SACM - United Kingdom
Permanent URI for this collectionhttps://drepo.sdl.edu.sa/handle/20.500.14154/9667
Browse
1820 results
Search Results
Item Embargo Investigating the ability of statin-mediated ERK5 activation to protect cardiac microvascular endothelial cells and cardiomyocytes against the adverse effects of doxorubicin.(Saudi Digital Library, 0025-04-10) Almaghrabi, Shrouq; Cross, MichaelDoxorubicin is a widely used chemotherapeutic agent known for its efficacy against various cancers; however, its clinical utility is limited by cardiotoxic side effects that involve both endothelial dysfunction and direct cardiomyocyte damage. This doctoral research investigates the protective role of statins—specifically simvastatin and atorvastatin—in mitigating doxorubicin-induced toxicity through activation of the ERK5 signaling pathway. Using human and mouse cardiac microvascular endothelial cells (HCMECs and MCMECs), as well as human cardiomyocyte-like AC16 cells, the study demonstrates that statins restore ERK5 phosphorylation and upregulate vasoprotective transcription factors KLF2 and KLF4. These molecular changes were associated with decreased inflammatory marker expression, preserved tight junction integrity, and improved cellular viability. The findings highlight a novel therapeutic potential for statins in preserving cardiovascular health during chemotherapy and underscore the significance of ERK5 as a molecular target for cardioprotection.28 0Item Restricted Assessing Knowledge, Confidence, and Communication Skills of Healthcare Students in Saudi Arabia Regarding the Risks and Benefits of E-Cigarettes and Vaping: Literature Review Using a Systematic Approach.(Saudi Digital Library, 1995-09-21) Almutairi, Nouf; Sharp, MartinAbstract Background: E-cigarette use poses a dual challenge, offering harm reduction potential but raising concerns over health risks and nicotine addiction. Healthcare students play a vital role in patient education, yet their preparedness to address vaping in Saudi Arabia remains underexplored. Aim: This study aims to evaluate the knowledge, confidence, and communication skills of healthcare students in Saudi Arabia regarding e-cigarettes. It assesses their preparedness to educate patients in comparison to standard expectations of preparedness in healthcare education. Methods: This literature review adopts a systematic approach to synthesise evidence from previous studies. It involves the selection and analysis of nine cross-sectional studies focusing on the knowledge, attitudes, and practices of healthcare students concerning e-cigarettes. The studies were critically appraised using the CASP tool to ensure validity and reliability. The findings were then categorised and analysed to identify gaps in knowledge, confidence levels, and the effectiveness of educational interventions. Results: The review identified significant knowledge gaps about e-cigarette risks and misconceptions regarding their efficacy as smoking cessation tools. Confidence levels in discussing e-cigarettes with patients were low, largely attributed to inadequate formal education. While some students reported gaining knowledge from personal experiences or informal sources like social media, this often perpetuated misinformation. A majority expressed a need for structured education to address these deficiencies. Conclusions: Healthcare students in Saudi Arabia are inadequately prepared to educate patients on e-cigarettes, primarily due to gaps in formal education. To enhance their readiness, it is recommended to integrate comprehensive, evidence-based training on e-cigarettes into healthcare curricula, emphasising hazards, cessation tools, and harm reduction strategies. Addressing these gaps is critical to improving public health outcomes related to vaping.10 0Item Restricted Problems and Benefits Faced by Joint Ventures between MNCS in the Real Estate Sector, as Illustrated by the Joint Venture between the Al-Futtaim Group and the Smith Group(Saudi Digital Library, 2011-12-07) Albishi , Fahad Saeed Daghsh; Durant, AlanAbstract: This study describes benefits and risks the Al-Futtaim Group and the Smith Group are likely to experience as a result of participating in a joint venture tie-up. A structured questionnaire was administered to a set of forty respondents chosen from the managerial levels of the two firms using random and purposive sampling methods. Thirty usable responses are obtained, yielding a survey rate of 75%, and the data thus collected was analyzed by means of the spearman correlation coefficient. Since the findings are based on responses given by managers from the two firms, it is quite possible that a number of risks and benefits beyond the perception of these managers (notwithstanding their experience) may have been overlooked by the study. However, those identified by the study include: the reduction of market entry costs and risks, increased access to new markets, and increased access to new resources and distribution channels. While the preponderance of research studies indicate that national cultural disparities negatively affect the performance of the joint venture, this study finds that this is not the case with the joint venture between the Al-Futtaim Group and the Smith Group. Instead, it suggests that in the case of Al-Futtaim and Smith Group, organizational culture plays a much more substantive role in the success of the merger than do national cultures. The study affirms that the two firms have indeed enjoyed the benefits associated with joint ventures, and finds that such benefits can be generalized for other joint venture partnerships. However, it finds that the impact of culture is context-specific and therefore finds no grounds to make generalizations on that score. A number of recommendations are made, and directions for future research in the same area given.10 0Item Restricted Exploring the Role of Digital Transformation in Enhancing Customer Experience for London Retailers: Strategies and Implementation Challenges(Saudi Digital Library, 1989-09-16) ALSHARMAH , MOFAREH; Chelekis, JessicaIn the findings and discussion of this chapter, we based the findings and discussion of this chapter from survey, case study insight, and literature bases. The study outlined how digital transformation significantly enhances customer experiences through convenience, personalization and accessibility. Retailers using technologies including AI-pushed recommendations, mobile cost alternative, and extra omnichannel methods noticed enriched consumer engagement and satisfaction. Nevertheless, smaller retailers find it difficult to take advantage of digital tools for financial and operational reasons. These survey results also matched existing literature on digital adoption and consumer behavior relating to customers liking seamless digital experiences while they should also be present but concerned about data security and privacy. In addition, in relation to customer satisfaction, the discussion went further on discussing the nexus between digital transformation and customer satisfaction and highlighted the role of strategic planning to customer satisfaction and resource allocation. Companies utilizing personalization and data analytics are more likely to promote higher customer loyalty and retention. Yet, challenges like cybersecurity threats, regulatory compliance and their techno change resistance persist. Also, this highlights the need for retailers to invest in securing the infrastructures, the need for effective change management strategies and the need for retailers to continually adapt as technologies evolve. These challenges can be tackled, and London retailers can optimize their digital strategy to achieve sustainable growth and increased customer satisfaction in a more and more digital retail environment.6 0Item Restricted The Impact of Leadership Styles on Project Team Performance in Educational Settings: A Comprehensive Analysis(Saudi Digital Library, 0006-11-24) Bajabir, Anas; Barber, MartinThis study investigates the impact of leadership styles on project team performance within Nigerian university settings. The study uses a number of different studies to look at how democratic, authoritarian, and laissez-faire leadership styles affect staff morale, teamwork, and how information is shared in schools. With a systematic literature review method, this study looks in depth at how different leadership styles affect how well teams do their work. The reviews divide studies into groups based on how well they respond to two basic research questions. This helps us see how different types of leadership affect project teams in Nigerian universities in a more organised way. The results clearly show that democratic leadership is preferred in Nigerian colleges. This is because it encourages active participation, job happiness, and teamwork, all of which improve the organization's performance. Autocratic and laissez-faire styles, on the other hand, had various results. Letting things happen on their own sometimes made employees lose faith in management, while letting things happen naturally worked well in some places, like university libraries. The study finds that leaders who are open and adaptable, with a background in strategic planning and a focus on meeting the needs of the company, are the best way to get teams to work better in schools. These findings are very important for university managers, policymakers, and educational leaders in Nigeria. They show how important it is to have leadership training and development programs that promote flexible, welcoming management styles. The study also discusses about some problems, like limited access to data and differences in how institutions do things, that make it hard to use the results in other situations. The paper suggests that more research be 6 done on how customised leadership development can improve the performance and behaviour of teams in a range of academic settings.20 0Item Restricted Cancer target discovery for biomarker development, imaging and radionuclide loaded nanoparticle therapy(Saudi Digital Library, 2023-12-04) Shabbir, Rekaya; Choudhury, Ananya; West, Catharine; Smith, TimBackground and aims: Patients with hypoxic muscle invasive bladder cancer (MIBC) have a poor prognosis and overall survival (OS) rate. There is a need to develop biomarkers for informing on hypoxia-targeting therapy. Gene expression signatures can predict benefit from hypoxia modification to improve outcome. Imaging genomics links medical images with molecular profiling to discover imaging biomarkers that could reflect hypoxia. Molecular radiotherapy (MRT) targets specific receptors expressed by cells. The overexpression of EGFR also associates with poor survival rates, EGFR inhibitors are promising but tumour heterogeneity is problematic. The thesis aims were to: 1) identify genes upregulated by hypoxia in bladder cancer cells; 2) investigate whether the West 24-gene bladder hypoxia signature is sensitive to changes in oxygen levels; 3) use MRI to identify hypoxia in large and small tumours in vivo; 4) identify new hypoxia-associated gene panels from transcriptomic data generated in vitro and in vivo; 5) identify bladder cancer hypoxic biomarkers and surface membrane targets for MRT using proteomics in MIBC; and 6) study the uptake and dose-distributions of EGFR-targeted 177Lu or 90Y radiolabelled-AuNPs. Methods: 1) Six BC cell lines (HT1376, T24, J82, UMUC3, RT4, RT112) were exposed to normoxia (21% O2) and hypoxia (1%, 0.1% and 0.2% O2) for 24h. RNA was extracted, transcriptomic data generated using Clariom S Microarrays and expression of hypoxia upregulated genes identified. 2) The data were used to explore changes in West 24-gene signature scores. 3) Small (300mm3) and large (700mm3) xenografts were established for HT1376 MIBC cells. Hypoxia was identified using pimonidazole (PIMO), OE-MRI and DCE-MRI. Differential gene expression was determined. 4) Gene panels were derived from in vitro and in vivo transcriptomic data and tested (log-rank Mantel Cox test) in a TCGA bladder cancer cohort (n=412). Hypoxia scores were generated using the median expression of the genes in a signature/panel. 5) HT1376, T24 and J82 cells were cultured in normoxia (21% O2) and hypoxia (1% and 0.1% O2) for 24h and 48h. Proteins were extracted and analysed using LC-MS and SWATH-MS, and the data used to identify surface membrane targets. Differential expression of EGFR and hypoxia markers (CAIX, GLUT-1) was measured using transcriptomics, proteomics, western blot and EGFR-ELISA. 6) Anti-EGFR conjugated radiolabelled (177Lu or 90Y) AuNPs were used to study dose distributions in vivo. Results: 1) 77 genes were significantly upregulated (padj≤ 0.001) in hypoxia (0.1% O2) across ≥3 cell lines. Three genes (DPYSL2, SYDE1, SLC2A3) were in both the West 24-gene signature and new 77-gene panel. 2) The expression of the 24-gene West signature increased with decreasing O2 levels. 3) Hypoxic regions were identified in small and large xenografted tumours using a combination of OE-MRI and DCE-MRI approaches. The in vivo transcriptomics analysis identified gene expression differences between PIMO-high(hypoxic) and PIMO-low(normoxic) regions and differences in HSs generated from the 24-gene signature (p<0.0052) and the new 77-gene panel (p<0.0025). 4) Gene signatures/panels were prognostic for overall survival: 24-gene (p<0.000064), 77-gene (p<0.01), 3 common genes (p<0.0013). 5) 26 proteins had consistently higher expression in hypoxia across all three cell lines. A gene panel based on the 26 proteins was prognostic in the TCGA cohort (p<0.00065). Eleven plasma membrane proteins were identified as upregulated under hypoxia. No significant differential expression of EGFR was seen in BC cells by hypoxia. The expression of hypoxia markers (CAIX and GLUT-1) was significantly increased by hypoxia using different measurement approaches in all bladder cells. 6) The coefficient of variation of EGFR-targeted 90Y-radiolabelled-AuNPs was less than EGFR-targeted 177Lu-radiolabelled-AuNPs in xenografted tumours. Conclusions: 1) Hypoxia influences the expression of many common genes across different bladder cancer cell lines. 2) The West 24-gene bladder hypoxia score is sensitive to changes in O2 levels in vitro showing it reflects differences in hypoxia. 3) Gene panels derived from hypoxic cells in vitro inform on hypoxia and prognosis 4) The West 24-gene signature performed best as a biomarker of hypoxia. 5) Proteomic profiling identified cell membrane markers to study for MRT. 6) Anti-EGFR radionuclides labelled AuNPs provided insight about the heterogeneity and dosimetry of MRT.5 0Item Restricted SMARTPHONE GNSS LOCALIZATION BY DDP AND PPP TECHNIQUES(University of Nottingham, 2020) Alluhaybi, Abdulaziz; Bingley, Richard; Moore, TerryThis dissertation illustrates the performance of a dual-frequency GNSS chip smartphone in GNSS localization in motion. The GNSS localization was performed using the DDP and PPP methods. The smartphone was in motion on a railway and observed the satellites' data for approximately 90 minutes. The smartphone dual-frequency data was processed as single frequency and code measurements due to the limitations of the GNSS processing software and the smartphone antenna. The accuracy of the smartphone DDP and PPP results were at meter level and very similar to each other, such that the difference did not exceed 1 m in all comparison aspects. In contrast, the difference was vast between the smartphone PPP and a geodetic receiver PPP that was running synchronized with the smartphone on the railway; the geodetic receiver PPP provided an accuracy of centimetre which could be possible from the smartphone in the future, but clearly is not yet possible.17 0Item Restricted Analytical challenges of measring sex steroids in mouse tissues(University of Edinburgh, 2020) Asfour, Asma; Homer, NatalieSex steroid hormones such as estrogens and androgens play a critical role in many areas of biology. Disruption to the balance of sex steroids can lead to metabolic disorders, cerebrovascular and cardiovascular diseases, and cancer. Men with estrogen insufficiency suffer from insulin resistance (IR) and increased visceral fat; while in women estradiol deficiency results in increased risk of metabolic syndrome, lipodystrophy, IR, and hyperandrogenism impairs insulin secretion and leads to type 2 diabetes. Recent observations of a higher incidence of mortality in men with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) suggests there may also be a role of sex hormones in this disease. To investigate the role of sex steroids in diseases then knock out mouse models are used. It is important that sex steroids are accurately measured in these mouse models, in both circulation and in tissues as steroids are known to have systemic but also local action – referred to as intracrinology. Measuring sex steroids accurately and comprehensively in tissues is critical to understanding their role, but this presents an analytical challenge as handling and extracting steroids from tissue is not a simple process and different tissues have different compositions. Historically, sex steroids have been measured by immunoassays in plasma or serum. However, this only allows measurement of one or two steroids in a single sample. There are also concerns over poor sensitivity and cross reactivity of immunoassays for sex steroid measurement. More recently mass spectrometry (MS) coupled with either liquid chromatography (LC) or gas chromatography (GC) have become the methods of choice, and in fact since 2014 this has been a requirement in clinical situations for plasma and serum sex steroid measurement. Mass Spectrometry has the added benefit of being able to profile multiple steroids in a single sample. This review aims 1to assess current published Mass Spectrometry methods used to measure sex hormones within mouse tissue. 14 articles were identified in the past ten years that used LC-MS/MS or GC- MS/MS to measure quantities of sex steroids in mouse tissues indicating that the technology is being used for sex steroid profiling in pre-clinical research tissue samples. The specifics of the methods were compared. Overall, several analytical challenges have been identified in murine tissue sex steroid analysis and need to be overcome in order for preclinical research studies to fully profile sex steroids in tissue. This review highlights that chromatographic MS methods often do not include all method details needed to repeat the method and that tissue homogenisation protocols need to match the tissue type, before extraction of the steroid for analysis. Thus, harmonisation of methods is needed across laboratories to be confident in the results of sex steroid analysis in mouse tissues. Mass spectrometry imaging (MSI) is emerging as an additional bioanalytical tool that allows mapping of sex steroids in tissues. MSI does not result in a concentration; it gives molecular histology of tissues which is important in understanding of intracrinology and regionalisation of steroids and their metabolites. This promises an additional dimension to understanding the role of sex steroids in mouse models.Overall the review indicates that mass spectrometry methods are being used to assess sex steroids in tissues from preclinical mouse models. Challenges of standardisation of methods for homogenisation, extraction and sufficient sensitivity for sex steroids are still to be overcome. Methods would benefit from expansion to profile more steroids, while standardisation of homogenisation and extraction techniques and continued innovation to improve method sensitivity so that more steroids could be profiled in small tissue samples would improve our understanding of the role of sex steroids in preclinical models of disease.7 0Item Restricted The use and evaluation of integrated diagnostics in haematological malignancy(Manchester, 2020-09-30) Altowairqi, Ahlam; Byers, RichardBackground: Haematologic malignancies are one of the most challenging diagnostic fields. Many discrepancies have been reported in diagnoses of this disease over the last few years that affect patient outcomes. Such discrepancies have promoted the introduction of guidelines and classifications to improve identification and predict an optimal therapy approach. The Specialist Integrated Haematological Malignancy Diagnostic Services (SIHMDS), which was introduced in the UK as a special service for haematologic malignancies, to provide a second review, promote multiple techniques for proper diagnosis and prognosis and to choose the best treatment approach. Objectives: This study aims to identify the effectiveness of diagnosing lymphoma using SIHMDS in Manchester by comparing this service to local in MRI and other hospitals diagnoses. Also, it aims to identify the role of interpretation and diagnostic techniques in accurate lymphoma diagnosis. Methods: A total of 2,014 cases were collected from January 2019 to December 2019 from HODS system in SIHMDS. Among these, 295 cases were lymphoma cases and their details were taken from an integrated report. The primary diagnoses of these cases were taken to compare and identify discrepancies. Results: From 295 cases, the discrepancy was 10% in the total cases diagnosed, while the discrepancy rate was lower in MRI (7.4%), and higher in other hospitals by (29%). The role and need of the second review and multiple techniques were confirmed to improve the diagnoses in the special service. Also, needle core biopsy was shown to be useful in lymphoma diagnosis. Conclusion: Introducing special diagnostic service in haematologic malignancies is crucial due to the great benefits of second review and multiple advance techniques. New advances in this field will further improve the diagnosis sensitivity and further enhance patient outcomes.18 0Item Restricted UTILISING HOT MELT EXTRUSION AND FUSED DEPOSITION MODELLING BASED 3D PRINTING TECHNOLOGY FOR THE SYNTHESIS OF SOLID PHARMACEUTICAL DOSAGE FORMS AND INNOVATIVE DRUG DELIVERY DEVICES(University of Birmingham, 2023-05) ALKOLAIB, ALI; Christopher, McConvilleFused deposition modelling (FDM) is a type of three dimensional (3D) printing technology that relies on melt extrusion of thermoplastic materials for the fabrication of objects with virtually limitless opportunities of designs or geometries. Therefore, involving FDM based 3D printing technology in the manufacturing of pharmaceutical dosage forms and medical devices will be a robust method for producing customised pharmaceutical dosage forms and medical devices. Although there are no commercially available solid dosage forms produced by the FDM based 3D printing technology, the past decade has seen an increasing in research efforts that demonstrated the capacity of FDM based 3D printing to produce pharmaceutical dosage forms with customised release profiles, geometries, and dosage forms with multiple drugs (polypills). Therefore, using this type of technology in the pharmaceutical industry will allow for the printing of limitless product designs and overcome the drawbacks of conventional pharmaceutical manufacturing associated with the production of dosage forms based on the ‘one-size-fits-all’ approach. The work conducted herein used hot melt extrusion (HME) and FDM based 3D printing technology to manufacture different solid pharmaceutical dosage forms and novel medical devices. The starting materials prepared in this thesis were prepared using HME technology to incorporate different types of pharmaceutical drugs into various polymers, which were later utilised as feed materials for two different types of FDM based 3D printers: filament-based 3D printer and pellet based 3D printer. The assessment of the prepared drug loaded formulations regarding the mechanical properties, rheological characteristics, drug content and drug homogeneity was conducted to determine the quality of HME extrudates. The first study examined the influence of various 3D printing processing parameters including (infill percentage, infill pattern, printing speed, and layer height) on 3D fabricated solid pharmaceutical dosage form (tablet) manufactured from commercially available drug free polymer; Poly lactic acid (PLA). The analysis assessed how these parameters influenced physical characteristics, including the weight, density, and dimensions of the resulting drug free tablets. In the second study, the investigation and analysis focused on the influence of various 3D parameters on the in vitro drug release profile of 3D printed tablets. Initially, drug loaded polymers were prepared by incorporating caffeine into either the water soluble polymer polyvinyl alcohol (PVA) or the water insoluble polymer PLA utilising HME technology. These HME prepared drug loaded polymers (filaments) underwent characterisation to assess drug loading, filament diameter, extrusion capability, and thermal properties. Subsequently, FDM based 3D printer was employed to manufacture drug loaded tablets, employing different 3D parameters such as infill percentage, layer height, and infill patterns. Finally, the study analysed the impact of these parameters on the in vitro drug release of the fabricated tablets. In the third study of this thesis, the feasibility of FDM based 3D printing technology to manufacture an oral solid dosage form (tablet) containing two different drugs Isoniazid (INH) and Pyridoxine Hydrochloride (PDX) was investigated. The drug combination is commonly used as a monotherapy for the treatment of tuberculosis infection (TB). All the pharmaceutical components of the dosage form were manufactured from FDA approved ingredients. The preparation of the drug loaded polymer formulation was initially performed by the HME process in two different ways. The first method involved loading the two drugs in a single polymer matrix to synthesise single layer tablet. The second method involved loading the drugs separately into two different extrudates and joining them during the 3D printing process using a dual extrusion 3D printer to manufacture a bilayer tablet. The prepared pharmaceutical drug loaded tablets of both types were analysed and compared in terms of in vitro drug release and physical properties.13 0