Various analogs have been synthesized from the fentanyl scaffold, including 2-furanylfentanyl, one of the most trafficked analogs from 2019 to 2024. Despite its prevalence, the\u003cem\u003ein vivo \u003c/em\u003eeffects of furanylfentanyl are not well characterized, especially regarding respiratory depression.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eObjectives:\u003c/em\u003e To characterize furanylfentanyl relative to fentanyl \u003cem\u003ein vitro\u003c/em\u003e and compare the effects of both drugs in mouse models of antinociception and respiratory depression.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eMethods:\u003c/em\u003e The affinity and potency of fentanyl and furanylfentanyl were determined in CHO cells overexpressing MOR. Male and female mice were administered (\u003cem\u003ei.p.\u003c/em\u003e) fentanyl or furanylfentanyl prior to measuring antinociception (warm-water tail withdrawal), respiration (whole-body plethysmography), or oxygen saturation (pulse oximetry).\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eResults:\u003c/em\u003e Furanylfentanyl behaves as a partial agonist \u003cem\u003ein vitro\u003c/em\u003e relative to fentanyl and morphine but with similar affinity and potency at MOR. In mice, fentanyl and furanylfentanyl produced similar effects on breathing parameters (including rate and inspiration time) that were greater than those induced by morphine, yet only fentanyl caused a drastic, long-lasting depletion of blood oxygen saturation. The discrepancy between effects on breathing and oxygen saturation may be explained by a greater number of apneas induced by fentanyl.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eConclusions:\u003c/em\u003e These results highlight the complexity of fentanyl-induced respiratory depression and indicate that recreational use of 2-furanylfentanyl in humans may pose a greater risk of overdose than morphine but lesser than fentanyl.\u003c/p\u003e","manuscriptTitle":"Fentanyl decreases blood oxygen more than furanylfentanyl despite similar effects on breathing","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-01-12 14:58:16","doi":"10.21203/rs.3.rs-8398857/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":"4534657c-4db3-4192-af30-c7da5a163ad8","owner":[],"postedDate":"January 12th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2026-05-12T13:46:40+00:00","versionOfRecord":[],"versionCreatedAt":"2026-01-12 14:58:16","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8398857","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8398857","identity":"rs-8398857","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}