2e97aecf0200915d442e806e3b2f5089 pmc_31470635.pdf 1cb4573e9ba97ee573154baf4a764b841ce14dd5 pmc_31470635.pdf 869bbdd33225b705b69a257998d7b645583486d8e0aa1a8c1934afd6e0209543 pmc_31470635.pdf Title: Machine Learning to Understand the Immune-Inflammatory Pathways in Fibromyalgia Subject: Fibromyalgia (FM) is a chronic syndrome characterized by widespread musculoskeletal pain, and physical and emotional symptoms. Although its pathophysiology is largely unknown, immune-inflammatory pathways may be involved. We examined serum interleukin (IL)-6, high sensitivity C-reactive protein (hs-CRP), CXCL-8, and IL-10 in 67 female FM patients and 35 healthy women while adjusting for age, body mass index (BMI), and comorbid disorders. We scored the Fibromyalgia Severity Score, Widespread Pain Index (WPI), Symptom Severity Scale (SSS), Hospital Anxiety (HADS-A), and Depression Scale and the Perceived Stress Scale (PSS-10). Clinical rating scales were significantly higher in FM patients than in controls. After adjusting for covariates, IL-6, IL-10, and CXCL-8 were lower in FM than in HC, whereas hs-CRP did not show any difference. Binary regression analyses showed that the diagnosis FM was associated with lowered IL-10, quality of sleep, aerobic activities, and increased HADS-A and comorbidities. Neural networks showed that WPI was best predicted by quality of sleep, PSS-10, HADS-A, and the cytokines, while SSS was best predicted by PSS-10, HADS-A, and IL-10. Lowered levels of cytokines are associated with FM independently from confounders. Lowered IL-6 and IL-10 signaling may play a role in the pathophysiology of FM. Keywords: fibromyalgia; widespread pain; cytokines; inflammation; neuro-immune Author: Laura Andrés-Rodríguez, Xavier Borràs, Albert Feliu-Soler, Adrián Pérez-Aranda, Antoni Rozadilla-Sacanell, Belén Arranz, Jesús Montero-Marin, Javier García-Campayo, Natalia Angarita-Osorio, Michael Maes and Juan V. 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yes yes no 102 0 MCBCCI+SourceSansRoman-Regular Type 1C Custom yes yes no 121 0 MCBCCM+SourceSansRoman.613wght Type 1C Custom yes yes no 122 0 MCBCCO+SourceSansRoman-Bold Type 1C Custom yes yes no 123 0 QLBIEB+URWPalladioL-BoldItal Type 1 Custom yes yes no 195 0 VUPETJ+Rpxb Type 1 Builtin yes yes no 196 0 WSRQGN+Rpxmi Type 1 Builtin yes yes no 212 0 JXPXXJ+EURM10 Type 1 Builtin yes yes no 317 0 TGMEOR+Rpcxr Type 1 Builtin yes yes no 361 0 CRUZTT+VnURWPalladioL-Italic Type 1 Custom yes yes no 464 0 Jhove (Rel. 1.22.1, 2019-04-17) Date: 2020-11-19 06:10:19 CET RepresentationInformation: pmc_31470635.pdf ReportingModule: PDF-hul, Rel. 1.12.1 (2019-04-17) LastModified: 2020-08-03 03:39:58 CEST Size: 656606 Format: PDF Version: 1.5 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 0 FreeObjects: 2 IncrementalUpdates: 0 DocumentCatalog: ViewerPreferences: HideToolbar: false HideMenubar: false HideWindowUI: false FitWindow: true CenterWindow: false DisplayDocTitle: false NonFullScreenPageMode: UseNone Direction: L2R ViewArea: CropBox ViewClip: CropBox PrintArea: CropBox PageClip: CropBox PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: ぉのぴひはつふっぴどはのぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸲ Item: Title: げづびふぬぴびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮ㄩ‾㸊⡜㌷㙜㌷㝜〰こはっどは〭いづねはでひちばとどっぜ〴ぜ〰ちのつぜ〴ぜ〰ぃぬどのどっちぬぜ〴ぜ〰いちぴちぜ〴ぜ〰どのぜ〴ぜ〰ぐちぴどづのぴびぜ〴ぜ〰ちのつぜ〴ぜ〰ぃはのぴひはぬびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮㈩‾㸊⡜㌷㙜㌷㝜〰ぁびびはっどちぴどはのびぜ〴ぜ〰あづぴぷづづのぜ〴ぜ〰ぃべぴはにどのづびぜ〴ぜ〰ちのつぜ〴ぜ〰いどちでのはびどびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮㌩‾㸊⡜㌷㙜㌷㝜〰ぐひづつどっぴどはのぜ〴ぜ〰はてぜ〴ぜ〰うきぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮㐩‾㸊⡜㌷㙜㌷㝜〰げづびふぬぴびぜ〴ぜ〰はてぜ〴ぜ〰ぎぎぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸳ Children: Item: Title: こはっどは〭いづねはでひちばとどっぜ〴ぜ〰ちのつぜ〴ぜ〰ぃぬどのどっちぬぜ〴ぜ〰いちぴちぜ〴ぜ〰どのぜ〴ぜ〰ぐちぴどづのぴびぜ〴ぜ〰ちのつぜ〴ぜ〰ぃはのぴひはぬびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮㈩‾㸊⡜㌷㙜㌷㝜〰ぁびびはっどちぴどはのびぜ〴ぜ〰あづぴぷづづのぜ〴ぜ〰ぃべぴはにどのづびぜ〴ぜ〰ちのつぜ〴ぜ〰いどちでのはびどびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮㌩‾㸊⡜㌷㙜㌷㝜〰ぐひづつどっぴどはのぜ〴ぜ〰はてぜ〴ぜ〰うきぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮㐩‾㸊⡜㌷㙜㌷㝜〰げづびふぬぴびぜ〴ぜ〰はてぜ〴ぜ〰ぎぎぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸳ Item: Title: ぁびびはっどちぴどはのびぜ〴ぜ〰あづぴぷづづのぜ〴ぜ〰ぃべぴはにどのづびぜ〴ぜ〰ちのつぜ〴ぜ〰いどちでのはびどびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮㌩‾㸊⡜㌷㙜㌷㝜〰ぐひづつどっぴどはのぜ〴ぜ〰はてぜ〴ぜ〰うきぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮㐩‾㸊⡜㌷㙜㌷㝜〰げづびふぬぴびぜ〴ぜ〰はてぜ〴ぜ〰ぎぎぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸳ Item: Title: ぐひづつどっぴどはのぜ〴ぜ〰はてぜ〴ぜ〰うきぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮㐩‾㸊⡜㌷㙜㌷㝜〰げづびふぬぴびぜ〴ぜ〰はてぜ〴ぜ〰ぎぎぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸳ Item: Title: げづびふぬぴびぜ〴ぜ〰はてぜ〴ぜ〰ぎぎぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸳ Item: Title: いどびっふびびどはのぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸴ Item: Title: きちぴづひどちぬびぜ〴ぜ〰ちのつぜ〴ぜ〰きづぴとはつびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㐮ㄩ‾㸊⡜㌷㙜㌷㝜〰ぐちひぴどっどばちのぴびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㐮㈩‾㸊⡜㌷㙜㌷㝜〰ぃぬどのどっちぬぜ〴ぜ〰きづちびふひづねづのぴびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㐮㌩‾㸊⡜㌷㙜㌷㝜〰あぬははつぜ〴ぜ〰ぁびびちべびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㐮㐩‾㸊⡜㌷㙜㌷㝜〰こぴちぴどびぴどっびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸵ Children: Item: Title: ぐちひぴどっどばちのぴびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㐮㈩‾㸊⡜㌷㙜㌷㝜〰ぃぬどのどっちぬぜ〴ぜ〰きづちびふひづねづのぴびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㐮㌩‾㸊⡜㌷㙜㌷㝜〰あぬははつぜ〴ぜ〰ぁびびちべびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㐮㐩‾㸊⡜㌷㙜㌷㝜〰こぴちぴどびぴどっびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸵ Item: Title: ぃぬどのどっちぬぜ〴ぜ〰きづちびふひづねづのぴびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㐮㌩‾㸊⡜㌷㙜㌷㝜〰あぬははつぜ〴ぜ〰ぁびびちべびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㐮㐩‾㸊⡜㌷㙜㌷㝜〰こぴちぴどびぴどっびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸵ Item: Title: あぬははつぜ〴ぜ〰ぁびびちべびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㐮㐩‾㸊⡜㌷㙜㌷㝜〰こぴちぴどびぴどっびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸵ Item: Title: 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Annotations: Annotation: Subtype: Link Rect: 177, 715, 214, 725 Annotation: Subtype: Link Rect: 212, 676, 250, 686 Annotation: Subtype: Link Rect: 100, 638, 137, 648 Annotation: Subtype: Link Rect: 143, 638, 179, 648 Annotation: Subtype: Link Rect: 479, 611, 516, 622 Annotation: Subtype: Link Rect: 208, 573, 246, 583 Annotation: Subtype: Link Rect: 252, 573, 288, 583 Annotation: Subtype: Link Rect: 100, 521, 137, 531 Annotation: Subtype: Link Rect: 143, 521, 179, 531 Annotation: Subtype: Link Rect: 136, 470, 173, 480 Annotation: Subtype: Link Rect: 201, 405, 238, 415 Annotation: Subtype: Link Rect: 261, 366, 299, 376 Annotation: Subtype: Link Rect: 479, 340, 516, 351 Annotation: Subtype: Link Rect: 460, 301, 498, 312 Annotation: Subtype: Link Rect: 136, 263, 174, 273 Annotation: Subtype: Link Rect: 180, 263, 216, 273 Annotation: Subtype: Link Rect: 100, 237, 137, 247 Annotation: Subtype: Link Rect: 143, 237, 179, 247 Annotation: Subtype: Link Rect: 323, 211, 361, 222 Annotation: Subtype: Link Rect: 326, 198, 519, 209 Annotation: Subtype: Link Rect: 97, 185, 164, 196 Annotation: Subtype: Link Rect: 76, 143, 166, 174 Annotation: Subtype: Link Rect: 234, 137, 407, 148 Checksum: 70b44e19 Type: CRC32 Checksum: 2e97aecf0200915d442e806e3b2f5089 Type: MD5 Checksum: 1cb4573e9ba97ee573154baf4a764b841ce14dd5 Type: SHA-1