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Item Restricted THE ANALYSIS OF A PATIENT SURVIVAL RATE AFTER KIDNEY TRANSPLANTATION IN KAZAKHSTANT(Nazarbayev University School of Medicine, 2023-04-25) Kuspanov, AbualiKidney transplantation has become a broadly used practice in Kazakhstan. However, it is vital to ensure the high survival rates of patients after this procedure. Therefore, this paper is trying to evaluate the extent to which factors such as age, donor type, HLA mismatch, and maintenance therapy affect survival. To perform this, the discharge reports of 77 patients were analyzed, and a database with the variables was created. Then, the Cox and logistic regression models were used to analyze the effect of variables on patient survival. Overall, ten or 13% of death cases were reported among this group, so the patient survival rate is 87%. However, the unadjusted Cox and logistic regression models showed no significant statistical effect of age, gender, donor type, HLA mismatch, and type of drugs used. Although the literature justifies their odds and hazard ratios, the small sample size might be the reason for their insignificant statistical effect. It is recommended to further analyze the patient survival rate with a much larger sample size and other potential risk factors.Item Restricted Assessing the role of EBV in modulation of gene expression profile of H4 neuroglioma and U118 glioblastoma cell lines consistent with Alzheimer's disease(Nazarbayev University School of Medicine, 2024-04-26) Omarova, ZhannurEpstein-Barr virus (EBV), a ubiquitous double-stranded DNA virus, also known as human herpesvirus 4, is implicated in a variety of neurological disorders. It is recognized as a major risk factor for multiple sclerosis. Recent studies have revealed a potential role for EBV infection in the pathogenesis of Alzheimer's disease (AD). EBV is known to influence host gene expression through its proteins and non-coding RNAs, including latent genes such as EBNA1 and LMP, as well as lytic genes such as BZLF1. Extensive research has examined the influence of EBV on cellular gene expression during tumorigenesis, however, little research has been conducted to understand how EBV influences gene expression associated with AD. This study aimed to explore the association between EBV and AD by testing the hypothesis that EBV elements, such as EBNA-1, cause changes in host gene expression consistent with the AD gene expression profile in the nervous tissue. To test this hypothesis, bioinformatics analysis of three GEO AD brain cell type-specific gene expression datasets was performed and the expression changes of the three identified genes – EBF1, EGR1, and GFAP – were examined in EBV-infected and uninfected H4 neuroglioma and U118 glioblastoma cell lines. EBV infection was carried out using cell-free viral supernatant. Changes in gene expression were assessed using qPCR. This study is the first to explore experimental methods for EBV infection of H4 and U118 cells. Although latent EBV infection was not detected in infected cells using primers for EBNA1, EBER1, and EBER2, the levels of EBF1, EGR1, and GFAP in infected cells changed at different days post-infection compared with control cells. Similar to AD brain cell types, EBF1 and GFAP were increased in infected U118 cells compared to uninfected cells. An increase in EGR1 was first observed in both cell lines after infection, followed by a downward trend, consistent with the results of the bioinformatics analysis. Further analysis is needed to assess whether these changes were specifically related to EBV infection. In conclusion, the thesis work highlights the need and importance of more research on the link between EBV infection and AD, as certain cellular changes after EBV infection were similar with brain cell types affected by AD.Item Restricted ASSESSING THE ROLE OF EBV PROTEINS IN AMYLOID-BETA AGGREGATION ASSOCIATED WITH INDUCTION OF ALZHEIMER'S DISEASE(Nazarbayev University School of Medicine, 2024-04-26) Berikkara, AsselBackground: Alzheimer’s disease represents the most prevalent form of neurocognitive decline. The key distinguishing pathological markers within the central nervous system involve the aggregation of senile plaques resulting from a two-step cleavage of the amyloid precursor protein by beta- and gamma-secretase enzymes sequentially. Previous studies have demonstrated a positive correlation between individuals who have mononucleosis due to EBV infection and their increased vulnerability to Alzheimer's disease. Hence, a new outlook on the disease etiology known as the "infectious hypothesis" has directed attention toward the Epstein-Barr virus (EBV), a double-stranded DNA virus, in terms of its potential contribution to plaque formation and inflammation associated with Alzheimer's disease. Methods: H4 neuroglioma and U118 glioblastoma cell lines were directly infected with EBV containing supernatant. The expression of APP and Tau mRNA was detected by qPCR. Protein levels were measured using ELISA with anti-APP antibodies, both before and after viral infection. Virus-free H4 and U118 cell lines were used as controls for comparative statistical analysis of mRNA and protein levels of the APP gene. Results: Infected U118 cell growth was maintained for more than 20 days, while H4 cells died out after the 7th day post-infection. qPCR results showed a consistent decrease in wild-type APP, APP-KPI, and APP-770 mRNA levels throughout the infection period, while Tau protein exhibited a statistically significant decrease in its expression level. In H4 cells, there was a decrease in WT APP and APP-KPI, while tau protein showed an enhanced mRNA level compared to the control. Conclusion: Direct EBV infection of glial cells resulted in alterations in the expression of Alzheimer's disease hallmark genes (WT APP, APP-770, APP-751, and Tau) in both H4 and U118 cell lines in a time-dependent manner.Item Open Access ASSOCIATIONS OF INSULIN RESISTANCE, Β-CELL FUNCTIONING, AND CARDIOVASCULAR RISK FACTORS WITH PREDIABETES IN A WORKING AGE POPULATION FROM TURKISTAN(Nazarbayev University School of Medicine, 2023-04-20) Li, Mariya; Sarria-Santamera, AntonioThe incidence of T2DМ will increase each year since the prevalence of people with prediabetes is even higher. This study is aimed to describe the clinical, biochemical, and metabolic characteristics of people with prediabetes, analyse the effect of insulin resistance (IR) and impaired β-cell function identified by the homeostasis model assessment values on prediabetes, and identify the risk factors for prediabetes, IR and impaired function of β-cell. The data for the study was obtained from workers of the Khoja Akhmet Yassawi International Kazakh-Turkish University (Turkistan, Kazakhstan). The final sample contained 419 participants aged between 27-69, including 237 healthy and 182 prediabetic individuals. Multivariable logistic regression models were computed. This study demonstrated prediabetes population has older age, a high median BMI and systolic blood pressure, high obesity prevalence, and dyslipidemia characteristics. IR and impaired β-cell function are positively correlated with prediabetes. Waist circumference, age, systolic blood pressure, IR, and poor β-cell are risk factors for prediabetes. Prediabetes is positively associated with IR and poor β-cell function. No model was found to describe IR risk factors in the population. Still, it revealed that age and total cholesterol levels could be used to predict poor β-cell function in prediabetic individuals.Item Restricted BURNOUT AMONG INFORMAL CAREGIVERS OF DEMENTIA AND ALZHEIMER’S PATIENTS: SYSTEMATIC REVIEW(Nazarbayev University School of Medicine, 2024-04-23) Rakhimzhanova, DilaraBackground: The increasing prevalence of patients with dementia and Alzheimer’s disease has increased demands for informal caregivers. Due to emotional and physical strain of informal caregivers of patients with neurodegenerative diseases there is a high risk of caregivers being exposed to burnout syndrome. This systematic review aims to combine a current knowledge on prevalence and risk factors of burnout syndrome among informal caregivers of demented patients. Methods: This is a systematic review which was conducted using search of three electronic databases: PubMed; Cochrane Library and Web Of Science, from 1993 to 2024. There was a focus on studies quantitatively measuring burnout in informal caregivers of individuals with both dementia and Alzheimer’s disease. Results: This review included twelve studies conducted in 9 different countries across 5 continents. Four of the studies used the Pines Burnout Measure and five studies used Maslach Burnout Inventory to assess burnout. According to findings of this review, anxiety, depressive symptoms, low quality of life, being a female caregiver, initially poor health of caregiver, lack of positive attitude towards caregiving can bring informal caregivers towards burnout. Conclusion: Specific target interventions should be developed in order to ease the strain of informal caregiving with a consideration of risk factors of the burnout syndrome among family caregivers. There is a desperate need for further research of the topic in order to support a growing community of informal caregivers who are at a high risk of burnout.Item Restricted CD320 as a potential clinical biomarker for GOF p53 mutants in non-small cell lung cancer(Nazarbayev University School of Medicine, 2024-04-26) Tolymbekova, AinurThe CD320 is the receptor responsible for the uptake of vitamin B12 bound to transcobalamin in humans. Due to the heavy reliance on DNA replication, proliferating cells require increased uptake of vitamin B12. Indeed, increased expression of CD320 was observed in many types of cancer, including lung cancer. The unpublished ribosome profiling data indicated increased ribosome protected fragments to mRNA ratio for CD320 in p53 gain-of-function mutant non-small cell lung cancer (NSCLC) cells compared to ones with wild-type p53. That evidence might point to the association between CD320 expression and p53 status. Specifically, it was hypothesized that GOF p53 mutant protein is associated with increased translation of CD320 protein in NSCLC cells. Aim of the study was to induce the TP53 knockout using CRISPR-Cas9 system in three NSCLC cell lines with different p53 status, isolate colonies with 100% KO pull, and assess the expression of CD320 on mRNA and protein level before and after the p53 knockout.Item Open Access DELIVERY OF BIOMATERIALS WITH CYTOKINES AND GROWTH FACTORS FOR MYOCARDIAL INFARCTION TREATMENT(Nazarbayev University School of Medicine, 2024-04-26) Khoschanova, DianaOne of the crucial and highly specialized organs in the human body is heart. It has limited regenerative and self-healing potential after the event of injury or illness. Therefore, heart transplantation is the primary treatment for end-stage cardiovascular disorders at the moment. Cardiovascular disease, particularly ischemic heart disease, continues to be one of the main causes of mortality worldwide. After a heart attack, the injured cardiomyocytes are lost and replaced with fibrotic scar tissue (Hashimoto et al., 2018). Cardiomyocyte loss has several consequences, for instance, the reduction of ventricular contraction, which triggers more cardiomyocyte loss, pathological cardiac dilatation, and ultimately heart failure. These series of events fall under the term “cardiac remodeling” (Tenreiro et al., 2021). The main objective of many treatments has been to prevent the gradual cardiac remodeling that leads to heart failure. Currently available effective treatments are medications, coronary artery bypass grafting, percutaneous coronary intervention and heart transplantation (Head et al., 2018). This paper aims to describe a treatment protocol that includes the sequential administration of a composite cryogel with specific cytokines and growth factors. Firstly, the cryogel containing interleukin-10 (IL-10) was directly injected intramyocardially immediately after the induction of myocardial infarction, with the aim to target the acute inflammatory response. A second injection of cryogel loaded with vascular endothelial growth factor (VEGF) and fibroblast growth factor-2 (FGF-2) was done on day 7 post-MI. The purpose of the second injection was to stimulate tissue regeneration and the formation of new blood vessels (neoangiogenesis). In the cohort treated with Cryogel/GF, the study’s results demonstrated significant myocardial tissue regeneration. Masson’s Trichrome staining verified the echocardiographic findings, which showed decreased fibrotic areas and increased ejection fraction as well as fractional shortening. Therefore, the newly-developed chitosan-based cryogel contains anti-inflammatory and proangiogenic components, making this biomaterial an excellent cargo for the controlled release of therapeutic factors. Consequently, this will significantly improve tissue regeneration post-myocardial infarction. Hypothesis: cryogel containing IL-10 cytokine and VEGF/FGF-2 growth factors delivered sequentially will improve cardiac regeneration after MI.Item Restricted DEVELOPING A SYSTEM FOR ANALYZING THE DOWNSTREAM EFFECTS OF CCL5 DERIVATIVES ON THE CCR5 PATHWAY(Nazarbayev University School of Medicine, 2023) Mustafa, KamshatBackground: Various types of diseases are known to be influenced by the ССL5/ССR5 pathway, including cancers and HIV. Inhibiting the attachment of CCL5 to CCR5 has shown promise in preclinical studies as a way to suppress the growth of the tumor and improve outcomes in cancer patients. In this study, we want to observe how p21, p53, and Mdm2 protein expressions that play important roles in cell growth will change with different modifications of CCL5. We aim to check the level of expression of these proteins in the cell line derived from brеаst саnсеr - МСF-7. Маtеrіаls & Меtһоds: МСF-7, МDА-МВ-231, СНО/CCR5, and СНО/WT cell lines were cultured for further RNA isolation, RT-PCR, and qPCR experiments. RNA isolation and RT-PCR were performed in order to check whether the expected genes exist. In order to check the expression levels of three target proteins quantitative PCR was done. Results: RT-PCR interpretation on a gel showed that cell lines express p21, Mdm2, and GAPDH genes, but failed to show p53. Only MDA-MB-231 cells were positive for CCR5 on a gel. qPCR analysis failed to determine Ct values for GAPDH and p53. That is why we were unable to calculate gene expression values for target genes and the experiment should be repeated.Item Restricted THE EFFECT OF METFORMIN TREATMENT ON AUTOPHAGIC FLUX IN BREAST CANCER(Nazarbayev University Graduate School of Medicine, 2024-04-26) Kazbek, IngkarAutophagy is a lysosome-mediated intracellular catabolic process that is involved in many physiological and pathological conditions, playing an essential role in preserving cellular homeostasis. Consequently, several studies have indicated dysregulation of autophagy in pathological diseases such as cancer and neurodegenerative disorders. Among various cancer types, breast cancer remains the most common in the world. The increased demand for breast cancer treatment requires advanced therapies and new approaches. Metformin, a commonly prescribed drug for type 2 diabetes, has recently attracted attention as a possible pharmacological autophagy modulator with an anticancer activity. Therefore, the goal of this thesis is to clarify the intricate connection between autophagy and the antidiabetic medication metformin by examining its impact on autophagic flux in breast cancer cell lines.Item Embargo ELECTROPORATION AS A TRANSFECTION METHOD FOR MB49 UROTHELIAL CARCINOMA CELL LINE(Nazarbayev University School of Medicine, 2023-04-25) Orazaliyeva, MadinaIn recent years, periostin has gained research interest as a possible prognostic biomarker tool for many cancer types due to its strong correlation with poor prognosis and metastasis. However, in the case of bladder cancer, the physiological role of periostin in its development and progression remains poorly understood. To explore this further, transfection, a research strategy commonly used to examine certain gene functions, was performed. In this study, the MB49 cells, a murine urothelial carcinoma cell line, were transiently transfected with periostin DNA in vitro via electroporation. The study aimed to determine whether electroporation is more effective for transfecting MB49 cells with periostin plasmid than chemical reagents. The results showed that electroporation efficiency was low relative to transfection efficiency obtained using chemical reagents, with a transfection efficiency rate of only 4.22%. This finding suggests that electroporation is not an effective method for transient transfection of MB49 cells with periostin plasmid in vitro compared to transfection using cationic lipid reagents, highlighting the limitations of this transfection method. In future studies, alternative physical and non-physical transfection techniques should be explored to improve the transfection efficiency of MB49 cells.Item Restricted ELUCIDATION OF AUTOPHAGIC FLUX UNDER GLUCOSE AVAILABILITY(Nazarbayev University School of Medicine, 2024-04-26) Zhuban, Aigerim JrAutophagy, crucial for maintaining cell homeostasis and cell renovation, has a significant role in the pathophysiology of various diseases. However, the association between autophagy and glucose accessibility remains insufficiently researched. The main objective of the research is to investigate autophagic flux under different concentrations of glucose, with a particular focus on its implications for cancer and diabetes. The findings of this study were based on the analysis of autophagic flux dynamics performed in MDA-MB231 and MCF7 human breast cancer cell lines subjected to different concentrations of glucose in the culture media. The methodology consisted of advanced laboratory techniques like MTT Assay, Western blotting, and Immunofluorescence Staining. We hypothesized that the pathways of autophagy may alter based on the different glucose availability within a cell. Investigating these dynamics provided insights into the thorough understanding of glucose-mediated autophagy and its relationship with pathologies, especially diabetes and cancer. A comprehensive understanding of the role of glucose in autophagy may have more considerable implications in the fields of medicine and healthcare, particularly in the development of therapeutic approaches to conditions characterized by dysregulated glucose metabolism, such as diabetes. The shift from normal to high glucose conditions did not produce a significant or consistent change in the autophagic flux of the breast cancer cell lines. Consequently, the modifications in glucose concentration within the normal to high range are not sufficient to solely inhibit or induce autophagy in MCF-7 and MDA-MB231 breast cancer cells.Item Restricted EXAMINATION OF THE EFFECTS OF SOCIAL MEDIA ON MENTAL HEALTH OF YOUNG ADULTS IN KAZAKHSTAN: A CROSS SECTIONAL PILOT STUDY(Nazarbayev University School of Medicine, 2024-04-23) Zhamashova, DinaraIntroduction. Previous investigations have shown that the presence and use of SM affects aspects of a person's life, both negatively and positively. The purpose of our study was to examine the association between the amount of screen time, multiple use of SM and level of engagement with SM on mental health of young people in Kazakhstan, focusing on positive mental health, and adjusting for the effect of demographic and health behaviors factors. Methods. A cross-sectional study was used as the study design. Data were collected from December 2023 through January 2024. The inclusion criteria were age from 18 to 35 years old and having a profile in any SM. Questionnaire consisted of 30 questions. Positive mental health (PMH) was measured using Short Warwick–Edinburgh Mental Well-Being Scale (SWEMWBS) scale; depression and anxiety with one-item questions. A total of 235 people participated. Linear and logistic regression were performed for multivariate analysis to predict PMH, depression and anxiety (p<0.05). Variables were also checked for interactions and multicollinearity. Results. Being moderately or not addicted to social media has a positive relationship with PMH. Individuals who spend more than 7 hours of time on social networks and have moderate to severe fear of missing out have increased odds of depression. Furthermore, those who consider themselves very addicted to social networks have higher odds of having anxiety. Conclusion. High amount of screen time and addiction to SM has been found to negatively impact psychological health. Whereas, moderate use of social networks, on the contrary, improves PMH. Further studies are recommended to examine how the nature of the content affects psychological health. In order to improve positive mental health and reduce depressive and anxiety symptoms, moderate use of social media, adequate quality sleep, and exercise are recommended.Item Restricted FACTORS ASSOCIATED WITH ATTITUDES TOWARDS SUCCESSFUL AGING IN MIDDLE-AGED AND OLDER ADULTS IN KAZAKHSTAN: A CROSS-SECTIONAL STUDY(Nazarbayev University School of Medicine, 2024-04-25) Malikova, AigerimBackground: Successful aging is the concept which refers to the ability of an individual to retain a high degree of physical, mental, and social well-being as one ages preferably without the presence of chronic illnesses or other age-related challenges. Attitudes towards aging are a comprehensive personal view of the experience of aging throughout the lifetime, which can be influenced by various factors, such as the levels of health, self-sufficiency, social, physical, psychological and demographic factors. The aim of our study was to identify the factors associated with attitudes towards successful aging among middle-aged and older adults in Kazakhstan by determination of the attitudes towards successful aging and identification of the socio-demographic and health-related factors associated with attitudes towards successful aging among middle-aged and older adults in Kazakhstan. Methods: This study was a quantitative cross-sectional study which involved an online survey targeting middle-aged adults (from 40 to 64) and older seniors (from 65 to 79) with a sample size of 70. The questionnaire was built in Qualtrics survey platform, and the link was disseminated through purposive and convenience sampling methods via social media networks (WhatsApp, Telegram, VK, Instagram). The survey covered socio-demographic information, a 12-item short form of attitudes towards aging questionnaire and health and leisure-time activities questions. The results of the study were obtained through the univariate and bivariate analyses on STATA 18 statistical software. Results: It was found that 27.14% of participants were in the category of 40-49 years, 32.86% in the age group of 50-59 years, 31.43% were the ones who were in 60-69 age category, while only 8.58% of participants belonged to the 70-79 age category. Most of the participants were females (67.14%) and the majority of participants identified themselves as representatives of Kazakh (69.57%) nationality. The average AAQ-SF score was 47.2 (SD ± 4.9) with the high internal consistency of 0.7728 in accordance with Cronbach's alpha score. The average scores of the AAQ-SF scale for the positive dimensions such as physical change and psychological growth were 15.5 (SD ± 2.4) and 16.5 (SD ± 1.6), respectively. While the score for the negative dimension, psychosocial loss, was 14.7 (SD ± 2.9), slightly lower than the other two positive dimensions. The results showed that gender, financial satisfaction, chronic diseases, physical health and mental health were found to be statistically significantly associated with the Attitudes to aging score. Conclusion: Study findings showed that the possible factors positively associated with attitudes towards successful aging were male gender, satisfactory financial status, absence of chronic diseases, good physical and mental health. Findings of this study may serve as one of the potential effective tools to develop public health strategies and health promotion programs aimed to support older adults in maintaining physical health, mental well-being, social connections, and overall quality of life. Keywords: Successful aging, Attitudes to successful aging, Factors influencing attitudes to aging, Middle-aged adults, Older adults, Cross-sectional studyItem Embargo FACTORS ASSOCIATED WITH MENTAL HEALTH AND WELLBEING OF ADULT PEOPLE LIVING WITH HIV IN KAZAKHSTAN(Nazarbayev University School of Medicine, 2024-04-24) Abenova, AdelAbstract Objectives The purpose of the current study was to investigate the association of a range of demographic, physical and psychosocial factors with positive mental health and mental illnesses (depression and anxiety), in adults living with HIV in Kazakhstan. Methods To conduct the current cross-sectional study, the Qualtrics online survey platform was utilized. We collected date from January to February 2024. The study included 170 individuals (18 years and older) living with HIV in Kazakhstan who agreed to participate by signing electronic informed consent. The online survey consisted of overall 48 questions and four parts: (1) Socio-demographic information ; (2) General health information, (3) Mental health , and (4) HIV related stigma. Results Only 33.53% of adults living with HIV are flourishing and have no mental illness. People in flourishing without mental illness group receive more social support. People who rated their physical functioning as mostly able and complete were least likely to fall into the flourishing with mental illness group. People who see themselves as not flourishing or languishing in life, can be more at risk for depression and anxiety due to lack of flourishing. Mental illness without flourishing (languishing) group accounted for 20.59% of the sample. People older than 44 years old are less likely to fall into this group. People who have a good assessment of their ability to perform daily physical activity are less likely to fall into this group. This group presented a high association with internal stigma. People living with HIV falling into this group receive less social support. Conclusions Our study demonstrated that a third of the present sample have positive mental health and are flourishing, and this was associated with high social support. People with more advanced levels of physical functioning were less likely to flourish in the presence of mental illness. Insufficient social support, internal stigma, difficulty in performing daily physical activities and younger age have an significant association with anxiety and depression without flourishing. Continued efforts are recommended on increasing public awareness of HIV infection in Kazakhstan, with a special focus on reducing discrimination in various spheres of life, which affects internal stigmatization and mental health of individuals with HIV in Kazakhstan. Practice implications It is recommended to increase availability of social services and support for individuals with HIV, as this could benefit their mental health and well-being.Item Embargo FUNCTIONAL ANALYSIS OF TYRO3 ISOFORMS IN BLADDER CANCER CELLS(Nazarbayev University School of Medicine, 2024-04-26) Ginayatova, IslanaBladder cancer (BC) is the 10th most common cancer type both in men and women and its incidence increases with age. TYRO3 is increased in 50% of muscle invasive bladder cancer (MIBCs), and TYRO3 overexpression confers TYRO3 dependence on bladder tumor cells. The downregulation of TYRO3 was linked to a decrease in bladder cancer cell growth and TYRO3 knockdown caused bladder cancer cell cycle arrest. The utilization of distinct BC cell lines in the investigations may imply that inhibiting TYRO3 has distinct effects. This thesis work hypothesizes that alternatively spliced TYRO3 isoform 2 is present in the nucleus of T24 and RT112 bladder cancer cells and regulates gene expression. Molecular cloning techniques were used to construct the recombinant plasmid, which were further transfected into T24 and RT112 cell lines and expression of protein were analyzed by Western Blotting method. The results of the thesis project are thoroughly presented and future perspectives are described.Item Restricted GENERAL ATTITUDES TOWARDS AND READINESS FOR MEDICAL ARTIFICIAL INTELLIGENCE AMONG STUDENTS AT NAZARBAYEV UNIVERSITY SCHOOL OF MEDICINE.(Nazarbayev University School of Medicine, 2023-04-25) Sembekova, AnaraIntroduction: Artificial intelligence is taking over the leading positions in medical technologies. AI in healthcare not only performs basic computational tasks, but also exceeds human performance in many areas of healthcare. Aim: This study aims to analyze the attitudes and readiness of students at Nazarbayev University School of Medicine (NUSOM) to the upcoming AI integration. Methods: 91 students were asked to fill out an online survey that collected data of respondents’ characteristics and AI familiarity, general attitudes, and general readiness assessment scales. The General Attitudes towards Artificial Intelligence Scale (GAAIS) developed by Schepman and Rodway (2020) and the Medical Artificial Intelligence Readiness Scale for Medical Students (MAIRS-MS; Karaca et al., 2021) were used in the study. Results: Most of the students had a low knowledge of AI with a mean = 45.56. Majority of the participants did not have any educational experience both in (95.6%) and outside (85.7%) the institution. Positive attitudes section: mean = 2.75 (SD = 0.64), while negative attitudes: mean = 3.01 (SD = 0.81). The readiness mean = 2.42 (SD = 0.60) out of 5.00. Conclusion: The research determined that most of the students had negative to neutral attitudes and poor readiness to medical AI. However, knowledge about AI and positive attitudes had a significant correlation with preparedness. The findings can be used to inform educational policymakers and educational institutions to develop curriculums involving AI, and ensure its ethical and optimized application in medicine. Keywords: artificial intelligence, machine learning, healthcare, medicine, attitudes, readiness, medical studentsItem Restricted Genetic manipulations with the AXL gene in bladder cancer cells using CRISPR-Cas9 system(Nazarbayev University School of Medicine, 2024-04-29) Syzdykova, AizhanThe TAM family of receptor tyrosine kinases (RTKs), composed of AXL, TYRO3, and MER, substantially influences various biological processes during tissue homeostasis (Lemke, 2013). A growing focus within cancer research is centred around the AXL RTK and its ligand GAS6, as abnormal activations and overexpression of the former appear to be linked to cancer progression, poor prognosis, metastasis, and lesser sensitivity to anti-cancer therapies (Lemke, 2013; Wieman et al., 2005). Mediated in a concentration-dependent manner, GAS6 is a ligand not only for AXL but for TYRO3 and MER as well, although its binding affinity is 3- to 10-fold stronger for AXL specifically (Weinger et al., 2009; Wu et al., 2014). AXL is critical in conferring resistance to conventional and targeted cancer treatment (Auyez et al., 2021). It accomplishes this by activating multiple downstream intracellular signalling routes, including AKT, MEK/ERK, and NF-κB, when it binds to GAS6 (Antony & Huang, 2017; Ekman et al., 2010). These pathways collectively create an anti-apoptotic environment, enhancing cellular survival and tumour invasiveness. Additionally, AXL has been implicated in the epithelial-to-mesenchymal transition (EMT), a process essential for cancer metastasis and progression (Antony & Huang, 2017). AXL undergoes a series of post-translational modifications involving proteolytic enzymes like ADAM10 and ADAM17 (Miller et al., 2016; Lu et al., 2017). These enzymes cleave AXL to create its soluble form (sAXL), which can dampen AXL activation by interacting with GAS6 and an intracellular domain (Lu et al., 2017). This mechanism also presents how cancer cells evade therapies targeting the BRAF/MAPK pathway (Rankin & Giaccia, 2016). Elevated sAXL levels in plasma have been correlated with cancer progression to advanced stages in different tumour types, suggesting its potential utility as a biomarker (Martínez- Bosch et al., 2022; Flem-Karlsen et al., 2020). However, a significant gap exists in our understanding, particularly concerning the effect of the inactivation of AXL on its downstream effectors in urinary bladder cancer cell lines . This thesis aims to fill this gap using CRISPR/Cas9 gene editing technology, a novel approach in this field, and inactivating the AXL gene. This will allow us to generate bladder cancer cell lines without AXL, providing a unique opportunity to study its role. This study will also explore the influence of AXL expression on mesenchymal cells. We plan to quantify the expression levels of sAXL in conditioned media obtained from our genetically engineered bladder cancer cell lines. Subsequent analyses will assess the influence of the deactivation on the expression of AXL's nuclear and soluble forms and further AXL's phosphorylation through Western blotting techniques. This thesis aims to shed new light on the complexity of AXL signalling in urinary bladder cancer by employing cutting-edge genome editing technologies. The experience and knowledge gained from this could significantly improve our understanding of cancer biology and potentially guide the development of more effective therapeutic strategies.Item Metadata only HOW DO CTHRC1 AND MATRIX METALLOPROTEINASES AFFECT PATHOLOGIC ACTIVITIES OF FIBROBLAST-LIKE SYNOVIOCYTES IN RHEUMATOID ARTHRITIS?(Nazarbayev University School of Medicine, 2023) Kozhdan, KamilyaRheumatoid arthritis (RA) is an intricate autoimmune condition impacting approximately 1% of the global adult population. One of the key characteristics of this disease is the tendency of activated fibroblast-like synoviocytes (FLS) to invade and damage joint tissues. Recently, there has been a significant focus on discovering biomarkers that can precisely forecast the development of RA. One potential set of biomarkers includes collagen triple helix repeat-containing protein 1 (CTHRC1) and metalloproteinases (MMPs) proteins associated with migration and invasiveness of fibroblast-like synoviocytes, which are responsible for instigating inflammation and joint destruction in RA. The objective of this work is to investigate how CTHRC1 and MMPs are associated with the movement and invasive properties of FLS in the progression of RA. The study aims to assess whether the expression of these proteins can be used to anticipate the development of RA. The research will entail evaluating how CTHRC1 and MMP levels affect FLS pathogenesis. The conventional diagnostic markers for RA were used to show the correlation between potential biomarkers expression and disease activity. The results of this study could be significant for developing new targets for treatment and therapies for RA.Item Open Access INTER- AND INTRA-OBSERVER VARIABILITY OF LEFT VENTRICULAR HEMODYNAMIC FORCES DERIVED FROM FEATURE-TRACKING CARDIAC MAGNETIC RESONANCE.(Nazarbayev University School of Medicine, 2023-04-25) Ismailov, TemirlanHemodynamic forces (HDF) analysis represents a novel approach to quantify intraventricular pressure gradients (IVPG). Recently, a new noninvasive method for evaluating HDF based on feature tracking has been proposed, however data on the reproducibility of this method is still scanty. Thus, the aim of this study is to assess the reproducibility of HDF parameters derived from cardiac magnetic resonance (CMR). Twenty athletes' CMR studies were analyzed by two independent observers and 15 of them were re-analyzed by the same observer one week apart. Intraclass Correlation Coefficient and Bland-Altman plots were used to assess association and agreement of the Longitudinal HDF (A-B), Transverse HDF (L-S), and Impulse Angle. For two different observer measurements, there was a good association for the A-B and L-S (ICC 0.82 and 0.85, respectively; p<0.001), and quite a good association for the Impulse Angle (ICC 0.67; p<0.012). For the same observer's measurements one week apart, the ICC values for A-B, L-S, and Impulse Angle showed excellent correlation and high statistical significance (0.89, 0.93, and 0.82, respectively; p<0.001). The results of this study showed a low inter- and intra-observer variability of HDF parameters derived from CMR.Item Embargo INVESTIGATING THE ROLE OF PERIOSTIN IN RHEUMATOID ARTHRITIS(Nazarbayev University School of Medicine, 2024-04-26) Sarkytbayev, KuanyshRheumatoid Arthritis (RA) is a chronic inflammatory disease, in which the immune system of the organism attacks its own tissue on different body parts (Finckh et al. 2022). Mostly, RA affects the joints of hands, feet, knees, shoulders, etc. According to the World Health Organization, in 2019, about 18 million people worldwide had RA and 70% were women (“Rheumatoid Arthritis,” n.d.). The specific causes of the disease are unknown, but several disease-associated risk factors have been identified, like, smoking, obesity, genetics, gender, and age (Weyand and Goronzy 2021). There are a few publications suggesting some possible roles of periostin in RA disease progression (Brown et al. 2018). Periostin is an extracellular matrix protein that has varying roles in inflammation and tissue remodeling (Sonnenberg-Riethmacher, Miehe, and Riethmacher 2021). It was revealed that periostin is upregulated in synovial cells and fluid of RA patients, which suggests that it may worsen inflammatory conditions in the RA affected body parts (Chijimatsu et al. 2015; Kasperkovitz et al. 2005). However, there are some studies that provide contradictory evidence, which demonstrate after artificial induction of RA in mice, disease progression is more severe in periostin-deficient mice compared to wild-type mice. So, the precise function of periostin in RA pathogenesis remains enigmatic. The aim of this master thesis project was to elucidate the unknown role of the periostin in the RA progression and examine its potential anti-inflammatory properties. Firstly, it was planned to establish a mouse model of rheumatoid arthritis to investigate the comprehensive role of periostin in the disease progression (Caplazi et al. 2015). For this purpose, RA was induced in wild-type and periostin-deficient mice using a collagen-induced arthritis method (Brand, Latham, and Rosloniec 2007; Inglis et al. 2008). After the RA induction, mice were monitored for the disease progression based on the 3 assessment methods: measurement of paw thickness, observation of walking and behavior, and palpation. Then, mice were euthanized and inflamed joints were used for the comparative analysis. Expression of periostin and IL-17 receptor A were analyzed with fluorescent immunohistochemistry. For the histopathological analysis, hematoxylin and eosin staining was implemented to identify structural differences in the inflamed tissue joints. This master thesis project contributes to advancing the knowledge of the periostin role in RA pathogenesis.