{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T06:53:15Z","timestamp":1777013595384,"version":"3.51.4"},"reference-count":61,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T00:00:00Z","timestamp":1773792000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T00:00:00Z","timestamp":1773792000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Neuropathology Appl Neurobio"],"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>\n                      In Duchenne muscular dystrophy (DMD), robust histological markers for assessing early disease progression remain elusive. We defined myofibre density (\n                      <jats:italic>MFD<\/jats:italic>\n                      ) as the count of myofibres per square millimetre, which, in our preliminary survey of DMD muscle biopsies, steeply declined with age (Spearman's\n                      <jats:italic>\u03c1<\/jats:italic>\n                      : \u22120.85). We aimed to characterise age\u2010dependent\n                      <jats:italic>MFD<\/jats:italic>\n                      dynamics in early\u2010stage DMD.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We retrospectively assessed 46 archival muscle\u2010biopsy slides (steroid\u2010na\u00efve; collected &gt;\u200940\u2009years ago) using semi\u2010quantitative image analysis with digital restoration.\n                      <jats:italic>MFD<\/jats:italic>\n                      and classical histological variables were quantified. Age\u2013\n                      <jats:italic>MFD<\/jats:italic>\n                      dynamics were modelled with segmented regression and validated using weakly informative Bayesian modelling. The primary measure was the\n                      <jats:italic>MFD<\/jats:italic>\n                      age\u2010breakpoint. Secondary measures included breakpoint\u2010detection power, age\u2010predictive\n                      <jats:italic>MFD<\/jats:italic>\n                      cut\u2010offs and behaviour of conventional variables across breakpoint\u2010defined age bands.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      After quality and age\u2010distribution screening, 35 slides (age 1\u201311\u2009years) were analysed. Segmented regression identified a breakpoint at 6.25\u2009years (95% confidence interval [CI]: 5.08\u20137.42); after which\n                      <jats:italic>MFD<\/jats:italic>\n                      plateaued at lower levels. Bayesian posterior estimate was 6.37\u2009years (95% credible interval: 5.24\u20137.66). A 10,000\u2010run Monte Carlo simulation (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200935) showed approximately 80% power to recapture the breakpoint within \u00b11.25\u2009years.\n                      <jats:italic>MFD<\/jats:italic>\n                      cut\u2010offs &gt;\u2009596 and &lt;\u2009426\u2009fibres\/mm\n                      <jats:sup>2<\/jats:sup>\n                      corresponded to 80% and 20% probabilities of age &lt;\u20096.25\u2009years. Between the early (&lt;\u20095\u2009years) and late (\u2265\u20097.5\u2009years) age bands defined by the breakpoint\u2013CI limits, myofibre\u2010size parameters, myofibre area and fat replacement shifted significantly.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      <jats:italic>MFD<\/jats:italic>\n                      , a simple metric, reveals a previously unrecognised phase of rapid myofibre loss lasting up to around age 6 in early\u2010stage DMD.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/nan.70068","type":"journal-article","created":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T12:01:01Z","timestamp":1773835261000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Myofibre Density Reveals a Critical Threshold Around Age 6 in Steroid\u2010Na\u00efve Duchenne Muscular Dystrophy: A Retrospective Observational Study"],"prefix":"10.1111","volume":"52","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-1434-5743","authenticated-orcid":false,"given":"Tetsuhiro","family":"Yamakado","sequence":"first","affiliation":[{"name":"Department of Cancer Pathology, Faculty of Medicine Hokkaido University  Sapporo Hokkaido Japan"},{"name":"Department of Pathology National Hospital Organization Hokkaido Medical Center  Sapporo Hokkaido Japan"},{"name":"Center for Neuromuscular Disease Child Health and Development, National Hospital Organization Hokkaido Medical Center  Sapporo Hokkaido Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1406-9768","authenticated-orcid":false,"given":"Yuka","family":"Ishikawa","sequence":"additional","affiliation":[{"name":"Center for Neuromuscular Disease Child Health and Development, National Hospital Organization Hokkaido Medical Center  Sapporo Hokkaido Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9682-9328","authenticated-orcid":false,"given":"Koki","family":"Ise","sequence":"additional","affiliation":[{"name":"Department of Cancer Pathology, Faculty of Medicine Hokkaido University  Sapporo Hokkaido Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6145-395X","authenticated-orcid":false,"given":"Lei","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Cancer Pathology, Faculty of Medicine Hokkaido University  Sapporo Hokkaido Japan"},{"name":"Institute for Chemical Reaction Design and Discovery (WPI\u2010ICReDD), Hokkaido University  Sapporo Hokkaido Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3770-9684","authenticated-orcid":false,"given":"Yoshitaka","family":"Oda","sequence":"additional","affiliation":[{"name":"Department of Cancer Pathology, Faculty of Medicine Hokkaido University  Sapporo Hokkaido Japan"},{"name":"Department of Surgical Pathology Hokkaido University Hospital  Sapporo Hokkaido Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5400-5905","authenticated-orcid":false,"given":"Masumi","family":"Tsuda","sequence":"additional","affiliation":[{"name":"Department of Cancer Pathology, Faculty of Medicine Hokkaido University  Sapporo Hokkaido Japan"},{"name":"Institute for Chemical Reaction Design and Discovery (WPI\u2010ICReDD), Hokkaido University  Sapporo Hokkaido Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-6017-1364","authenticated-orcid":false,"given":"Taichi","family":"Kimura","sequence":"additional","affiliation":[{"name":"Department of Cancer Pathology, Faculty of Medicine Hokkaido University  Sapporo Hokkaido Japan"},{"name":"Department of Pathology National Hospital Organization Hokkaido Medical Center  Sapporo Hokkaido Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4479-1070","authenticated-orcid":false,"given":"Masayoshi","family":"Nagao","sequence":"additional","affiliation":[{"name":"Department of Pediatrics National Hospital Organization Hokkaido Medical Center  Sapporo Hokkaido Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2390-6422","authenticated-orcid":false,"given":"Manabu","family":"Ito","sequence":"additional","affiliation":[{"name":"Department of Orthopedics National Hospital Organization Hokkaido Medical Center  Sapporo Hokkaido Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6470-3301","authenticated-orcid":false,"given":"Shinya","family":"Tanaka","sequence":"additional","affiliation":[{"name":"Department of Cancer Pathology, Faculty of Medicine Hokkaido University  Sapporo Hokkaido Japan"},{"name":"Institute for Chemical Reaction Design and Discovery (WPI\u2010ICReDD), Hokkaido University  Sapporo Hokkaido Japan"},{"name":"Department of Surgical Pathology Hokkaido University Hospital  Sapporo Hokkaido Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3474-2646","authenticated-orcid":false,"given":"Zen\u2010ichi","family":"Tanei","sequence":"additional","affiliation":[{"name":"Department of Cancer Pathology, Faculty of Medicine Hokkaido University  Sapporo Hokkaido Japan"},{"name":"Department of Surgical Pathology Hokkaido University Hospital  Sapporo Hokkaido Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2026,3,18]]},"reference":[{"key":"e_1_2_15_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474\u20104422(18)30024\u20103"},{"key":"e_1_2_15_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474\u20104422(18)30025\u20105"},{"key":"e_1_2_15_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474\u20104422(18)30026\u20107"},{"key":"e_1_2_15_5_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13023\u2010020\u201001430\u20108"},{"key":"e_1_2_15_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/S41572\u2010021\u201000248\u20103"},{"key":"e_1_2_15_7_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000002147"},{"key":"e_1_2_15_8_1","doi-asserted-by":"publisher","DOI":"10.1097\/NEN.0b013e3181aa31c2"},{"key":"e_1_2_15_9_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40478\u2010023\u201001657\u2010z"},{"key":"e_1_2_15_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365\u20102990.2012.01250.x"},{"key":"e_1_2_15_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/nan.12785"},{"key":"e_1_2_15_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/ANA.23982"},{"key":"e_1_2_15_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/14651858.CD003725.pub4"},{"key":"e_1_2_15_14_1","doi-asserted-by":"publisher","DOI":"10.3233\/JND\u2010210776"},{"key":"e_1_2_15_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2019.113086"},{"key":"e_1_2_15_16_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23031832"},{"key":"e_1_2_15_17_1","doi-asserted-by":"publisher","DOI":"10.3233\/JND\u2010210682"},{"key":"e_1_2_15_18_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev\u2010med\u2010081117\u2010010451"},{"key":"e_1_2_15_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13311\u2010022\u201001197\u20109"},{"key":"e_1_2_15_20_1","doi-asserted-by":"publisher","DOI":"10.3233\/JND\u2010210678"},{"key":"e_1_2_15_21_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2023.1183101"},{"key":"e_1_2_15_22_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13023\u2010024\u201003208\u20108"},{"key":"e_1_2_15_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymthe.2018.07.011"},{"key":"e_1_2_15_24_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2020.1484"},{"key":"e_1_2_15_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/mus.880060204"},{"key":"e_1_2_15_26_1","series-title":"Major Problems in Neurology","volume-title":"Muscle Biopsy: A Modern Approach","author":"Dubowitz V.","year":"1973"},{"key":"e_1_2_15_27_1","doi-asserted-by":"publisher","DOI":"10.5604\/01.3001.0010.5278"},{"key":"e_1_2_15_28_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365\u20102559.2012.04333.x"},{"key":"e_1_2_15_29_1","doi-asserted-by":"publisher","DOI":"10.1111\/cpr.13188"},{"key":"e_1_2_15_30_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0225841"},{"key":"e_1_2_15_31_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms232416080"},{"key":"e_1_2_15_32_1","doi-asserted-by":"publisher","DOI":"10.1117\/1.3625288"},{"key":"e_1_2_15_33_1","doi-asserted-by":"publisher","DOI":"10.1101\/pdb.top071795"},{"key":"e_1_2_15_34_1","doi-asserted-by":"publisher","DOI":"10.1088\/2057\u20101976\/ac9847"},{"key":"e_1_2_15_35_1","doi-asserted-by":"publisher","DOI":"10.1002\/sim.1545"},{"key":"e_1_2_15_36_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMe1906559"},{"key":"e_1_2_15_37_1","doi-asserted-by":"publisher","DOI":"10.1212\/wnl.17.9.902"},{"key":"e_1_2_15_38_1","volume-title":"Muscle Pathology for Clinical Practice","author":"Nonaka I.","year":"2021"},{"key":"e_1_2_15_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/0022\u2010510x(91)90068\u2010i"},{"key":"e_1_2_15_40_1","doi-asserted-by":"publisher","DOI":"10.1002\/mus.23902"},{"key":"e_1_2_15_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nmd.2022.02.012"},{"key":"e_1_2_15_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.arcped.2024.05.003"},{"key":"e_1_2_15_43_1","doi-asserted-by":"publisher","DOI":"10.3233\/JND\u2010221527"},{"key":"e_1_2_15_44_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2022.2480"},{"key":"e_1_2_15_45_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000208112"},{"key":"e_1_2_15_46_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature01154"},{"key":"e_1_2_15_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nmd.2020.05.002"},{"key":"e_1_2_15_48_1","doi-asserted-by":"publisher","DOI":"10.3233\/JND\u2010210689"},{"key":"e_1_2_15_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nmd.2022.12.007"},{"key":"e_1_2_15_50_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.4234"},{"key":"e_1_2_15_51_1","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.3819"},{"key":"e_1_2_15_52_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.2554"},{"key":"e_1_2_15_53_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41746\u2010020\u20100260\u20104"},{"key":"e_1_2_15_54_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtho.2021.01.1616"},{"key":"e_1_2_15_55_1","doi-asserted-by":"publisher","DOI":"10.1177\/22143602251360664"},{"key":"e_1_2_15_56_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00330\u2010020\u201006694\u2010z"},{"key":"e_1_2_15_57_1","doi-asserted-by":"publisher","DOI":"10.2463\/mrms.rev.2024\u20100053"},{"key":"e_1_2_15_58_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.crad.2024.04.022"},{"key":"e_1_2_15_59_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000009233"},{"key":"e_1_2_15_60_1","doi-asserted-by":"publisher","DOI":"10.1097\/00000478\u2010200312000\u201000011"},{"key":"e_1_2_15_61_1","doi-asserted-by":"publisher","DOI":"10.1038\/modpathol.2015.38"},{"key":"e_1_2_15_62_1","doi-asserted-by":"publisher","DOI":"10.1136\/practneurol\u20102019\u2010002465"}],"container-title":["Neuropathology and Applied Neurobiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/nan.70068","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/nan.70068","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/nan.70068","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T06:25:02Z","timestamp":1777011902000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/nan.70068"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,18]]},"references-count":61,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2026,4]]}},"alternative-id":["10.1111\/nan.70068"],"URL":"https:\/\/doi.org\/10.1111\/nan.70068","archive":["Portico"],"relation":{},"ISSN":["0305-1846","1365-2990"],"issn-type":[{"value":"0305-1846","type":"print"},{"value":"1365-2990","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,18]]},"assertion":[{"value":"2025-06-27","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-02-19","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-03-18","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70068"}}