Objective To investigate the role of salivary small non-coding RNAs (sncRNAs) in the diagnosis of sport-related concussion. Methods Saliva was obtained from male professional players in the top two tiers of England’s elite rugby union competition across two seasons (2017–2019). Samples were collected preseason from 1028 players, and during standardised head injury assessments (HIAs) at three time points (in-game, post-game, and 36–48 hours post-game) from 156 of these. Samples were also collected from controls (102 uninjured players and 66 players sustaining a musculoskeletal injury). Diagnostic sncRNAs were identified with next generation sequencing and validated using quantitative PCR in 702 samples. A predictive logistic regression model was built on 2017–2018 data (training dataset) and prospectively validated the following season (test dataset). Results The HIA process confirmed concussion in 106 players (HIA+) and excluded this in 50 (HIA−). 32 sncRNAs were significantly differentially expressed across these two groups, with let-7f-5p showing the highest area under the curve (AUC) at 36–48 hours. Additionally, a combined panel of 14 sncRNAs (let-7a-5p, miR-143-3p, miR-103a-3p, miR-34b-3p, RNU6-7, RNU6-45, Snora57, snoU13.120, tRNA18Arg-CCT, U6-168, U6-428, U6-1249, Uco22cjg1,YRNA_255) could differentiate concussed subjects from all other groups, including players who were HIA− and controls, immediately after the game (AUC 0.91, 95% CI 0.81 to 1) and 36–48 hours later (AUC 0.94, 95% CI 0.86 to 1). When prospectively tested, the panel confirmed high predictive accuracy (AUC 0.96, 95% CI 0.92 to 1 post-game and AUC 0.93, 95% CI 0.86 to 1 at 36–48 hours). Conclusions SCRUM, a large prospective observational study of non-invasive concussion biomarkers, has identified unique signatures of concussion in saliva of male athletes diagnosed with concussion. Data are available upon reasonable request. All data relevant to the study are included in the article or uploaded as supplementary information. Deidentified participant data available on request. Please contact the corresponding authors at the following address: v.dipietro@bham.ac.uk; a.belli@bham.ac.uk.

中文翻译：

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男性运动员唾液中脑震荡的独特诊断特征：通过 MicroRNA (SCRUM) 研究橄榄球联盟中的脑震荡

目的探讨唾液小非编码RNA（sncRNA）在运动相关脑震荡诊断中的作用。方法 唾液取自两个赛季（2017-2019）英格兰精英橄榄球联盟比赛前两级的男性职业球员。从 1028 名球员的季前赛中收集样本，并在其中 156 名球员的三个时间点（赛中、赛后和赛后 36-48 小时）进行标准化头部受伤评估 (HIA)。还从对照组（102 名未受伤的球员和 66 名肌肉骨骼受伤的球员）收集样本。诊断性 sncRNA 通过下一代测序鉴定，并使用定量 PCR 在 702 个样本中进行验证。基于 2017-2018 年数据（训练数据集）建立了预测逻辑回归模型，并前瞻性地验证了下一个赛季（测试数据集）。结果 HIA 过程确认了 106 名球员（HIA+）的脑震荡，并排除了 50 名球员（HIA-）的脑震荡。32 个 sncRNA 在这两组中显着差异表达，let-7f-5p 在 36-48 小时时曲线下面积 (AUC) 最高。此外，一组 14 种 sncRNA（let-7a-5p、miR-143-3p、miR-103a-3p、miR-34b-3p、RNU6-7、RNU6-45、Snora57、snoU13.120、tRNA18Arg-CCT , U6-168, U6-428, U6-1249, Uco22cjg1,YRNA_255) 可以在比赛结束后立即区分脑震荡受试者和所有其他组，包括 HIA− 和对照组的球员 (AUC 0.91, 95% CI 0.81 to 1)和 36-48 小时后（AUC 0.94, 95% CI 0.86 to 1）。在进行前瞻性测试时，专家组确认了高预测准确性（AUC 0.96, 95% CI 0.92 to 1 post-game and AUC 0.93, 95% CI 0.86 to 1 at 36–48 hours）。结论 SCRUM 是一项针对非侵入性脑震荡生物标志物的大型前瞻性观察研究，已经确定了被诊断为脑震荡的男性运动员唾液中脑震荡的独特特征。可根据合理要求提供数据。所有与研究相关的数据都包含在文章中或作为补充信息上传。可根据要求提供身份不明的参与者数据。请通过以下地址联系通讯作者：v.dipietro@bham.ac.uk；a.belli@bham.ac.uk。已经在被诊断患有脑震荡的男性运动员的唾液中确定了独特的脑震荡特征。可根据合理要求提供数据。所有与研究相关的数据都包含在文章中或作为补充信息上传。可根据要求提供身份不明的参与者数据。请通过以下地址联系通讯作者：v.dipietro@bham.ac.uk；a.belli@bham.ac.uk。已经在被诊断患有脑震荡的男性运动员的唾液中确定了独特的脑震荡特征。可根据合理要求提供数据。所有与研究相关的数据都包含在文章中或作为补充信息上传。可根据要求提供身份不明的参与者数据。请通过以下地址联系通讯作者：v.dipietro@bham.ac.uk；a.belli@bham.ac.uk。