Healthcare applications of single camera markerless motion capture: a scoping review

Funding This work was funded by a University of Aberdeen Elphinstone PhD scholarship. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Peer reviewedPublisher PD

GWAS meta-analysis of intrahepatic cholestasis of pregnancy implicates multiple hepatic genes and regulatory elements

Intrahepatic cholestasis of pregnancy (ICP) is a pregnancy-specific liver disorder affecting 0.5–2% of pregnancies. The majority of cases present in the third trimester with pruritus, elevated serum bile acids and abnormal serum liver tests. ICP is associated with an increased risk of adverse outcomes, including spontaneous preterm birth and stillbirth. Whilst rare mutations affecting hepatobiliary transporters contribute to the aetiology of ICP, the role of common genetic variation in ICP has not been systematically characterised to date. Here, we perform genome-wide association studies (GWAS) and meta-analyses for ICP across three studies including 1138 cases and 153,642 controls. Eleven loci achieve genome-wide significance and have been further investigated and fine-mapped using functional genomics approaches. Our results pinpoint common sequence variation in liver-enriched genes and liver-specific cis-regulatory elements as contributing mechanisms to ICP susceptibility

Genetic determinants of risk in pulmonary arterial hypertension: international genome-wide association studies and meta-analysis

Background Rare genetic variants cause pulmonary arterial hypertension, but the contribution of common genetic variation to disease risk and natural history is poorly characterised. We tested for genome-wide association for pulmonary arterial hypertension in large international cohorts and assessed the contribution of associated regions to outcomes. Methods We did two separate genome-wide association studies (GWAS) and a meta-analysis of pulmonary arterial hypertension. These GWAS used data from four international case-control studies across 11744 individuals with European ancestry (including 2085 patients). One GWAS used genotypes from 5895 whole-genome sequences and the other GWAS used genotyping array data from an additional 5849 individuals. Cross-validation of loci reaching genome-wide significance was sought by meta-analysis. Conditional analysis corrected for the most significant variants at each locus was used to resolve signals for multiple associations. We functionally annotated associated variants and tested associations with duration of survival. All-cause mortality was the primary endpoint in survival analyses. Findings A locus near SOX17 (rs10103692, odds ratio 1·80 [95% CI 1·55–2·08], p=5·13×10– ¹⁵) and a second locus in HLA-DPA1 and HLA-DPB1 (collectively referred to as HLA-DPA1/DPB1 here; rs2856830, 1·56 [1·42–1·71], p=7·65×10– ²⁰) within the class II MHC region were associated with pulmonary arterial hypertension. The SOX17 locus had two independent signals associated with pulmonary arterial hypertension (rs13266183, 1·36 [1·25–1·48], p=1·69×10– ¹²; and rs10103692). Functional and epigenomic data indicate that the risk variants near SOX17 alter gene regulation via an enhancer active in endothelial cells. Pulmonary arterial hypertension risk variants determined haplotype-specific enhancer activity, and CRISPR-mediated inhibition of the enhancer reduced SOX17 expression. The HLA-DPA1/DPB1 rs2856830 genotype was strongly associated with survival. Median survival from diagnosis in patients with pulmonary arterial hypertension with the C/C homozygous genotype was double (13·50 years [95% CI 12·07 to >13·50]) that of those with the T/T genotype (6·97 years [6·02–8·05]), despite similar baseline disease severity. Interpretation This is the first study to report that common genetic variation at loci in an enhancer near SOX17 and in HLA-DPA1/DPB1 is associated with pulmonary arterial hypertension. Impairment of SOX17 function might be more common in pulmonary arterial hypertension than suggested by rare mutations in SOX17. Further studies are needed to confirm the association between HLA typing or rs2856830 genotyping and survival, and to determine whether HLA typing or rs2856830 genotyping improves risk stratification in clinical practice or trials. Funding UK NIHR, BHF, UK MRC, Dinosaur Trust, NIH/NHLBI, ERS, EMBO, Wellcome Trust, EU, AHA, ACClinPharm, Netherlands CVRI, Dutch Heart Foundation, Dutch Federation of UMC, Netherlands OHRD and RNAS, German DFG, German BMBF, APH Paris, INSERM, Université Paris-Sud, and French ANR

Quantifying morphological changes in middle trapezius with ultrasound scanning and a novel histogram-matching algorithm for adults with and without Facioscapulohumeral dystrophy (FSHD)

AbstractBackground and ObjectivesFacioscapulohumeral dystrophy (FSHD) is a neuromuscular disease causing changes in muscle structure that can negatively affect upper-limb function. Echogenicity, measured using quantified muscle ultrasound, is a potential biomarker that could be used for informing decision making. Histogram-matching allows for image normalisation, which could enable comparison of echogenicity between different machine capture settings which is a current limitation. This study aimed to investigate if ultrasonography and histogram-matching can measure trapezius muscle echogenicity and morphology for differentiating between people with and without FSHD, and different levels of arm function.MethodsSingle measurement timepoint case control study of adults with FSHD and age- and sex-matched controls. Main outcomes were trapezius echogenicity and muscle thickness measured using 2D-ultrasound, and maximum thoracohumeral elevation angle, measured using 3D-movement analysis. A sensitivity analysis evaluating the effect of histogram-matching and different reference images was conducted. Between group differences for echogenicity were evaluated using an unpaired student t-test. Echogenicity, muscle thickness and range of movement were plotted to evaluate the explained variance between variables.ResultsData was collected for 14 participants (10M:4F), seven with FSHD and seven controls with a mean (SD) age of 41.6 (15.7). Normalisation was necessary and echogenicity values for the FSHD group were higher than the controls (118.2 (34.0) vs 42.3 (14.0) respectively, with statistically significant differences (p=0.002). An overall variance of 6.2 (LLOA −2.9 to ULOA 15.4) was identified between reference images. Echogenicity accounted for the largest explained variance in muscle thickness (R2=0.81) and range of movement (R2=0.74), whilst muscle thickness and range of movement was the lowest (R2=0.61).DiscussionPeople with FSHD demonstrated higher echogenicity, smaller muscle thicknesses and less range of movement. Histogram-matching for comparison of echogenicity values is necessary and can provide quantifiable differences. Different reference images affect echogenicity values but the variability is less than between group differences. Further work is needed to evaluate the longitudinal variability associated with this method on a larger sample of people with varying levels of arm function. Ultrasound scanning and post-histogram matching may be used to quantify and compare differences in muscle structure and function people with and without FSHD.</jats:sec

Step Length Asymmetry Predicts Rehabilitation Length in Subacute Post Stroke Patients

Background: During the rehabilitation of individuals post stroke, evaluations are performed in order to discern the patient’s prognosis and optimize the treatment plan. However, these tests do not focus on gait symmetry, which might be a predictor for rehabilitation outcomes. We aimed to correlate gait symmetry measures of subacute post stroke patients with rehabilitation outcome and find the symmetry measure that best predicts the variability of the rehabilitation duration. A secondary aim was to compare these measures between patients with right and left brain lesions. Methods: We recruited 30 subacute post stroke patients (14 with right side lesion). We collected the following measures: National Institutes of Health Stroke Scale (NIHSS), Functional Independence Measure (FIM), the 10 m walk test (10MWT), Functional Ambulation Categories (FAC), spatial-temporal gait measures, and gait symmetry and variability. Results: We found moderate correlations between the step length symmetry and the length of rehabilitation, NIHSS, FIM, FAC and 10MWT. The symmetry index of the step length predicted the length of the rehabilitation period as it explained 32.1% of its variance (p = 0.001). Discussion: We conclude that a simple test of the step length symmetry might be informative in predicting rehabilitation length in subacute post stroke patients

Falls in Post-Polio Patients: Prevalence and Risk Factors

Individuals with post-polio syndrome (PPS) suffer from falls and secondary damage. Aim: To (i) analyze the correlation between spatio-temporal gait data and fall measures (fear and frequency of falls) and to (ii) test whether the gait parameters are predictors of fall measures in PPS patients. Methods: Spatio-temporal gait data of 50 individuals with PPS (25 males; age 65.9 ± 8.0) were acquired during gait and while performing the Timed Up-and-Go test. Subjects filled the Activities-specific Balance Confidence Scale (ABC Scale) and reported number of falls during the past year. Results: ABC scores and number of falls correlated with the Timed Up-and-Go, and gait cadence and velocity. The number of falls also correlated with the swing duration symmetry index and the step length variability. Four gait variability parameters explained 33.2% of the variance of the report of falls (p = 0.006). The gait velocity was the best predictor of the ABC score and explained 24.8% of its variance (p = 0.001). Conclusion: Gait variability, easily measured by wearables or pressure-sensing mats, is an important predictor of falls in PPS population. Therefore, gait variability might be an efficient tool before devising a patient-specific fall prevention program for the PPS patient

Children and adolescents with all forms of shoulder instability demonstrate differences in their movement and muscle activity patterns when compared to age- and sex-matched controls.

Shoulder instability is a complex impairment and identifying biomarkers which differentiate subgroups is challenging. There is limited fundamental movement and muscle activity data for identifying different mechanisms for shoulder instability in children and adolescents which may inform subgrouping and treatment allocation. Children and adolescents with shoulder instability (irrespective of etiology) have differences in their movement and muscle activity profiles compared to age- and sex-matched controls (two-tailed). Young people between eight to 18 years were recruited into two groups of shoulder instability (SI) or and age- and sex-matched controls (CG). All forms of SI were included and young people with co-existing neurological pathologies or deficits were excluded. Participants attended a single session and carried out four unweighted and three weighted tasks in which their movements and muscle activity was measured using 3D-movement analysis and surface electromyography. Statistical parametric mapping was used to identify between group differences. Data was collected for 30 young people (15 SI (6M:9F) and 15 CG (8M:7F)). The mean (SD) age for all participants was 13.6 years (3.0). The SI group demonstrated consistently more protracted and elevated sternoclavicular joint positions during all movements. Normalized muscle activity in Latissimus dorsi was lower in the SI group and had the most statistically significant differences across all movements. Where differences were identified, the SI group also had increased normalized activity of their middle trapezius, posterior deltoid and biceps muscles whilst activity of their latissimus dorsi, triceps and anterior deltoid were decreased compared to the CG group. No statistically significant differences were found for pectoralis major across any movements. Weighted tasks produced fewer differences in muscle activity patterns compared to unweighted tasks. Young people with SI may adapt their movements to minimize glenohumeral joint instability. This was demonstrated by reduced variability in acromioclavicular and sternoclavicular joint angles, adoption of different movement strategies across the same joints and increased activity of the scapular stabilizing muscles, despite achieving similar arm positions to the CG. Young people with shoulder instability demonstrated consistent differences in their muscle activity and movement patterns. Consistently observed differences at the shoulder girdle included increased sternoclavicular protraction and elevation accompanied by increased normalized activity of the posterior scapula stabilizing muscles. Existing methods of measurement may be used to inform clinical decision making, however, further work is needed evaluate the prognostic and clinical utility of derived 3D and sEMG data for informing decision making within shoulder instability. [Abstract copyright: Copyright © 2024. Published by Elsevier Inc.

Cushioned Footwear Effect on Pain and Gait Characteristics of Individuals with Knee Osteoarthritis: A Double-Blinded 3 Month Intervention Study

One of the recommendations for individuals with knee osteoarthritis (OA) is the use of specific footwear, such as sturdy or cushioned shoes. However, the long-term use effects of using cushioned shoes on the pain and spatiotemporal gait parameters in individuals with knee OA are yet to be reported. We therefore aimed to compare the efficacy of cushioned sport footwear versus sham shoes on motor functions, pain and gait characteristics of individuals with knee OA who used the shoes for 3 months. In a double-blinded study, we provided 26 individuals with knee OA with cushioned sport shoes and 12 individuals with knee OA with similar sport shoes without cushioning for 3 months. The gait analysis, the timed up and go (TUG) test and the Western Ontario and McMaster Universities Arthritis Index (WOMAC) were conducted and the pain levels were measured at the baseline, 1 month, and 3 months after the baseline. We found that the cushioned shoes reduce the amount of pain (based on WOMAC) in the affected knee and increase functionality in the research group, but not in the control group. Gait velocity and cadence were increased in both groups. Gait spatiotemporal parameters and their symmetry were unaffected during the intervention. We conclude that the use of cushioned shoes should be recommended to individuals with knee OA for alleviating pain

Cell type-specific novel long non-coding RNA and circular RNA in the BLUEPRINT hematopoietic transcriptomes atlas.

Transcriptional profiling of hematopoietic cell subpopulations has helped to characterize the developmental stages of the hematopoietic system and the molecular bases of malignant and non-malignant blood diseases. Previously, only the genes targeted by expression microarrays could be profiled genome-wide. High-throughput RNA sequencing, however, encompasses a broader repertoire of RNA molecules, without restriction to previously annotated genes. We analyzed the BLUEPRINT consortium RNA-sequencing data for mature hematopoietic cell types. The data comprised 90 total RNA-sequencing samples, each composed of one of 27 cell types, and 32 small RNA-sequencing samples, each composed of one of 11 cell types. We estimated gene and isoform expression levels for each cell type using existing annotations from Ensembl. We then used guided transcriptome assembly to discover unannotated transcripts. We identified hundreds of novel non-coding RNA genes and showed that the majority have cell type-dependent expression. We also characterized the expression of circular RNA and found that these are also cell type-specific. These analyses refine the active transcriptional landscape of mature hematopoietic cells, highlight abundant genes and transcriptional isoforms for each blood cell type, and provide a valuable resource for researchers of hematologic development and diseases. Finally, we made the data accessible via a web-based interface: https://blueprint.haem.cam.ac.uk/bloodatlas/.The authors would like to acknowledge the participation of National Institute of Health Research (NIHR) Cambridge BioResource volunteers and thank the NIHR Cambridge BioResource staff for their support. The work was funded by a grant from the European Commission 7th Framework Program (FP7/2007–2013, grant 282510, BLUEPRINT) to XE, PF, JHAM, MY, HGS and WHO. WHO is an NIHR senior investigator and receives funding from Bristol-Myers Squibb, the British Heart Foundation, the Medical Research Council and the NIHR. OGI, FJM, AF, JMM, LC and PF are funded by the Wellcome Trust (WT108749/Z/15/Z) with additional funding for specific project components such as GENCODE from the National Human Genome Research Institute of the National Institutes of Health (2U41HG007234), accordingly the content of this manuscript is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. KD is a HSST trainee supported by NHS Health Education England. NF is funded by the NIHR Cambridge Biomedical Research Centre. FP is supported by the Fundação Carlos Chagas Filho de Amparo à Pesquisado Estado do Rio de Janeiro (FAPERJ; E-26/203.229/2016). NANJ is a recipient of a scholarship from the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - Brasil (CAPES; Finance Code 001). DS work has been supported in part by an Isaac Newton fellowship to MF. MF is supported by the British Heart Foundation (FS/18/53/33863)

Cell type-specific novel long non-coding RNA and circular RNA in the BLUEPRINT hematopoietic transcriptomes atlas.

Transcriptional profiling of hematopoietic cell subpopulations has helped to characterize the developmental stages of the hematopoietic system and the molecular bases of malignant and non-malignant blood diseases. Previously, only the genes targeted by expression microarrays could be profiled genome-wide. High-throughput RNA sequencing, however, encompasses a broader repertoire of RNA molecules, without restriction to previously annotated genes. We analyzed the BLUEPRINT consortium RNA-sequencing data for mature hematopoietic cell types. The data comprised 90 total RNA-sequencing samples, each composed of one of 27 cell types, and 32 small RNA-sequencing samples, each composed of one of 11 cell types. We estimated gene and isoform expression levels for each cell type using existing annotations from Ensembl. We then used guided transcriptome assembly to discover unannotated transcripts. We identified hundreds of novel non-coding RNA genes and showed that the majority have cell type-dependent expression. We also characterized the expression of circular RNA and found that these are also cell type-specific. These analyses refine the active transcriptional landscape of mature hematopoietic cells, highlight abundant genes and transcriptional isoforms for each blood cell type, and provide a valuable resource for researchers of hematologic development and diseases. Finally, we made the data accessible via a web-based interface: https://blueprint.haem.cam.ac.uk/bloodatlas/.The authors would like to acknowledge the participation of National Institute of Health Research (NIHR) Cambridge BioResource volunteers and thank the NIHR Cambridge BioResource staff for their support. The work was funded by a grant from the European Commission 7th Framework Program (FP7/2007–2013, grant 282510, BLUEPRINT) to XE, PF, JHAM, MY, HGS and WHO. WHO is an NIHR senior investigator and receives funding from Bristol-Myers Squibb, the British Heart Foundation, the Medical Research Council and the NIHR. OGI, FJM, AF, JMM, LC and PF are funded by the Wellcome Trust (WT108749/Z/15/Z) with additional funding for specific project components such as GENCODE from the National Human Genome Research Institute of the National Institutes of Health (2U41HG007234), accordingly the content of this manuscript is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. KD is a HSST trainee supported by NHS Health Education England. NF is funded by the NIHR Cambridge Biomedical Research Centre. FP is supported by the Fundação Carlos Chagas Filho de Amparo à Pesquisado Estado do Rio de Janeiro (FAPERJ; E-26/203.229/2016). NANJ is a recipient of a scholarship from the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - Brasil (CAPES; Finance Code 001). DS work has been supported in part by an Isaac Newton fellowship to MF. MF is supported by the British Heart Foundation (FS/18/53/33863)