{
  "abstract": "Background\n\nSkeletal muscle atrophy is a pervasive complication of critical illness that worsens survival and recovery, yet remains poorly explained by current clinical or molecular markers.Methods\n\nTo directly connect disease-associated 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-AW) and controls. This integrated approach provides a framework for validating molecular signals directly within the cellular and biomechanical context.Results\n\nDifferential expression analyses between control and ICU-AW myofibres show marked donor-level heterogeneity, with no differentially expressed features (FDR < 0.05). 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-AW, characterised by inflammatory and chemotactic gene programmes, intracellular structural remodelling and bioenergetic adaptation. Nineteen features were significantly (FDR < 0.05) 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-adaptation programme with selective post-translational control in fibres from patients with ICU-AW. 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-relaxed conformation, suggesting altered myosin energetics as a contributor to muscle dysfunction.Conclusions\n\nThese findings define a discrete, disease-associated myofibre state and validate a proof-of-concept integrative single-fibre framework for connecting multi-omic 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-acquired dysfunction and related muscle disorders.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.",
    "Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.",
    "Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, Università di Brescia, Brescia, Italy.",
    "Amsterdam UMC, Location VUmc, Department of Physiology, Amsterdam, the Netherlands.",
    "Department of Cellular and Molecular Medicine, University of Arizona, Tucson, Arizona, USA.",
    "ASST Spedali Civili di Brescia, ASST Spedali Civili, Dept. of Bone and Joint Surgery, Brescia, Italy.",
    "Department of Anesthesia, Critical Care and Emergency, ASST Spedali Civili University Hospital, Brescia, Italy.",
    "Centre of Human and Applied Physiological Sciences, School of Basic and Medical Biosciences, Faculty of Life Sciences & Medicine, King's College London, London, UK."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 11,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Alexandra M Winant",
      "orcid": "0009-0009-8934-1103"
    },
    {
      "affs": [
        1
      ],
      "name": "Roger Moreno-Justicia"
    },
    {
      "affs": [
        2
      ],
      "name": "Lucia Paolini",
      "orcid": "0000-0002-4410-5272"
    },
    {
      "affs": [
        3
      ],
      "name": "Wout J Claassen",
      "orcid": "0000-0001-5154-7311"
    },
    {
      "affs": [
        3,
        4
      ],
      "name": "Coen A C Ottenheijm",
      "orcid": "0000-0002-8808-4813"
    },
    {
      "affs": [
        1
      ],
      "name": "Atul S Deshmukh",
      "orcid": "0000-0002-2278-1843"
    },
    {
      "affs": [
        5
      ],
      "name": "Stefano Cattaneo",
      "orcid": "0000-0001-7562-1053"
    },
    {
      "affs": [
        2,
        6
      ],
      "name": "Simone Piva",
      "orcid": "0000-0002-5483-8007"
    },
    {
      "affs": [
        2,
        6
      ],
      "name": "Nicola Latronico",
      "orcid": "0000-0002-2521-5871"
    },
    {
      "affs": [
        7
      ],
      "name": "Robert A E Seaborne",
      "orcid": "0000-0003-2491-3747"
    },
    {
      "affs": [
        0
      ],
      "name": "Julien Ochala",
      "orcid": "0000-0002-6358-2920"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/dv9dtrdr8r53b.bib",
  "cited_by": 0,
  "doi": "10.1002/jcsm.70407",
  "fulltext_url": "https://europepmc.org/articles/PMC13680048",
  "id": "dv9dtrdr8r53b",
  "issns": [
    "2190-5991",
    "2190-6009"
  ],
  "landing_url": "https://europepmc.org/article/MED/42896625",
  "language": "eng",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "1312|Muscle Physiology and Disorders"
    ]
  ],
  "openalex": "W7222926979",
  "pdf_url": "https://europepmc.org/articles/PMC13680048?pdf=render",
  "pmcid": "PMC13680048",
  "pmid": "42896625",
  "published": "2026-10-01",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/dv9dtrdr8r53b.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:19:37Z",
      "native_id": "MED:42896625",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42896625"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|Muscle Physiology and Disorders",
      "subfield": "molecular-biology"
    }
  ],
  "title": "Integrated Single-Myofibre Multi-Omics Correlates Inflammatory State to Myosin Energetics in ICU-Acquired Weakness.",
  "title_text": "Integrated Single-Myofibre Multi-Omics Correlates Inflammatory State to Myosin Energetics in ICU-Acquired Weakness.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:19:37Z",
  "url": "https://research.draconitic.com/paper/dv9dtrdr8r53b",
  "venue": "Journal of cachexia, sarcopenia and muscle",
  "versions": []
}