{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,3,21]],"date-time":"2026-03-21T05:29:56Z","timestamp":1774070996724,"version":"3.50.1"},"posted":{"date-parts":[[2026,3,18]]},"group-title":"Microbiology","reference-count":77,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T00:00:00Z","timestamp":1773792000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,3,18]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:p>\n                  Bone infections, which are predominantly caused by\n                  <jats:italic>Staphylococcus (S.) aureus<\/jats:italic>\n                  , can be difficult to treat and have high rates of chronicity and reoccurrence. We previously identified that osteoclasts, the cells that break down bone matrix, may contribute to disease progression by allowing\n                  <jats:italic>S. aureus<\/jats:italic>\n                  to replicate intracellularly. There we identified that this bacterium\u2019s ability to grow intracellularly is tied to the maturation of osteoclasts. In this study we addressed whether osteoclast differentiation supports intracellular growth by changing the host cell\u2019s response to infection or by altering the host cell environment to better support\n                  <jats:italic>S. aureus<\/jats:italic>\n                  . Using dual species RNA-sequencing we analyzed host and bacterial transcripts of infected osteoclast and precursor bone marrow macrophage (BMM) cultures. Host transcript analysis suggests that infected osteoclasts are slow to upregulate bacterial response genes compared to BMMs. We also identify that the\n                  <jats:italic>S. aureus<\/jats:italic>\n                  transcriptional response is primarily determined by the host cell type, and that bacteria in osteoclasts upregulate carbon metabolism genes compared to those inside BMMs. By utilizing intracellular survival assays on\n                  <jats:italic>S. aureus<\/jats:italic>\n                  mutants deficient in carbon metabolism and related pathways we determine that\n                  <jats:italic>S. aureus<\/jats:italic>\n                  require glycolysis, acetyl-CoA synthesis, and aspartate biosynthesis for proliferation inside osteoclasts, although bacteria can survive without them. With differentiation, osteoclasts increase glutamine uptake, and this metabolite is required for S. aureus intracellular growth. Taken together, these findings suggest that osteoclasts support\n                  <jats:italic>S. aureus<\/jats:italic>\n                  intracellular growth by providing nutrients required to replicate in the context of a blunted antimicrobial response.\n                <\/jats:p>\n                <jats:sec>\n                  <jats:title>IMPORTANCE<\/jats:title>\n                  <jats:p>\n                    Infectious osteomyelitis, bone infection, is frequently caused by the bacterium\n                    <jats:italic>Staphylococcus aureus<\/jats:italic>\n                    . Intracellular infection of cells that build bone, osteoblasts, and cells that resorb bone, osteoclasts, have been implicated in disease progression by providing a niche for immune evasion. While\n                    <jats:italic>S. aureus<\/jats:italic>\n                    in osteoblasts are largely quiescent, bacteria in osteoclasts proliferate and therefore may be a source of reemergent infection. Factors that promote this growth in osteoclasts are poorly characterized. In this study we find that osteoclasts have a diminished transcriptional response to infection and show that\n                    <jats:italic>S. aureus<\/jats:italic>\n                    acquire glucose and glutamine, which have high flux in osteoclasts, to support intracellular growth. We further observe that\n                    <jats:italic>S. aureus<\/jats:italic>\n                    in osteoclasts require aspartate synthesis to grow intracellularly. This work highlights the importance of host cellular metabolism for the intracellular fate of\n                    <jats:italic>S. aureus<\/jats:italic>\n                    as an added factor beyond the direct antimicrobial response.\n                  <\/jats:p>\n                <\/jats:sec>","DOI":"10.64898\/2026.03.18.712565","type":"posted-content","created":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T03:15:18Z","timestamp":1773890118000},"source":"Crossref","is-referenced-by-count":0,"title":["The osteoclast intracellular environment fosters bacterial growth during\n                  <i>Staphylococcus aureus<\/i>\n                  infection"],"prefix":"10.64898","author":[{"given":"Luke D","family":"O\u2019Connor","sequence":"first","affiliation":[{"name":"Division of Bone & Mineral Diseases, Musculoskeletal Research Center, Washington University School of Medicine, Saint Louis, Missouri, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Saumya","family":"Bhagat","sequence":"additional","affiliation":[{"name":"Division of Bone & Mineral Diseases, Musculoskeletal Research Center, Washington University School of Medicine, Saint Louis, Missouri, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nidhi","family":"Roghati","sequence":"additional","affiliation":[{"name":"Division of Bone & Mineral Diseases, Musculoskeletal Research Center, Washington University School of Medicine, Saint Louis, Missouri, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4660-0952","authenticated-orcid":false,"given":"Gabriel","family":"Mbalaviele","sequence":"additional","affiliation":[{"name":"Division of Bone & Mineral Diseases, Musculoskeletal Research Center, Washington University School of Medicine, Saint Louis, Missouri, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1199-1167","authenticated-orcid":false,"given":"James E","family":"Cassat","sequence":"additional","affiliation":[{"name":"Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee, USA"},{"name":"Department of Biomedical Engineering, Vanderbilt University, Nashville, Tennessee, USA"},{"name":"Vanderbilt Institute for Infection, Immunology, and Inflammation, Nashville, Tennessee, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7101-5582","authenticated-orcid":false,"given":"Deborah J","family":"Veis","sequence":"additional","affiliation":[{"name":"Division of Bone & Mineral Diseases, Musculoskeletal Research Center, Washington University School of Medicine, Saint Louis, Missouri, USA"},{"name":"Department of Pathology and Immunology, Washington University School of Medicine; St. Louis, MO, US"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2026032019501097000_2026.03.18.712565v1.1","doi-asserted-by":"crossref","first-page":"1151","DOI":"10.1016\/j.ajpath.2020.02.007","article-title":"Current Concepts of Osteomyelitis: From Pathologic Mechanisms to Advanced Research Methods","volume":"190","year":"2020","journal-title":"Am J Pathol"},{"key":"2026032019501097000_2026.03.18.712565v1.2","doi-asserted-by":"crossref","unstructured":"Conterno LO , Turchi MD . 2013. Antibiotics for treating chronic osteomyelitis in adults. Cochrane Database Syst Rev CD 004439.","DOI":"10.1002\/14651858.CD004439.pub3"},{"key":"2026032019501097000_2026.03.18.712565v1.3","doi-asserted-by":"crossref","unstructured":"Gimza BD , Cassat JE . 2021. Mechanisms of Antibiotic Failure During Staphylococcus aureus Osteomyelitis. Front Immunol 12.","DOI":"10.3389\/fimmu.2021.638085"},{"key":"2026032019501097000_2026.03.18.712565v1.4","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.00415-18"},{"key":"2026032019501097000_2026.03.18.712565v1.5","doi-asserted-by":"crossref","unstructured":"Granata V , Possetti V , Parente R , Bottazzi B , Inforzato A , Sobacchi C . 2022. The osteoblast secretome in Staphylococcus aureus osteomyelitis. Frontiers in Immunology 13.","DOI":"10.3389\/fimmu.2022.1048505"},{"key":"2026032019501097000_2026.03.18.712565v1.6","doi-asserted-by":"crossref","unstructured":"Josse J , Velard F , Gangloff SC . 2015. Staphylococcus aureus vs. Osteoblast: Relationship and Consequences in Osteomyelitis. Frontiers in Cellular and Infection Microbiology 5.","DOI":"10.3389\/fcimb.2015.00085"},{"key":"2026032019501097000_2026.03.18.712565v1.7","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiu386"},{"key":"2026032019501097000_2026.03.18.712565v1.8","first-page":"e02447","article-title":"Staphylococcus aureus Infects Osteoclasts and Replicates Intracellularly","volume":"10","year":"2019","journal-title":"mBio"},{"key":"2026032019501097000_2026.03.18.712565v1.9","doi-asserted-by":"crossref","first-page":"e0018021","DOI":"10.1128\/IAI.00180-21","article-title":"Contemporary Clinical Isolates of Staphylococcus aureus from Pediatric Osteomyelitis Patients Display Unique Characteristics in a Mouse Model of Hematogenous Osteomyelitis","volume":"89","year":"2021","journal-title":"Infect Immun"},{"key":"2026032019501097000_2026.03.18.712565v1.10","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1146\/annurev-pathmechdis-031521-040919","article-title":"Osteoclasts, Master Sculptors of Bone","volume":"18","year":"2023","journal-title":"Annu Rev Pathol Mech Dis"},{"key":"2026032019501097000_2026.03.18.712565v1.11","doi-asserted-by":"crossref","first-page":"e10539","DOI":"10.1002\/jbm4.10539","article-title":"New Insights Into Osteoclast Biology","volume":"5","year":"2021","journal-title":"JBMR Plus"},{"key":"2026032019501097000_2026.03.18.712565v1.12","doi-asserted-by":"publisher","DOI":"10.1016\/8756-3282(85)90223-6"},{"key":"2026032019501097000_2026.03.18.712565v1.13","first-page":"221","article-title":"Longevity of osteoclasts in radiation chimaeras of osteopetrotic beige and normal mice","volume":"63","year":"1982","journal-title":"Br J Exp Pathol"},{"key":"2026032019501097000_2026.03.18.712565v1.14","doi-asserted-by":"publisher","DOI":"10.1007\/BF01042296"},{"key":"2026032019501097000_2026.03.18.712565v1.15","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.14.3.357"},{"key":"2026032019501097000_2026.03.18.712565v1.16","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-019-1105-7"},{"key":"2026032019501097000_2026.03.18.712565v1.17","doi-asserted-by":"publisher","DOI":"10.1038\/s41556-019-0437-8"},{"key":"2026032019501097000_2026.03.18.712565v1.18","first-page":"e00417","article-title":"Context-Dependent Roles for Toll-Like Receptors 2 and 9 in the Pathogenesis of Staphylococcus aureus Osteomyelitis","volume":"0","year":"2022","journal-title":"Infection and Immunity"},{"key":"2026032019501097000_2026.03.18.712565v1.19","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M115.663518"},{"key":"2026032019501097000_2026.03.18.712565v1.20","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.778078"},{"key":"2026032019501097000_2026.03.18.712565v1.21","doi-asserted-by":"crossref","first-page":"e73539","DOI":"10.7554\/eLife.73539","article-title":"Transferrin receptor 1-mediated iron uptake regulates bone mass in mice via osteoclast mitochondria and cytoskeleton","volume":"11","year":"2022","journal-title":"eLife"},{"key":"2026032019501097000_2026.03.18.712565v1.22","doi-asserted-by":"crossref","first-page":"4515","DOI":"10.1038\/s44319-024-00255-x","article-title":"Glutaminolysis provides nucleotides and amino acids to regulate osteoclast differentiation in mice","volume":"25","year":"2024","journal-title":"EMBO Rep"},{"key":"2026032019501097000_2026.03.18.712565v1.23","doi-asserted-by":"publisher","DOI":"10.1038\/nm.1910"},{"key":"2026032019501097000_2026.03.18.712565v1.24","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.2584"},{"key":"2026032019501097000_2026.03.18.712565v1.25","doi-asserted-by":"publisher","DOI":"10.1096\/fj.202000771R"},{"key":"2026032019501097000_2026.03.18.712565v1.26","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1038\/s41419-024-06475-2","article-title":"IL-17 promotes osteoclast-induced bone loss by regulating glutamine-dependent energy metabolism","volume":"15","year":"2024","journal-title":"Cell Death Dis"},{"key":"2026032019501097000_2026.03.18.712565v1.27","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1016\/j.biocel.2016.08.034","article-title":"Energy metabolism in osteoclast formation and activity","volume":"79","year":"2016","journal-title":"The International Journal of Biochemistry & Cell Biology"},{"key":"2026032019501097000_2026.03.18.712565v1.28","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.1976"},{"key":"2026032019501097000_2026.03.18.712565v1.29","doi-asserted-by":"publisher","DOI":"10.1359\/jbmr.2000.15.8.1477"},{"key":"2026032019501097000_2026.03.18.712565v1.30","doi-asserted-by":"publisher","DOI":"10.1172\/JCI8905"},{"key":"2026032019501097000_2026.03.18.712565v1.31","doi-asserted-by":"crossref","first-page":"100123","DOI":"10.1016\/j.xpro.2020.100123","article-title":"Dual RNA-Sequencing of Mycobacterium tuberculosis-Infected Cells from a Murine Infection Model","volume":"1","year":"2020","journal-title":"STAR Protocols"},{"key":"2026032019501097000_2026.03.18.712565v1.32","doi-asserted-by":"publisher","DOI":"10.1038\/s41587-019-0201-4"},{"key":"2026032019501097000_2026.03.18.712565v1.33","doi-asserted-by":"publisher","DOI":"10.1093\/NAR\/GKZ114"},{"key":"2026032019501097000_2026.03.18.712565v1.34","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btt656"},{"key":"2026032019501097000_2026.03.18.712565v1.35","doi-asserted-by":"publisher","DOI":"10.1186\/s12859-022-04644-8"},{"key":"2026032019501097000_2026.03.18.712565v1.36","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-014-0550-8"},{"key":"2026032019501097000_2026.03.18.712565v1.37","doi-asserted-by":"publisher","DOI":"10.1093\/NAR\/GKAC958"},{"key":"2026032019501097000_2026.03.18.712565v1.38","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1016\/S0140-6736(06)68231-7","article-title":"Complete genome sequence of USA300, an epidemic clone of community-acquired meticillin-resistant Staphylococcus aureus","volume":"367","year":"2006","journal-title":"The Lancet"},{"key":"2026032019501097000_2026.03.18.712565v1.39","doi-asserted-by":"crossref","first-page":"5923","DOI":"10.1038\/s41467-023-41629-4","article-title":"BAP1 promotes osteoclast function by metabolic reprogramming","volume":"14","year":"2023","journal-title":"Nat Commun"},{"key":"2026032019501097000_2026.03.18.712565v1.40","doi-asserted-by":"crossref","first-page":"ziaf093","DOI":"10.1093\/jbmrpl\/ziaf093","article-title":"Characterization of a mouse model of osteoarticular infection using clinical isolates of Staphylococcus aureus","volume":"9","year":"2025","journal-title":"JBMR Plus"},{"key":"2026032019501097000_2026.03.18.712565v1.41","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1922211117"},{"key":"2026032019501097000_2026.03.18.712565v1.42","first-page":"e01434","article-title":"Amino Acid Catabolism in Staphylococcus aureus and the Function of Carbon Catabolite Repression","volume":"8","year":"2017","journal-title":"mBio"},{"key":"2026032019501097000_2026.03.18.712565v1.43","first-page":"e04006","article-title":"Endogenous nitric oxide promotes Staphylococcus aureus virulence by activating autophagy","volume":"16","year":"2025","journal-title":"mBio"},{"key":"2026032019501097000_2026.03.18.712565v1.44","first-page":"e03596","article-title":"Nitrate Reductase NarGHJI Modulates Virulence via Regulation of agr Expression in Methicillin-Resistant Staphylococcus aureus Strain USA300 LAC","volume":"11","year":"2023","journal-title":"Microbiology Spectrum"},{"key":"2026032019501097000_2026.03.18.712565v1.45","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1006907"},{"key":"2026032019501097000_2026.03.18.712565v1.46","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.2006.05290.x"},{"key":"2026032019501097000_2026.03.18.712565v1.47","doi-asserted-by":"publisher","DOI":"10.1128\/JB.188.4.1648-1659.2006"},{"key":"2026032019501097000_2026.03.18.712565v1.48","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1016\/j.celrep.2019.06.018","article-title":"Nitric Oxide Modulates Metabolic Remodeling in Inflammatory Macrophages through TCA Cycle Regulation and Itaconate Accumulation","volume":"28","year":"2019","journal-title":"Cell Reports"},{"key":"2026032019501097000_2026.03.18.712565v1.49","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M302238200"},{"key":"2026032019501097000_2026.03.18.712565v1.50","doi-asserted-by":"crossref","first-page":"17023","DOI":"10.1038\/sigtrans.2017.23","article-title":"NF-\u03baB signaling in inflammation","volume":"2","year":"2017","journal-title":"Sig Transduct Target Ther"},{"key":"2026032019501097000_2026.03.18.712565v1.51","doi-asserted-by":"publisher","DOI":"10.1038\/srep35014"},{"key":"2026032019501097000_2026.03.18.712565v1.52","doi-asserted-by":"crossref","first-page":"2594","DOI":"10.3389\/fimmu.2019.02594","article-title":"Lipocalin 2 Protects Against Escherichia coli Infection by Modulating Neutrophil and Macrophage Function","volume":"10","year":"2019","journal-title":"Front Immunol"},{"key":"2026032019501097000_2026.03.18.712565v1.53","doi-asserted-by":"publisher","DOI":"10.1038\/nature03104"},{"key":"2026032019501097000_2026.03.18.712565v1.54","doi-asserted-by":"publisher","DOI":"10.1186\/s42269-019-0227-2"},{"key":"2026032019501097000_2026.03.18.712565v1.55","doi-asserted-by":"crossref","unstructured":"Gschwandtner M , Derler R , Midwood KS . 2019. More Than Just Attractive: How CCL2 Influences Myeloid Cell Behavior Beyond Chemotaxis. Front Immunol 10.","DOI":"10.3389\/fimmu.2019.02759"},{"key":"2026032019501097000_2026.03.18.712565v1.56","doi-asserted-by":"publisher","DOI":"10.1615\/CritRevImmunol.v32.i1.30"},{"key":"2026032019501097000_2026.03.18.712565v1.57","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M601502200"},{"key":"2026032019501097000_2026.03.18.712565v1.58","doi-asserted-by":"crossref","first-page":"2292","DOI":"10.1002\/art.39245","article-title":"Review: A20-Binding Inhibitor of NF-\u03baB Activation 1 Is a Physiologic Inhibitor of NF-\u03baB: A Molecular Switch for Inflammation and Autoimmunity","volume":"67","year":"2015","journal-title":"Arthritis & Rheumatology"},{"key":"2026032019501097000_2026.03.18.712565v1.59","doi-asserted-by":"crossref","unstructured":"Das T , Chen Z , Hendriks RW , Kool M . 2018. A20\/Tumor Necrosis Factor \u03b1-Induced Protein 3 in Immune Cells Controls Development of Autoinflammation and Autoimmunity: Lessons from Mouse Models. Front Immunol 9.","DOI":"10.3389\/fimmu.2018.00104"},{"key":"2026032019501097000_2026.03.18.712565v1.60","doi-asserted-by":"publisher","DOI":"10.1038\/nature02794"},{"key":"2026032019501097000_2026.03.18.712565v1.61","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M109.099895"},{"key":"2026032019501097000_2026.03.18.712565v1.62","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1016\/j.immuni.2017.06.018","article-title":"Hypoxia-Sensitive COMMD1 Integrates Signaling and Cellular Metabolism in Human Macrophages and Suppresses Osteoclastogenesis","volume":"47","year":"2017","journal-title":"Immunity"},{"key":"2026032019501097000_2026.03.18.712565v1.63","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.70.11.6373-6382.2002"},{"key":"2026032019501097000_2026.03.18.712565v1.64","doi-asserted-by":"crossref","first-page":"e1012425","DOI":"10.1371\/journal.ppat.1012425","article-title":"Citrate serves as a signal molecule to modulate carbon metabolism and iron homeostasis in Staphylococcus aureus","volume":"20","year":"2024","journal-title":"PLoS Pathog"},{"key":"2026032019501097000_2026.03.18.712565v1.65","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1411077111"},{"key":"2026032019501097000_2026.03.18.712565v1.66","doi-asserted-by":"publisher","DOI":"10.1111\/mmi.14479"},{"key":"2026032019501097000_2026.03.18.712565v1.67","first-page":"EMBR202050348","article-title":"Macrophage-driven nutrient delivery to phagosomal Staphylococcus aureus supports bacterial growth","volume":"21","year":"2020","journal-title":"EMBO Rep"},{"key":"2026032019501097000_2026.03.18.712565v1.68","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2017.12.021"},{"key":"2026032019501097000_2026.03.18.712565v1.69","doi-asserted-by":"publisher","DOI":"10.1128\/mbio.00045-15"},{"key":"2026032019501097000_2026.03.18.712565v1.70","doi-asserted-by":"publisher","DOI":"10.1128\/mbio.00814-21"},{"key":"2026032019501097000_2026.03.18.712565v1.71","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.1012544"},{"key":"2026032019501097000_2026.03.18.712565v1.72","doi-asserted-by":"publisher","DOI":"10.3389\/FIMMU.2020.620339\/BIBTEX"},{"key":"2026032019501097000_2026.03.18.712565v1.73","doi-asserted-by":"crossref","first-page":"121632","DOI":"10.1016\/j.biomaterials.2022.121632","article-title":"Human macrophage polarization determines bacterial persistence of Staphylococcus aureus in a liver-on-chip-based infection model","volume":"287","year":"2022","journal-title":"Biomaterials"},{"key":"2026032019501097000_2026.03.18.712565v1.74","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-017-02538-5"},{"key":"2026032019501097000_2026.03.18.712565v1.75","doi-asserted-by":"crossref","first-page":"7740079","DOI":"10.1155\/2022\/7740079","article-title":"RANKL Impairs the TLR4 Pathway by Increasing TRAF6 and RANK Interaction in Macrophages","volume":"2022","year":"2022","journal-title":"Biomed Res Int"},{"key":"2026032019501097000_2026.03.18.712565v1.76","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0010146"},{"key":"2026032019501097000_2026.03.18.712565v1.77","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.00537-12"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.64898\/2026.03.18.712565","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,21]],"date-time":"2026-03-21T02:50:20Z","timestamp":1774061420000},"score":1,"resource":{"primary":{"URL":"http:\/\/biorxiv.org\/lookup\/doi\/10.64898\/2026.03.18.712565"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,18]]},"references-count":77,"URL":"https:\/\/doi.org\/10.64898\/2026.03.18.712565","relation":{},"subject":[],"published":{"date-parts":[[2026,3,18]]},"subtype":"preprint"}}