Saudi Cultural Missions Theses & Dissertations
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Item Restricted Real-World Monitoring of Physical Activity Using an Accelerometer After Lower Limb Surgery for a Sarcoma.(University College London, 2023) Kaki, Lojain; Furtado, Sherron; Gerrad, Criag; Taylor, Steve; Pandegrass, CatherineIntroduction: Sarcomas are a rare type of cancer that affects bone and soft tissues. There is heterogeneity in the representation of the disease, even the treatment varies from one individual to another. This makes it difficult to provide the best recommendation for aftercare and rehabilitation. The literature lacks information on what actual physical activity levels patients achieve in their homes and communities and how this relates to their quality of life. Objectives: The main aim of this study is to monitor the real-world physical activity levels patients achieve after lower limb surgery for a sarcoma. Other aims are to investigate how physical activity relates to demographics, clinical factors, and other outcomes. Describe which patients perform well compared to those suffering as well as relate it to their quality of life. Methods: Patients were recruited as part of the STOMP (Stanmore Tumor Outcome Measure Project) at the Royal National Orthopedic Hospital NHS Trust, part of the London Sarcoma Service. They were asked to wear an accelerometer-based wearable monitoring device the ActivPAL ™ (PAL Technologies Ltd, Glasgow, Scotland), a triaxial accelerometer that measures the change in posture for seven consecutive days. Additionally, Patients were asked to fill out patient-reported outcome measures (PROMs) (Toronto Extremity Salvage Score (TESS), Modified Reintegration to Normal Living Index (mRNL), Quality of Life for cancer survivors(QoL CS), and EQ-5D). The ActivPAL provides the mean information as the number of steps and activity score (MET.h) which is the energy expenditure and the time spent in sitting, standing, cycling, and lying. The data was analyzed using Statistical Package for the Social Sciences (SPSS). Correlations were investigated using Spearman’s test and predictors of poor outcomes using regression models. Results: 23 patients with 12 bone and 11 soft tissue sarcomas participated. 13 were males and 10 were females. The median age of patients was 48 (IQR 40-63) years, and the time post-surgery was 4 (IQR 2-6) years. 21 underwent limb salvage surgeries and 2 amputations. The median scores of TESS was 76.8, QoL-CS 62.7, mRNL 90.9, and an EQ-5D index value 0.76. 73% of the patients led a sedentary lifestyle, wherein they spent more than 8 hours of their day sitting and lying. Only 2 patients did cycling. A positive significant correlation was seen between the type of sarcoma and PA (r= 0.441, p= 0.045*). Activity scores (MET.h) positively predicted QoL-CS (R2= 0.229, p= 0.021*), and so did number of steps (R2= 0.229, p= 0.021*). Sub-domains revealed that the number of steps positively predicted the psychological domain (R2= 216, p= 0.025*) and so did activity scores (MET.h) (R2= 0.235, p= 0.019*). Conclusion: An accelerometer-based wearable provides an objective snapshot of sarcoma survivors' challenges at home. Sedentary behavior is dominant and physical activity predicts important outcomes regarding quality of life. Physical activity is therefore important to assess and manage using tailored rehabilitation interventions. Along with PROMs and wearables which when combined can provide a detailed real-world perspective of patients’ personal participation restrictions. This identifies high-risk and struggling patients and can trigger timely support and therapy interventions.9 0Item Restricted Validation of Driver Genetic Aberrations in Undifferentiated Pleomorphic Sarcoma: Focus on the Role of YAP1 Utilising a CRISPR/Cas9 Approach.(Saudi Digital Library, 2023-11-21) Alshammari, Ahmad; Sisley, KarenSoft tissue sarcoma (STS) is a rare, diverse group of tumours that are characterised by genetic, pathological and clinical diversity. STS comprise less than 1% of all adult malignancies and consist of more than 100 histological and molecular subtypes. Undifferentiated pleomorphic sarcoma (UPS) is a sarcoma with no specific line of differentiation and a pleomorphic morphology. Although UPS is characterised by complex genetic abnormalities with numerous copy number aberrations, none of these abnormalities are specific to UPS. In this study, three amplified genes, previously identified by our research team as having a potential driver role in UPS tumorigenesis, were functionally analyzed to establish a correlation between the gene expression and the aberrant copy number. Initially, semi-quantitative analysis, by immunocytochemistry and western blotting were performed for YAP1, VGLLl3 and JUN. Based on these analyses, one of these genes, YAP1 was chosen for further study. The effects of YAP1 inhibition on the UPS cell lines, was investigated using a small molecule inhibitor (CA3). The inhibition of YAP1 resulted in a significant reduction of the proliferation of the UPS cells. Moreover, such inhibition resulted in inducing apoptosis in these cells. In the light of these finding, Crispr/Cas9 technology was successfully undertaken on the four UPS cell lines to knock out YAP1. The knockout efficiency was assessed by different approaches, Genomic cleavage detection (GCD) assay, tracking indels by decomposition (TIDE) and Inference of CRISPR Edits (ICE). Consequently, single cell colonies were derived from each cell line to obtain cells with homogeneously edited genomes. For these clones, the impacts of Crispr/Cas9 editing system were evaluated for both mRNA and protein levels. The proliferation, migration and invasion of these clones and their wild-type correspondent were therefore compared to investigate the impact of YAP1 knockout on the development and progression of UPS. Collectively, the findings in this present study suggest a driver role of YAP1 in the UPS tumorigenesis and provide a plausible therapeutic target for UPS treatment.25 0