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In patients presenting with low back pain (LBP), once specific causes are excluded (fracture, infection, inflammatory arthritis, cancer, cauda equina and radiculopathy) many clinicians pose a diagnosis of non-specific LBP. Accordingly, current management of non-specific LBP is generic. There is a need for a classification of non-specific LBP that is both data- and evidence-based assessing multi-dimensional pain-related factors in a large sample size. The "PRedictive Evidence Driven Intelligent Classification Tool for Low Back Pain" (PREDICT-LBP) project is a prospective cross-sectional study which will compare 300 women and men with non-specific LBP (aged 18-55 years) with 100 matched referents without a history of LBP. Participants will be recruited from the general public and local medical facilities. Data will be collected on spinal tissue (intervertebral disc composition and morphology, vertebral fat fraction and paraspinal muscle size and composition via magnetic resonance imaging [MRI]), central nervous system adaptation (pain thresholds, temporal summation of pain, brain resting state functional connectivity, structural connectivity and regional volumes via MRI), psychosocial factors (e.g. depression, anxiety) and other musculoskeletal pain symptoms. Dimensionality reduction, cluster validation and fuzzy c-means clustering methods, classification models, and relevant sensitivity analyses, will classify non-specific LBP patients into sub-groups. This project represents a first personalised diagnostic approach to non-specific LBP, with potential for widespread uptake in clinical practice. This project will provide evidence to support clinical trials assessing specific treatments approaches for potential subgroups of patients with non-specific LBP. The classification tool may lead to better patient outcomes and reduction in economic costs., Competing Interests: DLB, ST, MT, LS, SeS, HJW, MA, GT, KE, BF, JVO, CTM, PJO, SB, RD, SK declare no conflicts of interest. BB: declares no conflicts of interest relevant to the current work, but has previously received research support, consultancy fees and/or honoraria from AbbVie, Amgen, Biogen, GE/Lunar, Janssen, Galapagos, Gilead, Medimaps, MSD, Sanofi Genzyme, Theramex, UCB. TS: declares prior consulting fees from Johnson & Johnson, Amgen, Kaia Health Software, SpineArt, Implantcast and speaking and travel arrangements from Johnson & Johnson, ICOTEC, Nuvasive, Ulrichmedical, Silony, Amgen, Kaia Health Software. EE-K has received fees from painCert GmbH, Casquar GmbH and Omega Pharma GmbH, outside the submitted work. This does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2023 Belavy et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Methodologies for the quantitative assessment of the spine tissues, in particular the intervertebral disc (IVD), have not been well established in terms of long-term reliability. This is required for designing prospective studies. 1H water T2 in the IVD ("T2") has attained wider use in assessment of the lumbar intervertebral discs via magnetic resonance imaging. The reliability of IVD T2 measurements are yet to be established. IVD T2 was assessed nine times at regular intervals over 368 days on six anatomical slices centred at the lumbar spine using a spin-echo multi-echo sequence in 12 men. To assess repeatability, intra-class correlation co-efficients (ICCs), standard error of the measurement, minimal detectable difference and co-efficients of variation (CVs) were calculated along with their 95% confidence intervals. Bland-Altman analysis was also performed. ICCs were above 0.93, with the exception of nuclear T2 at L5/S1, where the ICC was 0.88. CVs of the central-slice nucleus sub-region ranged from 4.3% (average of all levels) to 10.1% for L5/S1 and between 2.2% to 3.2% for whole IVD T2 (1.8% for the average of all levels). Averaging between vertebral levels improved reliability. Reliability of measurements was least at L5/S1. ICCs of degenerated IVDs were lower. Test-retest reliability was excellent for whole IVD and good to excellent for IVD subregions. The findings help to establish the long-term repeatability of lumbar IVD T2 for the implementation of prospective studies and determination of significant changes within individuals., Competing Interests: The authors have declared that no competing interests exist. YL is employed by Imaging at Olympic Park, a commercial entity. Imaging at Olympic Park had no role in any aspect the study nor in the decision to publish. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Maximising research productivity is a major focus for universities world-wide. Graduate research programs are an important driver of research outputs. Choosing students with the greatest likelihood of success is considered a key part of improving research outcomes. There has been little empirical investigation of what factors drive the outcomes from a student's PhD and whether ranking procedures are effective in student selection. Here we show that, the research environment had a decisive influence: students who conducted research in one of the University's priority research areas and who had experienced, research-intensive, supervisors had significantly better outcomes from their PhD in terms of number of manuscripts published, citations, average impact factor of journals published in, and reduced attrition rates. In contrast, students' previous academic outcomes and research training was unrelated to outcomes. Furthermore, students who received a scholarship to support their studies generated significantly more publications in higher impact journals, their work was cited more often and they were less likely to withdraw from their PhD. The findings suggest that experienced supervisors researching in a priority research area facilitate PhD student productivity. The findings question the utility of assigning PhD scholarships solely on the basis of student academic merit, once minimum entry requirements are met. Given that citations, publication numbers and publications in higher ranked journals drive university rankings, and that publications from PhD student contribute approximately one-third of all research outputs from universities, strengthening research infrastructure and supervision teams may be more important considerations for maximising the contribution of PhD students to a university's international standing., Competing Interests: The authors have declared that no competing interests exist.

Purpose: To measure intervertebral disc (IVD) health parameters in middle-aged long-term runners compared to matched non-physically active controls., Methods: Seventeen males aged 44-62yr were included in the study: 9 runners with a running history of >10yr, averaging >50km/week, and eight matched non-physically active controls, the data from one participant had to be excluded. T2-relaxometry, diffusion weighted imaging, T1- and T2-weighted MR scanning, as well as T2 time mapping were performed. Morphological data relating to IVD were extrapolated., Results: Compared to controls on average, runners had 20% greater IVD height (p = 0.002) and seven percentage points greater IVD-vertebral body height ratio (p = 0.001). No significant differences were observed between groups for mean(SD) IVD hydration status, as indicated by similar T2-times (runners: 94.4(11.1)ms, controls: 88.6(23.6)ms), or apparent diffusion coefficients (runners: 249.0(175.2)mm2/s, controls: 202.3(149.5)mm2/s). Average Pfirrmann score for the L5-S1 IVD was 2.2(0.7) for runners and 3.3(1.0) for controls (p = 0.026), average scores for all lumbar levels (L2-S1) were 1.9(0.2) and 2.5(0.7), respectively (p = 0.036). Anterior annulus T2-time and overall average lumbar level Pfirrmann grades were strongly correlated (r = 0.787, p = 0.021 and r = -0.704, p = 0.034, respectively) with greater distances run per week. Average lumbar level Pfirrmann grades were also strongly correlated (r = -0.823, p = 0.006) to total years of running., Conclusion: Middle-aged long-term endurance runners exhibit less age-related decline in their lumbar IVDs. In addition, the measures of IVD morphology appeared to be better in those who had been running for a greater number of years, as well as in those who ran a greater distance per week., Competing Interests: The authors have declared that no competing interests exist.

Background: Muscle mass and function are perturbed by immobilization and remobilization. When muscle mass changes, the quality and quantity of the extracellular matrix protein, particularly the collagens, change with it. In this study, we investigated the temporal profile of three peptide biomarkers derived from turnover of collagen type III and type VI in a long-term immobilization and remobilization study. We also compared individual biomarker levels with Lean body Mass (LBM) and changes therein, hypothesizing that these biomarkers would be biomarkers of the remodeling processes associated with immobilization and/or remobilization., Methods: In the Berlin bed rest study, 20 young men were recruited and randomly assigned to 8-week's strict bed rest with or without resistive vibration exercise countermeasure. We measured three neo-epitope ELISA kits in the serum samples of this study: Pro-C3, measured the synthesis of collagen type III; Pro-C6, measured the synthesis of collagen type VI; and C6M measured the degradation of collagen type VI induced by MMP-2 and MMP-9 cleavage., Results: Pro-C3 and Pro-C6 biomarkers are up-regulated with both immobilization and remobilization, whereas C6M is hardly affected at all. We found that Pro-C3 and C6M levels are related to LBM at baseline and that high levels of Pro-C6 are associated with smaller changes in muscle mass during both immobilization and remobilization., Conclusion: The Pro-C3 and-C6 biomarkers change likely reflect remodeling changes in response to unloading or reloading, whereas C6M does not appear to respond to unloading. Pro-C3 and C6M levels correlate with LBM at baseline, while Pro-C6 is related to the anabolic and catabolic responses to unloading and reloading.