{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T18:18:52Z","timestamp":1784225932128,"version":"3.55.0"},"reference-count":31,"publisher":"Public Library of Science (PLoS)","issue":"2","license":[{"start":{"date-parts":[[2026,2,3]],"date-time":"2026-02-03T00:00:00Z","timestamp":1770076800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001982","name":"Action for M.E.","doi-asserted-by":"crossref","award":["Clare Francis Research Fellowship"],"award-info":[{"award-number":["Clare Francis Research Fellowship"]}],"id":[{"id":"10.13039\/501100001982","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:p>\n                    Myalgic Encephalomyelitis (ME) \/ Chronic Fatigue Syndrome is a disease of uncertain aetiology that affects up to 400,000 individuals in the UK. Exposure of cultured cells to the sera of people with ME has been proposed to cause phenotypic changes in these cells\n                    <jats:italic>in vitro<\/jats:italic>\n                    when compared to sera from healthy controls. ME serum factors causing these changes could inform the development of diagnostic tests. In this study, we performed a large-scale, pre-registered replication of an experiment from Fluge et al\u00a0(2016) that reported an increase in maximal respiratory capacity in healthy myoblasts after treatment with serum from people with ME compared to serum from healthy controls. We replicated the original experiment with a larger sample size, using sera from 67 people with ME and 53 controls to treat healthy cultured myoblasts, and generated results from over 1,700 mitochondrial stress tests performed with a Seahorse Bioanalyser. We observed no significant differences between treatment with ME or healthy control sera for our primary outcome of interest, oxygen consumption rate at maximal respiratory capacity. Results from our study provide strong evidence against the hypothesis that ME blood factors differentially affect healthy myoblast mitochondrial phenotypes\n                    <jats:italic>in vitro<\/jats:italic>\n                    .\n                  <\/jats:p>","DOI":"10.1371\/journal.pone.0341334","type":"journal-article","created":{"date-parts":[[2026,2,3]],"date-time":"2026-02-03T18:23:08Z","timestamp":1770142988000},"page":"e0341334","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":1,"title":["Indistinguishable mitochondrial phenotypes after exposure of healthy myoblasts to myalgic encephalomyelitis\/chronic fatigue syndrome or control serum"],"prefix":"10.1371","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-2248-2131","authenticated-orcid":true,"given":"Audrey A.","family":"Ryback","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles B.","family":"Hillier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0239-5064","authenticated-orcid":true,"given":"Camila M.","family":"Loureiro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0202-7816","authenticated-orcid":true,"given":"Chris P.","family":"Ponting","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline F.","family":"Dalton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,2,3]]},"reference":[{"key":"pone.0341334.ref001","doi-asserted-by":"crossref","DOI":"10.1093\/hmg\/ddaa169","article-title":"Genetic risk factors of ME\/CFS: a critical review","volume":"29","author":"JJ Dibble","year":"2020","journal-title":"Hum Mol Genet"},{"issue":"1","key":"pone.0341334.ref002","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1186\/s12916-023-02893-9","article-title":"Biomarkers for myalgic encephalomyelitis\/chronic fatigue syndrome (ME\/CFS): a systematic review","volume":"21","author":"R Maksoud","year":"2023","journal-title":"BMC Med"},{"issue":"1","key":"pone.0341334.ref003","doi-asserted-by":"crossref","first-page":"1417","DOI":"10.1186\/s12889-025-22603-9","article-title":"Unequal access to diagnosis of myalgic encephalomyelitis in England","volume":"25","author":"GL Samms","year":"2025","journal-title":"BMC Public Health"},{"issue":"4","key":"pone.0341334.ref004","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1080\/21641846.2022.2124775","article-title":"Research priorities for myalgic encephalomyelitis\/chronic fatigue syndrome (ME\/CFS): the results of a James Lind alliance priority setting exercise","volume":"10","author":"S Tyson","year":"2022","journal-title":"Fatigue Biomed Health Behav"},{"issue":"21","key":"pone.0341334.ref005","doi-asserted-by":"crossref","DOI":"10.1172\/jci.insight.89376","article-title":"Metabolic profiling indicates impaired pyruvate dehydrogenase function in myalgic encephalopathy\/chronic fatigue syndrome","volume":"1","author":"\u00d8 Fluge","year":"2016","journal-title":"JCI Insight"},{"issue":"3","key":"pone.0341334.ref006","doi-asserted-by":"crossref","first-page":"279","DOI":"10.4300\/JGME-D-12-00156.1","article-title":"Using Effect Size-or Why the P Value Is Not Enough","volume":"4","author":"GM Sullivan","year":"2012","journal-title":"J Grad Med Educ"},{"issue":"4","key":"pone.0341334.ref007","doi-asserted-by":"crossref","first-page":"201","DOI":"10.4049\/immunohorizons.2000006","article-title":"Human herpesvirus-6 reactivation, mitochondrial fragmentation, and the coordination of antiviral and metabolic phenotypes in myalgic encephalomyelitis\/chronic fatigue syndrome","volume":"4","author":"P Schreiner","year":"2020","journal-title":"Immunohorizons"},{"key":"pone.0341334.ref008","doi-asserted-by":"crossref","first-page":"106953","DOI":"10.1016\/j.vph.2022.106953","article-title":"Decreased NO production in endothelial cells exposed to plasma from ME\/CFS patients","volume":"143","author":"R Bertinat","year":"2022","journal-title":"Vascul Pharmacol"},{"issue":"8","key":"pone.0341334.ref009","doi-asserted-by":"crossref","first-page":"931","DOI":"10.3390\/ph15080931","article-title":"The Occurrence of Hyperactivated Platelets and Fibrinaloid Microclots in Myalgic Encephalomyelitis\/Chronic Fatigue Syndrome (ME\/CFS)","volume":"15","author":"JM Nunes","year":"2022","journal-title":"Pharmaceuticals (Basel)"},{"key":"pone.0341334.ref010","doi-asserted-by":"crossref","first-page":"103731","DOI":"10.1016\/j.mcn.2022.103731","article-title":"Elevated ATG13 in serum of patients with ME\/CFS 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Beyond myalgic encephalomyelitis\/chronic fatigue syndrome: redefining an illness. 2015."},{"key":"pone.0341334.ref016","unstructured":"National Institute for Health and Care Excellence. Myalgic encephalomyelitis (or encephalopathy)\/chronic fatigue syndrome: diagnosis and management. NICE guideline [NG206]. 2021. Available from: https:\/\/www.nice.org.uk\/guidance\/ng206"},{"key":"pone.0341334.ref017","doi-asserted-by":"crossref","first-page":"20","DOI":"10.3310\/nihropenres.13421.2","article-title":"Typing myalgic encephalomyelitis by infection at onset: A DecodeME study","volume":"3","author":"AD Bretherick","year":"2023","journal-title":"NIHR Open Res"},{"key":"pone.0341334.ref018","article-title":"pandas-dev\/pandas: Pandas 1.0. 5","author":"J Reback","year":"2020","journal-title":"Zenodo"},{"issue":"1","key":"pone.0341334.ref019","doi-asserted-by":"crossref","first-page":"1","DOI":"10.18637\/jss.v067.i01","article-title":"Fitting Linear Mixed-Effects Models Usinglme4","volume":"67","author":"D Bates","year":"2015","journal-title":"J Stat Soft"},{"issue":"13","key":"pone.0341334.ref020","doi-asserted-by":"crossref","first-page":"1","DOI":"10.18637\/jss.v082.i13","article-title":"lmerTest Package: Tests in Linear Mixed Effects Models","volume":"82","author":"A Kuznetsova","year":"2017","journal-title":"J Stat Soft"},{"key":"pone.0341334.ref021","doi-asserted-by":"crossref","DOI":"10.1007\/978-0-387-98141-3","volume-title":"ggplot2: elegant graphics for data analysis","author":"H Wickham","year":"2009"},{"key":"pone.0341334.ref022","author":"E Clarke","year":"2016","journal-title":"ggbeeswarm: Categorical Scatter (Violin Point) Plots. CRAN: Contributed Packages"},{"issue":"4","key":"pone.0341334.ref023","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1111\/j.1467-789X.2007.00347.x","article-title":"A comparison of direct vs. self-report measures for assessing height, weight and body mass index: a systematic review","volume":"8","author":"S Connor Gorber","year":"2007","journal-title":"Obes Rev"},{"issue":"7","key":"pone.0341334.ref024","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0199938","article-title":"OCR-Stats: Robust estimation and statistical testing of mitochondrial respiration activities using Seahorse XF Analyzer","volume":"13","author":"VA Y\u00e9pez","year":"2018","journal-title":"PLoS One"},{"key":"pone.0341334.ref025","unstructured":"Agilent. Application Note: Normalization Technical Guidelines. 2018. Available from: https:\/\/www.agilent.com\/cs\/library\/applications\/application-normalization-technical-guidelines-cell-analysis-5994-0022en-agilent.pdf"},{"issue":"10","key":"pone.0341334.ref026","doi-asserted-by":"crossref","first-page":"1066","DOI":"10.1038\/sj.ijo.0801036","article-title":"Serum leptin concentration in moderate and severe obesity: relationship with clinical, anthropometric and metabolic factors","volume":"23","author":"A Liuzzi","year":"1999","journal-title":"Int J Obes Relat Metab Disord"},{"issue":"4","key":"pone.0341334.ref027","doi-asserted-by":"crossref","first-page":"996","DOI":"10.1038\/s41591-023-02248-0","article-title":"Multiomic signatures of body mass index identify heterogeneous health phenotypes and responses to a lifestyle intervention","volume":"29","author":"K Watanabe","year":"2023","journal-title":"Nat Med"},{"key":"pone.0341334.ref028","first-page":"2025","article-title":"Initial findings from the DecodeME genome-wide association study of myalgic encephalomyelitis\/chronic fatigue syndrome","volume":"2025","author":"T Boutin","year":"2025","journal-title":"medRxiv"},{"issue":"6","key":"pone.0341334.ref029","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1111\/1740-9713.01462","article-title":"Replication Power and Regression to The Mean","volume":"17","author":"L Held","year":"2020","journal-title":"Significance"},{"key":"pone.0341334.ref030","unstructured":"Agilent. 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