{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T22:22:57Z","timestamp":1788992577188,"version":"build-2803163510"},"reference-count":45,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2024,10,19]],"date-time":"2024-10-19T00:00:00Z","timestamp":1729296000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,10,19]],"date-time":"2024-10-19T00:00:00Z","timestamp":1729296000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"NIH\/NIAMS","award":["T32 AR064194"],"award-info":[{"award-number":["T32 AR064194"]}]},{"name":"NIH\/NIAMS","award":["T32 AR064194"],"award-info":[{"award-number":["T32 AR064194"]}]},{"DOI":"10.13039\/100000738","name":"U.S. Department of Veterans Affairs","doi-asserted-by":"crossref","award":["I01 BX002234,I01 BX005927"],"award-info":[{"award-number":["I01 BX002234,I01 BX005927"]}],"id":[{"id":"10.13039\/100000738","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000738","name":"U.S. Department of Veterans Affairs","doi-asserted-by":"crossref","award":["I01 BX002234,I01 BX005927"],"award-info":[{"award-number":["I01 BX002234,I01 BX005927"]}],"id":[{"id":"10.13039\/100000738","id-type":"DOI","asserted-by":"crossref"}]},{"name":"UCSD Collaborative Center for Multiplexed Proteomics, and Janssen Pharmaceuticals."},{"name":"Janssen"},{"name":"National Institute of Health","award":["AR075990"],"award-info":[{"award-number":["AR075990"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Urate-lowering treatment (ULT) to target with xanthine oxidase inhibitors (XOIs) paradoxically causes early increase in gouty arthritis flares. Because delayed reduction in flare burden is mechanistically unclear, we tested for ULT inflammation responsiveness markers. Unbiased proteomics analyzed blood samples (baseline, 48 weeks ULT) in two, independent ULT out trial cohorts (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200919,\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200930). STRING-db and multivariate analyses supplemented determinations of altered proteins via Wilcoxon matched pairs signed rank testing in XOI ULT responders. Mechanistic studies characterized proteomes of cultured XOI-treated murine bone marrow macrophages (BMDMs). At 48 weeks ULT, serum urate normalized in all gout patients, and flares declined in association with significantly altered proteins (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.05) in clustering and proteome networks in sera and peripheral blood mononuclear cells. Sera demonstrated altered complement activation and regulatory gene ontology biologic processes. In both cohorts, a treatment-emergent serum interactome included key gouty inflammation mediators (C5, IL-1B, CXCL8, IL6). Last, febuxostat treatment decreased complement activation biologic process proteins in cultured BMDMs. Reduced gout flares are linked with a XOI treatment-emergent serum protein interactome that includes inflammation regulators, associated with altered complement activation and regulatory biologic processes. Serum and leukocyte proteomics could help identify when gouty inflammatory processes begin to subside in response to ULT.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:italic>Trial Registration<\/jats:italic>\n                    : ClinicalTrials.gov Identifier NCT02579096, posted October 19, 2015.\n                  <\/jats:p>","DOI":"10.1038\/s41598-024-74154-5","type":"journal-article","created":{"date-parts":[[2024,10,19]],"date-time":"2024-10-19T08:02:50Z","timestamp":1729324970000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Effective xanthine oxidase inhibitor urate lowering therapy in gout is linked to an emergent serum protein interactome of complement and inflammation modulators"],"prefix":"10.1038","volume":"14","author":[{"given":"Concepcion","family":"Sanchez","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anaamika","family":"Campeau","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ru","family":"Liu-Bryan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ted R.","family":"Mikuls","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James R.","family":"O\u2019Dell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David J.","family":"Gonzalez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Terkeltaub","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,10,19]]},"reference":[{"key":"74154_CR1","doi-asserted-by":"publisher","first-page":"2039","DOI":"10.1016\/s0140-6736(16)00346-9","volume":"388","author":"N Dalbeth","year":"2016","unstructured":"Dalbeth, N., Merriman, T. R. & Stamp, L. K. Gout. Lancet 388, 2039\u20132052. https:\/\/doi.org\/10.1016\/s0140-6736(16)00346-9 (2016).","journal-title":"Lancet"},{"key":"74154_CR2","doi-asserted-by":"publisher","unstructured":"Teoh, N. et al. The challenges of gout flare reporting: mapping flares during a randomized controlled trial. BMC Rheumatology 3. https:\/\/doi.org\/10.1186\/s41927-019-0075-6 (2019).","DOI":"10.1186\/s41927-019-0075-6"},{"key":"74154_CR3","doi-asserted-by":"publisher","first-page":"1448","DOI":"10.1136\/annrheumdis-2011-201215","volume":"71","author":"Y Zhang","year":"2012","unstructured":"Zhang, Y. et al. Purine-rich foods intake and recurrent gout attacks. Ann. Rheum. Dis. 71, 1448\u20131453. https:\/\/doi.org\/10.1136\/annrheumdis-2011-201215 (2012).","journal-title":"Ann. Rheum. Dis."},{"key":"74154_CR4","doi-asserted-by":"publisher","unstructured":"Terkeltaub, R. What makes gouty inflammation so variable? BMC Medicine 15. https:\/\/doi.org\/10.1186\/s12916-017-0922-5 (2017).","DOI":"10.1186\/s12916-017-0922-5"},{"key":"74154_CR5","doi-asserted-by":"publisher","DOI":"10.1016\/j.berh.2021.101723","volume":"35","author":"A Danve","year":"2021","unstructured":"Danve, A., Sehra, S. T. & Neogi, T. Role of diet in hyperuricemia and gout. Best Pract. Res. Clin. Rheumatol. 35, 101723. https:\/\/doi.org\/10.1016\/j.berh.2021.101723 (2021).","journal-title":"Best Pract. Res. Clin. Rheumatol."},{"key":"74154_CR6","doi-asserted-by":"publisher","first-page":"744","DOI":"10.1002\/acr.24180","volume":"72","author":"JD Fitzgerald","year":"2020","unstructured":"Fitzgerald, J. D. et al. 2020 American College of Rheumatology Guideline for the Management of Gout. Arthritis Care Res. 72, 744\u2013760. https:\/\/doi.org\/10.1002\/acr.24180 (2020).","journal-title":"Arthritis Care Res."},{"key":"74154_CR7","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1136\/annrheumdis-2016-209707","volume":"76","author":"P Richette","year":"2017","unstructured":"Richette, P. et al. 2016 updated EULAR evidence-based recommendations for the management of gout. Ann. Rheum. Dis. 76, 29\u201342. https:\/\/doi.org\/10.1136\/annrheumdis-2016-209707 (2017).","journal-title":"Ann. Rheum. Dis."},{"key":"74154_CR8","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1038\/s41584-021-00725-9","volume":"18","author":"HK Choi","year":"2022","unstructured":"Choi, H. K., Mccormick, N. & Yokose, C. Excess comorbidities in gout: the causal paradigm and pleiotropic approaches to care. Nat. Rev. Rheumatol. 18, 97\u2013111. https:\/\/doi.org\/10.1038\/s41584-021-00725-9 (2022).","journal-title":"Nat. Rev. Rheumatol."},{"key":"74154_CR9","doi-asserted-by":"publisher","first-page":"1626","DOI":"10.1136\/ard-2023-224731","volume":"82","author":"L Stamp","year":"2023","unstructured":"Stamp, L. et al. Is colchicine prophylaxis required with start-low go-slow allopurinol dose escalation in gout? A non-inferiority randomised double-blind placebo-controlled trial. Ann. Rheum. Dis. 82, 1626\u20131634. https:\/\/doi.org\/10.1136\/ard-2023-224731 (2023).","journal-title":"Ann. Rheum. Dis."},{"key":"74154_CR10","unstructured":"Peiteado, D., Villalba, A., Mart\u00edn-Mola, E. & de Miguel, E. Reduction but not disappearance of Doppler signal after two years of treatment for gout. Do we need a more intensive treatment?"},{"key":"74154_CR11","doi-asserted-by":"publisher","first-page":"1500","DOI":"10.1136\/annrheumdis-2020-217392","volume":"79","author":"HB Hammer","year":"2020","unstructured":"Hammer, H. B. et al. Ultrasound shows rapid reduction of crystal depositions during a treat-to-target approach in gout patients: 12-month results from the NOR-Gout study. Ann. Rheum. Dis. 79, 1500\u20131505. https:\/\/doi.org\/10.1136\/annrheumdis-2020-217392 (2020).","journal-title":"Ann. Rheum. Dis."},{"key":"74154_CR12","doi-asserted-by":"publisher","first-page":"SI81","DOI":"10.1093\/rheumatology\/keab533","volume":"61","author":"T Uhlig","year":"2022","unstructured":"Uhlig, T. et al. Two-year reduction of dual-energy CT urate depositions during a treat-to-target strategy in gout in the NOR-Gout longitudinal study. Rheumatology 61, SI81\u2013SI85. https:\/\/doi.org\/10.1093\/rheumatology\/keab533 (2022).","journal-title":"Rheumatology"},{"key":"74154_CR13","doi-asserted-by":"publisher","unstructured":"Schlesinger, N., Pillinger, M. H., Simon, L. S. & Lipsky, P. E. Interleukin-1\u03b2 inhibitors for the management of acute gout flares: a systematic literature review. Arthritis Res. Ther. 25. https:\/\/doi.org\/10.1186\/s13075-023-03098-4 (2023).","DOI":"10.1186\/s13075-023-03098-4"},{"key":"74154_CR14","doi-asserted-by":"publisher","first-page":"2633","DOI":"10.1002\/art.20386","volume":"50","author":"N Tramontini","year":"2004","unstructured":"Tramontini, N., Huber, C., Liu-Bryan, R., Terkeltaub, R. A. & Kilgore, K. S. Central role of complement membrane attack complex in monosodium urate crystal\u2013induced neutrophilic rabbit knee synovitis. Arthritis Rheum. 50, 2633\u20132639. https:\/\/doi.org\/10.1002\/art.20386 (2004).","journal-title":"Arthritis Rheum."},{"key":"74154_CR15","doi-asserted-by":"publisher","first-page":"239","DOI":"10.1016\/0090-1229(82)90235-5","volume":"24","author":"IJ Russell","year":"1982","unstructured":"Russell, I. J., Mansen, C., Kolb, L. M. & Kolb, W. P. Activation of the fifth component of human complement (C5) induced by monosodium urate crystals: C5 convertase assembly on the crystal surface. Clin. Immunol. Immunopathol. 24, 239\u2013250. https:\/\/doi.org\/10.1016\/0090-1229(82)90235-5 (1982).","journal-title":"Clin. Immunol. Immunopathol."},{"key":"74154_CR16","doi-asserted-by":"publisher","first-page":"1403","DOI":"10.1016\/s0140-6736(18)32158-5","volume":"392","author":"M Doherty","year":"2018","unstructured":"Doherty, M. et al. Efficacy and cost-effectiveness of nurse-led care involving education and engagement of patients and a treat-to-target urate-lowering strategy versus usual care for gout: a randomised controlled trial. Lancet 392, 1403\u20131412. https:\/\/doi.org\/10.1016\/s0140-6736(18)32158-5 (2018).","journal-title":"Lancet"},{"key":"74154_CR17","doi-asserted-by":"publisher","first-page":"2386","DOI":"10.1002\/art.40233","volume":"69","author":"N Dalbeth","year":"2017","unstructured":"Dalbeth, N. et al. Effects of febuxostat in early gout. Arthritis Rheumatol. 69, 2386\u20132395. https:\/\/doi.org\/10.1002\/art.40233 (2017).","journal-title":"Arthritis Rheumatol."},{"key":"74154_CR18","doi-asserted-by":"publisher","unstructured":"O\u2019Dell, J. R. et al. Comparative Effectiveness of Allopurinol and Febuxostat in Gout Management. NEJM Evidence 1. https:\/\/doi.org\/10.1056\/evidoa2100028 (2022).","DOI":"10.1056\/evidoa2100028"},{"key":"74154_CR19","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2023.113139","volume":"42","author":"H Gu","year":"2023","unstructured":"Gu, H. et al. MSU crystal deposition contributes to inflammation and immune responses in gout remission. Cell Rep. 42, 113139. https:\/\/doi.org\/10.1016\/j.celrep.2023.113139 (2023).","journal-title":"Cell Rep."},{"key":"74154_CR20","doi-asserted-by":"publisher","first-page":"6555","DOI":"10.1038\/ncomms7555","volume":"6","author":"A Ives","year":"2015","unstructured":"Ives, A. et al. Xanthine oxidoreductase regulates macrophage IL1\u03b2 secretion upon NLRP3 inflammasome activation. Nat. Commun. 6, 6555. https:\/\/doi.org\/10.1038\/ncomms7555 (2015).","journal-title":"Nat. Commun."},{"key":"74154_CR21","doi-asserted-by":"publisher","unstructured":"Nomura, J. et al. Xanthine oxidase inhibition by febuxostat attenuates experimental atherosclerosis in mice. Sci. Rep. 4. https:\/\/doi.org\/10.1038\/srep04554 (2014).","DOI":"10.1038\/srep04554"},{"key":"74154_CR22","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0075527","volume":"8","author":"J Nomura","year":"2013","unstructured":"Nomura, J. et al. Febuxostat, an Inhibitor of Xanthine Oxidase, Suppresses Lipopolysaccharide-Induced MCP-1 Production via MAPK Phosphatase-1-Mediated Inactivation of JNK. PLoS ONE 8, e75527. https:\/\/doi.org\/10.1371\/journal.pone.0075527 (2013).","journal-title":"PLoS ONE"},{"key":"74154_CR23","doi-asserted-by":"publisher","unstructured":"Kusano, T. et al. Targeted knock-in mice expressing the oxidase-fixed form of xanthine oxidoreductase favor tumor growth. Nat. Commun. 10. https:\/\/doi.org\/10.1038\/s41467-019-12565-z (2019).","DOI":"10.1038\/s41467-019-12565-z"},{"key":"74154_CR24","doi-asserted-by":"publisher","unstructured":"Nishikawa, T. et al. Xanthine oxidase inhibition attenuates insulin resistance and diet-induced steatohepatitis in mice. Scientific Reports 10. https:\/\/doi.org\/10.1038\/s41598-020-57784-3 (2020).","DOI":"10.1038\/s41598-020-57784-3"},{"key":"74154_CR25","doi-asserted-by":"publisher","unstructured":"Guma, M. et al. Xanthine oxidase inhibitor urate-lowering therapy titration to target decreases serum free fatty acids in gout and suppresses lipolysis by adipocytes. Arthritis Res. Ther. 24. https:\/\/doi.org\/10.1186\/s13075-022-02852-4 (2022).","DOI":"10.1186\/s13075-022-02852-4"},{"key":"74154_CR26","doi-asserted-by":"publisher","first-page":"1789","DOI":"10.1136\/annrheumdis-2015-208237","volume":"74","author":"T Neogi","year":"2015","unstructured":"Neogi, T. et al. 2015 Gout classification criteria: an American College of Rheumatology\/European League Against Rheumatism collaborative initiative. Ann. Rheumatic Dis. 74, 1789\u20131798. https:\/\/doi.org\/10.1136\/annrheumdis-2015-208237 (2015).","journal-title":"Ann. Rheumatic Dis."},{"key":"74154_CR27","doi-asserted-by":"publisher","first-page":"1217","DOI":"10.1038\/s41380-021-01339-z","volume":"27","author":"A Campeau","year":"2022","unstructured":"Campeau, A. et al. Multi-omics of human plasma reveals molecular features of dysregulated inflammation and accelerated aging in schizophrenia. Mol. Psychiatry 27, 1217\u20131225. https:\/\/doi.org\/10.1038\/s41380-021-01339-z (2022).","journal-title":"Mol. Psychiatry"},{"key":"74154_CR28","doi-asserted-by":"publisher","first-page":"1501","DOI":"10.1007\/s40265-023-01944-y","volume":"83","author":"R Terkeltaub","year":"2023","unstructured":"Terkeltaub, R. Emerging urate-lowering drugs and pharmacologic treatment strategies for gout: A narrative review. Drugs 83, 1501\u20131521. https:\/\/doi.org\/10.1007\/s40265-023-01944-y (2023).","journal-title":"Drugs"},{"key":"74154_CR29","doi-asserted-by":"publisher","first-page":"1311","DOI":"10.1016\/j.cell.2020.07.040","volume":"182","author":"JM Wozniak","year":"2020","unstructured":"Wozniak, J. M. et al. Mortality risk profiling of staphylococcus aureus bacteremia by multi-omic serum analysis reveals early predictive and pathogenic signatures. Cell 182, 1311-1327.e1314. https:\/\/doi.org\/10.1016\/j.cell.2020.07.040 (2020).","journal-title":"Cell"},{"key":"74154_CR30","doi-asserted-by":"publisher","unstructured":"Chang, W.-C. et al. Genetic variants of PPAR-gamma coactivator 1B augment NLRP3-mediated inflammation in gouty arthritis. Rheumatology, kew337. https:\/\/doi.org\/10.1093\/rheumatology\/kew337 (2016).","DOI":"10.1093\/rheumatology\/kew337"},{"key":"74154_CR31","doi-asserted-by":"publisher","unstructured":"Mckinney, C. et al. Multiplicative interaction of functional inflammasome genetic variants in determining the risk of gout. Arthritis Res. Therapy 17. https:\/\/doi.org\/10.1186\/s13075-015-0802-3 (2015).","DOI":"10.1186\/s13075-015-0802-3"},{"key":"74154_CR32","doi-asserted-by":"publisher","first-page":"1236","DOI":"10.1136\/annrheumdis-2015-207338","volume":"75","author":"A Cumpelik","year":"2016","unstructured":"Cumpelik, A., Ankli, B., Zecher, D. & Schifferli, J. A. Neutrophil microvesicles resolve gout by inhibiting C5a-mediated priming of the inflammasome. Ann. Rheumatic Dis. 75, 1236\u20131245. https:\/\/doi.org\/10.1136\/annrheumdis-2015-207338 (2016).","journal-title":"Ann. Rheumatic Dis."},{"key":"74154_CR33","doi-asserted-by":"publisher","first-page":"815","DOI":"10.1002\/art.37822","volume":"65","author":"S Steiger","year":"2013","unstructured":"Steiger, S. & Harper, J. L. Neutrophil cannibalism triggers transforming growth factor \u03b21 production and self regulation of neutrophil inflammatory function in monosodium urate monohydrate crystal\u2013induced inflammation in mice. Arthritis Rheumatism 65, 815\u2013823. https:\/\/doi.org\/10.1002\/art.37822 (2013).","journal-title":"Arthritis Rheumatism"},{"key":"74154_CR34","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1016\/j.cytogfr.2005.09.007","volume":"17","author":"D Danielpour","year":"2006","unstructured":"Danielpour, D. & Song, K. Cross-talk between IGF-I and TGF-\u03b2 signaling pathways. Cytokine Growth Factor Rev. 17, 59\u201374. https:\/\/doi.org\/10.1016\/j.cytogfr.2005.09.007 (2006).","journal-title":"Cytokine Growth Factor Rev."},{"key":"74154_CR35","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0151509","volume":"11","author":"S Eipper","year":"2016","unstructured":"Eipper, S. et al. Lactoferrin is an allosteric enhancer of the proteolytic activity of cathepsin G. PLOS ONE 11, e0151509. https:\/\/doi.org\/10.1371\/journal.pone.0151509 (2016).","journal-title":"PLOS ONE"},{"key":"74154_CR36","doi-asserted-by":"publisher","first-page":"794","DOI":"10.1002\/art.42413","volume":"75","author":"K Elsaid","year":"2023","unstructured":"Elsaid, K. et al. Amplification of Inflammation by Lubricin Deficiency Implicated in Incident, Erosive Gout Independent of Hyperuricemia. Arthritis Rheumatol. 75, 794\u2013805. https:\/\/doi.org\/10.1002\/art.42413 (2023).","journal-title":"Arthritis Rheumatol."},{"key":"74154_CR37","doi-asserted-by":"publisher","first-page":"268","DOI":"10.1111\/j.1524-475x.2009.00457.x","volume":"17","author":"A Medina","year":"2009","unstructured":"Medina, A., Brown, E., Carr, N. & Ghahary, A. Circulating monocytes have the capacity to be transdifferentiated into keratinocyte-like cells. Wound Repair Regener. 17, 268\u2013277. https:\/\/doi.org\/10.1111\/j.1524-475x.2009.00457.x (2009).","journal-title":"Wound Repair Regener."},{"key":"74154_CR38","doi-asserted-by":"publisher","first-page":"553","DOI":"10.1038\/s41573-019-0025-4","volume":"18","author":"WJM Mulder","year":"2019","unstructured":"Mulder, W. J. M., Ochando, J., Joosten, L. A. B., Fayad, Z. A. & Netea, M. G. Therapeutic targeting of trained immunity. Nat. Rev. Drug Discov. 18, 553\u2013566. https:\/\/doi.org\/10.1038\/s41573-019-0025-4 (2019).","journal-title":"Nat. Rev. Drug Discov."},{"key":"74154_CR39","doi-asserted-by":"publisher","first-page":"1018","DOI":"10.1093\/rheumatology\/kes326","volume":"52","author":"R Grainger","year":"2013","unstructured":"Grainger, R., Mclaughlin, R. J., Harrison, A. A. & Harper, J. L. Hyperuricaemia elevates circulating CCL2 levels and primes monocyte trafficking in subjects with inter-critical gout. Rheumatology 52, 1018\u20131021. https:\/\/doi.org\/10.1093\/rheumatology\/kes326 (2013).","journal-title":"Rheumatology"},{"key":"74154_CR40","doi-asserted-by":"publisher","first-page":"5485","DOI":"10.1073\/pnas.1620910114","volume":"114","author":"TO Cri\u015fan","year":"2017","unstructured":"Cri\u015fan, T. O. et al. Uric acid priming in human monocytes is driven by the AKT\u2013PRAS40 autophagy pathway. Proc. Natl. Acad. Sci. 114, 5485\u20135490. https:\/\/doi.org\/10.1073\/pnas.1620910114 (2017).","journal-title":"Proc. Natl. Acad. Sci."},{"key":"74154_CR41","doi-asserted-by":"publisher","first-page":"107909","DOI":"10.1016\/j.isci.2023.107909","volume":"26","author":"G Cab\u0103u","year":"2023","unstructured":"Cab\u0103u, G. et al. Hyperuricemia remodels the serum proteome toward a higher inflammatory state. iScience 26, 107909. https:\/\/doi.org\/10.1016\/j.isci.2023.107909 (2023).","journal-title":"iScience"},{"key":"74154_CR42","doi-asserted-by":"publisher","unstructured":"Ea, H.-K. et al. Systemic inflammatory cytokine profiles in patients with gout during flare, intercritical and treat-to-target phases: TNFSF14 as new biomarker. Ann. Rheumatic Dis. ard-2023-225305. https:\/\/doi.org\/10.1136\/ard-2023-225305 (2024).","DOI":"10.1136\/ard-2023-225305"},{"key":"74154_CR43","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1161\/atvbaha.118.311022","volume":"39","author":"AAJ Hamers","year":"2019","unstructured":"Hamers, A. A. J. et al. Human monocyte heterogeneity as revealed by high-dimensional mass cytometry. Arteriosclerosis Thrombosis Vasc. Biol. 39, 25\u201336. https:\/\/doi.org\/10.1161\/atvbaha.118.311022 (2019).","journal-title":"Arteriosclerosis Thrombosis Vasc. Biol."},{"key":"74154_CR44","doi-asserted-by":"publisher","first-page":"855","DOI":"10.1093\/geroni\/igaa057.3146","volume":"4","author":"L Haynes","year":"2020","unstructured":"Haynes, L. Immunological heterogeneity. Innov. Aging 4, 855\u2013855. https:\/\/doi.org\/10.1093\/geroni\/igaa057.3146 (2020).","journal-title":"Innov. Aging"},{"key":"74154_CR45","doi-asserted-by":"publisher","unstructured":"Chen, G. et al. Quantitative proteomics by iTRAQ-PRM based reveals the new characterization for gout. Proteome Sci. 19. https:\/\/doi.org\/10.1186\/s12953-021-00180-0 (2021).","DOI":"10.1186\/s12953-021-00180-0"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-024-74154-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-024-74154-5","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-024-74154-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,10,22]],"date-time":"2024-10-22T13:10:53Z","timestamp":1729602653000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-024-74154-5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,10,19]]},"references-count":45,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,12]]}},"alternative-id":["74154"],"URL":"https:\/\/doi.org\/10.1038\/s41598-024-74154-5","relation":{"has-preprint":[{"id-type":"doi","id":"10.21203\/rs.3.rs-4278877\/v1","asserted-by":"object"}]},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,10,19]]},"assertion":[{"value":"17 April 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"24 September 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"19 October 2024","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"DJG: Grant from Janssen Pharmaceuticals RT: Dr. Robert Terkeltaub has recently served, or currently serves, as a consultant for Allena, LG Chem, Fortress, Selecta Biosciences, Horizon Therapeutics, Atom Bioscience, Acquist Therapeutics, Generate Biomedicines, Astra-Zeneca, and Synlogic, and was a previous recipient of a research grant from AstraZeneca. He serves as the non-salaried President of the G-CAN (Gout, Hyperuricemia, and Crystal-Associated Disease Network) research society, which annually receives unrestricted arms-length grant support from pharma donors. The other authors declare that they have no conflict of interest.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}},{"value":"Cohort 1 human subjects were studied under informed consent, and with local IRB approval at the Jennifer Moreno San Diego Veterans Affairs Medical Center. The gout validation Cohort 2, was from the University of Nebraska Medical Center, in Omaha, NE research site, under informed consent and with local IRB approval.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"All authors consent to publication.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}}],"article-number":"24598"}}