{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T23:42:38Z","timestamp":1792453358578,"version":"4.5.0"},"reference-count":35,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T00:00:00Z","timestamp":1792368000000},"content-version":"vor","delay-in-days":18,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100003554","name":"Lundbeckfonden","doi-asserted-by":"publisher","award":["R434\u20102023\u2010311"],"award-info":[{"award-number":["R434\u20102023\u2010311"]}],"id":[{"id":"10.13039\/501100003554","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J cachexia sarcopenia muscle"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Skeletal muscle atrophy is a pervasive complication of critical illness that worsens survival and recovery, yet remains poorly explained by current clinical or molecular markers.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>To directly connect disease\u2010associated molecular states to the contractile machinery, this study combined sequential functional, transcriptomic and proteomic profiling of the same single human skeletal myofibres from critically ill patients in the intensive care unit with acquired weakness (ICU\u2010AW) and controls. This integrated approach provides a framework for validating molecular signals directly within the cellular and biomechanical context.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Differential expression analyses between control and ICU\u2010AW myofibres show marked donor\u2010level heterogeneity, with no differentially expressed features (FDR &lt;\u20090.05). Ranked gene set enrichment analyses revealed distinct transcriptional and proteomic signatures between conditions, as well as a subtle yet conserved myofibre state enriched in ICU\u2010AW, characterised by inflammatory and chemotactic gene programmes, intracellular structural remodelling and bioenergetic adaptation. Nineteen features were significantly (FDR &lt;\u20090.05) altered at both RNA and protein levels from the same myofibre. Overall, these 19 overlapping features link an inflammatory transcriptional landscape to a proteomic shift toward mitochondrial and translational machinery, revealing a coordinated stress\u2010adaptation programme with selective post\u2010translational control in fibres from patients with ICU\u2010AW. Further integration with the functional dataset revealed fibres in this state displayed selectively disrupted myosin dynamics, evidenced by prolonged ATP turnover time of myosin heads in their super\u2010relaxed conformation, suggesting altered myosin energetics as a contributor to muscle dysfunction.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>These findings define a discrete, disease\u2010associated myofibre state and validate a proof\u2010of\u2010concept integrative single\u2010fibre framework for connecting multi\u2010omic heterogeneity to molecular motor function in complex human disease. The identification of coordinated transcriptomic and proteomic programmes, validated through functional measurement, suggests that targeting this fibre state may offer new therapeutic opportunities in ICU\u2010acquired dysfunction and related muscle disorders.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/jcsm.70407","type":"journal-article","created":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T23:16:18Z","timestamp":1792451778000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Integrated Single\u2010Myofibre Multi\u2010Omics Correlates Inflammatory State to Myosin Energetics in ICU\u2010Acquired Weakness"],"prefix":"10.1002","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-8934-1103","authenticated-orcid":false,"given":"Alexandra M.","family":"Winant","sequence":"first","affiliation":[{"name":"Department of Biomedical Sciences, Faculty of Health and Medical Sciences University of Copenhagen  Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roger","family":"Moreno\u2010Justicia","sequence":"additional","affiliation":[{"name":"Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences University of Copenhagen  Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4410-5272","authenticated-orcid":false,"given":"Lucia","family":"Paolini","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Specialties, Radiological Sciences and Public Health Universit\u00e0 di Brescia  Brescia Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5154-7311","authenticated-orcid":false,"given":"Wout J.","family":"Claassen","sequence":"additional","affiliation":[{"name":"Amsterdam UMC, Location VUmc Department of Physiology  Amsterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8808-4813","authenticated-orcid":false,"given":"Coen A. C.","family":"Ottenheijm","sequence":"additional","affiliation":[{"name":"Amsterdam UMC, Location VUmc Department of Physiology  Amsterdam the Netherlands"},{"name":"Department of Cellular and Molecular Medicine University of Arizona  Tucson Arizona USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2278-1843","authenticated-orcid":false,"given":"Atul S.","family":"Deshmukh","sequence":"additional","affiliation":[{"name":"Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences University of Copenhagen  Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7562-1053","authenticated-orcid":false,"given":"Stefano","family":"Cattaneo","sequence":"additional","affiliation":[{"name":"ASST Spedali Civili di Brescia, ASST Spedali Civili Dept. of Bone and Joint Surgery  Brescia Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5483-8007","authenticated-orcid":false,"given":"Simone","family":"Piva","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Specialties, Radiological Sciences and Public Health Universit\u00e0 di Brescia  Brescia Italy"},{"name":"Department of Anesthesia, Critical Care and Emergency ASST Spedali Civili University Hospital  Brescia Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2521-5871","authenticated-orcid":false,"given":"Nicola","family":"Latronico","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Specialties, Radiological Sciences and Public Health Universit\u00e0 di Brescia  Brescia Italy"},{"name":"Department of Anesthesia, Critical Care and Emergency ASST Spedali Civili University Hospital  Brescia Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2491-3747","authenticated-orcid":false,"given":"Robert A. 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